How to best treat cN1 prostate cancer? Karim Fizazi Institut - - PowerPoint PPT Presentation

How to best treat cN1 prostate cancer?

Karim Fizazi Institut Gustave Roussy France

Disclosure

Participation to advisory boards/honorarium for: Astellas, AAA, Bayer, Curevac, Janssen, MSD, Orion, Sanofi

Randomized controlled trials in prostate cancer > 100 RCT > 20 RCT ≈ 0 RCT

T3N0 M1 N1

Radiotherapy for cN1? Yes or no?

= localized prostate cancer

T2-4, Nx or N0, M0 T2-3, N0, M0

Non-randomized STAMPEDE data cN1 Relapse-Free Survival by RXT use

STAMPEDE control arm (ADT), 2005-2014 n= 286 pts with cN+ M0 (and n=434 pts with cN0M0)

RXT cN+M0 No RXT James N, JAMA Oncol 2016; 2: 348-57 HR=0.48 (0.29-0.79)

OS=Immature

RXT benefits may extend to cN+ men, although biases may explained better outcome…

RXT planned RXT not planned James N, JAMA Oncol 2016; 2: 348-57

There are also likely biases in the US National database analysis

Seisen T, Eur Urol 2018; 73: 452-61 Local treatment No local treatment n=2967 cN1 pts

Patients in the control arm:

• Were older (p<0.001)
• Had a worse Charlson index (p=0.03)
• Had worse insurance coverage (p<0.001)
• Had a higher PSA (p<0.001)
• Had a higer Gleason score (p>0.001)

Radiotherapy of the primary in oligo-M1 Randomized data from STAMPEDE

Parker C, Lancet 2018

Radiotherapy for cN1? Field side.

= localized

T, N0, M0 (and >15% risk of N+)

Also quite weak evidence to support (or not) lymphadenectomy in cN1

Only n=51 pts with cN+ … Specific survival similar for cN0 and cN1

Moschini M, Eur Urol 2016

Abiraterone in high-risk M0 prostate cancer (STAMPEDE)

• Cohort selection:

Non-metastatic N=915 Metastatic N=1002 N+M0 N=384 N0M0 N=530 Randomised by Jan-2014 N=1,917 No RT N=70 RT N=314 RT N=519

Abiraterone: RFS in M0 subgroup (including cN+): STAMPEDE

ADT +/- Abi James N, ESMO 2017

cN+ ADT cN+ ADT+Abi

Pelvic vs retroperitoneal LN: really different?

PSMA-1007 PET

Giesel et al., Clinical Genitourinary Cancer 2017

a

18F-PSMA PET 18F-PSMA PET/CT

CT CT/LN Segmentation

SUVmax=12.5 SUVmax=14.5 SUVmax=17.9 SUVmax=10.7 SAD=6 mm SAD=5 mm SAD=4 mm SAD=5 mm

b

No Not even talking about PSMA-Pe Pet detected nodes…

Hofman et al BJUI 2018

Patient Selection: untreated, biopsy-proven prostate cancer, being considered for curative intent treatment. § PSA ≥ 20 ng/mL or Gleason Grade Group 3-5 or clinical stage≥T3 Randomisation 1:1

PSMA PET/CT CT + bone scan

Implementation of Final Management 6 months follow-up: repeat imaging Crossover to other arm unless ≥3 distant metastases

Up to 54 months follow-up for PSMA negative patients

• Accuracy

Primary

• Management impact
• Health economics
• Radiation exposure
• Reporter agreement
• Safety

Secondary

Trial Design Objectives

proPSMA | Prospective randomized study of PSMA PET/CT vs conventional imaging

Primary endpoint to be presented EAU 2020

proPSMA will address whether PSMA PET/CT should replace CT+ bone scan for initial staging. It will not tell us how best treat cN1.

Conclusion: cN1

• Insufficient level of evidence
• Need more RCT, next-generation imaging
• Current treatment:

– ADT? Likely yes. Duration? – Local treatment of the primary Yes – Local treatments of nodes? Likely yes – Large fields/PLND? Likely better than small – Abiraterone? If STAMPEDE RFS data translate into clinical endpoint – Docetaxel? More data at ESMO?

Thank you !

APCCC 2019 Basel 29-31 August 2019

www.apccc.org