Download 1 Comments by the SMM

USE OF PALLIATIVE SURGERY IN THE
TREATMENT OF CANCER PATIENTS
The Norwegian Center for Medical Technology Assessment
(SMM) Report no. 8/2003
Medical method assessment based on a review of the literature conducted by
a group of experts
Preface
Palliative surgical treatment of cancer patients is considered in Norwegian Official
Report no. 1997:20, Care and Knowledge: the Norwegian Cancer Plan. Among other
issues, this report focuses on various treatment principles for cancer and includes a
special section on palliative cancer surgery which underscores the need for more
knowledge about its symptom-preventing potential and calls for a clarification of the
indications for palliative surgical intervention.
The Norwegian Center for Medical Technology Assessment (SMM) was asked by the
Ministry of Health and Social Affairs to conduct a review of the literature on the use
and effect of palliative surgery in cancer patients. The study was conducted as an assessment of medical methods, i.e. a systematic retrieval and critical assessment according to predetermined criteria of all published and available scientific documentation.
To a greater extent, the SMM wants to include the views of patients and users. For this
method assessment we invited the Norwegian Cancer Society to act as a representative
of the users; their comments are included in chapter 5.3 on the ethical aspects of the
use palliative surgery for cancer patients. An appendix presents their views in greater
detail.
The group of experts was constituted in a meeting on 3 March 2000 and has had these
members:
Chair: Professor Karl-Erik Giercksky, The Norwegian Radium Hospital, Oslo
Professor Jon Erik Grønbech, St. Olav University Hospital, Trondheim
Ass. chair of department Tor Hammelbo, Vest-Agder Hospital, Kristiansand
Senior physician Henry Hirschberg, Rikshospitalet University Hospital, Oslo
Professor Tryggve Lundar, Rikshospitalet University Hospital, Oslo
Senior physician Odd Mjåland, Vestfold Hospital, Tønsberg
Senior physician Lodve Stangeland, Haukeland University Hospital, Bergen
Professor Jon Arne Søreide, Rogaland Central Hospital, Stavanger
Senior physician Clement Trovik, Haukeland University Hospital, Bergen
Chair of section Anders Walløe, Ullevaal University Hospital, Oslo
Chair of department Rolf Wahlqvist, Aker University Hospital, Oslo Clinic of Urology
Senior physician Nicolai Wessel, Aker University Hospital, Oslo Clinic of Urology
Project coordinators: research officer Krystyna Hviding and senior research officer
Lise Lund Håheim of the Norwegian Center for Medical Technology Assessment
The following were involved in an early phase of the project:
Senior physician Håkon Wæhre, Innlandet Hospital, Lillehammer
Chair of department Paal-Henning Pedersen, Haukeland University Hospital
Data on palliative surgery in Norwegian hospitals were compiled by senior adviser
Øyvind Christensen and data specialist Daniel Nguyen, both of the Norwegian Patient
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Registry, SINTEF Unimed, and senior adviser Leena Kiviluoto, Patient Funding and
Classification Unit, SINTEF Unimed.
The section of health economics is written by professor Ivar Sønbø Kristiansen and
the chapter on ethical aspects by associate professor Bjørn Hofmann, both of the
SMM. Contributing views from the Norwegian Cancer Society were presented by
information officers Anne-Liv Hval and Anne Grasdal.
All members of the group of experts have declared that they have no competing interests or commercial or other interests related to the project that would prevent them
from contributing to an assessment of the literature that is as objective a possible. The
report has been approved by the SSM’s steering committee. The translation into English is done by Sveinung Løkke.
Berit Mørland
Director
Lise Lund Håheim
Senior research officer
3
Contents
1
Comments by the SMM .......................................................................................... 6
2
Introduction ...........................................................................................................10
2.1 Background ......................................................................................................10
2.2 The group’s terms of reference ........................................................................11
3
Method 14
3.1 Mode of work ....................................................................................................14
3.2 Literature search ..............................................................................................14
3.3 Assessment of the literature .............................................................................16
4
Results 19
4.1 Gastroenterologic surgery ................................................................................19
4.1.1
Dysphagia caused by oesophageal cancer ........................................19
4.1.2
Icterus .................................................................................................24
4.1.3
Retention in pancreatic cancer............................................................26
4.1.4
Retention and/or bleeding in cases of gastric cancer ..........................27
4.1.5
Intestinal obstruction ...........................................................................28
4.1.6
Intestinal bleedings .............................................................................31
4.1.7
Pain • quality of life • prolongation of life .............................................32
4.2 Neurosurgery ....................................................................................................35
4.2.1
Quality of life, neurologic deficiency /svikt/QQQ and survival
in primary cancer of the brain ...........................................................................35
4.2.2
Neurologic deterioration and survival in brain metastasis ...................37
4.2.3
Neurologic deterioration in cases of metastasis to the spine ..............38
4.3 Orthopaedic surgery .........................................................................................40
4.3.1
Surgical treatment of bone metastases ...............................................40
4.3.2
Pain or fracture caused by metastases to the humerus ......................43
4.3.3
Pain or fracture caused by metastases to the femur ...........................43
4.3.4
Pain or fracture caused by metastases to the pelvis ...........................45
4.3.5
Pain or fracture caused by metastases to the spine ...........................46
4.4 Thoracic surgery ...............................................................................................48
4.4.1
Difficulty breathing and survival in metastasis to the lungs .................48
4.4.2
Obstruction of the central airways .......................................................49
4.4.3
Stenosis/occlusion of the superior vena cava .....................................50
4.5 Urologic surgery ...............................................................................................51
4.5.1
Haematuria .........................................................................................53
4.5.2
Urinary retention .................................................................................55
4.5.3
Flank pain ...........................................................................................57
4.5.4
Metabolic disturbances from renal cancer ..........................................57
4.5.5
Vesicovaginal/intestinal fistula ............................................................58
4.5.6
Malignant ureter obstruction ...............................................................58
5
Relevant assessment criteria ...............................................................................61
5.1 Economic aspects of palliative cancer surgery .................................................61
5.2 Palliative cancer surgery in Norwegian hospitals .............................................62
4
5.3 Ethical aspects of palliative surgery for cancer patients ...................................64
5.3.1
The duty to help ..................................................................................65
5.3.2
Compassion and vulnerability .............................................................65
5.3.3
Risk and lack of knowledge.................................................................65
5.3.4
The wish to do ”everything that is possible” ........................................66
5.3.5
Patient autonomy and information ......................................................67
5.3.6
Priorities ..............................................................................................68
Pursuant to Norwegian Official Reports no. 18, 1997, the health services
shall set priorities according to 1) severity, 2) benefits, and 3) cost
efficiency. This is specified in the Patients’ Rights Act (334), from which
it appears that the patient has a right to necessary help if: 1) the patient
either to some extent has a worse prognosis in terms of remaining
lifespan if help is delayed, and 2) the patient may have an expected
benefit of the help, and 3) expected costs are in a reasonable
relationship to the effect of the treatment. Incurable cancer meets the
requirement of severity. For most form of palliative surgery, the benefit
is either poor or undocumented. This does not necessarily imply that
there is no benefit, but that the requirement of documented benefit, b), is
not filled. If the benefit is not known, nothing can be said about cost
efficiency; c) the costs of palliative surgery are considerable (roughly
estimated at 50% of the resources in cancer surgery, cf. chapter 2.1).
Solely on the basis of priority criteria, palliative surgery will not be given
priority. 68
5.3.7
Research and ethics ...........................................................................69
5.3.8
Knowledge and ethics .........................................................................69
6
12
Discussion 71
Appendixes
12.1 Search strategies
12.2 Codes for relevant hospitalisations
5
1 Comments by the SMM
Background
As a follow-up of the Norwegian Cancer Plan, the Norwegian Center for Medical
Technology Assessment (SMM) was commissioned by the Ministry of Health and
Social Affairs with conducting a review of the literature on the use and effects of palliative cancer surgery and palliative procedures in the domain of surgery and examine
the Norwegian practice in this field.
Palliative cancer surgery is an important element in the field of palliation for cancer
patients. It is considered in Norwegian Official Report no. 1997:20, Care and
Knowledge: the Norwegian Cancer Plan, which has a special section devoted to palliative cancer surgery, underscoring the importance of a better knowledge basis on the
effect of this treatment: “Charting the effects of palliative symptom-preventing surgery should be given priority as an important issue in the care for cancer patients in
Norway.” Furthermore, reference is made to a committee set up under the Ministry of
Health and Social Affairs to investigate “Surgical intervention and treatment in palliative cancer therapy” from 1996 which points out the need for registration of treatments carried out: “It is important to establish systems that over time could increase
our knowledge about the impact of palliative surgery that could benefit Norwegian
patients.”
The purpose of palliative cancer surgery is the relief of symptoms and the prolongation of life, not cure. Patients who need such treatment have advanced cancer; the
treatment is directed towards the primary tumour, recidivation, metastases, or local
and regional problems. The methods are many and the surgery can be extensive. The
documentation of the treatment is of varying quality and partly deficient for several
procedures that are carried out, in spite of the great extent of and need for palliative
cancer surgery.
Method and approach
The terms of reference called for a critical review based on systematically identified
literature. It was a considerable task; the work was devided among the five most relevant surgical subspecialties: gastroenterologic surgery, neurosurgery, and orthopaedic,
thoracic and urologic surgery. Problems arising from gynaecologic cancer are mostly
covered by gastroenterologists and urologists.
After a review of 3731 abstracts, 166 studies have been used, with an emphasis on
patient series and a relatively few randomised controlled studies. The evidence level
in the literature selected varied between the fields.
Results
Palliation of symptoms
The group of experts has focused on surgical treatment of symptoms that hinder normal bodily functions as well as other unacceptable torments. A wide variety of treat-
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ment modalities have been used; some have been superceded new methods and are no
longer in use. Some main results of the review of the literature:
Surgical palliation of symptoms includes various way of relieving obstruction in the
alimentary tract: in the oesophagus, the stomach, the intestines, or the cystic tract. The
modalities are mainly bypass surgery, stenting or laser therapy. Stenting is increasingly used in the treatment of icterus or pruritus due to a stenosis in the cystic tract. Laser
therapy can be used for obstruction or bleeding in the oesophagus and in the lower
part of the colon and rectum.
Laser provides immediate relief of symptoms from obstruction in the central airways
and may be combined with other therapies such as stenting and brachytherapy. Stenting has an immediate effect on obstructions in the superior vena cava to the heart.
There are many modes of treatment of symptoms that arise from cancer in the urinary
bladder, prostate and kidneys. Blood in the urine due to prostate cancer or cancer of
the bladder is treated with a well established surgical method. Rinsing of the bladder
with a styptic solution is reasonably well documented.
Treatment of bleeding and also flank pain in cases of stenosis of the renal artery is
reliably documented and has generally speaking superceded conventional surgery.
Stenting can also be used in urinary retention in prostate cancer.
Pinching off of the ureter because of pressure or ingrowth of cancer tissue is now
treated with ostomy of the ureter or stenting of the ureter. These methods applied for
palliative purposes show documented benefit and have, in fact, replaced major urine
diverting operations.
Pain is the major symptom in bone metastases; if radiotherapy does not have the desired effect, surgery may be an option. Treatment of fractures must be done with
/avstivning/ QQQ so that the patient regains function as soon as possible, independently of the degree of healing.
Surgery for metastasis to the brain is beneficial for those with metastasis and an otherwise stable cancer condition. When metastasis to the spine leads to threatening palsies, treatment has to be carried out as soon as possible in order to have effect.
Prolongation of live
Some procedures have been assessed in terms of prolongation of life. There are indications to the effect that gastrectomy in incurable gastric cancer gives longer survival.
Resection of a pulmonary metastasis may increase remaining lifespan. Laser has the
advantage of saving lung tissue and it improves the chances of resecting metastases
that are difficult to access. Resecting the tumour instead of biopsy in glioma multiforme gives longer survival; so does resecting the metastasis in addition to radiotherapy.
Palliative procedures
Our review shows that elective palliative procedures, on the basis of documented effect, may be subdivided into four main groups:
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– A small number of procedures that in controlled clinical trials or large series of
patients have been shown to have a reliable and measurable effect compared to
other procedures. Examples included the use of laser or stenting for obstructions
of the oesophagus, or surgical bypass or stenting for obstructions in the biliary
ducts.
– Routinely used and often relative simple procedures, often with a high degree of at
least temporary effect, that represent a therapeutic tradition introduced before controlled clinical trials became the standard. Transurethral resection for bleeding and
urinary retention in cancer of the bladder and the prostate are typical examples of
this type of palliative treatment. There is clearly a danger of this tradition being
carried over into major procedures without palliative effect; this is illustrated by
the fact that resection of a spinal disk without /avstivning QQQ is now considered
to be without effect.
– The general rule is that it is difficult to document the effectiveness of symptomfree, life-extending palliative surgery (not directed towards symptoms). Still it
seems clear that when optimal preoperative and perioperative staging is done, patients who may profit from such procedures may be identified. Examples of this
are seen in the fields of neurosurgery and gastropancreatic surgery.
– The majority of the most common palliative procedures have a described effect,
though there is not sufficiently scientific documentation as they are based on selected patient materials and retrospective comparisons. As the nature of the problems (ileus, difficulty breathing, dysphagia etc.) rarely allows untreated controls,
the comparison will often be between procedures that clinically would be complementary (laser and stenting, blocking and tubing).
Relevant assessment criteria
For administrative purposes, Norway’s health services are organised in five regions.
Data on registered hospitalisations in these regions have been used to throw some
light on the extent of palliative cancer surgery and the resources it requires. There is
no special registration of whether the surgery had a palliative or curative intention.
During the 1999–2002 period, there was no overall increase in cancer surgery as a
percentage (8.3%) of all surgery. The five regions had varying proportions of cancer
surgery relative to all surgery, and variations by year. As regards surgical treatment of
metastases, there are few such procedures in urologic surgery, but many in cancers in
the alimentary tract.
Specific analyses of health economics aspects have not been carried out, though the
economic aspects of palliative cancer surgery are discussed in this report. Few studies
have been carried out that are suited to estimate the cost-benefit of palliative cancer
surgery; hence it is difficult to give a total assessment.
Ethical issues are considered with a focus on the role of the physician, the needs of the
patient, research ethics and research needs in relation to developing a basis for setting
priorities. Research in this area is morally and methodically challenging. However,
the paucity of high-level studies makes the knowledge basis weaker than what is
called for. Palliative surgery is a potentially valuable treatment, but for patients with a
short remaining lifespan, surgical treatment will not always be the best alternative for
relieving symptoms. Palliative surgery requires assessments with a moral basis as well
as surgical skills.
8
Comments
This systematic review of the literature shows that there are varying levels of evidence
for many procedures in these fields. This reflects complex clinical situations in which
to carry out randomised studies.
The group of experts has made a comprehensive effort and concludes that the scientific evidence presented in the available literature is inconclusive. In several areas
there is a need for additional documentation. Still, in the opinion of the group of experts this review of the literature gives Norwegian cancer care a platform that could
provide direction in relation to what should be the priorities in future research within
this field.
As palliative cancer surgery consumes a very considerable share of the resources
spent on the surgical care for cancer patients, all procedures should be registered as
palliative or curative when they are coded. Compared with data from the Norwegian
Cancer Registry, this would provide a new dimension for measuring the effect as well
as the costs of surgical cancer care.
The present report could provide a better foundation for advice to the individual patient on whether or not the relevant treatment is of benefit to him or her in terms of
improved functioning, relief of pain and other symptoms, and a better quality of life,
seen in relation to the patient’s reserve of treatment options and excepted remaining
lifespan. The report describes a large number of surgical treatments that to some extent are quite extensive. Patients will be in need of information on expected improvement after surgery and the disadvantages surgery may bring so that they may make a
choice on whether to go through palliative cancer surgery. The lack of documentation
of effect calls on the surgeon to exercise judgment in the choice of treatment in order
to contribute to the treatment being a benefit for the patient.
9
2 Introduction
2.1 Background
Symptoms from a tumour usually occur when the organ in question is no longer able
to perform its normal function or when the growing tumour for mechanical reasons
causes pain or reduced functioning in adjacent organs. Metastases from the primary
tumour add a new dimension to the clinical picture because the daughter tumours are
often localised in other organ systems and, hence, lead to the development of other
symptoms that are hard to predict. In some more rare cases, tumours make reactive
products that, brought with the bloodstream, inflict functional disturbances on other
organ systems.
In a relatively near future, according to the Norwegian Cancer Registry, every third
person in Norway will develop a malignant disease in the course of their lifetime. Almost half of them will develop spreads QQQ or have a local recidivation of the disease; sooner or later they will be evaluated for palliative treatment. If one also takes
into account the fact that a large number of primary cancer operations only have a
local palliative effect and not the desired curative effect, it is evident that more than
half of the surgical resources within cancer treatment are used either for purely palliative procedures or for procedures on the borderline between palliation and cure, primarily because of the fact that one still does not have exact knowledge about the real
extent of the disease at the time of treatment.
Palliative surgery is one of several therapeutic modalities that are not intended to cure
the patient’s cancer, but are carried out with an intention to prolong life, relieve symptoms, or prevent symptoms. One has chosen to define as necessary emergency surgery
acute palliative surgery which is intended to relieve acutely occurring and severe pain
or haemorrhage that cannot be relieved with optimised non-surgical or medical treatment. These issues have not been included in the selection of literature that we have
assessed.
The Norwegian Cancer Plan, Norwegian Official Report no. 1997:20, Care and
Knowledge (319) points out that there is evidence of effect of palliative surgery; the
literature is characterised by reports based on small and selected series of patients.
The Cancer Plan suggests that studies of palliative or symptom-preventing surgery
should be a priority in Norwegian cancer care. Moreover, there are no international
reports that satisfactorily address general issues of indication, effect, or use of resources.
Even after advanced literature searches in the field of palliative cancer, we could only
identify a highly limited number of controlled studies of satisfactory quality. This was
not an unexpected finding; it was the main reason why the Norwegian Cancer Plan
was intended as a stimulus to better documentation of and research into palliation.
Research results on palliative procedures have generally received less attention than
results related to curative methods. Moreover, many will see carrying out clinical research related to palliative aims and methods as less meritorious than research aimed
at cure. Various methodological problems have also been mentioned, i.e. what qualitative or quantitative criteria can or should be used, and how to measure and describe
10
them. This is also reflected by the fact that palliative reports generally are of lower
quality.
Surgery in Norway is mainly organised according to organ systems. The group of
expert includes surgeons with professional backgrounds in five areas in which palliative surgery is routinely considered as an option. Palliative cancer surgery is mainly
aimed at prolonging life, relieving symptoms, and preventing symptoms – and the
broader, symptom-oriented concept of quality of life. The aim of the treatment is not,
as in curative surgery, total resection of the tumour. This may be self-evident; still it is
an important realisation that the group of experts thinks make it easier to compare
various procedures. It could also provide a required framework for future cost analyses.
2.2 The group’s terms of reference
The group of experts shall systematically and critically assess the
documentation of palliative surgical interventions in the treatment
of cancer patients
The following issues shall be in focus:

Effect – Effect of surgical intervention with palliative intention in terms of
prolonging life, relieving symptoms and preventing symptoms. The effect of
surgical intervention shall also be assessed in relation to the best supportive
care and in relation to alternative therapeutic modalities in those cases when
this is relevant.

Consequences – Even though an assessment of methods primarily focuses on
clinical aspects, ethical and economic issues shall also be discussed. The use
of palliative surgery shall be assessed in the framework conditions of the Norwegian health services.

