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Case 982: Bill and his prostate
Authors and Affiliations
Dr. Simon Harley
A/Prof. Nick Brook
Department of Urology
Royal Adelaide Hospital
Case Overview
This case deals with one of the commonest malignancies in men and globally, the fifth most common
cancer.
Learning Objectives
The user should an understanding of:
the
presentation and work up of suspected prostate cancer
the
Gleason Score
the
benefits, side effects and alternatives to radical prostatectomy
the
mechanism of action of some anti-androgen medications used for prostate cancer
Question 1 : MS
Question Information:
Bill is a 65-year-old farmer who lives just outside Port Lincoln. Whilst battling a bush fire on his property
he hurt his back and goes to his general practitioner to get it checked out. Bill is of reasonable health.
He is a type II diabetic which is controlled with his diet (which he sort of sticks to) and takes captopril for
hypertension. His practitioner thinks this back pain is a simple strain and he prescribes analgesia and
physiotherapy. As it happens to be time for Bill's annual check-up, the doctor orders a battery of tests
including a PSA.
Two weeks later Bill returns for his results and his doctor tells Bill that his PSA in 7.6 compared to a
level of 2.5 two years ago. Bill is otherwise asymptomatic. He does not complain of any lower urinary
tract obstructive symptoms such as hesitancy, weak stream or nocturia. The doctor does a digital rectal
examination.
Question:
Which of the following digital assessments would suggest the presence of prostatic malignancy?
Choice 1: Nodularity Score : 1
Choice Feedback:
Correct. This would not be diagnostic, but could be suggestive of malignant change.
Choice 2: Asymmetry Score : 1
Choice Feedback:
Correct.
Choice 3: Tenderness Score : -1
Choice Feedback:
Incorrect. This is not seen in prostate cancer and would be more suggestive of infection.
Choice 4: Sponginess Score : -1
Choice Feedback:
Incorrect.
Choice 5: Firmness Score : 1
Choice Feedback:
Correct.
Choice 6: Enlargement Score : 1
Choice Feedback:
Correct. Although this may just represent benign prostatic hypertrophy (BPH).
Choice 7: Crepitations Score : -1
Choice Feedback:
Incorrect.
Question 2 : SC
Question Information:
The findings on digital rectal examination are quite variable for prostate cancer. The majority of cancers
are found in the peripheral zone, some of which is on posterior aspect of the gland. However, due to
stage migration associated with PSA testing, most prostate cancers are non-palpable. An enlarged,
nodular, asymmetrical gland should raise suspicion of prostate cancer; however, the prostate may feel
normal despite the presence of cancer. A tender prostate suggests prostatitis. Prostate size varies
bewteen individuals and with age, but 30cc is a †˜ normal†™ size in a middle aged man.
Assessment of size comes with experience.
Bill†™s general practitioner thinks that the left lobe of Bill's prostate is slightly larger than the right.
Question:
Which one of the following is the most appropriate next step in management?
Choice 1: CT chest/abdomen/pelvis Score : -1
Choice Feedback:
Incorrect. There is no diagnosis of a cancer at this stage. Any such investigations along the lines of CT
scans should be postponed until staging is required (if it is!).
Choice 2: Refer to urologist Score : 0
Choice Feedback:
Partially correct. This is often done. Perhaps soon, but hold off!
Choice 3: Trans-rectal ultrasound-guided biopsy of the prostate (TRUS) Score : 1
Choice Feedback:
Correct. A tissue sample of the prostate is now required. The gold standard is a 12 core biopsy of the
prostate, six biopsies from each lobe (side) which are taken from the base, mid and apical portion of the
lobes. In the presence of cancer, this will give us the Gleason score if prostate cancer is present. The
ultrasound will not only facilitate placement of the biopsy needle, but will give information on the texture
and size of the prostate.
