How to treat men with pN1 Prostate Cancer? Alberto BOSSI Dept of - PowerPoint PPT Presentation

Node Positive Prostate Cancer: How to treat men with pN1 Prostate Cancer? Alberto BOSSI Dept of Radiation Oncology

Research Support Ipsen, Janssen, Sanofi Employee Gustave Roussy, Villejuif, France Consultant Astellas, Bard, Elekta, Ipsen Major Stockholder --------- Speakers Bureau Astellas, BMS, Ferring, Sanofi Honoraria Astellas, Ipsen, Janssen, Ferring, Sanofi Scientific Advisory Board Astellas, Ipsen, Ferring

! ! T O N S I + N p … … T O H S I O G I L O

! ! T O N S I + N p … … T O H S I O G I L O Valerie Fonteyne

- pN+ PCa patients: an increasing, important problem - the local treatment - not all pN+ PCa patients are created equal - what are we doing and what should we do - the final picture Alberto Bossi RT-IGR

Jemal A, et al. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.

Who are those men with a lethal PCa? Jemal A, et al. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.

Who are those men with a lethal PCa? - Metastatic PCa - Lymph node positive PCa - High-risk localized PCa Locally advanced PCa Jemal A, et al. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.

34,888 men treated with RP and PLND at 3 Between 1998-2016, the rate of pN+ tertiary referral centers patients increased from 5% to 18% Bandini, AUA Meeting, 2018 P < 0.001 Courtesy of A Briganti

STAGE MIGRATION EXTENT OF PLND Low and intermediate risk , from 84.3% to 68.6%, p<0.001 p<0.0001 High risk , from 15.7% to 31.4%,p<0.001 to 68.6%, p<0.001 Bandini et al. AUA Meeting, 2018 Courtesy of A Briganti

Rates of pN+ in contemporary HIGH RISK patients Bandini, AUA Meeting, 2018 Courtesy of A Briganti

Local treatment for pN+ patients 10-year OS: Aborted RP vs. Engel, 2010 1,413 Aborted RP, 28 % Completed RP Completed RP, 64 % 10-year CSS PLND + ADT (n=50) vs. Steuber, 2011 158 PLND + ADT, 46 % RP-PLND + ADT( n=108) RP+PLND + ADT, 76 % PLND + orchiectomy (n=79) vs. 20-year CSS: 18 % vs. 59 % Bhindi, 2017 158 RP-PLND + orchiectomy (n=79) 20-year OS: 9 % vs. 22 % 10-year OS: NLT (n=657) Rusthoven, 2014 950 NLT, 42 % EBRT (n=293) EBRT, 65 % Alberto Bossi RT-IGR

SEER Database, 2004-2014 , pN+ pts 364 pts: aborted RP 3355 pts: completed RP PSA < 50 ng/ml 7 pN+ Bandini et al. Eur Urol Focus, 2019

Briganti, Eur Urol, 2009

Figure 4. Probability of metastasis free survival by number of positive nodes 2 positive nodes 1 positive node 1 positive node 3 positive nodes 2 positive nodes 3 positive nodes Biochemical Relapse Free Survival Metastasis Free Survival Gray line: One positive node Touijer, Eur Urol, 2014

- pT stage, pGS, R status - lymph node “density” - extra-nodal extension - size of the largest pN+ - site of pN+ (iliac vs obt. vs para-rectal) - expression of PD-L1 - … Boorjian 2007, Passoni 2014, Luchini 2017, Touijer 2018, Petiprez 2019

National Cancer Database Analysis Moon et al, Clinical Genito-urinary Cancer, 2017

83 % National Cancer Database Analysis Moon et al, Clinical Genito-urinary Cancer, 2017

OS CSS 1388 pN+ pts ( 3M, 1988-2010) 387 obs 676 ADT only ( lifelong ADT) 325 aRT+ADT (higher pGS, pStage, R1, 6 ys ADT) Touijer, Eur Urol, 2018

OS CSS 1388 pN+ pts 387 obs 676 ADT only ( lifelong ADT) 325 aRT+ADT (higher pGS, pStage, R1, 6 ys ADT) Touijer, Eur Urol, 2018

8074 NCDB pN+ pts (2004-2013) 4489 obs 2065 ADT only (younger, higher pGS, pStage, 1520 aRT+ADT R1, nodal burden) Gupta, BJUI, 2019