Definition and clarification of the terms of reference – Palliative surgery
implies a surgical treatment in which the objective is not cure, but to prolong
the patient’s life and prevent or alleviate the patient’s symptoms (NOU
1997:20; 319). The committee is called upon to focus its report on elective
surgery defined as follows: palliative surgical interventions that may be postponed for more than 24 hours; palliative surgical interventions in emergencies
shall be excluded. “Grey zone” cases shall be discussed in the context of
theme. The balance between positive effect and negative effect (complications/death) is interesting and important.
Definition/clarification of the matter under assessment
There are many grey zones in therapies that may be curative and palliative at the same
time. The main focus in this report is on the treatment of symptoms that are so distressing that non-emergency surgery is assumed to give the best palliation or prolon-
11
gation of life. Therapeutic modalities that strictly speaking are not surgical but which
are part of the surgeon’s responsibilities (for example, stenting) are included.
The clinical course of a cancer patient (figure 3.1) is a result of several factors and the
need for palliative treatment may arise at various stages in the chain of treatments. We
accentuate three relevant situations in which palliative treatment is an option for patients in advanced stages of cancer:
I. The patient may have had surgery, but has been found inoperable with a curative
intention or found incurable without surgery. Surgical palliative treatment could be
an option in order to alleviate symptoms or prolong life, for example in advanced
prostate cancer.
II. The patient is in need of palliative surgery because of metastasis, for example
treatment of a bone fracture caused by bone metastases, in order to keep the function intact.
III. The patient has distressing symptoms from his or her primary tumour and has to
have a resection in order to function, for example in cases of obstruction in the
central airways caused by cancer.
Figure 3.1. Various clinical courses
Potensiell kurativ
operasj.
Absolutt
kurativ, R0
Helbredet
Ingen kir.beh
Recidiv
R1/R2
reseksjon
Ikke tumorrettet
Inkurabel
sykdom./Fjerning
av primærtumor
Prim.operabel
(kurativ
intensjon)
III
Inkurabel sykdom/ikke
tumorrettet inngrep
Nye
pas.
Tumorrettet
II
“Åpne og lukke”
I
Andre faktorer
(Allmenntilstand etc.)
Ikkeoperable
Ikke operasjon
Tumorrelatert
faktorer
Ikke tumorrettet
Operasjon
Tumorrettet
Primary operable (curative
intention)
New patient
Inoperable
Potentially
curative surgery
Cured
Absolutely
curative, R0
No surgery
Incurable disease/resection of
primary tumour
Incurable disease/not tumouroriented surgery
“Open and shut”
cases
Other factors
Recidivation
R1/R2 resection
Tumouroriented
Not tumouroriented
No surgery
Not tumouroriented
Tumouroriented
Surgery
12
(general condition etc.)
Tumour-related
factors
The task at hand was limited to the following fields:





Gastroenterologic surgery: surgery related to the alimentary tract from the oesophagus to the rectum that improves functions, reduces pain or stops bleedings.
Neurologic surgery: surgery because of primary tumour or metastasis to the brain
or the spine/spinal medulla in order to preserve neurologic functions.
Orthopaedic surgery: surgery related to pain and/or fractures or required reinforcements of arm, leg or spine due to bone metastases.
Thoracic surgery: surgery on metastases in the lungs, reduction of compression of
the superior vena cava and procedures and keeps the airways open.
Urologic surgery: surgery related to the urinary tracts in order to provide passage
from the kidneys to the urinary bladder, facilitate voiding of the bladder, and stop
bleedings.
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3 Method
3.1 Mode of work
The group of experts worked in sections organised by field: gastroenterologic, neurologic, orthopaedic, thoracic and urologic surgery. The urologic surgery group was reorganised when one member left and a new member was appointed in the middle of
the project period. Work on gynaecologic surgery was started but not carried on, mainly because palliative procedures for all practical purposes are directed towards the urinary tracts and the digestive channel and are considered in the relevant sections.
The project manager organised the literature search according to the group’s terms of
reference and the plan for the project. Abstracts were retrieved and submitted to the
group members.
3.2 Literature search
Criteria for inclusion:
Interventions
– surgical intervention with palliative intent directed towards the primary tumour
– surgical intervention with palliative intent directed towards metastases
– not tumour-related surgical palliative intervention
Population
– patients to be treated with surgical intervention with a palliative intention
Study design
– What is under review is the effectiveness of surgical interventions in palliative
treatment of cancer patients; hence clinically controlled studies should constitute the backbone of the review. If possible, these should be
– meta-analyses of randomised controlled trials
– randomised controlled trials
The following other types of studies with a lower quality may also be included:
– controlled trials of good quality (controlled study with pseudo-randomisation,
non-randomised controlled study (cohort), case-control study)
– register data
– patient series
Review articles are included in the literature search only in order to retrieve data
from lists of references.
– Measures of effectiveness
–
Life-prolonging treatment: prolonged lifespan, either absolutely (months,
weeks), or relative improvement in percentage terms.
–
Symptom-preventing treatment: delayed time to onset of symptoms/recidivation. (The measure of effectiveness here will be time from start of treatment
to onset of symptoms.)
14
–
Symptomatic treatment: reduction of troublesome symptoms, cited as degrees of symptom relief, the proportion of patients with palliation and the duration of this effect. This may to some extent also be measured and objectivised,
for instance by use of instruments for measuring quality of life or functional
status.
Languages
– Articles whose quality and relevance may be assessed on the basis of abstracts
in one of these languages: English, German, French, the Scandinavian languages
Time period
– Articles from 1966 and onwards
Criteria for exclusion:
Interventions
– surgical intervention with a curative intention
– emergency surgery
– undocumented experimental modalities
Population
– children were not included
Study design: Seen as irrelevant were case histories or anecdotes, expert comments,
consensus reports, clinical trials of poor quality (e.g. lack of controls, too few patients
in relation to the relevant problem etc.) Consensus reports could, however, be useful
for ethical assessments.
Articles that only deal with curative treatment were not included. Survival results are
cited from included articles that also report data on palliative effect. Only results that
are relevant from a palliative perspective on cancer surgery are cited; hence results
from all patient groups in an article are not necessarily cited.
Search strategy
These bibliographic databases were used:
 Medline (1966–2000)
 HTA database (1992–2000)
 Cochrane Library:
Cochrane Database of Systematic Reviews (CDSR)
Cochrane Controlled Trials Register (CCTR)
 Database of Abstracts of Reviews of Effectiveness (DARE)
 Embase (1974–2000)
 NHS Economic Evaluation Database
 Cancerlit
Lists of references in relevant article were reviewed in order to identify relevant publications that were not identified through database searches.
15
Systematic searches were conducted for each field. Initially a general search was done
for advanced disease and palliative surgery for the various cancer diagnoses. This was
too unspecific, as treatment aimed at survival was prevalent and the palliative perspective less pronounced. The report is therefore based on searches in which specific
symptoms with a need for palliation were linked to advanced stage of the cancer in
question. This compilation was then seen in relation to specific surgical methods. For
search strategy, see chapter 12.1, search strategy. QQQ
This search strategy was used for a final updating search conducted 1 January 2003
for randomised studies, meta-analyses and systematic reviews of all the five subspecialties. The assessment of this literature was finalised on 28 February 2003.
3.3 Assessment of the literature
Stage 1 included reading of abstracts that were identified through the searches. Each
group had two or three experts. They read and assessed the abstracts independently of
each other (table 3.1) and submitted their results to the project manager. Included in
the number of articles for orthopaedic surgery are articles that were assessed jointly
with the neurosurgeons and were related to metastases to the spine.
Table 3.1. Stage 1: Number of abstracts read by each specialist group
Total no. of
Gastroarticles NeuroOrthoThoracic Urologic
of
enterologic surgery
paedic
surgery surgery
articles
surgery
Assessed,
3731
1716
462
277
480
796
total
Assessed
871
365
86
163
90
167
at stage 2
Assessed
320
104
20
64
37
95
at stage 3
Excluded
157
38
12
21
18
68
at stage 3
Included
163
66
8
43
19
27
at stage 3
For stage 2, articles selected on the basis of abstracts were retrieved. Articles that did
not meet the criteria for inclusion were excluded at this stage (table 3.1). The experts
decided on exclusion according to these criteria:
 Was the study design irrelevant?
 Was the patient group irrelevant?
 Was the intervention badly described?
 Were the endpoints not clearly defined?
 Was the study inadequately performed?
At stage 3, each article was thoroughly assessed for inclusion in the basis of literature
(table 3.1). The articles were discussed in plenary sessions and notes taken on special
types of information considered relevant in each article. Notes were also taken of sta-
16
tistical methods used and authors’ conclusions. The articles were checked for internal
validity according to check lists for randomised trials, case-control studies and cohort
studies; they were ranked (table 3.2) and assigned an evidence level (table 3.3). Total
evidence level (table 3.4) varied among the fields of surgery.
Articles at stage 3 were excluded because of weak validity; they might also be excluded from the basis of evidence at this stage if the method was badly described or
serious bias was not explained. A list was made of these articles with specification of
the reason for exclusion (chapter 10).
It was known in advance that there was a limited number of controlled studies (evidence level 1 or 2) in the field, hence articles at evidence level 3 were also included in
order to develop a survey of the literature available for the wide range of surgical procedure for which an assessment of effectiveness was relevant; hence, best evidence of
effectiveness will be at different levels among the fields. For some therapeutic modalities there were only small patient series or pilot studies and we cannot give a total
assessment of the total evidence level in this review.
Table 3.2. Ranking based of total assessment of quality
Rank Criteria
Used if all or most criteria in the check list are filled; if the criteria are not
++
filled: there is a high probability that the conclusions from the study or survey would not change
Used if some criteria in the check list are filled; if the criteria are not filled
+
or not adequately described: if the conclusions from the study or survey
would probably not change
Used if few or none of the criteria in the check list are filled; if the criteria
are not filled or not adequately described: if the conclusions from they study
or survey would be expected to change
Table 3.3. Study types and study quality
Level
Study types and study quality
1++
Very good meta-analysis, systematic survey of randomised controlled trials (RCT) or RCTs with very little risk of bias
Well conducted meta-analysis, systematic survey of RCT or RCT with
little risk of bias
Meta-analysis, systematic survey of RCT or RCT with great risk of bias
Very good systematic survey of case-control or cohort studies with very
little risk of confounding factors, bias or coincidence and a high probability that the claimed association is real
Well conducted case-control or cohort studies with little risk of confounding factors, bias or coincidence and a moderate probability that the
claimed association is real
Case control or cohort study with a high risk of confounding factors, bias,
or coincidence and a significant risk that the claimed association is not real
Not controlled studies (with an element of comparison), register studies,
1+
12++
2+
23
17
4
patient series
Statements by experts, descriptive studies, case reports
18
4 Results
4.1 Gastroenterologic surgery
Introduction
Palliative surgery addresses symptomatic problems and their amelioration. The volume of abdominal surgery seen relation to incidence and median survival is presented
by averages for the 1996–2000 period (table 4.1.1).
Table 4.1.1 Survey of the main groups of gastrosurgical cancer in Norway
Organ
Oesophagus
No. per year1
160
Operated2
19%
Median survival3
Operated: 9 months
Not operated: 9 months
Ventricle
650
36%
Pancreas
590
9%
Operated: 18 months
Not operated: 7 months
Total 7 months
Colon
2090
>90%
Rectum
1000
>90%
Dukes A–C: >5 years
Dukes D: 8 months
Dukes A-C: >5 years
Dukes D: 11 months
1
Average incidence 1996–2000. Norwegian Cancer Registry: Kreft i Norge 2000. Rounded off to 10.
The proportion of resections is the average of resection procedures 1999–2001, Norwegian Patient
Registry, SINTEF Unimed, in relation to the average incidence 1996–2000.
3
Estimated values from five-year survival curves. Norwegian Cancer Registry: Kreft i Norge 1999.
2
Below we start with symptoms related to functions in the digestive tract and its adjacent organs that can be alleviated by gastroenterologic surgery:
1. Dysphagia caused by oesophageal cancer and in some instances tumours/metastases that put pressure on the oesophagus from the outside.
2. Icterus caused by a mechanical pinch on the biliary tracts.
3. Retention (poor or no passage from the stomach to the small intestine) caused by
cancer in distal biliary ducts, pancreas, or the stomach.
4. Intestinal obstruction/ileus caused by stenosis or obstruction or pinch on the
intestinal tract.
5. Intestinal bleeding caused by bleeding from the gastrointestinal tract.
6. Pain • Quality of life • Survival
4.1.1 Dysphagia caused by oesophageal cancer
Each year about 160 new cases of oesophageal cancer are diagnosed in Norway.
These are often older patients (70+) who not infrequently have comorbidity
/ledsagende sykdommer QQQ that are of decisive importance in relation to the choice
of relevant treatment.
19
Dysphagia could be a symptom of cancer of the oesophagus or in the cardia. Patients
with cancer of the oesophagus and dysphagia at the time of diagnosis are often in an
advanced stage of the disease, hence the prognosis is often very serious; total fiveyear survival is estimated at 5–10%. Surgical treatment with curative intention could
be an option for a small proportion of these patients (approx. 20%). The others will
often be in need of palliative treatment in order to obtain improved oesophageal functioning.
The aim of palliative treatment in this setting is to help the patient to achieve an oesophageal function that enables normal intake of fluids and nutrition. At the same
time, the procedure-related rate of complications must be low and the procedure
should give as little discomfort for the patient as possible.
Available palliative methods include:
 Surgical treatment
 Laser therapy
o Laser versus injection
o Laser versus intubation
o Laser versus photodynamic treatment
 Endoscopic intubation: rigid tube versus self-expanding stent
 Oncologic non-surgical modalities together with surgical palliative procedures
We have not identified relevant studies according to the above criteria, studies of
comparable modalities such as bipolar coagulation or argon plasma coagulation. Furthermore, we have not identified studies that compare palliative surgical treatment
with purely palliative radiotherapy and/or chemotherapy. Such treatment has, however, not infrequently been given to some of the patients who, in the studies we have
evaluated, have been given surgical or non-surgical treatment, a fact that complicates
the assessment of treatment effect.
It is a debatable point whether all these methods are “surgical”; in many countries
there are often other specialists (medical gastroenterologists, dedicated units for endoscopy, interventional radiologists etc.) that use such therapeutic modalities. In
Norway, these patients are by and large treated by surgeons. We still found it appropriate to include these alternatives in this literature review. The methods all have their
advantages and disadvantages; below we give an account of the scientific evidence.
Few good prospective studies (RCTs) have been published within the field of gastroenterologic palliative cancer surgery. In this literature search, only five such studies
were identified (2,4,11,50,68); we have also assessed a prospective controlled study
(29) that focuses on palliative treatment of dysphagia. By and large the literature can
be classified as in the table below:
20
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Dysphagia
Cancer of the
oesophagus
Surgery
Laser therapy
47 Segalin
2 Alderson
11 Carter
29 Loizou
1 Ahlquist
54 Spinelli
7 Barr
12 Carter
32 Naveau
37 Paolucci
50 Siersema
68 Adam
67Knyrim
14 Cowling
47 Segalin
15 Cwikiel
35 O’Sullivan
No relevant
literature
3
1
1
1
2
3
3
3
3
3
1
1
2
3
3
3
3
Intubation/
stenting
Oncologic
treatment and
surgery
Surgery
A retrospective study (47) reports the results after palliative resection of tumour tissue
and surgical by-pass; results after intubation and laser treatment are also reported by
the same centre. Severe complications after palliative surgery for cancer of the oesophagus were frequent, with mortality above 20% after palliative by-pass surgery. The
same authors also cite mortality above 10% after intubation. The rate of complications
is above 30–40% after various palliative procedures.
Palliative procedures lead to considerable morbidity and mortality, a fact that underscores the need for alternative, non-surgical modalities for this group of patients with
disabling dysphagia and with a severe prognosis.
Laser therapy
Three randomised studies compare endoscopic laser treatment with, on the one hand,
injections with polidocanol, a cytotoxic agent (4), intubation with latex tubes (2,11),
or the use of self-expanding stents (68). The fifth study compares latex tubes with
self-expanding stents (50). The studies are by and large small (<40 patients included),
but they provide a certain basis for suggesting that by far the most patients who need
palliative treatment for their dysphagia can profit from the use of these non-surgical
methods.
In three prospective series of patients (1,7,12), the effect of palliative endoscopic laser
therapy was assessed. An important palliative effect on oesophageal symptoms was
achieved in between 80% and 95% of patients, but a large proportion of the patients
had to be re-treated, some of them several times. Although laser therapy is considered
as relatively gentle and safe, the numbers of procedure-related complications are not
inconsiderable (12).
21
How long the result of the treatment lasts is important to the patient. A retrospective
study (22) reports lasting good oesophageal function in about one third of the patients
after 3 months and in a little less that one fourth of the patients after 6 months. This
underscores the need for repeated procedures in many patients. Palliation of symptoms was associated with the effect of the first procedure; in patients with longer stenoses the effect of the treatment did not last as long. It is suggested that a combination
of laser therapy and radiotherapy and chemotherapy (12) could further reduce dysphagia and improve nutritional status, though there are not good data that substantiate
it in this study.
– Laser versus injection
In one randomised study with few patients (4), endoscopic laser therapy was compared with endoscopic local injection of a 3% concentration of the cytotoxic agent
polidocanol. In more than 80 % of patients, normalised oesophageal functioning was
achieved. Although one patient had an oesophageal perforation after an injection, both
alternatives are considered safe and effective. Injection treatment is probably not
much used in Norway, as not inconsiderable investments in necessary equipment are
needed.
– Laser versus intubation
In two randomised studies (2,11), laser therapy was compared with the use of latex
tubes (Atkinson tube or Celestin tube). Good palliation of the dysphagia was achieved
in a majority of patients. Laser therapy more often required repeat procedures (2); the
weight loss was less in those treated with laser, though this did not translate into improved survival (11). The authors conclude (2) that laser therapy is primarily an option in cases of shorter stenoses (<4 cm). These observations are in line with the results of a controlled trial (29) in which good palliative effect was found with both alternatives, but better palliation after intubation in distal oesophageal/cardiac stenoses.
Perforation after intubation was observed in 13% of patients as compared with 2%
after laser therapy. From a retrospective study (37), it was also reported more symptom-free days after tube treatment compared with laser therapy and, in total, fewer
days of hospitalisation required by the need for repeat procedures. Patient satisfaction
was higher among patients treated with tubes but this group had higher mortality (4%)
and higher morbidity (10%).
Endoscopic laser therapy (32,37,54) is an efficient method of recanalisation. Between
75% and 85% of patients experienced improvement or elimination of their dysphagia.
Some patients needed several treatments for a satisfactory result to be achieved (32).
Compared to patients treated with perturbation, laser-treated patients spent significantly more days in hospital (37).
Treatment results from two British hospitals were compared in a controlled trial (29).
Over the 1987–89 period, 43 patients were treated with endoscopic laser (in London)
and 30 patients with endoscopic intubation with the Atkinson tube (in Nottingham).
For smaller thoracic oesophageal tumours, the percentage of patients achieving improvement of their dysphagia was high (95–100 %) and just as good with both modalities. Patients with distal stenoses/tumours had significantly better effect from intubation than from laser therapy. The perforation rate was lower in the laser-treated group
(2% vs. 13%). The authors emphasise that for individual patients the two techniques
should be regarded as complementary.
22
The literature in this field is to a large extent comprised of retrospective studies based
on single-centre data. Quite often, the criteria used for choice of treatment are not
presented explicitly, and not rarely patients have received other oncologic treatment
such as chemotherapy or radiotherapy in addition to the specific palliative symptomatic therapy (stenting, intubation, or laser). The selection of patients and specification of
complications are problems in retrospective studies. The scientific publications are
relatively rarely based on prospective studies; randomised trials are even rarer. Given
these deficiencies in documentation, it is hard to draw firm conclusions.