Choice 4: PET Scan Score : 0
Choice Feedback:
Incorrect. Not indicated. PET scans are used rarely in prostate cancer due to the poor uptake of the
radioactive tracer 18-FDG. In addition, pooling of the contrast in the bladder leads to poor imaging of
the prostate. In any case, this would be an inappropriate time to order such imaging.
Choice 5: Whole Body Bone Scan (WBBS) Score : 0
Choice Feedback:
Incorrect. Not indicated at this time. Bone scans are only indicated in those prostate cancers that are
symptomatic or classified as intermediate or high risk. We do not have enough information at this stage
Choice 6: Wait for now and repeat PSA in 3 months Score : 0
Choice Feedback:
Incorrect. The information you have is a rising PSA with suspicious findings on DRE in a man of the
right age to get prostate cancer. Further investigations must be done.
Question 3 : SC
Question Information:
Bill undergoes a TRUS biopsy of the prostate. An ultrasound probe is placed within his rectum and
utlrasongraphic visualisation of the prostate aids in taking 12 core biopsies. Results show the following
Gleason Score:
Left
base †“ 4+3 = 7
Left
mid †“ 4+4 = 8
Left
apex †“ 4+4 = 8
Right
base †“ no malignancy
Right
mid †“ no malignancy
Right
apex †“ no malignancy
Question:
On which one of the following is the Gleason Score based?
Choice 1: Architectural features Score : 1
Choice Feedback:
Correct.
Choice 2: Cytological features Score : 0
Choice Feedback:
Incorrect.
Choice 3: PSA plus histological findings Score : 0
Choice Feedback:
Incorrect.
Choice 4: PSA, DRE findings and histological findings Score : 0
Choice Feedback:
Incorrect. This information can, however, we used to stratify prostate cancer into risk categories.
Question 4 : FT
Question Information:
The Gleason Score is an important assessment tool when trying to determine the prognosis in an
individual with carcinoma of the prostate.
Question:
Describe how the Gleason Score is determined.
Choice 1: null Score : 0
Choice Feedback:
The Gleason Score is a grading system which is based only on the architectural features of the cells of
the prostate. The architecture of the tissue biopsy was historically graded from 1 to 5 with 1 indicating a
well differentiated architecture and 5 indicating poor differentiation. Nowadays, if prostate cancer is
present, the lowset score it is given is 3, i.e. the minimum combined Gleason score is 3+3=6. The
scores of the two most prevalent architectural patterns are added together, the most prevalent being
indicated by the first number in the equation.
Question 5 : SC
Question Information:
With the explanation now provided for how a Gleason score is derived, it should be possible to look
critically at the scoring system.
Question:
Does Gleason 3+4 = 7 and 4+3 = 7 correlate with the same clinical behaviour?
Choice 1: Yes Score : -1
Choice Feedback:
Incorrect.
Choice 2: No Score : 1
Choice Feedback:
Correct. Using Bill†™s biopsy results from the left upper zone; grade 4 was the most prevalent
architectural pattern (primary grade) followed by grade 3 (secondary grade). This gives a result of 4+3 =
7. Following on from the previous questions you can now see that a 3+4 = 7 is NOT the same as 4+3 =
7 as it indicates a different predominant architecture.
Question 6 : MS
Question Information:
Given these biopsy findings, Bill is referred to a urologist.
Question:
Which of the following investigations should the urologist order?
Choice 1: CT chest/abdomen/pelvis Score : 1
Choice Feedback:
Correct. The disease must now be staged.
Choice 2: Repeat PSA Score : -1
Choice Feedback:
Unnecessary.
Choice 3: MRI prostate Score : 1
Choice Feedback:
Correct. MRI of the prostate is used for pre-operative workup. It is currently undergoing investigation
relating to its usefulness in confirming organ specific disease (T2) vs extra-prostatic disease (T3),
however there does appear to be dis-concordance.
