Download Local Prostate Cancer - Alberta Health Services

CLINICAL PRACTICE GUIDELINE GU-012
Version 1
Local Prostate Cancer
Effective Date: January, 2017
The recommendations contained in this guideline are a consensus of the Alberta Provincial GU Tumour Team and
are a synthesis of currently accepted approaches to management, derived from a review of relevant scientific
literature. Clinicians applying these guidelines should, in consultation with the patient, use independent medical
judgment in the context of individual clinical circumstances to direct care.
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
BACKGROUND
Prostate cancer is the most common cancer among Canadian men, and is the 3rd leading cause of
cancer related death in men in Canada. In 2016, it is estimated that 21,600 (age-standardized incidence
rate of prostate cancer is 115 per 100,000) men will be diagnosed with prostate cancer in Canada,
representing 21% of all new cancers in men. Approximately 1 in 8 Canadian men is expected to develop
prostate cancer during their lifetime, and 1 in 27 will die from prostate cancer. In Alberta, 2600 new
prostate cancer diagnoses are anticipated in 20161.
GUIDELINE QUESTIONS



How should patients with localized prostate cancer be risk stratified?
How should patients with localized prostate cancer be managed?
How should patients with localized prostate cancer be followed after they have completed treatment?
DEVELOPMENT AND REVISION HISTORY
This guideline was reviewed and endorsed by the Alberta Provincial GU Tumour Team. Members of the
Alberta Provincial GU Tumour Team include (medical oncologists, radiation oncologists, surgical
oncologists, nurses, pathologists, and pharmacists). Evidence was selected and reviewed by a working
group comprised of members from the Alberta Provincial GU Tumour Team and a Knowledge
Management Specialist from the Guideline Resource Unit. A detailed description of the methodology
followed during the guideline development process can be found in the Guideline Resource Unit
Handbook.
This guideline was originally developed in (January, 2017).
TARGET POPULATION
Adult men (18 years of age or older) with a suspicion or recent diagnosis of localized prostate cancer.
RECOMMENDATIONS
For a complete list of early diagnosis and screening recommendations please see the Early Diagnosis
and Screening for Prostate Cancer guideline located
(http://www.albertahealthservices.ca/info/cancerguidelines.aspx) and the Canadian Task Force on
Preventive Health Care guidelines (http://canadiantaskforce.ca/guidelines/published-guidelines/prostatecancer/)
1. Staging
A. Assessment for patients who are being considered for active surveillance or treatment with
curative intent should consist of:
i. History and physical examination.
ii. PSA (which should be done prior to biopsy.
iii. Radionuclide bone scan and CT scan abdomen/pelvis is indicated only in patients with
high-risk disease* or if clinical suspicion, and may be considered in select patients with
high-tier intermediate risk disease*.
Page 2 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
2. Definition of risk categories for clinical staging:
A. Low-risk: Must have all of the following: T1-T2a/b, Gleason score ≤6, PSA <10 ng/mL*.
B. Intermediate-risk: This group can be further divided into low-tier intermediate (one
intermediate risk feature) or high-tier intermediate (more than one intermediate risk feature) for
those patients who do not clearly segregate into low or high risk groups. Intermediate-risk features
include: T2c, Gleason score 7, and PSA 10-20 ng/mL* 2.
C. High-risk: Any one of the following: T3a or higher, Gleason score ≥8, or PSA >20ng/mL*.
*In patients taking 5-alpha reductase inhibitors, measured PSA should be doubled for the purposes of risk
stratification.
3. Any patient being considered for curative-intent treatment for prostate cancer should be
strongly encouraged to explore treatment options with a urologist and a radiation oncologist.
Treatment options (e.g. prostatectomy, brachytherapy, and/or external beam radiotherapy (EBRT))
have equivalent cancer-specific outcomes, with different toxicity profiles.