– Laser vs. photodynamic therapy
From a study (54) of malignant obstruction in the upper as well as the lower gastrointestinal tract one may extract results from a group of patients (with upper gastrointestinal obstructions) who underwent laser or photodynamic therapy. The group was heterogeneous and the study is hard to evaluate. Recanalisation was achieved in most
patients and subjective palliations of symptoms in three quarters of patients (both
groups included). No deaths were related to the endoscopic treatment.
Intubation/stenting
– Use of self-expanding stent
During the last few years, treatment with self-expanding stents has been generally
available for clinicians and has contributed to giving more patients a palliative nonsurgical alternative. It is maintained that stenting extends the palliative measures that
can be offered to the patients in question beyond what can be achieved or is technically feasible with latex tubes (48). Several different types of stents with larger or smaller differences are on the market; their use varies from country to country and from
clinic to clinic. Given the fact that several different types of stents are used on to some
extent heterogeneous series of patients, comparisons and assessments of results are
exceedingly difficult to make.
Stenting is done endoscopically, with or without x-ray imaging, usually under total
anaesthesia. Self-expanding stents have a very good palliative effect in more than
95% of patients (14,67,68). Good information about the course of the disease in patients after stenting is often lacking. However, one study (14) found that 9% of patients had recurrent distressing dysphagia after on average 22 weeks. Procedurerelated mortality was considered low (2–10%).
More recent studies (14,15,35) have shown that stenting provides good palliation of
dysphagia in 9 out of 10 patients, with low procedure-related mortality and morbidity.
Still it should be noted that the rate or complication is given as between 20% (35) and
45% (15), and procedure-related (thirty-day) mortality between 1% and 6% has also
been observed (35,48). Long-term results from these studies are lacking; still it is
clear from relatively short observation periods that some patients are in need of retreatment because of tumour ingrowth into the stent, or overgrowth (14). In order to
reduce ingrowth, plastic-covered stents have been introduced. This clearly reduces the
risk of ingrowth, though it substantially increases the risk of stent migration (68). The
attending physician should assess each patient individually and take a number of factors into account – type of obstruction, its length and level, fistula problems, the range
of application of the stent, and costs.
23
– Placement of a tube in the oesophagus: rigid tube vs. self-expanding stent
We have identified only two randomised prospective studies (50,67) that compare
stenting with intubation. There were substantially more major complications in the
group receiving latex tube prosthesis. Thirty-day morality was twice as high (29% vs.
14%) in the group that was intubated (67). More than a fourth of the patient in both
groups had recurrent dysphagia because of tumour growth or tube migration. Prior
radiotherapy or chemotherapy increased the risk of complications, especially among
those who were intubated (43% vs. 17%) (50). The two methods may be seen as complimentary. The introduction of self-expanding stents has enhanced the therapeutic
options for patients with malignant dysphagia (48).
Oncologic non-surgical therapeutic modalities
No relevant literature was identified.
Conclusion
Considerable morbidity and mortality is associated with surgical palliative treatment
in these patients. Non-surgical methods such as endoscopic stenting or laser therapy
should be preferred, as both methods give a rapid and relatively good palliation. Laser
therapy must often be repeated in order to maintain the oesophageal function.
4.1.2 Icterus
Symptom
Type of cancer
Treatment
Reference
Evidence
level
Pruritus because
of an obstruction
Pancreatic cancer
Surgery vs.
stenting
55 Taylor
3 Andersen
8 Bornman
49 Sheperd
51 Smith
53 Spear
1+
1+
1+
1+
1+
1-
30 Lumen
3
Quality of life
Pancreatic cancer
Percutaneous vs.
endoscopic
stenting
Stenting
Palliative treatment of pruritus
Obstructive icterus caused by malignant disease occurs in about 70% of patients with
pancreatic cancer (expanding from the exocrine part of the pancreas) (25). In patients
who cannot undergo surgery with a curative intention, palliation of pruritus related to
icterus is one of the most important objectives. If pruritus can be treated effectively in
other way, or if pruritus initially is not a prominent symptom, it is not clear whether
treatment for icterus is of any substantial importance for other symptoms such as nausea, weak appetite or general well-being.
Quality of life
In a prospective institution-based study using validated methods (EORCT QLQ-C-30)
in order to assess quality of life before and 28 days after stenting for obstruction (due
to malignant extrahepatic structure) in biliary tracts, it was found considerable relief
24
of symptoms such as icterus, pruritus and diarrhoea but also a small but statistically
significant improvement in relation to tiredness, sleep or appetite. On a functional
scale there was statistically significant improvement in emotional and cognitive functions and global health (30). The study did not include controls, hence it is hard to
assess how big an effect the treatment of primary symptoms such as icterus and pruritus had on other symptoms.
Surgery vs. stenting
Treatment of obstructive icterus caused by malignant disease can be done by surgical
bypass or by stenting the obstructed area. Four randomised controlled trials were published over the 1986 to 1994 period comparing stenting with surgical bypass
(3,8,49,51). One of these trials (8) has a transhepatic placed stent as one arm, the other
trials endoscopically placed stents. The success rate, defined as normalised or nearly
normalised bilirubin, varied in the stenting groups from 84% to 94% and in the surgical bypass groups from 76% to 92%, not a significant difference. Thirty-day mortality
varied in the stenting groups from 8% to 20%, in the surgical bypass groups from
13% to 27%. The rate of complication varied in the stenting groups from 28% to 36%,
in the bypass groups from 32% to 58%. Only in one of these trials were procedurerelated mortality (but not 30-day mortality) and the frequency of serious complications significantly lower in the stenting group (51). Recurrent icterus requiring hospitalisation was, when specified, more frequent in the stenting groups. Median survival
after treatment varied in the stenting groups from 12 to 22 weeks and in the bypass
groups from 14 to 26 weeks.
In a meta-analysis (55) of three RCTs (3,49,51) with endoscopically placed stents as
one arm, it was found that the odds ratios for treatment failure and serious complications were so heterogeneous that a common odds ratio could not computed. Thirtyday mortality was the same in the stenting and bypass groups. More retreatment sessions were necessary in the stenting groups assessed by odds ratio and confidence
interval.
These trials have been criticised because of high mortality in the surgery groups. Two
large retrospective studies from specialised high-volume centres report mortality in
surgical bypass of 2% and 3.3% and procedure-related morbidity of 32% and 27%
(25,59). This patient material is, however, not comparable with those of the prospective studies summarised above. Patients undergoing surgery in these studies were
largely operated with an initially curative intention. This means that the preoperative
evaluation had not documented definitive criteria for surgical treatment (criteria for
inoperability), hence it is probable that the risk profile in this group of patients was
different because of less advanced diseases. In a large Norwegian population study, it
was found a procedure-related mortality of 12.4% and a morbidity of 24% for this
type of surgery (5).
Percutaneous vs. endoscopic stent
In a published randomised controlled trial (53), percutaneously transhepatically
placed stent was compared with endoscopically placed stent. The success rate (adequate bilirubin decline) was 61% in the group with stenting done in open surgery and
81% in the group with endoscopically placed stent, a significant difference. Thirtyday mortality was also significantly different; 33% in the group with percutaneously
placed stent and 15% in the group with endoscopically placed stent.
25
Type of surgery
In the largest systematic review article published on palliative surgical procedures in
pancreatic cancer, risk of recurrent icterus was estimated at above 10% after cholecystoenterostomy (95). More than 10 000 patients were included. In a large retrospective
series of patients (17), recidivation of icterus was observed in 12.8% of patients undergoing choledochoenterostomy and in 21.4% of those undergoing cholecystoenterostomy. There are no controlled studies focusing on this problem.
A major prospective population study reports procedure-related mortality from cholecystoenterostomy of 13.5% and 12% from of choledochoenterostomy (33). The large
systematic review article cited above (95) also did not identify a difference in procedure-related mortality from cholecystoenterostomy compared with choledochoenterostomy.
4.1.3 Retention in pancreatic cancer
Symptom
Type cancer
Treatment
Reference
Evidence
level
Obstruction
Pancreatic cancer
Gastroenterostomy (simple
bypass)
22 Gough
38 Potts
44 Sarr
19 Espat
3
3
3
3
Nausea and
vomiting
Pancreatic cancer
28 Lillemoe
51 Smith
44 Sarr
16 de Rooij
22 Gough
52 Sohn
1+
1+
2+
3
3
3
Espat on need
Simple vs. double bypass
Need for treatment
In one case-control series and two non-prospective patient series about pancreatic
cancer, the frequency of surgery needed for treatment for ventricle retention varied
from 10% to 15% (22,38,44). In contrast to these studies, there is a published retrospective study from a high-volume centre on pancreatic cancer patients in which laparoscopic staging was used as the last step before potentially curative surgery. Out of
the 155 patients who were inoperable after this procedure, only 3 (2%) needed relieving gastroenterostomy over the course of their remaining lifetime (19).
Single vs. double bypass in cancer of the distal biliary ducts and the pancreas
Nausea and vomiting are prominent symptoms in up to 50% of patients with malignant disease in the distal biliary ducts and the pancreas. The frequency of mechanic
obstruction, diagnosed by x-ray examination or endoscopy as the reason for this, is
unknown, but probably applies to far less than half of the cases. One randomised
study is published, done in a high-volume centre, that compares routine biliary bypass
combined with gastroenterostomy to biliary bypass alone (28). Only patients with no
significant risk of developing an obstruction of the duodenum were included, though
this is not specified with objective criteria. No difference in median survival was
found after, respectively, 8 months after double bypass and 6 months after single biliary bypass. Procedure-related morbidity was 33% and 32% respectively, and there
26
was no procedure-related mortality in any of the groups (28). It was found that the
risk of developing ventricle retention needing treatment was 19% with only biliary
bypass, while no patients developed ventricle retention after double bypass.
In the surgical arm of a randomised study designed to investigate the effect of stenting
vs. surgery for obstructive icterus (51), 18% of patients operated with simple bypass
developed ventricle retention, while the corresponding frequency for patients operated
with double bypass was 2% (a significant difference).
A well-balanced case-control study showed the same mortality in both groups (44).
Three large retrospective patient series cite mortality from such procedures varying
from 0 to 14%; no difference was established between simple and double bypass
(16,22,52). Procedure-related morbidity varied from 1% to 15–30% and was approximately 10% higher (a significant difference) in double bypass than in single bypass in
two studies (16,52).
Conclusion
Stenting or surgical bypass has the same effect in obstruction of the biliary ducts. Rate
of complications after these procedures are relatively high.
4.1.4 Retention and/or bleeding in cases of gastric cancer
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Retention
and/or bleeding
Gastric cancer
Complete or
partial gastrectomy
23 Haugstvedt
60 Bonenkamp
18 Doglietto
36 Ouchi
3
3
3
3
Less than 40% of patient with gastric cancer can undergo potentially curative surgery.
No studies have been found that provides objective data on improved quality of life, if
any, after surgical palliative procedures. A large Norwegian prospective population
study, in which 503 patients received palliative treatment, compares procedure-related
mortality and survival in patients who had undergone various form of gastric resection
with patients who underwent various other types of treatment (non-resective procedures) (23). No difference in procedure-related mortality was found in these two
groups, 13% and 14% respectively. In a subgroup of patients of the same age (70) and
the same preoperative weight loss, a doubling of median survival was found in stage
III as well as in stage IV in favour of resection. A large number of the patients undergoing resection, 64 out of 182, underwent total gastrectomy. Procedure-related mortality from gastrectomy in this study (12%) was not different from that of distal resection (11%). This is in keeping with observations from a large prospective populationbased study from the Netherlands (60), in which 285 out of a total of 995 patients had
non-curable disease when undergoing laparotomy. Out of these, 152 patients underwent partial (31%) or total (22%) gastrectomy and 133 patients only bypass (20%) or
exploration (27%). The magnitude of the disease was the decisive factor determining
whether resection could be done. Postoperative mortality (in-hospital mortality) was
low among those who only underwent exploration (5%), but somewhat higher and
quite the same for the groups that underwent bypass (14%) or resection (10–11%).
27
Median survival after palliative resection (8.5 months) was statistically significantly
better (p<0.002) compared with exploration only, or bypass (5.5 months).
A major retrospective study (18) gave fundamentally the same conclusion: all patients
were in stage IV; no difference in procedure-related mortality could be established
between resection procedures (11.8%) and bypass (10.2%). Mortality in total gastrectomy was 13.1%. Statistical analysis revealed that resection is independently associated with better survival. Median survival in the resection group was 16.3 months
vs. 7.1 months in the bypass group. Local metastasis /spread QQQ was significantly
more pronounced in the resection group, but all were in stage IV at the start of the
study.
A retrospective study from Japan underscores the importance of peritoneal dissemination for postoperative survival after hospitalisation and total survival (36). In cases of
distal ventricle resection and total gastrectomy, two-year survival with peritoneal metastasis /bukhulespredning/QQQ near the primary tumour was, respectively, 28% and
18%. In cases of disseminated peritoneal metastasis, two-year survival with distal
resection was 17 % and with total gastrectomy 0%. Out-of-hospital survival for more
than 3 months was observed in 83% of patients after various type of gastric resection,
in 33% of patients after gastrojejunostomy, and in 56% of patients after explorative
laparotomy only.
Conclusion
If gastric cancer cannot be treated with a curative intention, there is still a certain
amount of documentation to the effect that gastrectomy (total or partial) under certain
conditions could contribute valuable palliation through longer survival, prevention of
serious bleeding and removal of a relative obstacle in a passage.
4.1.5 Intestinal obstruction
Symptom
Type cancer
Treatment
Reference
Evidence
level
Intestinal obstruction
Colorectal or gynaecological cancer
Surgical
20 Feuer
43 Sarela
9 Branum
13 ClarkePearsons
10 Camunez
65 Lobato
34 Orth
54 Spinelli
3
3
3
3
Non-surgical;
i.e. laser therapy, cryotherapy or
stenting
3
3
3
3
Intestinal obstruction as a consequence of a primary or metastatic tumour is an important problem in gastroenterologic surgery. Colorectal or gynaecologic cancer is the
main cause of obstruction of the small intestine as well as the colon.
Twelve studies that deal with this topic have been identified. Eight of these studies are
non-prospective patient series (evidence level 3), while three studies are prospective
institutionally-based patient series (evidence level 3). None of these studies have adequate control groups, though one study (54) compares the effects of laser therapy on
28
the upper or lower intestinal tract. The Cochrane Library published a review of the
literature on this topic in 2000 (20).
Surgery
Feuer´s review article (20) deals with malignant obstruction in advanced gynaecologic
and gastrointestinal cancer. The total number of patients in the studies included cannot
be determined with exactness; an estimate would be 1500 patients. Included were
studies that comprised the following specific post-surgical data: on morbidity and
mortality, palliation of symptoms, rate of re-obstruction, and quality of life. Most of
the studies are of ovarian cancer. There are no data that throw light on a possible difference between gastrointestinal and gynaecologic cancer. None of the studies was of
a quality that allowed statistical analysis; consequently the review article only presented a qualitative analysis. There were considerable differences in the definition of
symptoms as well as palliation. The inclusion criteria in the 14 studies were also very
different. Control of symptoms was achieved in between 42% and 80% of patients.
Thirteen retrospective studies include re-obstruction rates, but data on time interval
before re-obstruction are lacking in most of these studies. Re-obstruction rates are
given as between 10 % and 50%. Two studies specify median time to re-obstruction
of, respectively, 106 days and 2 months Twenty-two retrospective studies included
data on mortality and morbidity. The definition of both variables varied considerably
and thirty-day mortality was given as 5% to 32%. None of the studies included data
on quality of life.
One study (43) is a prospective observational study QQQ of 24 patients (average age
70) with stage 4 colorectal cancer without symptoms of obstruction. Patients were
treated with chemotherapy and followed up in relation to need for later surgery. The
primary tumour was localised in the descending colon in 8, in the transverse colon in
1, in the sigmoid in 8 and in the rectum in 7 patients. Median survival was 10 months.
Four patients with cancer of the sigmoid developed symptoms of obstruction. Two of
these underwent surgery without complications and 2 were stented after 1, 3, 12 and
20 months from the time of diagnosis. A further 3 patients underwent right-sided
hemicolectomy because of pain, but did not achieve palliation. One patient had a potentially curative rectal and liver resection after successful chemotherapy.
Two studies deal with purely operational treatment with traditional surgery. In
Branum’s study (9), 42 patients with non-radical resection (bypass and/or debulking)
of metastases to the intestine from malignant melanoma were compared with 36 patients with radical resection. There was no operative mortality; median survival was
7 and 17 months respectively. For the whole group, 92% experienced reduction of
symptoms such as pain, obstruction or breeding, while all patients who underwent
radical resection had a symptomatic effect. Neither the course of the disease nor preoperative clinical status could serve to predict the end result. Clarke-Pearson’s study
(13) included 49 patients with intestinal obstruction (small intestine 30, colon 16,
combined 3) after ovarian cancer. Major complications (not defined in more detail)
occurred in 49%; 14% died within 30 days of surgery. 73% of patients survived more
than 60 days post-surgery, a median estimated survival of 170 days. The material was
worked up by statistical analyses of survival such as Kaplan-Meier analysis, Cox
analysis as well as a univariate logistic regression analysis. One found that clinically
established ascites increased the risk of postoperative complications and mortality.
With no ascites, survival could be more than 60 days. Correspondingly, preoperative-
29
ly reduced nutritional status and clinically advanced tumour status increased postoperative mortality and reduced survival, less than 60 days.
Non-surgical therapy: laser, cryotherapy, or stenting
Seven studies deal with non-surgical therapy of the distal part of the colon and/or obstruction of the rectum. Five of these deal with laser therapy, 1 with cryotherapy and
1 with stenting.
Over a four-year period, Camunez (10) selected 80 out of 173 patients with suspected
malignant obstruction of the colon for treatment with self-expanding stents. The tumour was in the passage between rectum and colon in 31, in the sigmoid colon in 41,
and in the distal part of the descending colon in 8. Average age was 69 (36–96). The
stenting was done by radiologists with x-ray imaging but without sedation or anaesthesia. The procedure was successful in 70 out of 80 patients (88%), imaging averaged 31 minutes; in 67 out of 70 patients the procedure was clinically and radiologically successful. There were 4 perforations, 2 of them uncomplicated as the stent covered the perforation, 2 underwent laparotomy of whom one died of myocardial infarction postoperatively (procedure-related mortality 1.3%). 33 patients underwent elective surgery after on average 7 days, 35 patients kept their stents as final therapy. 91%
of the stents remained open after 3, 6 and 9 months. Average survival was 147 days
(span:125–169 days).
Over a four-year period, Lobato (65) included 41 patients with clinical symptoms of
obstruction from 2 days to several months before hospitalisation. In one patient, the
obstruction was in the left colic flexure, in 17 in the sigmoid colon, and in 23 in the
rectum. In all patients the placement of a self-expanding stent was successful and uncomplicated. In 38 (93%), the stent did away with the symptoms. Two patients later
underwent an ostomy. When the study was closed, 80% of the patients had died, on
average after 4.5 months (span 1–18 months).
Over the ten-year period 1982-1991, Orth (34) treated 182 out of 855 patients with
rectal cancer with cryotherapy, applied with two to four days’ intervals until results
were achieved. Average patient age was 74; 71 received cryotherapy because of general inoperability, 41 because of tumour-related inoperability, 18 because of local recidivation, and 17 because of a combination of general and tumour-related inoperability. There was one perforation among those with tumour-related inoperability; complications in the form of bleeding, stenoses, incontinence and a need for relieving
ostomy occurred in 4% to 15% of the cases. For the individual symptoms of tenesmus, secretion of mucosa, leaking haemorrhage, larger major haemorrhage and perineal pain, lasting therapeutic effect was achieved in 51%, 53%, 24%, 0% and 33% of
the cases. 63% of the patients survived for one year, 27% for two years, and 14% for
three year after the therapy. Differences in survival between the various groups cannot
be extracted from this study.