Choice 4: PET Scan Score : -1
Choice Feedback:
Incorrect. PET scans are used rarely in prostate cancer due to the poor uptake of the radioactive tracer
18-FDG. In addition, pooling of the contrast in the bladder leads to poor imaging of the prostate. In any
case, this would be an inappropriate time to order such imaging.
Choice 5: Whole body bone scan Score : 1
Choice Feedback:
Correct. Results currently suggest that bone scans may be unneccessary for men with well or
moderately differentiated prostate cancer (7: 3+4), PSA < 20 and asymptomatic. However, in patients
with poorly differentiated tumours and locally advanced disease, a staging bone scan should be
obtained irrespective of the serum PSA value.
Choice 6: Circulating prostate cancer cells Score : -1
Choice Feedback:
Incorrect.
Question 7 : MS
Question Information:
Staging of Bill†™s prostate cancer is indicated given his Gleason score. Based on Gleason score,
staging and PSA levels, we can predict the likelihood of finding occult metastatic disease on
Technetium-99 bone scan and MRI. Those with low risk features such as PSA <10 or Gleason Score
<7 are unlikely to have disease elsewhere. Those with intermediate to high risk features however such
as Gleason 8 or higher, T2b (unilateral disease affecting the whole lobe) or PSA >20 warrant further
imaging. MRI prostate is used to locally stage the extent of the adenocarcinoma, and allows
examination of pelvic lymph nodes.
An MRI scan shows that the cancer is isolated to the left side of the prostate without involvement of the
prostatic capsule, bladder neck of seminal vesicles. No pathologically enlarged nodes are identifiable.
The bone scan is normal. Bill is a given a clinical staging score of T2bN0MX. The urologist discusses
treatment options with Bill. Thise includes radical prostatectomy with left extended lymph node
dissection or external beam radiotherapy with brachytherapy. Bill elects to have a radical
prostatectomy. Informed consent in obtained for the procedure.
Question:
Which of the following are risks specific to this procedure?
Choice 1: Erectile dysfunction Score : 1
Choice Feedback:
Correct. The incidence of this complication depends on the man†™s erectile function prior to the
operation and whether nerves close to the prostate are removed. For those with good erectile function
prior to surgery and nerve-sparing surgery, around 30% will still have problems getting an erection; this
number gets to over 80% in those where both nerve bundles are not preserved.
Choice 2: Urinary incontinence Score : 1
Choice Feedback:
This is common in the first six months or so and men may require pads. In 2-5% of men this is severe
and permanent.
Choice 3: Incomplete excision/upstaging of disease Score : -1
Choice Feedback:
Incorrect. This is not so much a risk, but a fact of life when a patient faces any surgical procedure for
malignancy. The staging obtained by clinical and radiological assessment is then compared with
eventual surgical and histological findings and the initial work up may have underestimated the extent of
disease which might be upstaged based on the findings at operation and/or subsequent histological
assessment.
Choice 4: Infertility Score : 1
Choice Feedback:
Correct. He will be unable to ejaculate.
Choice 5: Sciatica Score : -1
Choice Feedback:
Incorrect.
Choice 6: Port site hernia Score : -1
Choice Feedback:
Incorrect. This is a potential risk for all laparoscopic surgery and not just prostate surgery.
Question 8 : FT
Question Information:
Allied health disciplines contribute in different ways to help care for of a man undergoing a
prostatectomy.
Question:
List the disciplines that are likely to be involved and discuss their roles.
Choice 1: null Score : 0
Choice Feedback:
Cancer Care Nurse:
Psychosocial
Patient
support
education
Familiarisation
with support groups
Physiotherapist
Training
in pelvic floor exercises
Sexual Counsellor
Education
on ways to help with sexual function
General Practitioner
This
will be the primary carer of the man in some cases where only hormone therapy is required and
PSA has been undetectable for year. GPs usually know the patient better than any other doctor.
Social Worker
Aids
with transport, finances etc
Pharmacist
Questions
regarding interactions with other medications etc.
