Local Prostate Cancer

Transcription

1 Local Prostate Cancer Effective Date: January, 2018

2 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 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. 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. All cancer drugs described in the guidelines are funded in accordance with the Outpatient Cancer Drug Benefit Program, at no charge, to eligible residents of Alberta, unless otherwise explicitly stated. For a complete list of funded drugs, specific indications, and approved prescribers, please refer to the Outpatient Cancer Drug Benefit Program Master List. 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. Page 2 of 12

3 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 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, and subsequently updated in January, 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 ( and the Canadian Task Force on Preventive Health Care guidelines ( 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 3 of 12

4 iv. MRI-prostate is not routinely recommended. 2. Definition of risk categories for clinical staging: A. Low-risk: Must have all of the following: T1-T2a/b, Gleason score 6 (Grade Group 1) 31 (REF), 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). Intermediate-risk features include: T2c, Gleason score 7 (Grade Group 2-3), and PSA ng/ml* 2. C. High-risk: Any one of the following: T3a or higher, Gleason score 8 (Grade Group 4-5), 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 both urology and radiation oncology. 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 surveillance 3,4 : 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. 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 subsequent biopsies every 2-3 years or as clinically indicated. c. MRI-prostate can be considered if there is discordance between clinical and pathological information. iv. Disease progression: a. Pathological progression defined as presence of Gleason pattern 4 or an increase in the number of positive cores or percentage of core volume involved. b. Additional factors to consider repeat biopsy include: -Clinical progression: increase in clinical stage (on DRE) from baseline status. -Biochemical progression: PSA doubling time <3 years. c. If there are signs of disease progression, intervention is recommended with curative therapy (ie: radical prostatectomy, EBRT, or brachytherapy). v. For patients that will not benefit from curative therapy, watchful waiting or other therapies (e.g. androgen deprivation therapy (ADT) or palliative radiotherapy) can be considered, see the Advanced/ Metastatic Prostate Cancer guideline for a complete list of recommendations ( Page 4 of 12

5 B. Treatment options 5 : Radical treatment is not appropriate for patients with a life expectancy of <10 years. i. Radical prostatectomy 6-8 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) Brachytherapy 9-11 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 ADT 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 radiotherapy 12 a. 3D-conformal radiotherapy or intensity modulated radiation therapy (IMRT) should be utilized to deliver an International Commission on Radiation Units (ICRU) dose to the prostate of Gy in Gy fractions 13. b. Hypofractionated radiation (e.g. 60 Gy in 20 fractions) may be considered 14. c. Daily image guidance is standard of care d. The clinical target volume (CTV) is defined as the prostate alone. iv. Cryosurgery 15 a. There is less long-term data for efficacy and toxicity compared to the other treatment modalities. C. Alternative therapeutic options for patients who are not eligible or declining standard therapies: i. High intensity focused ultrasound (HIFU) 16. D. Follow-up i. PSA every 6 to 12 months for 5 years, then yearly. ii. Evaluation of treatment morbidity and/or complications. 6. Management of intermediate-risk disease A. Treatment options 5 : i. Radical prostatectomy plus bilateral pelvic lymph node dissection 17. ii. External beam radiotherapy 13,18,19 a. 3D-conformal radiotherapy or intensity modulated radiation therapy (IMRT) should be utilized to deliver an International Commission on Radiation Units (ICRU) dose to the prostate of Gy in Gy fractions. b. Hypofractionated radiation (e.g. 60 Gy in 20 fractions) may be considered 14. c. Short term (neoadjuvant + concurrent, 4-6 months total) ADT may be considered for select patients undergoing radiotherapy (REF 33, 34). d. The clinical target volume (CTV) is defined as the prostate +/- seminal vesicles. Page 5 of 12

