This document summarizes key points about treatment options for high risk prostate cancer. It discusses controversies around using androgen deprivation therapy alone versus tri-modality treatment with surgery, radiotherapy and ADT. Clinical trial data is presented showing improved survival with radiotherapy alone or with ADT compared to ADT alone. Challenges with surgery are noted along with long term functional outcomes data with radiotherapy. The importance of a multi-disciplinary approach and shared decision making is emphasized. While further randomized controlled trial data is still needed, the document argues against avoiding radiotherapy in high risk prostate cancer treatment.

1. ACRO 2015
1
Drew Moghanaki, MD, MPH
Hunter Holmes McGuire Veterans Affairs Hospital
Virginia Commonwealth University
Richmond, Virginia
High Risk Prostate Cancer

2. Disclosures
I am employed by the healthcare system that brought you this
2
PIVOT, NEJM 2011

3. What’s So Controversial?
• Nihilism about the value of radiotherapy for high risk
– ADT alone?
• Justifying toxicity of tri-modality treatment
– Surgery, Radiotherapy, and ADT
• Publications by data scientists
– Misinforming urologists
– Confusing patients
– Irritating radiation oncologists
3

4. 4
ADT Alone?

5. Lancet, 2009
HR: 0·44 (0·30–0·66, p<0·0001)
1996-2002
78% = T3
23% = SV+
40% = PSA>20
Max PSA <70

6. Lancet, 2011
1995-2005
83% = T3
4% = T4
18% = GS 8-10
63% = PSA >20
Max PSA <70

7. 7

8. Challenges for Urologists
• Difficult to “get it all”
• MRI may help
– Outperforms Partin Tables
– Unintended consequence
• False reassurance
• More aggressiveness NVB sparing
• Higher positive margin
8
Gupta et al, Urol Oncol 2014
Borofsky et al, Urol 2013
Brown et al, Urol oncol 2009

9. Non-Believers
• Failure after Prostatectomy
– Urologists preferred to observe
– Some considered ADT, at time of symptoms
– Gradually, salvage RT was considered
• Data showed  OS with salvage RT
– Fast PSA doublers (Trock, 2008)
– Slow PSA doublers (Cotter, 2011)
9

10. RADIOTHERAPY
Helping Improve Urologists’
Outcomes in High Risk Patients
for Decades
10

11. Gambling with High Risk
11Karlin et al, J Urol 2014

12. ASTRO/AUA Guideline
Clinical Principle: Physicians should “offer”
adjuvant radiotherapy to patients with adverse
pathologic findings [SV, EPE, +Margin]
12

13. Still believes he will live longer
13

14. 15 year: Urinary Function
Resnick, NEJM 2013

15. 15 year: Sexual Function
Resnick, NEJM 2013

16. 15 year: Bowel Function
Resnick, NEJM 2013

17. Data Scientists and Big Data
17

18. Low Risk Interm Risk High Risk
Scandinavian Registry
Sooriakumaan et al, BMJ 2014

19. }
The survival of CURED
patients should be equal,
irrespective of treatment.
IF BASELINE HEALTH
WAS SIMILARAT
BASELINE
OBVIOUSLY,
THEYARE NOT
Slideby JulianRosenman,MD, PhD
}
RadiotherapySurgery
Scandinavian Registry
n >30,000

20. Years
Survival
0 —
60 —
70 —
80 —
90 —
100 —
|
14
|
10.5
|
7
|
3.5
|
0
Cured radiation patients
Cured surgery patients
Why such a difference?
What is missing?
Slide by Julian Rosenman, MD, PhD
Survival of Cured Patients

21. The Absurd
21Nat Rev Urology 2013

22. Hope and the ASCENDE Trial
276 = High Risk
12 months LHRH
+
46 Gy EBRT
32 Gy EBRT vs 115 Gy I-125
7y DFS
Nadir + 0.2 38% 82%
Nadir + 2 71% 86%
22ASCO GU, 2015
ABS, 2015
ESTRO, 2015

23. Take Home Points
• Sharp instruments often miss tumor
– Leave behind toxicity
• Routine tri-modality therapy should be avoided
– No need to bother with surgery
• Don’t get fooled by data scientists
– QOL, Shared Decision, Multi-Disciplinary Clinics
23

24. Dr. Ehdaie may want you to believe
• He knows how to interpret the data
– Yes, he does.
• Surgery helps pts live longer.
– Yes, for high risk in PIVOT
– (Halsted once challenged radiotherapy)
• He’ll concede we need a RCT
– SPCG 15 (open, est. completion 2027)
– VA High Risk Study (concept)
24

25. What Dr. Ehdaie may forget to mention
Gatekeeper effect…
He may be less familiar with this
(Since Zelefsky helps keeps things honest at MSKCC)
25