Five studies present the results of laser therapy for distal colorectal cancer. Patient
materials are relatively homogenous with an age span of 72–80 and with a proportion
of rectal cancers of 60% to 95%. A total of 877 patients were included. In all studies
advanced cancer was the main indication; medical and age-related indications as well
as patient preference were of less importance for the choice of therapy. Median survival was about seven months. In all studies patients received repeated out-patient
30
therapy sessions; in haemorrhage, diarrhoea and obstruction were cited as main problems. The endpoints are not easily comparable and the difference between immediate
and durable effect is also not always clearly defined. Immediate effect was achieved
in 82–97%, while effective long-term palliation varied between 41% and 88%. Mortality varied from 0 to 2.3% with a total of 12 procedure-related deaths (mainly intestinal perforation) among 877 patients (1.4%). Complications varied from 3% to
15%, but they are not directly comparable.
Taken together, these five studies show that repeat out-patient therapy sessions give a
good palliative short-term and long-term effect in advanced inoperable distal colorectal cancer, with low mortality and rate of complications. The effect on the various
symptoms varies somewhat from study to study, though generally short strictures and
primary tumour are good predicators of a positive result.
Conclusion
Obstruction of the intestine in cancer is relatively frequent and requires palliative gastroenterologic surgery. The degree of control of symptoms achieved varies a great
deal; 50% of patients develop a new obstruction within 2 to 3 months.
4.1.6 Intestinal bleedings
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Bleeding or
obstruction
Cancer in the
distal part of
colon or
rectum
Laser
21 Gevers
31 Mesko
45 Schulze
54 Spinelli
57 van
Cutsem
34 Orth
3
3
3
3
3
Cryotherapy
3
Six retrospective series of patients, and all the 12 studies that are also reviewed under
gastrointestinal obstruction, describe bleeding from cancers of the distal colon and,
mainly, the rectum. None of these studies have control groups. All studies cite number
of patients with bleedings as the main or partial QQQ symptom. The proportion with
bleeding and obstruction as their main symptom varies considerably, but bleeding
seems to represent as great a problem as obstructions in terms of numbers. Spinelli
(54) (n = 86+52), Mesko (31) (n = 34), Schulze (45) (n = 27), van Cutsem (57) (n =
18+21) and Gevers (21) (n = 76) used repeat out-patient laser therapy sessions with 92
to 100% initial therapeutic effect. The long-term effects were, however, considerably
worse.
In Spinelli’s study (54), half of the patients developed a new bleeding over the course
of a follow up period of median 11 weeks. However, Gevers (21) reports long-term
palliation in 83; the 3 other articles have no data on long-term effect. In the light of
the patients’ short expected remaining lifespan (median 7 months), the results of outpatient laser therapy seem to represent an alternative for relevant patient groups.
31
Only one study (34) reports results from cryotherapy. A temporary effect was
achieved in 28 out of 47 patients, while long-term effects were only observed in
9 patients (19%). Cryotherapy was also carried out on an ambulatory basis.
None of these studies report specifically on complications related to patients with
bleeding as their main or a partial QQQ symptom, but these are hardly different from
the total material (3–15%).
Conclusion
Laser therapy or cryotherapy can be used as an alternative to surgery that is often
more comprehensive in cancer of the rectum or the distal colon. Stenting is also an
alternative. The documentation on effect is, however, weak.
4.1.7 Pain • quality of life • prolongation of life
Symptom
Type of cancer
Pain
Gastric cancer
Pancreatic cancer
Quality of life
Prolongation
of life
Cancer of the
biliary ducts
Colorectal cancer
Gastric cancer
Pancreatic cancer
Cancer of the
biliary ducts
Colorectal cancer
Gastric cancer
Pancreatic cancer
Cancer of the
biliary ducts
Colorectal cancer
Treatment
Reference
Evidence level
No relevant studies
Injection of
alcohol in the
celiac plexus
26 Lillemoe
3
No relevant studies
No relevant studies
Radical surgery,
possibly combined with adjuvant therapy
Stent
No relevant studies
6 Bakkevold
24 Huguier
27 Lillemoe
52 Sohn
30 Luman
3
3
3
3
3
Laser
21 Gevers
3
Resection
23 Haugstvedt
56 Valen
36 Ouchi
3
Injection of
alcohol in the
celiac plexus
26 Lillemoe
24 Huguir
3
3
3
3
No relevant studies
Resection
41 Rosen
43 Sarela
46 Scoggins
3
3
3
In a special section we have chosen to focus on pain and quality of life on the basis of
the reviewed literature on palliative gastroenterologic cancer therapy. It is, moreover,
a point to look into possible effects on survival of palliative measures, which in point
of principle are more directed towards the patients’ symptoms and pain.
32
Gastric cancer
In a large Norwegian multicentre study (n = 1165 patients) of surgical treatment, patients with gastric cancer QQQ (23), 503 patients underwent non-curative therapy
(35% resection/gastrectomy, 14% bypass, 31% explorative laparotomy, 16% no surgery). On the basis of multivariate analyses the authors conclude that resection doubles survival (stage III, 9 vs. 4.5 months; stage IV, 6 vs. 3 months) when controls are
made for age and pre-operative weigh loss. In another report based on the same patient material (56), it was found that there were big differences among regions between various types of hospitals (university clinics, regional hospitals, county hospitals) in patient characteristics and the type of treatment used. This point highlights the
problem of patient selection.
Survival and quality of life (including ”out-of-hospital survival”) have been focused
on in a study from Japan (36), after palliative surgery on patients with gastric cancer
(11.5% of all those who underwent surgery for gastric cancer over a seven-year period) with varying degrees of peritoneal metastasis. Survival and ”hospital-free survival” for three months or longer was significantly better in patients who underwent gastrectomy compared with gastrojejunostomy. In patients with marked peritoneal metastasis (P2/P3), neither palliative gastrectomy nor gastrojejunostomy had any positive
effect on survival or quality of life.
Pancreatic cancer
A possible palliative effect from ”radical” pancreatic surgery has for long been discussed. ”Palliative pancreatico-duodenectomy” is often used when postoperative morphologic examination of samples from the surgery shows that the procedure was not
radical (residual tumour tissue, microscopically or macroscopically, R1 procedure). As
shown in a Norwegian multicentre study (6), (the radically operated patients had the
best functional status, reasonably enough as it must be assumed that these patients
were good candidates for extensive surgery. In this study it was observed that bypassoperated patients (not tumour-directed surgery) were more in need of strong analgesics; they were also more afflicted by nausea and vomiting than those who had undergone radical surgery. There was no difference in palliative effect between simple or
double bypass.
In another large study (24) it is also observed significantly better survival in radically
(tumour-oriented) operated patients without metastases compared with those operated
with bypass; it was a significant difference in postoperative mortality, 10% and 15%
respectively. Based on a retrospective review of 64 patients, Lillemo et al. (27 ) are
also of the view that radical pancreatic surgery has a palliative role. In their study,
patients had also undergone chemotherapy and radiotherapy. Another study from the
same institution (52) reports that palliative surgery could be carried out with a mortality of 3.1%, not significantly different from that among the radically operated
(1.9%); the postoperative rate of complications was significantly lower (22%) among
the palliatively operated compared with radical surgery (35%). It is worth noting that
75% of patients had the celiac plexus blocked as palliative therapy.
Chemical splanchnicectomy with alchohol injection in the celiac plexus has been used
in patients with pancreatic cancer. A prospective randomised study (26) has clearly
demonstrated that this therapy is efficient for treating or preventing pain in patients
33
with non-resectable pancreatic cancer. Significantly better survival is also demonstrated in patients who had a blockade. It is not known to what extent this therapy is
used for this group of patients in Norway.
Biliary ducts
Patients with extrahepatic cholestasia with icterus and pruritus will often profit from
stenting. A quality of life study including 47 patients (30), confirmed that stenting had
a significant and positive effect on icterus and pruritus. Through the use of quality of
life instruments (EORCT QLQ-30, GHS), it was also observed that these patients experienced a significant improvement in relation to appetite, diarrhoea and sleep. Emotional, cognitive and global health scores were also significantly improved.
Colorectal cancer
For patients with colorectal cancer, other palliative measures than surgery should necessarily be considered and possibly be carried out. A retrospective study (21) of more
than 200 patients with inoperable colorectal cancer assessed the benefits of endoscopic laser therapy in terms of effect on the obstruction, bleeding or other ailments (soiling, diarrhoea, tenesmus). Primarily, 92% achieved a good palliative effect for their
main symptom and there were no differences between the three groups. Good longterm effect was achieved in 83% of patients, with the lowest effect (65%) in patients
with symptoms of obstruction. This group also had the highest number of repeated
laser therapies. Procedure-related mortality was <3%, and there were relatively few
complications (perforation, fistula, abscess, bleeding). Laser therapy may be effective
in some patients, but selection of patients is necessary (see page 25).
Patient with advanced colorectal stage IV cancer at the time of diagnosis have a serious prognosis, also in the short term, and ambitions for treatment could be controversial. In a recently published study from the USA (41), it was found in a retrospective
review of a patient material that median survival was 14.4 months, five-year survival
only 10%. Advanced age (>65), carcinomatosis and pronounced/bilobular metastases
to the liver were associated with low survival and higher postoperative morbidity and
mortality. The authors conclude that resection of the primary tumour and surgery for
metastasis should be offered to some of these patients who in this way could still get a
better prognosis.
Sarela et al. (43) focused on the same group of patients but they also assessed the irresectable synchronous metastases. In this study, 24 patients with advanced colorectal
cancer were primarily treated with 5-FU based chemotherapy without other palliation.
Median survival was 10 months, one-year survival 44%. The authors conclude that
patients with minimal symptoms from their stage IV disease only have a small risk of
development of new or more symptoms or complications before they die from their
disease. A similar conclusion may be dawn from a retrospective study (46) of 23
asymptomatic patients with advanced colorectal cancer who primarily were treated
with chemotherapy or a combination of radiotherapy and chemotherapy. Two patients
(8%) had to have a gastric relief /tarmavlastning/QQQ during the course of their disease.
It would seem that in stage IV patients with few or minimal symptoms of their colorectal cancer, surgical treatment does not seem to improve or prevent symptoms or
34
offer a better prognosis. Other palliative measures should be considered when this is
deemed necessary on the basis of the clinical issue involved (43,46).
Conclusion
Pain, prolongation of life, and survival are important aspects in the assessment of palliative cancer surgery, but the literature is very limited. Palliation in inoperative pancreatic cancer can be achieved though injection of alcohol in the coeliac plexus. The
quality of live is improved by fewer symptoms of icterus, pruritus, obstruction and
bleeding in the bowel.
4.2 Neurosurgery
Effect of palliative surgery on patients with cerebrospinal malignant tumour
This report deals with three categories of patients that belong under neurosurgery:
1.
Primary intracranial tumours, i.e. anaplastic astrocytoma or glioblastoma multiforme, which constitute the greater proportion of malignant gliomas.
2.
Metastatic intracranial tumours.
3.
Metastatic intraspinal tumours; this area is shared with orthopaedic cancer
surgery and is considered in the chapter on orthopaedic surgery.
4.2.1 Quality of life, neurologic deficiency /svikt/QQQ and survival in
primary cancer of the brain
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Survival:
1. Determine
histologic
diagnosis
2. Relieve
signs and
symptoms of
increased
intracranial
pressure
3. Prolong
survival
Better quality
of life
Glioblastoma
multiforme
Surgery:
Biopsy or resection (total or
partial)
105 Simpson
109 Jeremic
111 Stummer
107 Kreth
108 Kiwit
110 Deveaux
1+
2+
3
3
3
3
Glioblastoma
multiforme
Biopsy
Resection (total
or partial)
107 Kreth
111 Stummer
108 Kiwit
110 Deveaux
3
3
3
3
Effect of surgery on average survival
The therapy for this group of patients usually includes some form of surgery: biopsy
or resection of the tumour, either total or partial, followed by some form of oncologic
postoperative therapy, usually radiotherapy, the primary therapeutic alternative.
35
Surgery for gliomas has three main objectives:
1. Determining histologic diagnosis
2. Relieving signs and symptoms of increased intracranial pressure
3. Prolonging survival and achieving a better quality of life
There is general agreement on the use of surgery for objectives 1 and 2. Sometimes it
is clear that either a simple biopsy or radical resection should be done. Resection is
relevant when there are clear clinical signs of increased intracranial pressure, or reducing the size of the tumour (cytoreduction) is necessary. However, if the tumour is
located in an area of the brain that is difficult to access or a resection would cause
significant neurologic symptoms postoperatively, biopsy is clearly the best choice.
Objective no. 3 above is still controversial, as the majority of patients are in a grey
zone in which there does not seem to be sufficient information on which procedure
will give the best quality of life or prolong survival.
Simpson et al, (105) brought together data on individuals from three trials with 645
patients with glioblastoma multiforme. These were randomised controlled trials of
either dose-response effects in radiotherapy or benefit from chemotherapy combined
with radiotherapy. No significant difference in median survival was found between
the treatment groups, hence the data could be analysed combined. Total resection resulted in a clearly longer survival compared to biopsy (11.3 vs. 6.6 months). Both
groups of patients were also given radiotherapy. It was also found that resection gives
longer survival when compared to biopsy (10.4 vs. 6.6 months).
Similar results are reported from several other retrospective studies: Deveaux et al.
(110), Kiwit et al. (108), and Jeremic et al. (109).
In a study reported by Stummer et al. (111) on 52 patients in whom an intraoperative
method was used to establish the scope of tumour resection, total tumour resection
gave significantly increased average survival compared with partal resection of the
tumour.
In a retrospective study, Kreth (107) reported no significant difference in survival
between resection and biopsy. Patients who underwent biopsy were assessed as inoperable or in such severe neurologic condition that the risk associated with surgery
was too great. In spite of this they did as well as the group that had their tumours resected.
Similar results that raise some doubt as to the effect of tumour resection on survival,
at least in glioblastoma multiforme, were reported in two review articles that were not
included here (117,119). No studies fulfill the Cochrane RCT requirement (113).
Effect of cytoreductive surgery on quality of life
All publications mentioned used median survival time as the main measurement of
effect of biopsy vs. cytoreductive surgery. Quality of life of patients was not assessed
in detail, but five studies used Karnovsky Performance Scale (KPS) in order to assess
the functional status of patients.
Several studies show that KPS is an important predictor of survival (106,108,110,
111). Kiwit presents results from pre- and postoperative measurements and finds no
36
improvement in patients that underwent biopsy. In contrast, Kreth et al. (107) showed
in a retrospective series of patients that six weeks after treatment there was no difference in clinical status between resection and biopsy.
Conclusion
Setting the histological diagnosis: This is generally done by biopsy. On the other
hand, stereotactic biopsy underestimates the diagnosis of glioblastoma multiforme vs.
anaplastic astrocytomas compared to resection, with resulting bias towards the biopsy
patients. This is the situation, given that glioblastoma multiforme patients who are
erroneously diagnosed as having anaplastic astrocytomas have a worse prognosis than
what would be expected (112).
Mild signs and symptoms of increased intracranial pressure: Cytoreductive surgery
gives an obvious improvement and should be carried out.
Prolonged survival and better quality of life: Cytoreductive surgery seems superior to
biopsy in terms of prolonged survival as well as quality of life. All publications that
found only a small difference between biopsy and partial resection compared to total
resection were based on the surgeon’s own assessment of the degree of residual tumour. This method has been proven to be highly unreliable, as the surgeon almost
always underestimates the amount of residual tumour tissue. In the two reports in
which an objective measurement of residual tissue was carried out (109,111), radical
resection turned out to be definitely the best alternative. Radical resection usually
does not lead to deterioration of neurologic status and often improves it compared to
partial resection; it should be the preferred choice.
4.2.2 Neurologic deterioration and survival in brain metastasis
Symptom
Type of
Treatment
Reference Evidence
cancer
level
Prolongation of
life. Reduced
neurologic
symptoms.
Various
types of
primary
cancer
Surgery and
radiotherapy vs.
biopsy and radiotherapy
104 Vecht
106 Patchell
1++
1++
There are far more patients with metastasis to the brain than with primary brain tumour. Patients with intracranial metastasis have three therapeutic options:
1.
Biopsy followed by conventional external radiotherapy
2.
Surgical removal of the tumour followed by conventional external radiotherapy
3.
Stereotactic radiotherapy either as single therapy (1 fraction so-called gamma
or Linac knife surgery) or in several fractions (usually 2 or 3; Linac radiotherapy). The therapeutic options mentioned under this point 3 are not considered surgical and will not be dealt with in this report.
Two randomised trials are included of therapy in cases with a single brain metastasis
(104,106) in which resection plus radiotherapy vs. biopsy plus radiotherapy are compared. For patients with stable extracranial disease, both trials clearly show the benefit
of open surgery plus radiotherapy compared to biopsy only plus radiotherapy in terms
of survival as well as quality of life.
37
Vecht et al. (104) reported a series of 63 randomised and evaluable patients of whom
32 were randomised to surgery and 31 to radiotherapy after biopsy only. Median survival for those undergoing surgery was 12 months compared to 7 months for those
who were only given radiotherapy. At one year, 50% of the patients in the surgery
group were functionally independent as against 17% in the biopsy group, irrespective
of type of tumour. Many patients had an improved WHO functional status after treatment and kept their WHO status 0 or 1 until they died. Patchell et al. (106) reported a
study including 48 patients (25 to surgery plus radiation, 23 to biopsy plus radiation).
Median survival in the surgical group was 40 weeks compared to 15 weeks in the biopsy/radiation group. Additionally, there was new tumour growth in the original metastasis site in 20% of the surgical group vs. 52% in the biopsy/radiation group.
Measured by median functional independence (KPS>70), the surgical group achieved
an interval of 38 weeks compared to 8 weeks for the biopsy/radiation group.
Conclusion
Patients highly likely to benefit most from surgery are:
1. Those who have one metastasis
2. Those with either no or other (extracranial) stable disease
3. Controlled cancer, limited to primary tumour
4. Expected remaining survival >2 months
Surgery and radiotherapy are superior to biopsy plus radiotherapy in terms of longer
median survival as well as functional independence.
4.2.3 Neurologic failure in cases of metastasis to the spine
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Deteriorating
neurologic
function
Various
types of
primary
cancer
Surgery
185 Young 129
Cappeletto
151 Jackson
138 Galasko
139 Gilbert
172 Olerud
156 Kluger
146 Harrington
176 Sundaresan
179 Turner
173 Jónsson
1+
3
3
3
Eleven publications were included in the final analysis on neurologic functioning.
Only one study was prospective and randomised; the others were non-randomised
prospective or retrospective series of patients. The publications reaching stage 3 in the
evaluation process were independently assessed by orthopaedists and neurosurgeons.
There was complete agreement except for one article by Cappeletto et al.(129), which
was excluded by the orthopaedists because it included too few patients.
As most patients suffering from intraspinal metastatic tumours die from their primary
tumour, the purpose of surgery in these cases is not longer survival per se. Median
time of survival for patients with spinal metastasis varies depending on the type of
38
primary tumour and the degree of metastasis. In the study by Turner et al., patients
with metastasis had a median survival of only 4.1 months, while patients with more
localised metastases had a median survival of 14 months. Comparable survival was
also found in the study by Jackson et al. (151) on renal cancer (12.3 months).
Hence, the objectives of treatment of metastatic intraspinal tumours are:
1.
To reduce pain
2.
To maintain or regain neurologic functioning
Patients with intraspinal metastatic disease have the following therapeutic options:
1.
Radiotherapy (RT) only
2.
Laminectomy (only) + RT (posterior radiation)
3.
Posterior stabilisation +/- laminectomy + RT
4.
Anterior access (resection of vertebra) with anterior/posterior/combined stabilisation + RT
All these procedures are described in the articles included here.