6 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 disease c. Brachytherapy may be delivered as either low dose rate (LDR) or high dose rate (HDR) d. Short term (neoadjuvant + concurrent, 4-6 months total) ADT may be considered for select patients undergoing brachytherapy (REF 33, 34). iv. Cryosurgery 23. a. There is less long-term data for efficacy and toxicity compared to the other treatment modalities. C. Follow-up i. PSA every 6 to 12 months for the first 5 years, then yearly. ii. Evaluation of treatment morbidity and/or complications. 7. Management of high-risk disease A. Treatment options 5 : i. EBRT + ADT a. 3D-conformal radiotherapy, intensity modulated radiation therapy (IMRT should be utilized to deliver an International Commission on Radiation Units (ICRU) dose to the prostate of Gy in Gy fractions b. There is growing evidence for hypofractionation (ie: 68Gy in 25 fractions) in this patient group c. The clinical target volume (CTV) is defined as the prostate + seminal vesicles +/- regional lymph nodes.. d. EBRT with a brachytherapy boost (+/- ADT) is an option for patients with high risk disease e. ADT should be administered for an month duration and may be initiated prior to radiotherapy or concurrently with EBRT 27. f. 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). g. Refer to the Bone Health for Prostate cancer guideline for recommendations regarding bone health for patients on ADT ( ii. Radical prostatectomy and pelvic lymphadenectomy 28 a. Should be considered only for patients where the intent is to achieve negative margins. b. Patients should be counselled that there is a significant likelihood of requiring post-operative radiotherapy +/- ADT. iii. Cryosurgery a. Cryosurgery can be considered in patients with Gleason score 8, as long as PSA <20 AND clinical stage T1-T2. Patients must understand that there is a higher risk of biochemical failure compared to those with low or intermediate risk disease. Page 6 of 12

7 There is less long-term data for efficacy and toxicity compared to the other treatment modalities. 8. Post-prostatectomy Treatment A. Radical RT 29 i. 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: a. Positive surgical margins b. Seminal vesicle involvement (pt3b) c. Extraprostatic extension (pt3a) ii. Early salvage radiotherapy should be considered at the time of biochemical failure (PSA 0.2 ng/ml on at least 2 readings) iii. ADT can be considered in post-operative radiation therapy; the optimal type and duration of ADT has not been established. iv. The standard clinical target volume (CTV) is the prostate bed; addition of pelvic lymph node regions may be considered v. The total dose to the prostate bed should be at least 60-66Gy in standard fractionation B. Alternative therapeutic options of those patients not eligible for, or declining curative local treatment: i. ADT alone a. Refer to the Bone Health for Prostate cancer guideline for recommendations regarding bone health for patients on ADT ( 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. 9. Biochemical recurrence following local radical therapy 30 A. Definition of biochemical recurrence: i. Following prostatectomy PSA 0.2 ii. Following radiotherapy PSA nadir +2 ng/ml B. Investigations (to rule out metastatic disease) Post-op: if PSA>2 Post-RT: for all patients being considered for definitive salvage therapy i. Bone scan ii. CT scan iii. Post-RT: Repeat prostate biopsy to confirm local recurrence C. Local Salvage Therapy i. Post-radical prostatectomy: a. Salvage radiotherapy, with or without concurrent or adjuvant ADT b. ADT can be considered in post-operative radiation therapy; the optimal type and duration of ADT has not been established Page 7 of 12

8 c. The standard clinical target volume (CTV) is the prostate bed; addition of pelvic lymph node regions may be considered d. The total dose to the prostate bed should be at least 60-66Gy in standard fractionation ii. Post-radiotherapy: Recommended options include: a. Salvage Cryosurgery b. Salvage Brachytherapy c. ADT alone if salvage therapy is not offered Page 8 of 12

9 SEARCH STRATEGY For the 2018 update, guidelines were updated according to a consensus meeting without a formal literature search. 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 If critical new evidence is brought forward before that time, however, the guideline working group members will revise and update the document accordingly. Page 9 of 12

10 REFERENCES 1. Canadian Cancer Statistics Toronto, ON: Canadian Cancer Society. Canadian Cancer Society's Advisory Committee on Cancer Statistics 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): 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): 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): 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: 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): 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: 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): 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): 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): 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): Page 10 of 12

11 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): 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): 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): 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): 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): 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): 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): 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): 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): 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) 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): Page 11 of 12

12 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): 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): 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): 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): 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): 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): 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): Roach M(3rd), Hanks G, Thames H(Jr.), Schellhammer P, Shipley WU, Sokol GH, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006 Jul 15:65(4): Moch H, Humphrey PA, Ulbright TM, Reuter (Eds) VE. WHO Classification of Tumours of the Urinary System and Male Genital Organs (4th edition). IARC: Lyon Page 12 of 12