8074 NCDB pN+ pts 4489 obs 2065 ADT only (younger, higher pGS, pStage, 1520 aRT+ADT R1, nodal burden) Gupta, BJUI, 2019

5498 NCDB pN+ pts (2004-2015) 3200 ADT only 2298 aRT+ADT number of pN+ pGS pT stage surgical margins Abdollah, Eur Urol, 2018

5498 NCDB pN+ pts (2004-2015) 3200 ADT only 2298 aRT+ADT number of pN+ pGS pT stage surgical margins 75 % Abdollah, Eur Urol, 2018

PCa Specific Mortality Risk for pN+ pts LOW HIGH Briganti, 2011 Abdollah, 2018 Touijer, 2018 Gupta, 2019

PCa Specific Mortality Risk for pN+ pts LOW HIGH GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN

PCa Specific Mortality Risk for pN+ pts LOW HIGH GS = 6 GS = 7-10 < pT3b < pT3a R0 R0 NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN

PCa Specific Mortality Risk for pN+ pts LOW HIGH GS = 6 GS = 7-10 GS = 7-10 < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN

PCa Specific Mortality Risk for pN+ pts LOW HIGH GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN observation / eSalvageRT +/- ADT

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN observation / eSalvageRT +/- ADT aRT + ADT

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN observation / eSalvageRT +/- ADT aRT + ADT ADT / systemic TT

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN observation / eSalvageRT +/- ADT aRT + ADT ADT / systemic TT

PCa Specific Mortality Risk for pN+ pts Strength rating Recommendations seminal vesicles. LOW HIGH Only discuss adjuvant treatment in men with a post-operative prostate-specific antigen (PSA) Strong Discuss three management options with patients with pN+ disease after an extended lymph Weak < 0.1 ng/mL. node dissection, based on nodal involvement characteristics: < 0.5 % 14 % 75 % 11 % 1. Offer adjuvant ADT for node-positive (pN+). GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 2. Offer adjuvant ADT with additional radiotherapy. > 4 pos LN < pT3b < pT3a pT3b – pT4 ed R0 R0 R1 the 3. Offer observation (expectant management) to a patient after eLND and ≤ 2 nodes with NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA microscopic involvement, and a PSA < 0.1 ng/mL and absence of extranodal extension. MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN ymph observation / eSalvageRT +/- ADT aRT + ADT ADT / systemic TT

PCa Specific Mortality Risk for pN+ pts LOW HIGH < 0.5 % 14 % 75 % 11 % GS = 7-10 GS = 6 GS = 7-10 GS = 7-10 > 4 pos LN < pT3b < pT3a pT3b – pT4 R0 R0 R1 NEG post-RP PSA NEG post-RP PSA NEG post-RP PSA MAX 2 pos LN MAX 2 pos LN 3 - 4 pos LN ? ? ? ? observation / eSalvageRT +/- ADT aRT + ADT ADT / systemic TT

PART trial : rationale and update “Elective P ara- A ortic R adiation as part of combination T herapy in prostate cancer patients with positive pelvic lymph nodes: a new step to improve clinical relapse-free survival” Prospective, non-randomised phase 2 trial C. Berghen, S. Joniau, G. De Meerleer, UZ Leuven, Belgium

Courtesy of C Berghen Rigatti Eur Urol 2011 and Rischke et al Strahlenter Onkol 2015

Courtesy of C Berghen Rigatti Eur Urol 2011 and Rischke et al Strahlenter Onkol 2015

GETUG 12 trial: Design Courtesy of K Fizazi R A ADT (3 years) N Stratification Local DE D - Gleason ³ 8 treatment x 4 cycles at 3 months O - PSA>20 M - T3 I ADT (3 years) - pN+ / pN- ZE Local (pelvic LND) treatment at 3 months ADT=Androgen Deprivation therapy, DE= Docetaxel-Estramustine

Patient population: n= 413 patients Accrual: 2002-2006 ADT + DE ADT n=207 n=206 Median age (y) 63 (47- 77) 64 (47-77) T3-T4 139 (67%) 139 (67%) Gleason ≥ 8 87 (42%) 88 (43%) PSA > 20 ng/mL 123 (59%) 121 (59%) pN+ 59 (29%) 60 (29%)

PRIMARY ENDPOINT: RELAPSE-FREE SURVIVAL (RFS) (233 event S ) Median RFS: 11.6 [9.1; NR] vs 8.1 [7.3; 9.6] years p=0.0109 49.4% [42.5%; 56.3%] HR=0.71 [0.55-0.93] 36.3% [29.7%; 43.5%] p=0.0109

SUBGROUP ANALYSIS OF RFS

conclusions…