Aboriginal Liaison
Very
important for Aboriginal and Torres Straight Islanders
Multidisciplinary Meeting
Urologists,
oncologist, radiologists, pathologists, social workers, cancer care nurse discuss each
case and suggest best management.
Question 9 : SC
Question Information:
Bill†™s procedure goes well and he makes a good recovery. His staging is shown to be pT2bN0M0.
His PSA is initially undetectable but 18 months later it rises to 0.2. Bone scan and CT Pelvis are
negative and he undergoes salvage localised radiotherapy for presumed local recurrence.
In some cases of prostate cancer, men will undergo androgen deprivation therapy such as Goserelin.
Question:
Which one of the following most accurately describes the mechanism of actions?
Choice 1: Inhibition of the actions of testosterone directly on prostate cells Score : 0
Choice Feedback:
This is the action of bicalutamide which is often given at the same time as goserelin to prevent acute
flares. Especially important if metastatic bone disease is present as goserelin initial rise in
gonadotropins may lead to increased bone pain and risk of pathological fractures.
Choice 2: Action as a gonadotropic-releasing hormone antagonist which leads to reduced levels of testosterone
Score : 0
Choice Feedback:
Incorrect.
Choice 3: Acts as a gonadotropic releasing hormone agonist, which leads to reduced levels of testosterone
Score : 1
Choice Feedback:
Correct.
Choice 4: Increase in urinary excretion of testosterone through the distal convoluted tubule Score : -1
Choice Feedback:
Incorrect.
Synopsis
Each year, over 3000 men die in Australia from prostate cancer; this is similar to the number of women
dying of breast cancer.
There continues to be debate over the best form of screening for prostate cancer. A well designed
screening program must target a health problem that is significant to the individual and community.
There needs to be an asymptomatic (pre-clinical) phase at which suitable and acceptable screening
tests can be used. There must be acceptable treatment and the natural history of the disease needs to
be well understood. Screening must confer survival and morbidity benefit to the individual and be cost
effective from a societayl point of view. Australia currently abides by the European Association of
Urology†™s Guidelines on Prostate Cancer which recommends †˜ opportunistic screening†™as
opposed to mass screening. The Prostate Cancer Foundation of Australia recommends opportunistic
screening (with either PSA or DRE) to begin at 50 years in men with no family history of prostate cancer
and 40 in those with a positive family history. A screening interval of around 8 years may be appropriate
in those whose PSA in below 1.0. Screening in men over the age of 75 is not recommended because
the clinical impact of early detection is small.
Clinical staging of prostate cancer differs from pathological staging. Clinical staging incorporates
findings on DRE, PSA level and Gleason Score. Pathological staging substitutes the DRE for for
histopathological findings on the resected prostate specimen.
Once biopsy results are established further imaging is only indicated in those who have symptomatic
bone pain or are in the intermediate to high risk prognostic groups. Technetium-99 Bone scan and MRI
Prostate are currently the most used modalities.
Prostate cancer treatment can be difficult to grasp and is continually evolving. Multidisciplinary meetings
are important in decision making. Prognostication is based on TNM staging, PSA level and Gleason
score.
Risk features TNM PSA Gleason:
Low
T2a (unilateral with less than half lobe affected) <10 <7
Intermediate
High
T2b (unilateral with more than half lobe affected) 10-20 7
T2c (bilateral disease without extra-capsular spread) >20 >7
Prognostic Groups are based on the number of features found above and astute readers can find
details on these in other texts.
Treatment options include active surveillance, watching waiting, radical prostatectomy (with/without
extended lymph node dissection), external beam radiation therapy, brachytherapy and androgen
deprivation therapy.
Post-management complications can have a significant impact on the man†™s (and partner†™s) life
and it†™s important to become familiar with these. The multidisciplinary approach is important to help
maintain or improve the patient's quality of life.
Further reading:
Graham J, Kirkbride P, Cann K et al. Prostate cancer: summary of updated NICE guidance. BMJ 2013;
348:f7524.