The only randomised and prospective trial (185) compared laminectomy (without
stabilisation) plus radiotherapy to radiotherapy alone. The trial is more than 20 years
old and rather small, including a total of 29 patients with 16 in the surgical group.
Painlessness was achieved in about 50% of patients. There was a moderate improvement in neurologic functioning. No significant difference was observed between the
two groups in terms of painlessness or improved neurologic functioning. Similar results have been reported by Gilbert in a non-randomised trial including 65 patients
treated with laminectomy and radiotherapy compared to 170 patients treated with radiation only.
In three other patient series (129, Jónsson et al., 138) in which posterior stabilisation
with or without decompressive laminectomy was used, painlessness was achieved in
between 80% and 90% and improved neurologic functioning in 50 to 60% of patients.
In Jónsson’s study (173), 19 out of 25 immobilised patients regained their ability to
walk.
Conclusion
Because of better diagnostic methods (CT, MRI), improved or simplified surgical
techniques and better oncologic therapy there is now a more active attitude to surgical
treatment of spinal metastases.
No randomised prospective studies have been carried out in order to compare some of
the surgical methods or to compare surgery to any type of stabilisation without radiotherapy only. All patient series reported here (9 of which have been assessed by us)
showed very good palliative effect in all patients, irrespective of surgical method.
Laminectomy combined with radiotherapy but without stabilisation was no better than
radiotherapy only in terms of palliation or of improved neurologic status and cannot
be recommended. Surgery with anterior access with decompression and stabilisation
is usually used for cervical metastases in which pain is the dominating symptom in
most patients. The limited posterior surgical access with a pedicle screw stabilisation,
with or without laminectomy, seems to be the most promising type of primary surgery
for the majority of patients (173) with thoracic or lumbal metastases. More extensive
forms of surgery in such conditions (for instance, with anterior access) should be con-
39
sidered a secondary procedure limited to patients with metastatic disease who are still
in good physical condition and have a life expectancy of more than 12 months.
Radiotherapy should not be given preoperatively because of the increased risk of surgical complications, but should be given postoperatively.
Patients with paraplegia or severe paraparesis showed little or no neurologic improvement after surgery.
This underscores the importance of an early diagnosis, speedy transfer to a hospital
that offers this treatment and immediate surgery if severe neurologic failure has been
of short duration (less than 12 hours).
4.3 Orthopaedic surgery
4.3.1 Surgical treatment of bone metastases
Introduction
In 2000, a total of 22 185 persons developed cancer in Norway1, 11 434 men and
10 751 women. Breast cancer is the most prevalent cancer in women, constituting
23% of all cancers in women. Prostate cancer is the most prevalent cancer in men,
accounting for 13.7% of all cancers and 26% of all cancers in men. Cancers in the
digestive organs account for 23% of all cases in men as well as women. Bone metastases are a sign of spread of the disease but not necessarily a sign of terminal disease.
In the largest groups of cancers, median survival after such metastases is several
years. Bone metastases most often originate in breast or prostate cancers.
Not all patients with bone metastases develop pain that require treatment. Karolinska
Institutet in Stockholm has developed a special therapeutic programme for bone metastases to which patients may be referred. The experience from this group shows that
the risk of a breast cancer patient developing metastases that require treatment could
be 10 to 15%; 20% of these patients undergo surgery, either because of a fracture
caused by disease in an extremity or because of metastasis to the spine with neurologic complications (322). The others receive radiotherapy or medical palliation.
Our review covers 277 articles, but very few prospective studies and only one prospective randomised study (185). The most important work relevant to the situation in
Norway has been published by the Stockholm group (183,322). Among the other articles, many are quite old, possibly because it has been difficult to publish retrospective
studies during the last few years. Several articles are about patients with various forms
of primary cancer and in different stages of their disease.
Assessing surgical treatment we have emphasised indications, methods and results.
Endpoints have been failure of the surgical reconstruction, time to failure, and rate of
infection. The functional level is expressed as proportion of patients with selfassessed free use of their arms and the proportion of ambulatory patients, with or
1
Source: Kreft i Norge 2000, National Cancer Registry.
40
without aids. Most of the articles have a follow-up period of more than 24 months for
survivors.
Fracture and/or pain is often an indication for surgical stabilisation. Evaluating pain is
difficult, and few studies have been carried out with preoperative pain grading with a
visual analogue scale and/or use of analgesics.
The various surgical methods have been assessed according to localisation in bone,
use of open or closed technique, cement reinforcement, and complications.
Results have been assessed in terms of complications, protracted pain, function in the
extremity (for the back, neurologic function has been assessed), peri- and postoperative (four-week) mortality, and survival. Only a couple of studies have attempted to
assess improvements in terms of quality of life.
It is not possible to assess palliative surgical treatment of bone metastases without
examining the results of the other therapeutic options that exist, hence we have included in our selection of the literature articles on radiotherapy, chemotherapy, hormonal therapy, and bisphosphonates. No therapeutic option has been shown to prolong life (169,170,323).
Radiotherapy has good documented effect on pain in bone metastasis (342). There are
also some reports on new bone tissue formation in osteolytic metastasis. It is doubtful
whether radiotherapy only can heal the fracture; there is, on the contrary evidence that
suggests that radiotherapy interferes with the chondrogenesis that is necessary for the
healing of a fracture (150). This provides theoretical support for choosing prophylactic stabilisation before radiotherapy.
Surgical treatment of fractures
Table 4.1.
Symptom
Fracture
Load pain as an
indication for
prophylactic
stabilisation
Type of
cancer
Treatment
Reference
Evidence
level
Various types
of primary
cancer
Various types
of primary
cancer
Surgery
183 Wedin
134 Dijstra
144 Harrington
154 Kerr
150 Hipp
153 Keene
142 Haentjens
322 Wedin
165 Mirels
4
3
4
3
4
4
4
4
4
Surgery
There is broad agreement to the effect that patients with pathologic fractures need
surgery because the patient’s remaining lifespan is so short that one cannot wait for
the healing of a fracture before the extremity can be used; hence there is also broad
agreement on the choice of an osteosynthesis or a reconstruction that is so strong that
it allows an immediate load and lasts throughout the patient’s remaining lifespan.
41
We have included two patient series (134,154) in the basis of evidence, but also used
review articles in order to describe the issue (table 4.1). Four-week perioperative mortality of 0 to 18% has been reported in 26 articles. The three largest studies including
a total of 846 patients cite, respectively, 8%, 15% and 18% mortality (134,144, 183).
23 articles allowed estimates of postoperative infection rates; 0–12% is reported. The
two biggest, including a total of 613 patients, both report 5% infections.
In this report an attempt has been made to assess the results according to localisation
and type of primary cancer disease.
Most studies report results in several types of cancers. Breast cancer is the major type,
with from 70% to 80% of included patients, followed by prostate cancer. There are
some studies that only assess results with breast cancer and renal cancer with bone
metastases that require surgery (124,125,153,155).
Prophylactic stabilisation of factures
There is substantial disagreement on the indications for prophylactic stabilisation.
There are three major objections. By far the largest numbers of metastatic patients
receive sufficient palliation without surgery, even with extensive destruction of bone
tissue. Adequate stabilisation has relatively high mortality (154) and causes in itself
reduced mobility over a long period relative to the remaining lifetime. There are no
reliable methods at hand for assessing the remaining bone’s resistance to fracture. The
best method is probably CT, taken together with recordings of several phantoms
/skjelettfantomer, QQQ/ with known maximum load in relation to bone density (150).
This illustrates that the strength of the remaining bone and the size of the bone are of
greater importance than the amount of destroyed bone tissue.
By far the most of the studies that have been carried out are based on femoral destruction. The most important criterion is the pain caused by load, followed by whether or
not the lesion is in the proximal part of the femur. Dislocation [QQQ; avløsning av] of
the lesser trochanter/destruction of calcar is an auxiliary indication. Most pathologic
fractures happen in lytic metastases. Several authors also report that destructions
above 2.5 cm and/or above 50% of the circumference give increased risk of fracture.
It is, however, hard to assess this and no criteria have been validated in major studies
(125,142,153,165).
It is difficult to recommend prophylactic surgery on the basis of the documentation we
have identified. A weighted scoring system has been proposed for the assessment of
when prophylactic surgery should be carried out (165). It has been evaluated, but few
references are made to it in the literature.
The sensitivity to radiation of the metastasis is of importance to the order in which
stabilisation and radiotherapy should be carried out when the criteria mentioned are
met. Moreover, most authors recommend an individual approach to the decision for
each patient, underscoring the importance of close contact between doctors that attend
to cancer patients and the orthopaedists who carry out the prophylactic stabilisation.
Patients also have differing requirements as to autonomy and physical ability in the
final stage of life. The biology of the primary tumour, the speed with which the metastasis grows, and the patient’s remaining lifespan are just as important as the status
recorded by x-rays (165).
42
4.3.2 Pain or fracture caused by metastases to the humerus
Table 4.2.
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Pain, fracture
Various
types of
primary
cancer
Surgery
142 Haentjens
134 Dijstra
160 Lancaster
4
3
3
There are only a few studies on treatment of metastasis in the upper arm; we have not
included any of them in our pool of evidence. The issue is described in one included
and two excluded articles (table 4.2). Most authors recommend primary radiotherapy
and surgery if the pain requires this or a fracture occurs; no evidence is cited as to
what should be the method of choice. The methods mentioned are marrow nailing
with or without cement reinforcement, plates with or without cement reinforcement
and prosthesis (134,142,160). The marrow nails described in the relevant studies are
not of the contemporary types. It could be that a modern marrow nail provides sufficient stability in order to provide palliation. It seems doubtful whether orthosis therapy is sufficient for patients with pathologic fractures in the upper arm.
4.3.3 Pain or fracture caused by metastases to the femur
Table 4.3
Symptom
Type of
cancer
QQQ
Treatment
Reference
Evidence
level
Pain, fracture
Various
types of
primary
cancer
Collum/caput
Surgery
Trochanteric and
subtrochanteric
part
Shaft of femor
(diaphyseal part)
Surgery
3
3
3
Distal part
Surgery
134 Dijstra
149 Helwig
141 Habermann
183 Wedin
131 Colyer
132 Coran
140 Graupe
135 Douglass
154 Kerr
157 Korkala
158 Krawzak
159 Kurock
184 Yazawa
144 Harrington
141 Habermann
183 Wedin
Surgery
3
3
3
3
3
3
3
3
3
3
3
3
3
By far the greater number of fractures occurring when the patients is not in the terminal stage require surgery. The choice of method depends of the localisation of the metastasis. Most article report that after reconstruction, 80 to 90% of patients were ambulatory with little pain in the remaining years of their lives unless the reconstruction
43
broke down; hence a lasting reconstruction is the most important criterion of success.
The selected literature is based on patient series (table 4.3).
In many patients with deconstruction and pain, radiotherapy will be the first choice.
The literature does not support prophylactic reconstruction, though sound judgment
indicates that patients with pain that cannot be alleviated and who have reduced walking capacity should undergo surgery. Bone destruction involving the neck of femur
(with affection of the greater trochanter or medial cortex in the head of femur)
strengthens the indication for surgery.
Neck of femur, head of femur
13 articles describe experience with 523 patients in whom standard prosthesis was
used after resection of neck/head of femur localised metastasis. This reconstruction
failed in 0–10% of patients, though most articles report 2–3% failure. The main reason is a loose prosthesis. Two articles describe failure in 30% and 100% of patients
undergoing surgery with osteosynthesis and cement (134,149).
Conclusion
In pathological fractures of the head of femur there is a choice between osteosynthesis
reinforced by cement, resection only without reconstruction (Girdlestone), or reconstruction with endoprosthesis. Osteosynthesis only is a poor solution; sufficient stability is not achieved and redislocation often occurs, especially in destruction of the calcar. Resection of the head of femur without reconstruction gives good palliation in
pre-fracture non-ambulatory patients with severe pain. Most patients with neck of
femur fracture are suitable for resection of the head of femur and endoprosthesis replacement. If the pelvis is not destructed, a hemiprosthesis is used that is cemented
into the femur, preferably with a long shaft.
In cases of concurrent destruction of the pelvis, a total hip prosthesis is made with
reinforcement of the pelvis. As with facture in the upper part of the humerus, severe
destruction might necessitate special prostheses.
Upper part of the femur
Four articles including 180 patients report experience with plate osteosynthesis reinforced by cement, with failure in 10%, 40%, 55% and 100%, respectively. One
study of a few patients without cement reported 100% failure; another, including 47
patients, had no failures with the use of a reconstruction nail (γ-nail) in subtrochanteric localisation (141). This study dealt with γ-nail with or without cement. Twelvemonth survival was highest in the cement-reinforced group, 51% as against 39%,
though it is not clear whether the groups were otherwise similar. The difference in
survival was interpreted as related to the degree of stability and hence to degree of
mobility for the patient.
Conclusion
Fractures in this region make for the biggest problems of reconstruction. All methods
have a greater tendency to fail than endoprostheses in the neck/head of femur region.
The literature provides support for selecting endoprosthesis as well as intramedullary
nailing of the so-called reconstruction type with a screw to the head of femur. Endoprostheses probably pose the least risk of reoperation if there is no need to remove all
of the trochanter. By resection of major parts of the trochanter, a resection prosthesis
44
will often (in 20% of cases) become loose. The procedure is time-consuming and
must be assumed to give a high rate of complications in this group of patients. A reconstruction nail /med sperring QQQ/ is a smaller procedure, and there is a basis for
preferring this to plate osteosynthesis reinforced by cement.
Shaft of femur
Three articles including 35 patients describe the experience of plate osteosynthesis
reinforced by cement with, respectively, 3%, 28% and 50% failure. Seven articles
including 113 patients describe closed intramedullary nailing without cement with 0%
to 8% failure. Three articles with 81 patients report intramedullary nailing procedure
/sperremargnagling QQQ/ reinforced by cement, of which no-one failed during the
patients’ lifetime.
Conclusion
Closed intramedullary nailing with blocking proximally and distally usually immediately gives a load-stable fracture. Cement does not seem to be necessary. Reconstruction nails, thicker than ordinarily intermedullary nails, are recommended. They are
made from titan, which means that complications with nail breaks are avoided if the
fracture does not heal. In prophylactic intermedullary nailing and use of long-stem
femur prosthesis, sudden and fatal hypotension /blodtrykksfall QQQ/ has been reported. This may be caused by bone marrow and tumour tissue being pressed out in the
circulation. This risk is probably reduced by first scraping out the metastasis and/or
making an opening in the medullary cavity in the distal metaphysis. As far as we have
found, there is no evidence indicating that the drilling into the medulla increases the
risk of spread of tumour cells in the medullary cavity with ensuing new metastases. It
is, however, reported that the medullary drilling can result in spread of thrombi to the
lungs, possibly also of tumour cells.
The distal part of the femur
Two articles with a total of 57 patients report specifically on this localisation (141,
183) and cite failure frequencies of 8% and 10% with various forms of osteosynthesis
and cement reinforcement. Others relate their experience without citing data.
Conclusion
These metastases are treated with scraping, always bone cementing; as osteosynthesis
there is a choice between / vinkelplate, glideskrue QQQ/ or retrograde /marrow nail
QQQ/. There are no data that provide a basis for preferring any of these; there is,
however, less experience with retrograde nailing.
4.3.4 Pain or fracture caused by metastases to the pelvis
Table 4.4
Symptom
Pain
Type of
cancer
Treatment
Reference
Evidence
level
Various
types of
primary
cancer
Surgery
145 Harrington
163 Marco
181 Vena
3
3
3
45
Metastases to the pelvic bone are highly usual. Radiotherapy will nearly always be
tried before surgery; it is unusual that surgery is necessary. When the destruction has
progressed that far, the general condition of the patient is most often assessed as being
too bad for him or her to tolerate the big procedures that are necessary for palliative
stabilisation. The principle is that if the destruction involves the pelvis, cement with
metal reinforcement and possibly prosthesis is used.
There are three articles (table 4.4) with a total of 130 patients that to some extent
compare three methods of reconstruction. These three methods are standard prosthesis
only, reinforcement with an acetabular ring (e.g. Burke-Schneider), and reinforcement
with 6 mm thick Steinmann pins (145,163,181). For prosthesis, a 20% failure rate is
reported, 10–15% after about 4 months with an acetabular ring, and 0% and 10% after
about 12 months for acetabular ring. A couple of articles also describe the so-called
saddle prosthesis.
Conclusion
Pathologic pelvis fractures (acetabular fractures) could give extremely strong pain
from the pelvis and loss of ambulatory function. If the destruction is so big and the
remaining lifespan so long (more than three months) that surgery must be carried out,
scraping and cementing with pin reinforcement is probable the most durable solution.
4.3.5 Pain or fracture caused by metastases to the spine
Table 4.5
Symptom
Pain, fracture.
Prophylactic
stabilisation
Type of
cancer
Treatment
Reference
Evidence level
Various
types of
primary
cancer
Surgery
185 Young
139 Gilbert
172 Olerud
138 Galasko
156 Kluger
146 Harrington
176 Sundaresan
179 Turner
173 Jónsson
151 Jackson
155 King
174 Rompe
182 Venbrocks
1+
3
3
3
3
3
3
3
3
Bone metastases are frequently to the spine and proximal parts of the long bones. The
true incidence of bone metastases from all forms of cancer requiring treatment is unknown. If one assumes that metastases from other cancers give the same need of
treatment as metastases from breast cancer, in Norway about 1000 patient will be in
need of treatment and about 150 undergo surgery. About 5% of patients with metastasis to the spine will be in need of surgery because of neurologic complications.
In 70% of cases, the metastases are localised to the thoracic region, 20% to the lumbar
region, and 10% to the cervical region. In most cases the corpus of the spine is attacked; isolated metastases to the intervertebral joints or the spinous process of vertebra rarely occur (171).
46
One single article reports that patients with lumbal metastases had a median survival
of eight months (172). Remaining lifespan is best related to the time from the discovery of the primary tumour up until the time when the spinal metastasis gave symptoms: 15 % of the metastases have onsets without known primary focus.
Most studies date back a number of years (table 4.5). In many, radiotherapy is recommended as the first choice (138,185). It is, however, a big problem that patients
who develop neurologic /utfall QQQ/ could quickly become paraplegic; quite naturally this will have big consequences for their functioning during their remaining
lifespan. Still there is no basis for treating these patients prophylactically.
As mentioned, radiation is the first treatment of choice, but in cases of osteolytic metastasis with fracture and instability, radiation probably is of little effect (138,156).
These patients should therefore be evaluated for surgical relief and stabilisation. Recommendations include standard x-ray examination, CT of the relevant region, and
MRI of the total column before surgery. Remaining-lifespan prognosis will be a contributing factor for whether or not one decides on surgery. A scoring system has been
developed for preoperative evaluation of remaining lifespan for patients with spinal
metastases (178), but has not been validated.
Patients with spinal metastases should definitely be operated on before they develop
large neurologic QQQ /utfall/. Patients with quick onset of total paralysis have a bad
prognosis for improved neurology, irrespective of treatment. In cases of minor neurologic /utfall QQQ/ and slower onset, 80% will improve and 50% regain good ambulatory functioning with surgical relief and stabilisation (139,146,156, 176).
Earlier, only laminectomy was commonly used. This might increase instability and
hence the pain and is no longer recommended as the only procedure. The only prospective randomised trial we have found is done between laminectomy only and laminectomy with radiation added. This trial showed no reliable difference between these
groups but is not relevant now as surgical methods have been improved (185).
It is now discussed more often whether or not one should use anterior or posterior
access to the vertebral corpus on these patients (166,179). Most authors recommend
that the back is stabilised. According to the literature, posterior access gives lower
morbidity and mortality. Cement reinforcement could also be an option for these patients. In patients with metastases from renal cancer, embolisation of the blood vessel
to the tumour 24 hours preoperatively is recommended. There are, however, conflicting reports in the literature on this point too (172,185).
