This house believes that locally advanced prostate cancer should be treated with radiotherapy and hormone deprivation

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This house believes that locally advanced prostate cancer should be treated with radiotherapy and hormone deprivation AGAINST Theo M. de Reijke MD PhD FEBU Department of Urology Academic Medical Center Amsterdam

Bolla et al N Engl J Med 360:2516-2527, 2009

Van Poppel & Joniau Eur Urol 53:253-259, 2008 CSS after RRP in ct3/high-risk prostate cancer Combination of RRP +/- EBRT (+/- ADT) CSS 5 year 10 year 15 year 85-99% 72-92% 76-84%

Definition of high-risk prostate cancer D Amico EAU PSA >20 or GS 8-10 or T2c PSA >20 or GS 8-10 or T3a NCCN any 2 of: T2b-c, GS 7, PSA 10-20 RTOG, CAPRA At surgery: frequent overgrading and overstaging

Yossepowitch et al J Urol 178:493-499, 2007 Outcome according to definiton of high-risk Progression-free probability: 35-76%

Donohue et al J Urol 176:991-995, 2006 RRP for high-risk prostate cancer Gleason score 8-10 238 patients with biopsy Gleason 8-10 Down grading: 45% of patients had GS 7 in RRP specimen Other studies suggest that 1/3 of high-risk patients with GS 8 are down graded

Wilt et al N Engl J Med 376:203-213, 2012

Vickers et al Eur Urol 62:204-209, 2012 SPCG-4: 695 patients T1-2 randomized for RRP or WaWa

Surgery or EBRT for high-risk prostate cancer? No prospective randomized trials Retrospective evidente comes from high volume centers High rates of multimodal treatments Recent shift towards modern treatment approaches (high dose EBRT, eplnd) Why not EBRT and ADT?

Saigal et al Cancer 110:1493-1500, 2007 22.816 patients: 4810 ADT for 36 months : 18.006 no ADT in conjunction with RRP/EBRT At 5 year significant difference in CV events (p <0.001) ADT: 1.2 times increased risk of CV death

ADT and cardiovascular risk Summary Androgen deprivation therapy in prostate cancer and cardiovascular risk: a science Advisory from the American Heart Association, American Cancer Society, and American Urological association: endorsed by the American Society for Radiation Oncology Proven impact on standard CV risk factor Proven impact on CV events Disputable effect of CV death Levine et al Circulation 121:833-840, 2010

Bostrom & Soloway Eur Urol 52:973-982, 2007 Acute GU and GI toxicity Late GU and GI toxicity Fatigue from EBRT Secondary bladder and GI cancer

Nieder et al J Urol 180:2005-2010, 2008 Brenner et al Cancer 88:398-406, 2000 Moon et al Cancer 107:991-998, 2006 Rectal cancer: Relative risk after EBRT, Brachy, and EBRT/Brachy, compared with RRP: 1.26, 1.08, and 1.21, respectively Bladder cancer: Increased risk after EBRT with a risk ratio of approximately 1.5

Resnick et al et al N Engl J Med 368:436-445, 2013

Need for ADT Early and late radiotoxicity Risk of second cancer Functionally not better at long term

Sooriakumaran et al BMJ, 2014 21.553 RRP vs 12.982 EBRT National Prostate Cancer Registry since 1996

Lee et al Eur Urol 2014 Epub ahead of print

How to approach high-risk prostate cancer? >T2 and GS >7 and high PSA Good imaging The tumour must be operable Involve the patient Discuss possible adjuvant treatments

Why surgery for locally advanced prostate cancer? Good results in experienced centers Pathological down grading and staging No ADT Possibility to individualize adjuvant treatment