ACRO 2015

1

Drew Moghanaki, MD, MPHHunter Holmes McGuire Veterans Affairs Hospital

Virginia Commonwealth UniversityRichmond, Virginia

High Risk Prostate Cancer

Disclosures

I am employed by the healthcare system that brought you this

2PIVOT, NEJM 2011

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

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4ADT Alone?

Lancet, 2009

HR: 0·44 (0·30–0·66, p<0·0001)

1996-200278% = T3

23% = SV+40% = PSA>20

Max PSA <70

Lancet, 2011

1995-200583% = T34% = T4

18% = GS 8-1063% = PSA >20

Max PSA <70

7

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

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Gupta et al, Urol Oncol 2014Borofsky et al, Urol 2013Brown et al, Urol oncol 2009

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)

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RADIOTHERAPY

Helping Improve Urologists’ Outcomes in High Risk Patients for

Decades10

Gambling with High Risk

11Karlin et al, J Urol 2014

ASTRO/AUA Guideline

Clinical Principle: Physicians should “offer” adjuvant radiotherapy to patients with adverse pathologic findings [SV, EPE, +Margin]

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Still believes he will live longer

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15 year: Urinary Function

Resnick, NEJM 2013

15 year: Sexual Function

Resnick, NEJM 2013

15 year: Bowel Function

Resnick, NEJM 2013

Data Scientists and Big Data

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Low Risk Interm Risk High Risk

Scandinavian RegistrySooriakumaan et al, BMJ 2014

}

The survival of CURED patients should be equal, irrespective of treatment.

IF BASELINE HEALTH WAS SIMILAR AT BASELINE

OBVIOUSLY, THEY ARE NOT

Slide by Julian Rosenman, MD, PhD

}

Rad

ioth

erap

ySu

rger

yScandinavian Registry

n >30,000

Years

Surv

ival

0 —

60 —70 —80 —90 —

100 —

|14

|10.5

|7

|3.5

|0

Cured radiation patientsCured surgery patients

Why such a difference? What is

missing?

Slide by Julian Rosenman, MD, PhD

Survival of Cured Patients

The Absurd

21Nat Rev Urology 2013

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, 2015ABS, 2015ESTRO, 2015

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

Clinics23

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

What Dr. Ehdaie may forget to mention

Gatekeeper effect…

He may be less familiar with this

(Since Zelefsky helps keeps things honest at MSKCC)

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