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

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

Oct 25, 2023 364 likes •820 views

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

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SLIDE 1

Alberto BOSSI Dept of Radiation Oncology Node Positive Prostate Cancer:

How to treat men with pN1 Prostate Cancer?

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SLIDE 2

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

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SLIDE 3

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

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SLIDE 4

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

Valerie Fonteyne

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SLIDE 5

Alberto Bossi RT-IGR

  • 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
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SLIDE 6

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

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SLIDE 7

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

Who are those men with a lethal PCa?

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SLIDE 8

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

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SLIDE 9

Between 1998-2016, the rate of pN+ patients increased from 5% to 18%

P < 0.001

34,888 men treated with RP and PLND at 3 tertiary referral centers

Bandini, AUA Meeting, 2018 Courtesy of A Briganti

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SLIDE 10

Bandini et al. AUA Meeting, 2018

EXTENT OF PLND

p<0.0001

STAGE MIGRATION

Low and intermediate risk , from 84.3% to 68.6%, p<0.001 High risk , from 15.7% to 31.4%,p<0.001 to 68.6%, p<0.001

Courtesy of A Briganti

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SLIDE 11

Rates of pN+ in contemporary HIGH RISK patients

Courtesy of A Briganti Bandini, AUA Meeting, 2018

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SLIDE 12

Engel, 2010

1,413

Aborted RP vs. Completed RP 10-year OS: Aborted RP, 28 % Completed RP, 64 %

Steuber, 2011

158

PLND + ADT (n=50) vs. RP-PLND + ADT( n=108) 10-year CSS PLND + ADT, 46 % RP+PLND + ADT, 76 %

Bhindi, 2017

158

PLND + orchiectomy (n=79) vs. RP-PLND + orchiectomy (n=79) 20-year CSS: 18 % vs. 59 % 20-year OS: 9 % vs. 22 %

Rusthoven, 2014

950

NLT (n=657) EBRT (n=293) 10-year OS: NLT, 42 % EBRT, 65 %

Alberto Bossi RT-IGR

Local treatment for pN+ patients

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SLIDE 13

Bandini et al. Eur Urol Focus, 2019

PSA < 50 ng/ml SEER Database, 2004-2014 , pN+ pts 364 pts: aborted RP 3355 pts: completed RP 7 pN+

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SLIDE 14

Briganti, Eur Urol, 2009

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SLIDE 15

Figure 4. Probability of metastasis free survival by number of positive nodes Gray line: One positive node

1 positive node 2 positive nodes 3 positive nodes Biochemical Relapse Free Survival Metastasis Free Survival

Touijer, Eur Urol, 2014

1 positive node 2 positive nodes 3 positive nodes

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SLIDE 16
  • 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

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SLIDE 17

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

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SLIDE 18

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

83 %

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SLIDE 19

Touijer, Eur Urol, 2018

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

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SLIDE 20

Touijer, Eur Urol, 2018

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

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Gupta, BJUI, 2019

8074 NCDB pN+ pts (2004-2013) 4489 obs 2065 ADT only 1520 aRT+ADT

(younger, higher pGS, pStage, R1, nodal burden)

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SLIDE 22

8074 NCDB pN+ pts 4489 obs 2065 ADT only 1520 aRT+ADT

(younger, higher pGS, pStage, R1, nodal burden) Gupta, BJUI, 2019

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SLIDE 23

Abdollah, Eur Urol, 2018

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

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SLIDE 24

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 %

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SLIDE 25

PCa Specific Mortality Risk for pN+ pts

LOW HIGH Briganti, 2011 Abdollah, 2018 Touijer, 2018 Gupta, 2019

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SLIDE 26

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN

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SLIDE 27

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN

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SLIDE 28

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

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SLIDE 29

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN GS = 7-10 > 4 pos LN

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SLIDE 30

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

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SLIDE 31

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

  • bservation / eSalvageRT +/- ADT
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SLIDE 32

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

aRT + ADT

  • bservation / eSalvageRT +/- ADT
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SLIDE 33

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

aRT + ADT

  • bservation / eSalvageRT +/- ADT

ADT / systemic TT

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SLIDE 34

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

aRT + ADT

  • bservation / eSalvageRT +/- ADT

ADT / systemic TT

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SLIDE 35

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

aRT + ADT

  • bservation / eSalvageRT +/- ADT

ADT / systemic TT

seminal vesicles. Discuss three management options with patients with pN+ disease after an extended lymph node dissection, based on nodal involvement characteristics:

  • 1. Offer adjuvant ADT for node-positive (pN+).
  • 2. Offer adjuvant ADT with additional radiotherapy.
  • 3. Offer observation (expectant management) to a patient after eLND and ≤ 2 nodes with

microscopic involvement, and a PSA < 0.1 ng/mL and absence of extranodal extension. Weak Recommendations Strength rating Only discuss adjuvant treatment in men with a post-operative prostate-specific antigen (PSA) < 0.1 ng/mL. Strong ed the ymph

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SLIDE 36

PCa Specific Mortality Risk for pN+ pts

LOW HIGH

GS = 6 < pT3b R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 < pT3a R0 NEG post-RP PSA MAX 2 pos LN GS = 7-10 pT3b – pT4 R1 NEG post-RP PSA 3 - 4 pos LN

< 0.5 % 14 % 75 % 11 %

GS = 7-10 > 4 pos LN

aRT + ADT

  • bservation / eSalvageRT +/- ADT

ADT / systemic TT

? ? ? ?

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SLIDE 37

PART trial : rationale and update

“Elective Para-Aortic Radiation as part of combination Therapy 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
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SLIDE 38

Rigatti Eur Urol 2011 and Rischke et al Strahlenter Onkol 2015

Courtesy of C Berghen

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SLIDE 39

Rigatti Eur Urol 2011 and Rischke et al Strahlenter Onkol 2015

Courtesy of C Berghen

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SLIDE 40

ADT (3 years) DE x 4 cycles

R A N D O M I ZE

Stratification

  • Gleason³ 8
  • PSA>20
  • T3
  • pN+ / pN-

(pelvic LND)

ADT (3 years)

Local treatment at 3 months Local treatment at 3 months

GETUG 12 trial: Design

ADT=Androgen Deprivation therapy, DE= Docetaxel-Estramustine

Courtesy of K Fizazi

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SLIDE 41

Patient population:

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%)

n= 413 patients Accrual: 2002-2006

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SLIDE 42

PRIMARY ENDPOINT: RELAPSE-FREE SURVIVAL (RFS) (233 eventS)

p=0.0109 HR=0.71 [0.55-0.93] p=0.0109

Median RFS: 11.6 [9.1; NR] vs 8.1 [7.3; 9.6] years

49.4% [42.5%; 56.3%] 36.3% [29.7%; 43.5%]

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SLIDE 43

SUBGROUP ANALYSIS OF RFS

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SLIDE 44

conclusions…