Anterior access requires special surgical skills and is only recommended for patients
with a good remaining lifespan prognosis. If the morbidity after anterior access is to
be defensible, the remaining lifespan must be one to two years. For patients with spinal metastases, this is not often the case. With anterior access there is 10% four-week
perioperative mortality and 12% infections, while the corresponding figures for posterior access are 3–4% and 2–3% (138,156,179). In patients with long expected remaining lifespan, anterior stabilisation is, however, required in order to prevent failure of
the reconstruction. The more recent literature recommends posterior access, possibly
47
with resection of /bue/base QQQ and tumour in corpus, followed by stabilisation
(156,173).
Conclusion
Bone metastases that give strong pain should be treated. The first choice is radiotherapy. Surgery is an option for fractures and for those patients in whom radiotherapy has no effect.
Surgery on the extremities may be done in all departments that carry out prosthesis
surgery and fracture surgery. The choice of method of surgery on the extremities will
depend on localisation and the degree of destruction of tissue because of metastasis.
Spinal surgery requires collaboration with an oncologist, a radiologist and, as the case
may be, a neurosurgeon and an orthopaedists and should be carried out in regional
hospitals. For spinal surgery, posterior access with relief /avlastning QQQ/ and stabilisation is often recommended.
The prognosis for survival is severe and the treatment will not prolong life. Although
there are no good prospective studies, there is much to indicate that quality of life is
considerably enhanced with surgical treatment, provided that there is a good indication.
Today there is a scientific basis for developing good guidelines. The annual need in
Norway is estimated at 100 procedures on extremities and 50 spinal procedures.
4.4 Thoracic surgery
Three therapeutic areas have been assessed:
1. Surgical management of metastases aimed at prolonging survival
2. Obstruction of central airways aimed at relief of symptoms
3. Stenosis or occlusion of the superior vena cava aimed at palliation.
In addition to conventional surgery, we include laser therapy as well as various forms
of blocking and stenting, these being within the scope of work of the surgeon.
It could be said that surgical management of metastases often has a curative aim and
hence is beyond the scope of this report. In by far the most cases, however, the aim
will be to prolong life and the disease-free /symptom-free? QQQ interval, and we
have chosen to consider this intervention as palliative.
A total of 90 articles have been assessed, 37 of which in depth. By far the greater
number has been patient series. There are few prospective randomised studies. Eight
articles on surgical management of metastases have been included, nine on airways
obstructions, and three on stenosis/occlusion of the superior vena cava.
4.4.1 Difficulty breathing and survival in metastasis to the lungs
48
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Pain, difficulty
breathing, accumulation of
mucus
Various
types of
primary
cancer
Conventional
surgery, or laser
196 Mineo
186
Billingsley
187
Billingsley
204 Weiser
195 Meyer
200 Schirren
202 Mead
203 van Geel
1++
3
3
3
3
3
3
3
Several factors are important:
-
Type of primary tumour is important. Among the various type of cancer, cancer of the testis has by far the best results (Schirren); up to 67% five-year survival is reported. The included literature on treatment of metastases from soft
tissue sarcomas also shows good results (186,187,202-204). Three-year survival is reported from 54% (two-year, 50%) and five-year survival from 25 to
38%. Weiser (204) reports median survival after resection of metastases from
osteosarcomas of 11 months.
-
The disease-free interval from the treatment of primary tumour up until metastases occur is of importance; the longer the interval, the better the results.
There is disagreement as to what the limit is, but from 1 to 2.5 years is suggested (186,187,203).
-
All authors agree on the importance of all metastases being resectable and on
complete resection. In soft tissue sarcoma, Ueda (202) reports that the number
is not important, nor is it important whether they are unilateral or bilateral. For
osteosarcoma, Weiser (204) reports that increased number and bilateral occurrence is important for the prognosis.
Conventional surgery is the traditional approach, and still valid. There are, however, a
number of reports on resection of metastasis with laser. The advantage is that it preserves more parenchyma, hence it can be used in sites where traditional resection
would have been impossible (196). It can also be repeated (204); resection of up to
110 metastases in one patient has been reported (202).
4.4.2 Obstruction of the central airways
Symptom
Type of
cancer
Treatment
Reference
49
Evidence level
Pain, problems
breathing, accumulation of
mucus
Bronchial
primary
cancer or
local metastasis from
adjacent
organs.
Stenting or laser
therapy
191Chella
192 DiazJimenez
188 Bolliger
190 Brutinel
193 George
197 Miyazawa
198 Monnier
205 Wilson
325 Cacalier
1+
1+
3
3
3
3
3
3
3
Centrally located bronchial cancer, sometimes also malignant processes in adjacent
organs, can choke the airways partially or completely. Symptoms will be coughs,
dyspnoea, haemorrhage, atelectasis and pneumonia; they reduce quality of life and
could be life-threatening.
In two randomised studies, laser surgery was compared with either photodynamic
therapy (192) or combined with brachytherapy (191). Photodynamic therapy turned
out to be just as good as laser therapy, but there were staging differences between the
groups that make the results inconclusive. A combined treatment with brachytherapy
and laser gave the most prolonged palliation. This is a small study with 15 and 14 in
each group and the randomisation is inadequately described.
In a prospective series of 28 patients, 23 (82%) had improved ventilation and perfusion of the lungs (193). Another prospective study of 116 patients who underwent
176 treatments showed reduced breahing difficulty in 66%, while 41.2% had reduced
symptoms of pneumonia. Repeated laser treatment is often necessary; a series of 1839
patients underwent a total of 2610 treatments (223).
Either silicon stents (188) or self-expanding metal stents (197,198,205) have been
used. Laser therapy of the process of stenosis, possibly combined with stenting, immediately relieves symptoms. Experienced operators have few complications. Naturally, the effect is gradually declining as new tumour growth occurs, but then the
treatment can be repeated Treatment results can be measured objectively by parameters of respiration physiology (FVC, FEV 1 and PF). Clear results are also found
through quality of life measurements (Karnofsky Index, WHO Index).
4.4.3 Stenosis/occlusion of the superior vena cava
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Plethora, face
swelling, strong
headache with
visual disturbances, influence
on consciousness
Most often
local metastasis from
bronchial
cancer
Stenting
194 Marcy
199 Shah
201 Thony
3
3
3
50
More often than not, the reason for the obstruction of the superior vena cava is local
metastasis from bronchial carcinomas. This condition gives a vast oedema in the upper half of the body in which the cerebral symptoms are the most troublesome and,
after some time, life-threatening.
Often it is possible to improve the patient’s condition quite quickly through percutaneous blocking preceded thrombolysis, as the case may be. In most cases this therapy
should be followed by stenting. Reports of the results from three series of patients
with, respectively, 13, 26 and 39 patients tell of immediate and good palliation with a
method with few complications (194,199,201). These patients invariably have advanced disease; usually the vein will stay open until the patient dies from his or her
cancer. Median survival in these studies is, respectively, 4.8 months, 13.5 weeks and
5.5 months.
Conclusion
In some patient groups, metastasectomy prolongs life. Patients with metastases from
soft tissue carcinomas or carcinomas of the testis have the best prognosis.
Obstruction of the central airways caused by cancer could in most cases be treated
with good symptomatic effect, though life is not prolonged. Laser and, possibly, stenting are the preferred methods.
Stenosis or occlusion of the superior vena cava can be treated with blocking and stenting, possibly preceded by thrombolysis. This treatment gives immediate symptomatic
relief and is recommended.
4.5 Urologic surgery
Introduction
The urologic types of cancer include prostate cancer, cancer of the bladder, renal cancer, cancer of the renal pelvis, of the ureter, testis and penis. In 1999 there were
21 200 new cancer cases in Norway, of which 23% (4928) were urologic cancers. In
the same year the total number of patients with urologic cancer in the population
(prevalence) was 30 877 (21% of all cancer cases) and 1774 persons died from urologic cancer. The majority of these deaths were caused by prostate cancer (1119)
while only 10 patients died from cancer of the testis and 8 from cancer of the penis. In
comparison, the prevalence of cancer of the testis was 3921, of the penis 288. These
mortality figures correspond well to the resources needed for palliative treatment of
the various form of urologic cancer. For example, palliation of advanced prostate cancer requires considerable efforts at several levels, in hospital and ambulatory.
We have been tasked with assessing the documented effect of surgical palliation in
urologic cancer. Oncologic (radiation) and other palliative therapies have not been
included. On the basis of clinical experience with the need for palliation, supported by
statistics, we have chosen to limit our assessment to prostate cancer, cancer of the
bladder, and renal cancer. Numerically speaking, cancer of the penis is a very small
problem, and the few men who die from advanced disease are only in exceptional
cases in need of surgical palliation. For cancer of the testis the need for palliation is
small, as by far the most patients are cured. Close to 100% of patients with local or
51
regional diseases are cured, and even among those with highly advanced disease about
80% are cured. For those few who die from cancer of the testis, surgical palliation is
not a relevant issue.
In addition to local problems from the affected organ, the cancer could cause locoregional disease which may call for palliation. This may be due to direct ingrowth
from the tumour or metastasis to nearby lymph nodes. An important problem in a urologic context is a cancer that grows in such a way that it produces malignant obstruction of the ureter followed by uraemia. This may be urologic cancer (of the prostate or
bladder) or other types of cancer, most frequently colorectal or gynaecologic cancers.
Literature searches have been conducted specifically on this issue; it turned out to be
the search that gave most of the relevant hits. Non-urologic symptoms caused by urologic cancer disease are considered in the respective chapters (gastrosurgery, neurosurgery and orthopaedic surgery).
Distant metastasis from other types of cancer to the urogenital organs very rarely occurs. Metastases to the kidneys and testicles (most frequently from lymphomas) may
occur; they are of small practical importance.
Over the last few decades, urologic surgery has changed a great deal; open surgery
and traditional endoscopic surgery in the lower urinary tracts have been replaced by or
supplemented by less invasive methods. This applies above all to radiologic procedures such as embolisation and various catheter insertions (e.g. internal ureteral stenting and percutaneous nephrostomy), hence we have found it relevant to include these
semi-invasive techniques in our searches.
After the last stage in the assessment of the articles identified by the searches, 31 articles remain in which we are inclined to find that the palliative intent is clearly formulated, and which to some extent can illuminate the issue by way of data. The material
is certainly varied (from 3 to 118 patients). Articles focusing on techniques only as
well as case reports have been excluded. It should also be noted that articles from the
1970s and 1980s are not up to the standards of documentation etc. that are required
today.
Only one randomised controlled study was found ( 229) in addition to one casecontrol study (239). The others were non-prospective patient series, mostly institutionally based.
It may seem as if the final number of articles is low when the issues involved are
prevalent conditions. The reason is probably that some of the therapeutic modes seem
so evident that they are in fact not evaluated in these groups of patients, quite apart
from the difficulty of conducting studies with patients in the terminal stage of cancer.
Epidemiology
Prostate cancer
In 1999, 14 376 patients in Norway lived with a diagnosis of prostate cancer; 1119
persons died from the disease. The incidence increases steadily from the age of fifty,
but very few patients are diagnosed before they reach this age. Prostate cancer is characterised by a high degree of biological indeterminacy in the individual patient. On
the basis of the data in the Norwegian Cancer Registry one might say that cancer ex-
52
clusively in the prostate gland has a five-year relative survival of about 80%, while
the corresponding figure in disease with distant metastases is about 20%. Disease that
is locally advanced, metastatic or in which radical therapy (radical surgery or radiation) has failed, is treated hormonally. Standard hormone therapy is surgical or medical castration which eliminates the testicles’ production of testosterone. This therapy
is in point of principle palliative and will help about 80% of patients. For patients with
distant metastases, average duration of the response will be slightly less than two
years before the disease progresses into a so-called hormonally refractive phase and
the patient dies after on average six months. The same goes for hormonally treated
locally advanced disease, but the time horizon could then be substantially longer than
with metastatic disease. It is particularly in this phase, when hormonal therapy has
ceased to have effect, that there is a need for various forms of palliation.
Renal cancer
In 1999 there were 448 new cases of renal cancer in Norway, 2866 persons living
with this diagnosis and 304 dying from this disease. Most die from distant metastases
after resection of the kidney with the primary tumour. Only a small minority have not
had their primary tumour resected, either because it was impossible to operate or because the disease had several metastases at the time of diagnosis. By and large, patients with an intact primary tumour are candidates for locally oriented urologic palliation. A characteristic of renal cancer is that it is highly resistant to radiotherapy as
well as chemotherapy.
Cancer of the bladder
In Norway in 1999, there were a total of 8750 patients with cancer of the bladder; 797
new men were diagnosed and 272 women. Age-adjusted incidence in the same year
was 21/100 000 among men and 5.5/100 000 among women. The incidence has gone
up steadily among men and been relatively stable among women. Cancer of the bladder strikes down in the elderly part of the population with increasing incidence from
the age of forty-five, and reaches a top among people in their seventies; five-year survival is 72% in men and 62% in women. The difference might be explained by the
fact that women are diagnosed at a later stage with more severe disease. For localised
cancer of the bladder, five-year survival among men is 80%, among women 70%. The
corresponding figures for regional disease are 22% among men and 21% among
women. Most cases of cancer of the bladder are superficial and rarely develop into
locally advanced disease, hence only a minority of patients will have locally advanced
disease that requires palliative surgery. The literature on palliative surgery in the conditions of haematuria and vesicointestinal fistula has been assessed.
4.5.1 Haematuria
Symptom
Type of
cancer
Treatment
Reference
Evidence level
Haematuria
Prostate cancer
TUR
Embolisation
Nephrectomy
Embolisation
No relevant studies
No relevant studies
No relevant studies
250 Marx
251 Nurmi
3
3
Renal cancer
53
Cancer of the
bladder
TUR
Laser
Embolisation
Irrigation
No relevant studies
No relevant studies
323 Guillou
242Brühl
241Arrizabadaga
245 Ludgate
248 Servadio
322 Fair
3
3
3
3
3
3
Prostate cancer
Macroscopic haematuria, partly with clot retention (”bladder tamponade”) in patients
with advanced prostate cancer is a routine problem in departments of urology; the
individual patient may experience this several times daily. The standard treatment is
transurethral evacuation of coagula from the bladder, possibly combined with a transurethral resection/revision of the prostate (TURP). In our review of the literature we
did not, in fact, find any studies of this approach, the reason probably being that this
treatment is so self-evident and so well documented through decades of clinical practice that no-one has found it worth studying. Patients with several such episodes are
offered palliative local radiotherapy of the prostate; this is, however, outside the scope
of our literature search.
It is also known that selective/super-selective radiologic embolisation of branches to
the prostate from the internal iliac artery has been used in patients in whom haemostasis by way of TURP or radiation has not succeeded. We have, however, not found
any literature with a patient material that documents the effect of this treatment, such
as in cancer of the bladder (see below).
Renal cancer
Visible bleeding into the renal pelvis from a primary tumour can produce pain in the
flanks caused by clot obstruction in the ureter and anaemia requiring transfusion. In
earlier years, attempts at nephrectomy used to be an approach, but no patient material
on this has been found. There is, however, now widespread agreement to the effect
that embolisation of the renal artery is the method of choice in this situation. The
method has been described for benign renal tumours, as in angiomyolipoma, but patient materials on treatment of bleeding from renal cancers are scant. Two publications (250,251) do, however, report on this method applied on the indication of macroscopic haematuria. Marx et al. (250) treated 13 patients with renal bleedings. In all
patients the macroscopic bleeding stopped after embolisation, while 3 patients developed a new bleeding after 1 to 10 months. In a report from Nurmi (251), the macroscopic haematuria was stopped in 11 out of 14 patients. Both groups report that most
patients have temporary flank pain and fever (1–5 days) and there were, respectively,
2 and 1 fatal outcomes in connection with this treatment. It is not clear whether or not
these were related to the treatment or were a consequence of advanced disease. Hypertension in patients who used to be normotensive occurs in a small minority of both
patient groups.
Cancer of the bladder
Haematuria is the most common symptom in renal cancer and is routinely treated with
transurethral resection of the bleeding tumour (TURB). We found no publication on
this therapeutic modality, probably because it represents a long and appropriate thera-
54
peutic tradition. Patients may, however, develop haematuria from a locally advanced
tumour of the bladder that cannot be controlled with TURB.
Rinsing the bladder with various substances in order to stop a bleeding has been described. Several authors have used continuous rinsing with a 1% aluminium potassium sulphate solution. The procedure does not require anaesthesia. Arrizabadaga et al.
(241) achieved complete response in 66% (10/13) of the patients, partial response in
15% and no effect in 20%. The side effects were few (tenesmus/spasm of the bladder)
and no cases of aluminium poisoning, shrinking of the bladder, QQQ or vesicoureteral
reflux were observed.
Irrigation with formalin (1%–10%) is described in older publications (248,322). It is
an efficient method, 7/8 with complete response reported by Servadio and Nissenkorn
in 1976 (248), and similarly 14/18 according to Fair in1974 (322). Serious side effects
have been reported from the use of formalin 10%, with shrunken bladder /skrumpblære QQQ/, vesicoureteral reflux and ureteral obstruction. The procedure is done in
general anaesthesia or epidural anaesthesia, often done when aluminium rinsing is not
successful.
Selective obstruction of the internal iliac artery or more peripheral vessels is described
in two articles with 7 and 3 patients respectively (223,242). The procedure has been
carried out unilaterally as well as bilaterally with “prolonged” symptomatic “good”
effect and without “major” side effects. The authors recommend the procedure for
strong bleedings that cannot be controlled with TURB or rinsing of the bladder, but
the documentation is weak.
Hyperthermic perfusion (45C) of the distended urinary bladder is described as a
treatment for intractable cases of haematuria in cancer of the bladder (245). The
method was effective in all 13 patients but requires epidural anaesthesia and an advanced irrigation procedure. There is no report of the method being used in Norway.
We have not assessed palliative radiotherapy in haematuria.
4.5.2 Urinary retention
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Urinary retention
Cancer of the
bladder
Prostate
Urinary diversion
Transurethral
resection
(TUR)
Stenting
309 Montie
3
229 Thomas
246 Mazur
1+
3
249 Yachia
240 Anson
3
3
Difficulty in voiding the bladder is a very usual problem in prostate cancer. Mazur
and Thompson (246) have reviewed the results from ”channel” TURP in 41 patients
with prostate cancer, 70% with metastatic disease, the others with locally advanced
disease. 22% were patients with urinary retention requiring a catheter; 78% had subjective difficulties voiding. All patients were able to void spontaneously after the procedure without additional treatment. Nine patients had to undergo a new TURP after
on average 15 months and another 2 patients had to undergo a third TURP. There
55
were no perioperative deaths, but 2 patients became completely incontinent as one
deliberately operated down in the external sphincter because of cancer ingrowth. Two
patients who had previously undergone radiotherapy developed stress incontinence.
The authors are of the opinion that TURP in advanced prostate cancer gives a somewhat higher risk of incontinence than in surgery for benign prostate hypertrophy but
that this risk is still acceptable. Caution should be taken if the disease affects the external sphincter and the risk of incontinence is also increased following previous local
radiotherapy (about 7%).
In a randomised controlled study of 22 patients, Thomas et al. (229) compared TURP
plus bilateral orchiectomy and quick postoperative removal of the catheter (group A)
with bilateral orchiectomy only and removal of the catheter after 1 month (group B).
