PCa: against RX + ADT as standard of care

N. Mottet

Urology department

St Etienne

Chairman EAU-ESTRO-SIOG prostate cancer guidelines

Disclosures

A dogma for locally advanced PCa "RX + ADT: standard of care "

The correct wording MUST be:

"RX + ADT: standard of care for locally advanced PCa" . . .

. . . . if RX is considered.

Outside this, purely speculative . . .NO RCT at all ! treatment of voiding problems Easier follow upBetter outcome ?Better salvage TTT ?

1. D’Amico. JAMA 1998; 2. Thomson. J Urol 2007; 3. Mottet EAU guidelines 2016; 4. NCCN guidelines 2015; 5. Joniau Eur Urol 2015

What are we talking about ?No real consensus definition !

Guidelines Year Definition

D’Amico1 1998 ≥T2c or Gleason 8-10 or PSA >20 ng/ml

AUA2 2007 cT2 or Gleason 8-10 or PSA >20 ng/ml

EAU3 2015 Localized: T2c or Gleason > 7 or PSA >20 ng/mlLocally advanced: cT3 -4 or cN1

NCCN4 2015 High risk: T3a or Gleason 8-10 or PSA >20 ng/mlVery high risk: T3b-T4, primary grade Gleason 5, > 4 biopsies with Gleason 8-10

Joniau5 2015 PSA > 20 ng/ml or cT3–4 or Gleason > 7

cT3 @ 15 years

Ward BJU Int 2005

CSS

cT2

cT3

cT3

pT2

pT3

pN+

ADT: adjuvant: 51% / salvage: 26%RX: adjuvant: 16% / salvage: 15%

Remember: CSSRTOG 92-02 8 years: 90%EORTC 22863: 10 years: 89%RTOG 8531: 10 years: 84%

90% @ 10 years

Even worse: cT4

Base SEER N = 1093. cT4. (Johnstone Cancer 2006)

N = OS (5 years)

RP (± adjuvant / salvage)

72 72.6

RX alone 81 61.8

ADT alone 395 41.5

RX + ADT 257 71.1

Surveillance 278 39.8

Surgery . . . Only if extended

Margins: key objective R0

Margins, Gleason > 7, pN: RFS risk factors Karakiewicz Urology 2005

Margins / pT: only independent risk factors for RFS Budaus J Urol 2010

pN+: Local treatment important

Engel Eur Urol 2010

Multivariate (adjusted for age, pT, G, pN)OS: HR: 2.04 si RP stopped

RP stopped PR done

N = 250 688

T3 44.7% 47.7%

N+ 2-3 44% 32%

N+ ≥ 4 28% 17.2%

Overall survival

pN+: Local treatment important

N = 158 pN+ Steuber BJU Int 2011

50: RP stopped / 108: RP done

ADT adjuvant: 92% / salvage: 8%

Overall Paire comparison (38/arm)

+ PR

- PR

RP in advanced PCa: outcome

Same surgeon Gontero Eur Urol 2007

51 cT3, N0-1 / 152 cT1-2

Other cohort (Ward BJU Int 2005) No real difference cT3 / cT1-2

cT1-2 ≥ cT3 cN0-1

N = 152 51

transfusion 29% 47%

Intensive care unit 0% 6%

Hospital stay 7 d 9 d

Lymphocele 3% 12%

Ureteral injury 0 6%

Bladder neck stenosis 18.5% 27%

Full continence @ 1 year 78% 80%

Severe incontinence @ 1 year

10% 16%

Surgery vs radiotherapy ? ? ? Wallis Eur Urol 2016

Meta-analysis from 95 791 patients

OS CSS

Surgery vs radiotherapy ? ? ?

Major limitations - NO RCT

- comparison as a whole [no stratification] (RX + ADT in intermediate / high risk: standard: never mentioned / specificaly analysed)

- No information on RX template / dose

- Only restrospective data

Retrospective / prospective data

Dugenais. Curr Cardiol Rep 2000

β-carotene and CV mortality

PROTEC ( Hamdy N Engl J med 2016 )

To solve this question . . . . .

But NOT in locally advanced !

BUT SPCG 15

EAU-ESTRO-SIOG guidelines