4. Patients should be offered clinical trials wherever available.
5. Management of low-risk disease
A. Active surveillance3,4:
i. This is the preferred management option in low-risk patients with the understanding that
curative treatment will be offered if follow-up demonstrates either worrisome PSA elevation
or worsening biopsy characteristics (e.g. Gleason grade and or/volume changes)
ii. The patient may choose to proceed with curative therapy due to personal preference at
any time.
iii. Curative intervention may be required later and patients may be candidates for clinical
trials.
iv. Patients with localized, low-risk prostate cancer can consider an active surveillance
protocol to monitor their disease for signs of disease progression. A reasonable
surveillance protocol would include:
a. PSA assessment every 3-6 months, DRE annually (at the physician's discretion).
b. Consider repeat biopsies 1-2 years after initial diagnosis, then consider further
biopsies every 2-3 years or as clinically indicated.
v. Disease progression:
a. Pathological progression defined as presence of Gleason pattern ≥4 or an
increase in the number of positive cores.
b. Additional factors to consider repeat biopsy include:
-Clinical progression: increase in clinical stage from baseline status.
-Biochemical progression: PSA doubling time <3 years.
c. If there are signs of disease progression, intervention is recommended with
curative therapy (radical prostatectomy, EBRT, or brachytherapy).
vi. For patients that will not benefit from curative therapy, watchful waiting or other
therapies (e.g. hormonal therapy or palliative radiotherapy) can be considered, see the
Advanced/ Metastatic Prostate Cancer guideline for a complete list of recommendations
(http://www.albertahealthservices.ca/info/cancerguidelines.aspx).
B. Treatment options 5:
Page 3 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
Radical treatment is not appropriate for patients with a life expectancy of <10 years.
i. Radical prostatectomy6-8 options include:
a. Open retropubic prostatectomy.
b. Robotic assisted laparoscopic surgery.
c. Both treatments have similar oncological outcomes; furthermore, a wait time of
up to 3 months for treatment in low-risk prostate cancer is not associated with
worse outcomes.
d. Pelvic lymph node dissection in this group is optional, but yield is very low in lowrisk patients.
ii. Low dose rate (LDR) Brachytherapy9-11
a. Patients with pubic arch interference may not be eligible for brachytherapy.
b. Patients with borderline pubic arch interference may be considered for a short
course of hormones to reduce gland size
c. Patients with a prior transurethral resection (TURP) should be assessed on an
individual basis.
d. Patients with significant baseline obstructive symptoms may not be eligible for
brachytherapy (i.e. American Urological Association symptom score >20).
iii. External beam radiotherapy12
a. 3d-conformal radiotherapy or intensity modulated radiation therapy (IMRT) should
be utilized to deliver an International Commission on Radiation Units (ICRU) dose of
74-78 Gy in 1.8-2.0 Gy fractions 13.
b. Hypofractionated radiation (e.g. 60 Gy in 3 Gy fractions) may be considered14.
c. Daily image guidance is standard of care
d. The clinical target volume (CTV) is defined as the prostate alone.
C. Alternative therapeutic options for patients who are not eligible or declining standard
therapies:
i. Cryosugery 15.
ii. High intensity focused ultrasound (HIFU)16.
D. Follow-up
i. PSA every 6 to 12 months for 5 years, then yearly.
ii. Digital rectal examination yearly, but may be omitted if PSA undetectable.
iii. Evaluation of treatment morbidity and/or complications.
6. Management of intermediate-risk disease
A. Treatment options5:
i. Radical prostatectomy plus bilateral pelvic lymph node dissection17.
ii. External beam radiotherapy13,18,19
a. Based on current evidence, the recommended prescribed dose to the target is
74-78 Gy in standard fractionation.
b. Hypofractionated radiation (e.g. 60 Gy in 3 Gy fractions) may be considered14.
c. Short term (neoadjuvant + concurrent) androgen deprivation therapy (ADT) may
be considered for select patients undergoing radiotherapy (REF 33, 34).
iii. Brachytherapy
a. Brachytherapy alone is a treatment option for low-tier intermediate risk patients
(REF 31-33).
b. EBRT with a brachytherapy boost (+/- ADT) is an option for patients with high-tier
intermediate risk disease20-22.
Page 4 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
c. Brachytherapy may be delivered as either low dose rate (LDR) or high dose rate
(HDR)20-22.
d. Short term (neoadjuvant + concurrent) androgen deprivation therapy (ADT) may
be considered for select patients undergoing radiotherapy (REF 33, 34).
B. Alternative therapeutic options for patients who are not eligible or declining standard
therapies:
i. Cryosurgery23.
C. Follow-up
i. PSA every 6 to 12 months for the first 5 years, then yearly.
ii. Digital rectal examination yearly.
iii. Evaluation of treatment morbidity and/or complications.