The two groups were comparable and comprised patients with locally advanced cancer (stage T3/T4) who had not undergone hormonal therapy. In group A, 5 out of 10
patients immediately had spontaneous voiding after postoperative removal of the
catheter. Four patients had to have a catheter for 1 month postoperatively and the last
patient had to undergo a new TURP after 2 months. In group B, 10 out of 12 patients
were voiding spontaneously 1 month postoperatively while 2 patients had to undergo
a new TURP after 2 months. There were only small differences in length of hospitalisation, and the number of complications in the TURP group was low (2 blood transfusions and 1 urinary tract infection). The authors recommend hormonal therapy followed by removal of the catheter as the therapy of choice for this group of patients.
TURP should be held in reserve for patients unable to void spontaneously after 2
months. The authors do not, however, provide data on how long the therapeutic effect
lasted. It should also be noted that surgical castration was carried out in this group of
patients, though medical castration with a GnRH agonist is now standard procedure.
As the effect of castration occurs a few weeks later with medical castration, one
should allow for 2 months with catheter if this therapeutic modality is chosen. Hospitalisation is, however, eliminated or substantially reduced with medical as opposed to
surgical castration.
Two more recent articles (240,249) have looked into the use of temporary prostatic
stents (ProstaCoil) placed in the prostatic part of the urethra pending the effect of initiated hormonal therapy, a therapy used for patients with carcinoma of the prostate
who still has hormonal therapy in reserve. Anson et al. (240) used this therapy on 10
patients with locally advanced disease with or without distant metastases. The patients
were hormonally treated with either antiandrogen (9 patients) or with GnRH agonist
(1 patient). Eight out of 10 patients kept their stents for 3 months, as intended. One
patient had to have the stent removed after 2 weeks because of local pain from the
stent and underwent a TURP; the other patient lost his stent spontaneously after 4
weeks. Yachia and Aridogan (249) used a self-expanding prostate stent in 27 patients
with locally advancer prostate cancer and urinary retention combined with hormonal
therapy. 24 patients voided spontaneously after insertion of the stent while 3 patients
had to be treated for retention of coagula in the bladder. The majority (16) of the patients had their stents removed after 3–6 months; the others somewhat later. After on
average 2 years (24.8 months), 15 patients voided satisfactorily assessed on the basis
of urine flow and measurements of residual urine (<100 ml). Both groups of authors
view stenting of the prostate as a very good alternative to TURP or to transurethral
catheter until hormonal therapy has taken effect.
56
4.5.3 Flank pain
Symptom
Type of
cancer
Treatment
Reference
Evidence level
Flank pain
Renal cancer
Nephrectomy
250 Marx
251 Nurmi
3
3
A renal tumour may completely fill out the flank and generate pain because of its volume as well as infiltration in the surrounding structures. Attempts at palliative nephrectomy will usually be hazardous or impossible. The frequency of flank pain requiring treatment is not given in the literature, but experience indicates that it is low.
Various types of analgesic treatment, from drugs to epidural analgesia, might be considered.
However, two publications from the 1980s report experience with infarction QQQof
the kidney by embolisation of the renal artery as a treatment for flank pain from a
locally advanced tumour (250,251). This intervention was originally launched about
30 years ago in order to technically ease removal of a kidney with a large tumour and,
it was believed, improve survival through unclear immunological mechanisms. These
indications have, however, been abandoned. Still, the experience reported in these two
articles shows that embolisation could be used in the treatment of flank pain. In a material of a total of 29 patients with renal cancer who underwent transfemoral catheter
embolisation of a kidney, Marx et al. (250) report that 5 patients were treated on the
indication of pain; all of them achieved palliation of local pain, though neither the
degree nor the duration of the pain is stated. Nurmi et al. (251) treated 25 patients in a
similar manner, 6 of whom on the indication of pain. Three of them achieved an (undefined) palliation of severe local pain.
4.5.4 Metabolic disturbances from renal cancer
Symptom
Type of
cancer
Treatment
Reference
Evidence
level
Symptom
Hypercalcaemia
Renal cancer
Local spreading/advanced
disease or metastatic cancer
Nephrectomy
239 Walther
2
Paraneoplastic
symptoms
Renal cancer
Nephrectomy
No relevant
studies
No relevant
studies
Embolisation
It is well known that some renal tumours can produce metabolic/endocrine disturbances, either through local spreading or metastatic cancer. One of the reasons for this
is probably that these tumours produce peptides that mimic the effect of several hormones (including insulin, prednisone, parathyroid hormone, thyroids). Whether this
phenomenon is caused by the primary tumour, metastases or both is not clear. Traditionally it has been seen as a possible indication for nephrectomy, even in metastatic
disease when nephrectomy is not otherwise indicated. We have, however, identified
only one clinical report in which the effect of nephrectomy has been studied. In a
case-control study, Walther et al. (239) studied 15 patients with metastatic renal can-
57
cer who had hypercalcaemia and underwent nephrectomy. 18 normocalcaemic patients with metastatic renal cancer and 4 normocalcaemic patients without renal cancer were used as controls. The authors conclude that cytoreductive surgery (nephrectomy) has a temporary effect (<16 weeks) on hypercalcaemia, but that it may enable
these patients to undergo immunotherapy, which otherwise would have been difficult.
4.5.5 Vesicovaginal/intestinal fistula
Symptom
Type of
cancer
Treatment
Reference
Vesicovaginal/
intestinal fistula
Cancer of the
bladder
Cystectomy
No relevant
studies
257 Olsson
Exenteration
Evidence
level
3
A vesicointestinal fistula or a vesicovaginal fistula based on a locally advanced cancer
of the bladder is a rare sequela that is highly disabling, with considerable reduction of
quality of life. There are hardly any studies of this condition. Olsson et al. 1976 (233)
recommend pelvic exenteration on a liberal indication, even in patients with incurable
disease; 5 out of 8 patients who underwent surgery and later died, lived at least 10
months without local symptoms.
4.5.6 Malignant ureter obstruction
Symptom
Type of
cancer
Treatment
Reference
Evidence level
Ureteral obstruction
Other types
of cancer
Urinary diversion
232 Sharer
224 Meyer
235 Meyer
234 Emmert
228 Janetchek
230 Fukuoka
225 Kearney
237 Shekarriz
243 Gasparino
244 Harrington
227 Amadzadeh
238 Wawrochek
No relevant studies
3
3
3
3
3
3
3
3
3
3
3
3
233 Olsson
226 Casparini
231 Hepperlen
247 Minhas
3
3
3
3
Percutaneous
nephrostomy
Percutaneous
nephrostomy
and/or ureteral
stenting
Ureteroneocystomy QQQ
Exenteration
Ureteral stenting
Various types of cancer can lead to ureteral obstruction caused by local spreading or
metastatic cancer. The obstruction may occur with metastases to the retroperitoneum,
mainly in breast cancer, lymphoma or sarcoma, or in locally advanced tumours or
lymph node metastases from cancer of the bladder, prostate cancer, gynaecologic cancer or colorectal cancer.
58
This condition is not rare and untreated bilateral ureter obstruction leads to renal failure. Unilateral obstruction could cause pain and infections. Today, the obstruction
may be relieved with simple techniques as opposed to earlier approaches with open
surgical techniques such as nephrostomy and cutaneous ureterostomy. Deciding
whether a patient with locally advanced or metastatic disease could be treated for ureteral obstruction can be difficult. There are several different contemporary methods
for resolving ureteral obstruction; nephrostomy (percutaneous or open) ureteral stenting (internal JJ stent, extra-anatomic or metal stent), cutaneous ureterostomy,
ureteroneocystostomy /finnes ikke på Medline QQQ/. In our review of the literature
we have assessed these indications of effect: time outside institution, length of remaining life, and complications.
The articles often report on patient groups with various forms for cancer, hence it is
difficult to come up with specific therapeutic recommendations for the various forms
of cancer at different stages. A general recommendation is to show caution in recommending relief to patients with general metastatic disease. Several authors (234,235,
243,244) limit the treatment to three groups of patients:
 Those who have not yet been given oncologic treatment or have been given insufficient treatment
 Patients who have been given radiation
 When it is unclear whether or not there is recidivation and to patients in good general condition
The authors report that 41–77% could leave the hospital after relief (224,230,235,
237,243,244). These patients spent from 62% (230) to 86% (243) of their remaining
lifespan outside hospital. In one study (231), the proportion of patients who spent their
remaining lifespan in hospital was 4.6% of patients with regional metastases and
11.1% with metastatic disease. Only one study (237) gives Karnofsky Performance
Score for patients treated with a JJ stent or nephrostomy. Median score is 2 (confined
to their beds at home, with pain in spite of analgesics).
How long the patients lived after palliation is highly variable and the reports state this
in different ways. Average survival is given as 5–19 months (234,237,243). Others
report that, respectively 33.3 % (235) and 40.5 % (244) survived 6 months.
The various procedures reverse to a great extent the renal failure in 73–82% (235,243,
244). In Norway today, one prefers to use percutaneous technique or JJ stent inserted
retrograde or antegrade. The studies show failure in up to 61% of cases (243) with
inserting a JJ stent because of strictures that one cannot perforate. Percutaneous
nephrostomy thus has a higher success rate but there are complications such as infections, sepsis, leaks and dislocation. With JJ stenting there are complication such as
obstruction, infections and sepsis. Reference 326 cites 63% fewer complications and
5.4% serious complications. No study specifies the effect on palliation in terms of
pain and infection.
For the other relief methods there have so far not been documented advantages in relation to JJ stenting or nephrostomy, but they may be alternatives when these fail.
Conclusion
59
There are practically no randomised studies; still there are results from retrospective
patient series that provide a reasonably good support for clinical work on palliation of
symptoms from advanced urologic cancers.
Haemorrhage from the lower urinary tracts in prostate cancer and cancer of the bladder is primarily treated with transurethral evacuation of blood from the bladder and, if
needed, resection of bleeding cancer tissue, although this therapeutic modality is not
described for this indication. In case of repeated bleedings, radiotherapy is recommended. If these modalities are not successful in bleeding cancer of the bladder, bladder rinsing with aluminium potassium sulphate may be used. Alternatively, rinsing
with formalin may be tried, but this approach has potentially more serious side effects.
Embolisation of veins to the bladder is also described, but the documentation of effect
is as yet weak. Still it is an alternative if all the modalities described above fail.
Bleeding from a kidney with a cancer in cases in which the kidney has not been resected, either because it is inoperable or the patient has several metastases, is effectively treated with embolisation of the blood supply to the kidney.
Urinary retention in prostate cancer is effectively treated with TURP. The frequency
of complications is low, but patients who have received radiotherapy to the prostate/bladder have a somewhat higher risk of postoperative incontinence. If the prostate
cancer grows down in the external sphincter, the risk of incontinence is so high that
one should maintain an attitude of reserve towards TURP.
In prostate cancer patients with urinary retention who have hormonal therapy as a
reserve option, hormonal therapy plus catheterisation in 1 to 2 months may be preferred to hormonal therapy plus primary TURP (randomised study). Temporary stenting of the urethra pending effect of hormonal therapy is documented as an alternative
to TURP.
Flank pain in renal cancer may be relieved through radiologic embolisation of the
kidney, although the documentation is somewhat scant.
Results of surgical treatment of a cancer-induced fistula between bladder and vagina
or between bladder and intestine are not sufficiently documented.
Modern treatment of malignant ureteral obstruction with percutaneous nephrostomy
and JJ stenting is relatively well documented. The majority of patients no longer have
renal failure and may spend most of their remaining lifespan outside hospital. The
main problem with this condition is the selection of patients. Material emphasis in
determining the indication should be placed on patients’ general condition and life
expectancy.
60
5 Relevant assessment criteria
5.1 Economic aspects of palliative cancer surgery
The pubic health services have several and to some extent contradictory objectives. A
committee set up to assess health care priorities in Norway and headed by a former
president of the University of Oslo, Inge Lønning, which received broad support in
the Norwegian parliament, laid down that effectiveness, severity and cost-effectiveness should be the fundamental criteria for setting priorities in the health services.
Quite clearly, palliative cancer surgery fills the criterion of severity. It comprises a
great variety of procedures with varying evidence levels. As the effect of several palliative surgical procedures is not documented through randomised controlled trials, it
is difficult to give a comprehensive assessment of whether or not the criterion of effectiveness is filled. Few studies are available on the cost-benefit relationship of palliative surgery; i.e. that the estimated costs of surgery stand in a reasonable relationship
to its effectiveness.
We did not search specifically for literature on the costs of palliative cancer surgery,
as our terms of reference did not include conducting a comprehensive cost-benefit
analysis. We did, however, identify two articles on gastroenterologic surgery for icterus caused by pancreatic cancer which compared costs related to type of stent and
surgery. In a randomised controlled study (39), three groups of patients were compared: 1 group in which a plastic stent is inserted and replaced when needed; one
group with plastic stent and planned replacement every three months and one group
with primary insertion of a self-expending metal stent.
Procedure-related morbidity and mortality as well as median survival were the same
in these groups. Time to symptoms of stent dysfunction was significantly longer with
planned replacement of the stent compared to replacement of the stent when needed.
In a cost-benefit analysis with questionable transferability to Norwegian conditions, it
was found that costs were lower with primary plastic stents when expected patient
survival was less than 3 months, without this having a negative effect on the frequency of symptoms of recidivation. The cost estimates were the same for the three therapeutic strategies given an expected patient survival of less than 3 months, without this
having a negative influence on the frequency of symptoms of recidivation. The cost
estimates were also the same for the 3 strategies with a survival of 3–6 months; metal
stents gave lower cost with survival of more than 6 months.
A retrospective study from the Mayo Clinic compared surgical bypass with stenting
(40) in patients who had inoperable pancreatic cancer. There were no significant differences in survival, procedure-related morbidity, or mortality. The costs of bypass
surgery were significantly higher than with stenting, also when the costs of stent replacement were taken into account. Again, the transferability to Norwegian conditions
is uncertain.
All treatment requires resources and there are always alternative uses for these resources. Resources used for the treatment of one patient will necessary be at the ex61
pense of another – usually anonymous – patient. This is the argument for cost-benefit
being a criterion when priorities are set. The logical consequence is that the health
services should not commit resources to treatment with no effect or negative effect.
Lack of documentation of treatment is no proof that the treatment is without effect.
Hence, when there is a paucity of documentation of effect for some form of palliative
surgery, it does not mean that the type of surgery in question should be given low priority. The effectiveness of a considerable proportion of diagnostics and therapy in
modern health services is still not documented. Considering that one knows little
about the effect of palliative cancer surgery (and hence about its cost-efficiency), but
that a patient’s condition is very severe, it seems reasonable to assign less importance
to the criterion of cost-effectiveness when deciding on the priority of this type of
treatment.
5.2 Palliative cancer surgery in Norwegian hospitals
The objective is to use register data in order to have some indication of the scope of
and in palliative cancer surgery over the period 1999–2002 and changes that may have
taken place over this period.
Information about Norwegian practice is based on data from the Norwegian Patient
Registry (NPR) and developed in collaboration with the Patient Classification and
Funding (PaFi) Unit, both at SINTEF Unimed. The data basis is all hospitalisations in
approved public hospitals and private institutions over the 1999–2002 period. Foreigners who are not resident in Norway have been excluded. The results are subdivided by region of residence; these are comparable over the period. The datasets
start with 1999, chosen because of the introduction of ICD-10.
During the period, the number of hospitalisations with surgery exceeded 300 000 a
year, with cancer surgery accounting for 8.2–8.4%. It should be noted that the number
of cancer procedures includes major as well as minor procedures in hospital, for instance conisation in malignant disease. Cancer surgery here includes all ICD-10 codes
starting with a C and codes for preinvasive tumours (carcinoma in situ) D00–D09.
Table 5.2.1 Cancer surgery in Norway as a proportion of total surgery
NORWEGIAN TOTAL
No. of hospitalisations, all surgery
No. of hospitalisations, cancer surgery
Cancer surgery as a proportion of all surgery
1999
299 900
24 901
8.3%
2000
306 992
25 721
8.4%
2001
329 239
26 952
8.2%
2002
345 841
28 707
8.3%
Total numbers are broken down by region of residence so that table 5.2.2 shows total
number of procedures, table 5.2.3 number of cancer procedures, and table 5.2.4 cancer
procedures as a proportion of all surgically procedures. This proportion varies among
regions; residential region North has increased its proportion (6.7% to 7.6%), it is
reduced in the South region (8.6% to 8.2%), East is stable, West and Middle Norway
somewhat varying. The lowest proportion is shown for the North region in 1999
(6.7%), the highest for the West region in 2000 (8.9%).
62
Table 5.2.2 No. of hospitalisation, all surgery, by region of residence
No. of hospitalisations for
surgery, total
Health region (region of residence)
East
South
West
Middle Norway
North
Total
1999
105 856
60 454
56 346
43 760
33 484
299 900
2000
106 792
63 474
57 776
44 093
34 857
306 992
2001
115 951
67 669
61 797
46 427
37 395
329 239
2002
121 854
72 440
63 466
48 638
39 443
345 841
Table 5.2.3 No. of hospitalisation, cancer surgery, by region of residence
No. of hospitalisations for
cancer surgery
Health region (region of residence)
East
South
West
Middle Norway
North
Total
1999
8 983
5 220
4 814
3 642
2 242
24 901
2000
9 144
5 317
5 156
3 694
2 410
25 721
2001
9 755
5 513
5 344
3 715
2 625
26 952
2002
10 193
5 941
5 523
4 047
3 003
28 707
Table 5.2.4 Cancer surgery as a proportion of all hospitalisations for
surgery by region of residence
Cancer surgery, proportion
Health region (region of residence)
East
South
West
Middle Norway
North
1999
8.5 %
8.6 %
8.5 %
8.3 %
6.7 %
2000
8.6 %
8.4 %
8.9 %
8.4 %
6.9 %
2001
8.4 %
8.1 %
8.6 %
8.0 %
7.0 %
2002
8.4 %
8.2 %
8.7 %
8.3 %
7.6 %
Population rates for the regions are given in table 5.2.5; they show an increase for all
regions over the period, with the biggest increase in the North region, from 1.9% to
2.6%.
Table 5.2.5 Hospitalisations per year for cancer surgery per unit of population by region of residence
Cancer surgery, no. by year
Population by health region (region of
residence*
East (average 1 610 054)
South (average 880 452)
West (average 924 502)
Middle Norway (average 636 699)
North (average 463 526)
1999
2.3%
2.4%
2.1%
2.3%
1.9%
63
2000
2.3%
2.4%
2.3%
2.3%
2.1%
2001
2.4%
2.5%
2.3%
2.3%
2.3%
2002
2.5%
2.7%
2.4%
2.5%
2.6%
*Population numbers are averages for the years 1999–2002. The proportions of populations are computed on the basis of the annual population figures. Source: Statistics Norway.
Whether the surgical treatment had a curative or palliative intention is not registered,
hence it has been difficult to extract completely relevant data. It has, however, been
generated a survey of hospitalisations registered with surgery for metastases, though
this gives an incomplete picture of the total of relevant palliative surgery.
A sample has been drawn based on diagnostic codes (ICD-10) and procedural codes
(NCSP) (see appendix 12.2). Metastasis is used as the main indicator of palliative
treatment, hence any curative treatment of metastasis is included in these figures. Metastasis could be the main or sub-diagnosis (table 5.2.6).
Table 5.2.6. Hospitalisations for surgery on patients with metastases in gastroenterologic, orthopedic, neurologic, thoracic and urologic cancer in Norway
Sample of patients
1999
2000
2001
2002
Surgery on patients with bone metas330
302
552
418
tases
– Of this, spinal surgery
102
122
120
131
Surgery on patients with pulmonary
247
355
420
521
metastasis
Surgery on patients with metastasis in
10
14
41
24
the urinary tracts
Surgery on patients with cerebral me167
231
211
238
tastasis
Surgery on patients with metastasis in
2515
2737
2751
2829
the alimentary tract
Summary
Cancer surgery as a proportion of all surgery 1999–2002 averages 8.3%, a relatively
stable level considering the population increase. Annually, more than 2% of the population undergo such surgery. There are variations between regions and over the period; in two regions the proportion increased, in one it fell, and in two the proportion
varies from year to year. The population rates show an increase in all regions over the
period in question.
