How to deal with patients with isolated peritoneal metastases

Transcription

1 ESMO Preceptorship Programme Colorectal Valencia May 2018 Michel DUCREUX, MD, PhD Gustave Roussy Cancer Centre, Grand Paris, FRANCE How to deal with patients with isolated peritoneal metastases

2 DISCLOSURE SLIDE Participation to advisory boards: ROCHE MERCK SERONO AMGEN NOVARTIS SANOFI BAYER SIRTEX LILLY SERVIER IPSEN Speaker in symposiums: ROCHE MERCK SERONO NOVARTIS IPSEN LILLY AMGEN Research funding: ROCHE MERCK SERONO PFIZER My wife is the Head of The Oncology Business Unit in Sandoz Company (French Affiliate) ESMO PRECEPTORSHIP PROGRAM 2

3 1. Liver metastases and peritoneal carcinomatosis: same fight. 3

4 Liver metastases and peritoneal carcinomatosis: same survival when an aggressive treatement is done 10-year survival 102/612 pts =16.6% 5-year survival 24/148 pts =16.2% 5-year survival 17/107 pts =15.9%

5 Experience of «agressive» treatment of peritoneal metastases and liver metastases: same survival Patients treated with local agressive surgery: 287 pts with Liver Mets 119 pts with PC Median follow-up: 62 months 5y- OS LM 38.5% PC 36.6% 72% 12% 39% 18% Elias et al. Ann Surg 2014

6 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 6

7 Standard treatment with chemotherapy 2095 patients Median survival Patients with carcinomatosis: 12.7 months Patients without carcinomatosis: 17.6 months Franko et al. J Clin Oncol 2012

8 395 exclusive CP (44%) 3 Periodes : : (5FU/FA) : (5FU/FA; oxaliplatin & CPT11) : (5FU/FA; oxaliplatin, CPT11; bevacizumab; cetuximab) Median survival Patients without other distant metastases 12 Months 14 Months 19 Months

9 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 9

10 Progress in diagnosis and staging, Diffuse MRI lesion < 10 mm

11 Interest of diagnosis andstaging with laparoscopic examination

12 Interest of diagnosis andstaging with laparoscopic examination

13 Agressive surgical treatement: Complete resection and HIPEC (together.)

14 First reports of efficacy Cytoreductive surgery: case-control studies Elias et al.(j Clin Oncol 2008) o Cytoreduction + HIPEC vs Modern systemic CT o Limited carcinomatosis o Median survival of 62 vs 24 months Franco et al.(cancer 2010) o Cytoreduction + HIPEC vs Modern systemic CT o Advanced carcinomatosis o Median survival of 35 vs 17 months

15 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 4. Selection of the patients 15

16 Peritoneal Surface Disease Severity Score (PSDSS)

17 Peritoneal Surface Disease Severity Score (PSDSS) American Society of Peritoneal Surface Malignancies patients Ann Surg Oncol 2014

18 French Registry: 504 colorectal patients treated with HIPEC: Survival rates according to the Peritoneal Index (p< ) Elias et al. JCO 2010; 28: 63-68

19 French Registry: 504 colorectal patients treated with HIPEC: Survival rates according to the cytoreduction CC-2 ou 3 CC-0 CC-1 CC-0 Elias D J Clin Oncol 2010

20 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 4. Selection of the patients 5. Role of preoperative chemotherapy 20

21 Role of preoperative chemotherapy Objective response pts Stable 19 Progression 19 Non evaluable 20 Passot G et al. Ann Surg

22 Role of preoperative chemotherapy Pilot study 10 pts non resectable colorectal PC CT-Scan Pet-scan Laparoscopy 4c CAPOX +/- beva CT-scan Petscan Laparoscopie OS : 8.3 ( ) m 7 progression 2 stable 1 exclusion due to extraperitoneal mets Hompes D et al. Colorectal Dis

23 Role of preoperative chemotherapy Hompes D et al. Colorectal Dis

24 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 4. Selection of the patients 5. Role of preoperative chemotherapy 6. Role of postoperative chemotherapy 24

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26 Adjuvant chemotherapy N=523 (23 centres, French Surgical Society Cohort) Aftet HIPEC Elias D et al. J Clin Oncol 2010

27 Adjuvant chemotherapy N=151 CCR carcinomatosis Cashin O et al. Eur J Surg Oncol 2012

28 Adjuvant chemotherapy Adjuvant CT: Prognostic factor Even if Peritoneal Carcinomatosis is not very sensitive to CT Role of targeted therapies??? No clear data Main interest: Control of extraperitoneal disease?

29 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 4. Selection of the patients 5. Role of preoperative chemotherapy 6. Role of postoperative chemotherapy 7. Exact role of HIPEC??? 29

30 Cytoreductive surgery and systemic chmotherapy gives intersting results PFS OS Désolneux G et al plos One DOI: ,

31 Large recent Meta-Analysis 76 studies 15 used in the metaanalysis One randomized 14 non-randomized Question: HIPEC versus Cytoreductiv srugery and systemic CT HR: 2.67 [ ] Huang CQ et al Oncotarget 2017;8:

32 PRODIGE 7 (F Quenet) RANDOMISED FRENCH TRIAL Peritoneal carcinomatosis treated or non treated with systemic CT RANDOMISATION Complete cytoreductive surgery RANDOMISATION HIPEC oxaliplatin No HIPEC Optimal systemic CT for six months

33 1. Liver metastases and peritoneal carcinomatosis: same fight. 2. Role of chemotherapy alone 3. Improvement of surgery, HIPEC 4. Selection of the patients 5. Role of preoperative chemotherapy 6. Role of postoperative chemotherapy 7. Exact role of HIPEC??? 8. A preventive role of HIPEC??? 33

34 Who are High-risk patients? Systematic review of the literature published from High-risk: > 40% - Synchronous PM (resected): 54-75% - Ovarian metastases: 56-62% - Perforated primary tumor: 24-54% No High-risk: < 20% - T4 tumor: 8-17% - Positive cytology: 9-36% - Histologic subtype: 11-36% - Occlusion / Bleeding: < 15% Honoré et al. Ann Surg Oncol 2013; 20:

35 French randomized multicentric trial: Prophylochip (prophylactic HIPEC) High-risk group after first surgery 6 months of IV Folfox (then complete work-up: if no detectable recurrence:) Aim: to increase the 3-year DFS rate from 40% to 65% n= 130 pts Randomization Nothing Surgery, with HIPEC «de principe» (at 8th month)

36 Do not forget to treat the symptoms. Is the patient fit for surgery? Is there a place for stenting? Is it necessary to use a venting nasogastric tube (NGT) in inoperable patients? What drugs are indicated for symptom control? What is the proper route for their administration? When should a venting gastrostomy be considered? What is the role of total parenteral nutrition? What is the role of parenteral hydration?

37 1. Liver metastases and peritoneal carcinomatosis: same fight. yes 2. Role of chemotherapy alone more and more important 3. Improvement of surgery, HIPEC.. congrat 4. Selection of the patients some patients do not benefit from agressive treatment (high PCI) 5. Role of preoperative chemotherapy minor but allow to evaluate the disease 6. Role of postoperative chemotherapy prevent dissemination? 7. Exact role of HIPEC???... We will see at ASCO 8. A preventive role of HIPEC???... We will see at ASCO 9. Do not forget symptomatic treatement 37