7. Management of high-risk disease
A. Treatment options5:
i. EBRT + ADT 24-26
a. Radiotherapy should treat the prostate planning target volume with 74-78 Gy in
standard fractions +/- regional lymph nodes
b. EBRT with a brachytherapy boost (+/- ADT) is an option for patients with high
risk disease20-22.c. Hypofractionated radiation (e.g. 60 Gy in 3 Gy fractions) may be
considered14.
d. ADT should be administered for at 18 – 36 months duration and may be initiated
prior to radiotherapy or concurrently with EBRT 27.
e. An anti-androgen could be co-administered with a LHRH agonist and be
continued for at least 7 days for possible flare in testosterone with initial LHRH
agonist alone.
f. Refer to the Bone Health for Prostate cancer guideline for recommendations
regarding bone health for patients on ADT
(http://www.albertahealthservices.ca/info/cancerguidelines.aspx)
ii. Radical prostatectomy and pelvic lymphadenectomy28
a. Patients should be counselled that they there is a significant likelihood of
requiring post-operative radiotherapy +/- ADT.
iii. Post-prostatectomy radical RT29
a. Patients with any of the following pathological risk factors for local recurrence
should be offered referral to a radiation oncologist for a discussion regarding
adjuvant therapy within 6 months of surgery:
-Positive surgical margins
-Seminal vesicle involvement (pT3b)
-Capsular perforation (pT3a)
b. Early salvage radiotherapy should be considered at the time of biochemical
failure (PSA ≥0.2 ng/mL on at least 2 readings)
c. ADT can be considered in post-operative radiation therapy; the optimal type and
duration of ADT has not been established.
B. Alternative therapeutic options of those patients not eligible for, or declining curative
local treatment:
i. ADT alone24-26
a. Refer to the Bone Health for Prostate cancer guideline for recommendations
regarding bone health for patients on ADT
(http://www.albertahealthservices.ca/info/cancerguidelines.aspx)
Page 5 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
C. Follow-up
i. First post-operative PSA should be done 4-12 weeks after surgery.
ii. Routine PSA should be done every 6 months, unless otherwise specified.
iii. Low-risk patients (pT2, Gleason ≤ 3+4, margins negative) may have PSA done yearly.
Page 6 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
SEARCH STRATEGY
For the 2017 update, guidelines were updated according to a consensus meeting without a formal
literature search.
For the 2015 update, no formal literature review was conducted.
For the 2014 update of this guideline, the Pubmed database was searched using the search terms Locally
Advanced Prostate Cancer and Metastatic Prostate Cancer from 2010 to 2014. Only phase III trials were
evaluated for inclusion.
For the 2012 update of this guideline, Ovid Medline was searched using the term Prostatic neoplasms
(MeSH term, subheadings drug therapy, surgery, therapy and radiotherapy), limited to clinical trials
involving humans published in English, between August 2011 and August 2012. Articles were excluded if
they were not phase II-IV trials, did not include survival or recurrence outcomes, was retrospective.
Cochrane Database of Systematic Reviews was searched using the term “prostate cancer”, published
2011-2012.
Medline & Embase were further searched using the term prostate cancer (keyword), limited to clinical
trials related to “therapy (best balance of sensitivity and specificity) involving male humans published in
English between August 2011-2012.
Page 7 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
GLOSSARY OF ABBREVIATIONS
Acronym
ADT
CTV
EBRT
HDR
HIFU
ICRU
IMRT
LDR
PSA
RT
TURP
Description
Androgen deprivation therapy
Clinical target volume
External beam radiotherapy
High dose rate
High intensity focused ultrasound
International commission on radiation units
Intensity modulated radiotherapy
Low dose rate
Prostate specific antigen
Radiotherapy
Transurethral resection
DISSEMINATION



Present the guideline at the local and provincial tumour team meetings and weekly rounds.
Post the guideline on the Alberta Health Services website.
Send an electronic notification of the new guideline to all members of CancerControl Alberta.
MAINTENANCE
A formal review of the guideline will be conducted at the Annual Provincial Meeting in 2017. If critical new
evidence is brought forward before that time, however, the guideline working group members will revise
and update the document accordingly.
CONFLICT OF INTEREST
Participation of members of the Alberta Provincial GU Tumour Team in the development of this guideline
has been voluntary and the authors have not been remunerated for their contributions. There was no
direct industry involvement in the development or dissemination of this guideline. CancerControl Alberta
recognizes that although industry support of research, education and other areas is necessary in order to
advance patient care, such support may lead to potential conflicts of interest. Some members of the
Alberta Provincial GU Tumour Team are involved in research funded by industry or have other such
potential conflicts of interest. However the developers of this guideline are satisfied it was developed in an
unbiased manner.