Surgery in cases of metastasis has increased substantially.
5.3 Ethical aspects of palliative surgery for cancer patients
Palliative surgery means surgery in which the objective is not curative, but prolonging
life and alleviating symptoms (327). The aim is to help persons who are in a very difficult situation (with incurable diseases) in the best possible manner, by a) trying to
prolong his or her life, b) alleviating the patient’s symptoms, and c) preventing symptoms. This objective substantially corresponds to the general objectives of the health
services, for example as they are expressed in the Code of Ethics of the Norwegian
Medical Association, article 1: “A doctor shall protect human health. A doctor shall
cure, alleviate and console.” Still there are some aspects of palliative surgery in the
64
treatment of cancer that are morally challenging; in the following these are tied in
with crucial aspects of medical ethics.
5.3.1 The duty to help
The duty to help has a strong standing in modern medicine; in many ways it is the
deontological (the theory about moral duty) core in all health related disciplines. The
corresponding duty to attend to and care for the weak has a very long tradition. The
same goes for the duty to learn. All these duties are relevant to palliative surgery.
In medicine, the duty to help has been challenged by serious examples of overtreatment. Surgeons have been accused of being more ready to take action than their
knowledge basis justifies and of having too much professional autonomy. In the days
when one removed the colon in order to cure epilepsy, removed the adrenal glands
because of hypertension and pinched off the internal thoracic artery in order to treat
angina pectoris (328), it was surely based in a desire to help. With the benefit of hindsight such examples stand out as manifestations of over-treatment, paternalism and
hubris rather than of the duty to help.
The duty to help may a) be understood in too absolutist terms, b) be misinterpreted, or
c) not counterbalanced by other considerations. There is a danger of this in relation to
palliative surgery in which the patient is weak, vulnerable and in great pain, the
knowledge basis on effectiveness and risks is limited, and the patient expects that
“everything that is possible” is done.
This means that palliative surgery is an area in which the duty to help has to be approached with a great degree of caution and with reference to the duty to obtain benefits and balance benefits against risks, in normative ethics usually referred to as “benevolence” and be weighed up against the non nocere duty (330).
5.3.2 Compassion and vulnerability
Facing a patient suffering from cancer, with considerably reduced level of functioning, and strong pain invokes pity and compassion, which are among the core virtues
of medicine (332,333). Selfless help to those who are weak and vulnerable is a tradition of long standing and seems particularly relevant in relation to cancer patients with
strongly crippling and painful symptoms.
Pity and compassion may be seen as tied in with the helper’s moral sensitivity and
good intentions; these virtues are, however, necessary but not sufficient conditions.
Compassion also implies an awareness of whether compassionate acts really help the
person that one wishes to help. Benevolence as an ideal requires that one does not act
blindly. Drastic interventions with lack of knowledge cannot be justified by reference
to the interventions being based on pity and compassion.
5.3.3 Risk and lack of knowledge
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There is limited knowledge about palliative surgery; this applies to effects as well as
risks. There are very few studies of acceptable quality; moreover, there seems to be
considerable variations from hospital to hospital in the treatment of the same condition. Knowledge about preventive palliative surgery is particularly scant (chapter 7).
This lack of knowledge about effects, risks and degree of prevention seems morally
relevant. Professor Alan G. Johnson of the University of Sheffield Surgical Unit expresses this in this way:
Many operations for cancer have not been properly evaluated by randomized controlled trials, and there
are situations where the placebo effect is likely to be strong but the specific effect may even be harmful. One concerns the pressure on the surgeon to ”do something” such as operating even if it is impossible to remove all of the tumour. Sometimes palliation can be achieved, but in others, the ’benefit’ is
the patient’s knowledge that much of the tumour has been removed, even at the expense of a depression
of the immune system, which could lead to a more rapid spread. (329)
For some conditions there is an undocumented tradition of treatment that is seen as
valuable and obviously effective also without documentation. It is considered unethical not to conduct such procedures and seen as a loss to the patient if they are not
done (chapter 7). On the other hand it is considered unethical to carry out surgical
procedures that are of no use to the patient seen in relation to the strain and risk they
represent (331).
Regrettably there are examples of traditional procedures without any effect, also in the
field of palliative surgery (laminectomy without fixation in spinal compression, palliative nephrectomy for flank pain), hence it always seems important to identify documentation that is as good as possible. Because of the deficient knowledge basis, extreme caution should be exercised in relation to the danger of overtreatment. The
Norwegian Cancer Plan (327) states that the danger of overtreatment is particularly
great in symptom-oriented palliation (3.2.2.5). The crucial duty to help and to do everything that is possible also calls for soberness in assessing benefit against risk (benevolence).
This limited knowledge basis opens up for the danger of renouncing on the requirement of scientific documentation, though it does call for research on palliative surgery. The Norwegian Cancer Plan made it clear that there is a considerable need for
defining the knowledge basis and indications for palliative surgery. It seems that this
has not been sufficiently followed up. The medical community has a special responsibility for taking stock of and analyse procedures that are considered “obviously useful” and of which it is thought that it would to be detrimental to patients if they go out
of use.
With regard to preventive palliative surgery, the challenge with regard to uncertainty
is particularly striking; not only is there uncertainty as to the effect of the treatment
but also as to the extent to which the patient would have developed the assumed
symptoms if he or she had remained untreated. Operating on an asymptomatic person
with an incurable cancer who will need all available resources in order to meet the
(uncertain) course of the disease requires a good justification and special caution.
5.3.4 The wish to do ”everything that is possible”
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Many patients are of a persuasion that calls for doing “everything that is possible”. As
long as one acts (operates), there is hope. If the physicians do not act, the patient
could perceive it as “being given up by the health services”.
This wish, to do “everything that is possible”, is a challenge in several respects: it
could reinforce a misconceived “duty to help” (overtreatment), it is also a challenge in
relation to informing patients and their families (see below). A hard question is
whether the patient has the ability to critically evaluate what “everything that is possible” means. A thorough evaluation of the knowledge basis, risks and the possibility of
overtreatment is usually not part the wish to have “everything that is possible” done.
Many patients have great faith in the quality and control of modern medicine, including a faith in the options being many and good and the risk minimalised. Surgery in
particular is the emblem of what modern medicine can achieve. Added to this: cancer
is also a disease with a special symbolic character; metaphors like “fighting cancer”
and “cancer crusade” are used. Fighting and crusading allow strong measures, though
in many contexts it is the weakest who suffer the most.
In an era in which patient autonomy and patient rights are crucial concerns, many
would claim that one should go far in complying with the wishes of patients and their
families. The challenge arises when the benefit (and cost-benefit) of the relevant
treatment is uncertain. Should we operate on patients “so that they do not lose their
hope”? Is surgery, with its consequences, possible side effects and complications, the
right way of instilling hope in patients? What is the role of information in this context?
5.3.5 Patient autonomy and information
Pursuant to the Norwegian Patients’ Rights Act (334)2, the patient is entitled to participate in the implementation of his medical treatment (section 2-1), has a right to be
informed (section 3-2), and the right to give consent (section 4-1) to the health care
that is given (section 4-1). Patients have the right to be informed about their situation,
what the treatment implies, and of possible risks and side effects. Health personnel
have a duty to provide such information adapted to the patient’s individual condition
(section 3-5).
There are several reasons why this duty to inform is particularly difficult and important in relation to cancer patients in general and to palliative surgery in particular:
a) There is limited knowledge (that is, documented effect) about the benefit
b) The patient is especially vulnerable and with a limited ability to receive and understand information
c) The patient’s state of health could change rapidly
d) The risk related to some procedures could be considerable (perioperative mortality, postoperative infection rate, morbidity)
e) There are great expectations to the effect that the health services will do ”everything that is possible” without there being nuanced views of what this means in
terms of uncertain effect and risk
2
http://odin.dep.no/hd/engelsk/news/new_publ/030071-200002/index-dok000-b-n-a.html
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f) Patients could fear that they are being ”given up” by the health services if surgery
is not done
g) There could be other types of palliation than surgery that are not well known.
Giving sober information without destroying hope or giving false hope is one of the
most usual dilemmas in palliative surgery (333). It turns out that a large proportion of
patients remember little of the information about risk that they got before certain operative procedures (337,339). Patients also have difficulty understanding the reality
they are facing and this leads to a great deal of misunderstanding (339). The boundaries between information, persuasion and paternalism are not clear-cut when it comes
to vulnerable patients. There being no alternatives is a source of confidence, but also
of power (340).
Similarly, the circumstances listed under a–g above that pertain to patients’ right to
participation, to consent to or refuse treatment (section 49) are real-life challenges. Is
a very ill patient in a state in which he can exercise these rights? If the patient’s condition is worsening, is it certain that he still wishes to undergo the procedure? What
should be done when the patient does not find that he is capable of receiving information in such a situation? How well are sorrowful and despairing relatives able to
take care of the patient’s interests? Will they tend to recommend that “everything that
is possible” is done for those closest to them because of anticipated decision regret? In
this respect, health personnel are facing great practical and fundamental problems.
5.3.6 Priorities
Pursuant to Norwegian Official Reports no. 18, 1997, the health services shall set priorities according to 1) severity, 2) benefits, and 3) cost efficiency. This is specified in
the Patients’ Rights Act (334), from which it appears that the patient has a right to
necessary help if: 1) the patient either to some extent has a worse prognosis in terms
of remaining lifespan if help is delayed, 2) the patient may have an expected benefit
of the help, 3) expected costs are in a reasonable relationship to the effect of the
treatment. Incurable cancer meets the requirement of severity. For most form of palliative surgery, the benefit is either poor or undocumented. This does not necessarily
imply that there is no benefit, but that the requirement of documented benefit, b), is
not filled. If the benefit is not known, nothing can be said about cost-benefit; c) the
costs of palliative surgery are considerable (roughly estimated at 50% of the resources
used on cancer surgery, cf. chapter 2.1). Solely on the basis of priority criteria, palliative surgery will not be given priority.
Lack of documented benefit is not unique for palliative surgery; it applies to a range
of therapeutic modalities generally and to surgery in particular. This means that in
setting priorities between surgical procedures, palliative surgery stands up reasonably
well on the basis of severity. Some will maintain that there is a limit here: cure is
more important than palliation. In the choice between a seriously ill patient who could
be cured and a severely ill patient for whom there is only the potential for palliation,
and in a situation in which the methods are otherwise just as badly or well documented, one should give priority to the patient who has a potential for cure, among other
things because he or she may live longer. In no way is it clear that one has reached
this stage in setting priorities.
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5.3.7 Research and ethics
The lack of knowledge about benefit and risk is a moral as well as a scientific challenge. Some observers point to a paternalistic tradition in surgery as a reason for the
lack of knowledge (324): surgeons have been accustomed to being able to take decisions, chose and develop methods for the benefit of their patients (paternalistically)
without the need to document their usefulness. The lack of a knowledge basis to some
extent could be seen as the outcome of a paternalistic tradition, the great expectations
for the health services to do “everything that is possible”, the health services’ preparedness to act on the basis of the duty to help, the ”evident usefulness” of some procedures, a long undocumented tradition for some methods, and lack of a tradition of
research in some fields. This is, however, hardly a complete explanation.
There seems to be several methodological challenges in the field of palliative surgery.
Patients’ state of health may change rapidly and, in consequence, so may treatment
objectives. Other aspects that pose methodological problems are treatment and selection bias, randomisation, surgical learning curves, grey zones in relation to emergency
treatment, and variations between therapists. Documenting preventive palliative surgery seems to be particularly difficult (chapter 7).
There are a range of moral concerns related to these methodological problems:
a) Some maintain that reexamining procedures that are considered ”evidently useful”
is immoral.
b) Many consider placebo surgery immoral.
c) Some think it immoral to included seriously ill people in research.
d) It is problematic to obtain informed consent from the seriously ill.
e) Assessing the effect of surgical intervention against best supportive care is seen as
immoral.
This has made some maintain that ethics stands in the way of knowledge enhancement
in palliative surgery (324).
5.3.8 Knowledge and ethics
The limited knowledge basis for palliative surgery represents moral challenges that
may be seen in the light of different perspectives within normative ethics. If there is
not enough knowledge about effect and risk, it is difficult to apply the principles of
benevolence and non nocere. Consequence analysis of benefit and risk could be speculative without an adequate knowledge basis. Correspondingly, in situations with limited knowledge it is a challenge to respect the autonomy of patients, their right to participation in decision making, to give consent and receive good information. This is
all the more difficult because of the patients’ condition.
Virtues such as compassion and mercy as well as the duty to help seem strong in relation to this group of patients. The principle of justice and the prioritisation criterion of
severity could also benefit palliative surgery, though areas with limited knowledge
require special caution.
There are, therefore, many ethical challenges that follow from the limited knowledge
basis. To some extent the cause of the lack of documented knowledge can be traced to
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the necessary research being considered unethical. This might have a self-reinforcing
effect and be seen as paradoxical: Lack of knowledge is unethical but so is also developing new knowledge. This is hardly an adequate explanation. Providing the foundation for offering palliative surgery to patients on the basis of the best possible
knowledge is a methodological and moral challenge which the professional community must take seriously, also in relation to registration.
Palliative surgery is a potentially valuable treatment for a group of patients that are
particularly exposed. It is essential that these very vulnerable patients are not exposed
to unnecessary treatment, that they get as good palliative care as possible, that their
rights as patients are respected, in particular that they get as good information as possible on effects as well as risks, and, as the case may be, on the lack of documentation
of these factors. When the patient has a short remaining lifespan and there is great risk
associated with a surgical procedure, non-surgical palliation will be the best alternative.
Palliative surgery calls for a considerable degree of skills, in moral and communicative terms as well as in surgical terms.
Addendum
The Norwegian Cancer Society’s comments have been incorporated in the text above.
They consider it important to bring out the issues related to treatment of patients with
palliative needs. They see it as a strength that this theme is approached with a questioning attitude with no hard conclusions. In particular they point to discussion and
advice to patients and their families and the importance of communicating well. Information is important and knowledge about the benefits and risks is useful for those
that are going to inform them. Patients and their families have a need to understand, to
find a meaning and to find comfort in the belief in that all the best that can be done for
them is done. The Society agrees that palliative surgery requires moral as well as surgical skills and good communication skills.
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6 Discussion
A cancerous tumour is no longer curable when it cannot be resected surgically or destructed through radiotherapy or chemotherapy. Treatment of such cancerous disease
is defined as palliative and aims at delaying or reducing symptoms and prolonging
life. It is underscored that non-surgical treatment in many situations will be the best
alternative, especially in situations when the patient has a short expected lifespan and
the risk of a surgical procedure must be assumed to be great. In all cases of palliative
surgery there is broad agreement that patients and their families should be involved in
decision making. If such a joint assessment from patient and family shall be of more
than symbolic value, opportunities and limitation of any palliative procedure must be
as well documented as possible.
Because symptomatic treatment, not cure, is the objective in palliative surgery, the
SMM and its group of experts have chosen to concentrate efforts on two main problems:
 The effect of procedures that reduce symptoms from various organ systems, irrespective of the origin of the primary tumour.
 The effect of procedures that aim at preventing well-known future symptoms from
an incurable primary tumour.
This approach may be exemplified by palliative thoracic surgery. Instead of going
through all procedures of thoracic surgery and check which of these are documented
in palliative cancer problems or examine the results of surgical procedures done on
thoracic structures and isolate those who may be palliative, one has focused on those
thoracic symptoms that thoracic surgeons are particularly equipped to take care of.
This reduces the scope to three main problems: difficulty breathing, obstruction of the
superior vena cava, and prolonging life through excision of lung metastases.
The most difficult assessment in palliative surgery is the use of procedures that may
prevent or delay symptoms. This requires extensive knowledge of the “natural” course
of the disease and defined endpoints of the effectiveness of the procedure. Knowledge
about the course of the disease will usually be based on post hoc statistical estimates
and cannot with certainty be applied to the individual patient. Prophylactic procedures
should be simple, have a reliable effect, and low risk of complications.
The group of experts finds that this approach is a better reflection of the real clinical
situation within palliative surgery. Textbooks usually focus on primary tumour types
in a single organ, staging, procedures and survival, with strikingly little focus on and
evaluation of the problem of palliation. Surgeons are therefore often left with their
colleagues’ and their own experience as a supplement to a literature that is hard to
survey and of doubtful quality. Palliative surgery is not a small and sporadic practice
but a substantial part of the surgical approach to cancer, hence this is an activity that
will benefit from a systematic review of and standardisation of methods that will be of
help in the evaluation of the individual patient.
The structure on which surgical specialisation in Norway is based is also reflected in
the composition of the group of experts. The subspecialties have explained in detail
what studies are available on their respective palliative problems and in conclusions
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summed up the basis of evidence for their respective treatments. In the first part of the
project, when a search strategy was developed and the first results were obtained, it
became clear that palliative procedures in gynaecologic cancer so much involved urinary tracts and the intestine that it was a natural thing to do for surgeons in these field
to evaluate the documentation on palliative procedures. This is underlined by the
Cochrane review of reports on malignant intestinal obstruction, in which metastases
from ovarian cancer were the largest group (20). Metastases that threaten the spinal
channel are an area in which neurosurgeons and orthopaedists have overlapping skills.
In such areas, experts from both fields have independently assessed and classified the
available documentation. It turned out that there was full agreement between the two
groups with the exception of one article (129), which was excluded by the orthopaedist on the grounds that it included too few patients.
For some widely used palliative procedures there is no documentation of effect in the
available databases (which often cover only the last 15 to 25 years); examples are
palliative transurethral resections for bleeding of the mucosa of the urinary bladder or
the prostate. Still it would have been beneficial for patients if one systematically registered effect, complications and limitations and studied combinations with other
methods. There is little reason to question the effect of the transurethral methods mentioned, but an undocumented therapeutic tradition also carries a risk that less effective
procedures that require a great deal of resources are carried on with. Laminectomy
without fixation in impending or manifest spinal compression is a traditional method
which a review of documented effects clearly shows is inferior to other methods for
relieving pressure.
Under optimal conditions, palliative cancer surgery should be evidence-based. As it
will appear from the results presented in this report, this is only in exceptional cases
the case. There is little reason to believe that this will change radically in the foreseeable future, because the primary scientific method, randomised clinical trials, is generally difficult (but not impossible) to apply in the evaluation of surgical procedures,
and because a randomisation between active (surgical) and palliative supportive
treatment poses great practical and ethical problems. Compulsory registration of cancer surgery as palliative and/or potentially curative would obviously be an improvement in relation to present practice.
With a figure or a letter included with the necessary release of a surgical DRG code,
the basis for future evaluation of effects could be greatly improved. With a link to the
Norwegian Cancer Registry, the cost of palliative surgery could easily be estimated,
as well as median lifespan and variations and prevention of the symptoms that require
treatment. A longitudinal registration such as this would be a better way of mirroring
the population’s needs and problems than randomised studies, which always have an
inclusion-based bias.
Our primary objective, as will appear from our terms of reference, not been achieving
consensus, but assessing the documentation available. Because there is usually no
documentation of particular problems that makes it possible to determine the absolute
value of a method, we have focused on a “best evidence” approach. This means that
we started out with broad search criteria and included prospective as well as retrospective studies. The large number of excluded studies in the final assessment is the
result of a wish to start out with all studies that might be relevant to the problem. This
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approach appreciably prolonged the time period needed for the project. In order to
avoid that new documentation published during the project period was not included in
the assessment, a final attempt at updating was conducted in February 2003. Although
a few reports were identified, there are still no major international assessments that
satisfactorily answer the questions that are included in our terms of reference.
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