COPYRIGHT DISCLOSURE
Copyright © (2017) Alberta Health Services.
This material is protected by Canadian and other international copyright laws. All rights reserved. This
material may not be copied, published, distributed or reproduced in any way in whole or in part without the
express written permission of Alberta Health Services (please contact the Guideline Resource Unit
Manager at CancerControl Alberta at [email protected]).
Page 8 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
This material is intended for general information only and is provided on an "as is", "where is" basis.
Although reasonable efforts were made to confirm the accuracy of the information, Alberta Health
Services does not make any representation or warranty, express, implied or statutory, as to the accuracy,
reliability, completeness, applicability or fitness for a particular purpose of such information. This material
is not a substitute for the advice of a qualified health professional. Alberta Health Services expressly
disclaims all liability for the use of these materials, and for any claims, actions, demands or suits arising
from such use.
REFERENCES
1. Canadian Cancer Statistics 2016. Toronto, ON: Canadian Cancer Society. Canadian Cancer Society's
Advisory Committee on Cancer Statistics.&nbsp; 2016.
2. Rodrigues G, Lukka H, Warde P, Brundage M, Souhami L, Crook J, et al. The prostate cancer risk
stratification (ProCaRS) project: recursive partitioning risk stratification analysis. Radiother Oncol
2013 Nov;109(2):204-210.
3. Dahabreh IJ, Chung M, Balk EM, Yu WW, Mathew P, Lau J, et al. Active surveillance in men with
localized prostate cancer: a systematic review. Ann Intern Med 2012 Apr 17;156(8):582-590.
4. Simpkin AJ, Tilling K, Martin RM, Lane JA, Hamdy FC, Holmberg L, et al. Systematic Review and Metaanalysis of Factors Determining Change to Radical Treatment in Active Surveillance for Localized
Prostate Cancer. Eur Urol 2015 Jun;67(6):993-1005.
5. Grimm P, Billiet I, Bostwick D, Dicker AP, Frank S, Immerzeel J, et al. Comparative analysis of
prostate-specific antigen free survival outcomes for patients with low, intermediate and high risk
prostate cancer treatment by radical therapy. Results from the Prostate Cancer Results Study Group.
BJU Int 2012 Feb;109 Suppl 1:22-29.
6. Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, et al. Radical prostatectomy or
watchful waiting in early prostate cancer. N Engl J Med 2014 Mar 06,;370(10):932-942.
7. Iversen P, Madsen PO, Corle DK. Radical prostatectomy versus expectant treatment for early
carcinoma of the prostate. Twenty-three year follow-up of a prospective randomized study. Scand J
Urol Nephrol Suppl 1995;172:65-72.
8. Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, et al. Radical prostatectomy versus
observation for localized prostate cancer. N Engl J Med 2012 Jul 19,;367(3):203-213.
9. Jabbari S, Weinberg VK, Shinohara K, Speight JL, Gottschalk AR, Hsu IC, et al. Equivalent
biochemical control and improved prostate-specific antigen nadir after permanent prostate seed
implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose
conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010 Jan 1;76(1):36-42.
Page 9 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
10. Zelefsky MJ, Yamada Y, Pei X, Hunt M, Cohen G, Zhang Z, et al. Comparison of tumor control and
toxicity outcomes of high-dose intensity-modulated radiotherapy and brachytherapy for patients with
favorable risk prostate cancer. Urology 2011 Apr;77(4):986-990.
11. Merrick GS, Butler WM, Wallner KE, Galbreath RW, Adamovich E. Permanent interstitial
brachytherapy in younger patients with clinically organ-confined prostate cancer. Urology 2004
Oct;64(4):754-759.
12. Morris DE, Emami B, Mauch PM, Konski AA, Tao ML, Ng AK, et al. Evidence-based review of threedimensional conformal radiotherapy for localized prostate cancer: an ASTRO outcomes initiative. Int
J Radiat Oncol Biol Phys 2005 May 1;62(1):3-19.
13. Kuban DA, Tucker SL, Dong L, Starkschall G, Huang EH, Cheung MR, et al. Long-term results of the
M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys
2008 Jan 1;70(1):67-74.
14. Dearnaley D, Syndikus I, Mossop H, Khoo V, Birtle A, Bloomfield D, et al. Conventional versus
hypofractionated high-dose intensity-modulated radiotherapy for prostate cancer: 5-year outcomes of
the randomised, non-inferiority, phase 3 CHHiP trial. Lancet Oncol 2016 Aug;17(8):1047-1060.
15. Chin JL, Ng CK, Touma NJ, Pus NJ, Hardie R, Abdelhady M, et al. Randomized trial comparing
cryoablation and external beam radiotherapy for T2C-T3B prostate cancer. Prostate Cancer Prostatic
Dis 2008;11(1):40-45.
16. Crouzet S, Chapelon JY, Rouviere O, Mege-Lechevallier F, Colombel M, Tonoli-Catez H, et al. Wholegland ablation of localized prostate cancer with high-intensity focused ultrasound: oncologic
outcomes and morbidity in 1002 patients. Eur Urol 2014 May;65(5):907-914.
17. Boorjian SA, Karnes RJ, Rangel LJ, Bergstralh EJ, Blute ML. Mayo Clinic validation of the D'amico
risk group classification for predicting survival following radical prostatectomy. J Urol 2008
Apr;179(4):1.
18. Zietman AL, DeSilvio ML, Slater JD, Rossi CJ, Miller DW, Adams JA, et al. Comparison of
conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of
the prostate: a randomized controlled trial. JAMA 2005 Sep 14,;294(10):1233-1239.
19. Peeters STH, Heemsbergen WD, Koper PCM, van Putten, Wim L J, Slot A, Dielwart MFH, et al.
Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter
randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 2006 May
01,;24(13):1990-1996.
20. Morris WJ, Tyldesley S, Pai HH, et al. A multicenter, randomized trial of dose-escalated external beam
radiation therapy (EBRT-B) versus low-dose-rate brachytherapy (LDR-B) for men with unfavorablerisk localized prostate cancer (abstract). J Clin Oncol 2015(Suppl 7):3.
Page 10 of 11
CLINICAL PRACTICE GUIDELINE GU-012
Version 1
21. Prestidge BR, Winter K, Sanda MG, et al. Initial report of NRG Oncology/RTOG 0232: a phase 3
study comparing combined external beam radiation and transperineal interstitial permanent
brachytherapy with brachytherapy alone for selected patients with intermediate-risk prostatic
carcinoma (abstract). 2016.
22. Hoskin PJ, Rojas AM, Bownes PJ, Lowe GJ, Ostler PJ, Bryant L. Randomised trial of external beam
radiotherapy alone or combined with high-dose-rate brachytherapy boost for localised prostate
cancer. Radiother Oncol 2012 May;103(2):217-222.
23. Cohen JK, Miller RJ,Jr, Ahmed S, Lotz MJ, Baust J. Ten-year biochemical disease control for patients
with prostate cancer treated with cryosurgery as primary therapy. Urology 2008 Mar;71(3):515-518.
24. Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, et al. Combined androgen
deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase
3 trial. Lancet 2011 Dec 17;378(9809):2104-2111.
25. Mason MD, Parulekar WR, Sydes MR, Brundage M, Kirkbride P, Gospodarowicz M, et al. Final Report
of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy
Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer. J Clin Oncol
2015 Jul 1;33(19):2143-2150.
26. Brundage M, Sydes MR, Parulekar WR, Warde P, Cowan R, Bezjak A, et al. Impact of Radiotherapy
When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term
Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial. J Clin Oncol 2015
Jul 1;33(19):2151-2157.
27. Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh, A C, Oddens J, Poortmans PM, et al.
Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 2009 Jun
11;360(24):2516-2527.
28. Briganti A, Spahn M, Joniau S, Gontero P, Bianchi M, Kneitz B, et al. Impact of age and comorbidities
on long-term survival of patients with high-risk prostate cancer treated with radical prostatectomy: a
multi-institutional competing-risks analysis. Eur Urol 2013 Apr;63(4):693-701.
29. Rusthoven CG, Carlson JA, Waxweiler TV, Raben D, Dewitt PE, Crawford ED, et al. The impact of
definitive local therapy for lymph node-positive prostate cancer: a population-based study. Int J
Radiat Oncol Biol Phys 2014 Apr 1;88(5):1064-1073.
Page 11 of 11