Cytoreductive Surgery and Intraperitoneal Chemotherapy
Garrett Nash MD, MPH Assistant Attending Surgeon
Memorial Sloan-Kettering Cancer Center September 28th, 2012
Peritoneal Mesothelioma
About me
• Training in Colorectal Surgery and Surgical Oncology
• Peritoneal based diseases
–Appendix Cancer
–Metastatic Colorectal Cancer
–Peritoneal Mesothelioma
Peritoneal Mesothelioma
Peritoneal Mesothelioma
• What is the disease?
• What are the surgical options?
• What are the outcomes after surgery?
Peritoneal Mesothelioma
Peritoneal Mesothelioma
• 2nd most common site of mesothelioma is the peritoneum
– 10-30% of cases of mesothelioma
– 300-400/cases in U.S. year
Peritoneal Mesothelioma
Background • Causes
– Asbestos exposure
– Simian virus-40
– Radiation
– Chronic inflammation of the peritoneum
• Presentation – Increased abdominal girth
– Ascites (fluid in the abdomen)
– Abdominal pain
– Weight loss
Peritoneal Mesothelioma
Treatment Options
• “Traditional”
– Chemotherapy (doxorubicin and cisplatin)
– Radiation
– Drainage of abdominal fluid to alleviate pressure (palliative paracentesis)
– Surgical excision of some of the tumor to alleviate intestinal blockage (palliative debulking)
Peritoneal Mesothelioma
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
Surgical Options
• Cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (IPC)
– Surgical cytoreduction to eliminate visible disease by destroying tumor (burning/peeling/wiping) or removing organs
– Delivery of chemotherapy directly to the peritoneal surfaces to eliminate microscopic disease
Peritoneal Mesothelioma
Intraperitoneal Chemotherapy
• EPIC – Early Postoperative Intraperitoneal Chemotherapy
– Taxol/5FU
• HIPEC – Hyperthermic (heated) Intraperitoneal Chemotherapy
– Cisplatin/Doxorubicin/Mitomycin C
Peritoneal Mesothelioma
Management of Ovarian Cancer
Gynecologic Oncology Group. N Engl J Med. 2006.5;354:34-43.
415 patients with peritoneal metastasis were randomized 1. Intraperitoneal chemotherapy (post operative) 2. Intravenous chemotherapy after cytoreductive surgery
Peritoneal Mesothelioma
Verwaal. J Clin Oncol. 2003;21(20):3737-43.
Management of Colorectal Cancer
Peritoneal Mesothelioma
105 patients with peritoneal metastasis were randomized 1. Intravenous chemotherapy 2. Cytoreductive surgery + intraperitoneal chemo + intravenous
chemo
CRS + IPC + IVC
IVC
• Review of cytoreductive surgery and IPC
• 7 non randomized studies
• 240 patients
Peritoneal Mesothelioma
Inclusion Criteria
• Histological diagnosis of diffuse malignant peritoneal mesothelioma (DMPM)
• Patients undergoing cytoreductive surgery (CRS) + intraperitoneal chemo (IPC)
Exclusion Criteria
• Surgical debulking without IPC
• Studies that mix in other cancer types
Peritoneal Mesothelioma
Annals of Oncology 18:827-834, 2007
Survival after CRS with IPC
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
Survival after CRS with IPC
• Range of average survival by study: 3-7 years
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
• Average length of operation 6-10 hours
• Average hospital length of stay 16 days
• Surgical complication rate 25-40%
• Hematological toxicity 8-26%
• Perioperative mortality 0-8%
Complications and Mortality after Cytoreductive Surgery and IPC
Annals of Oncology 18:827-834, 2007
Peritoneal Mesothelioma
How can we predict prognosis?
• No widely accepted staging system for peritoneal mesothelioma
• No information on National Cancer Institute website (cancer.gov)
Peritoneal Mesothelioma
• 8 institutions prospective collected data
• 294 patients treated with cytoreductive surgery and intraperitoneal chemotherapy
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
• Primary objective: Formulate a staging system through identification of prognostic factors.
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Patient Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Classification of Peritoneal Mesothelioma
• 3 histological subtypes
– Epithelial
– Sarcomatoid
– Mixed/biphasic
Peritoneal Mesothelioma
Epithelial
Sarcomatoid
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Peritoneal cancer index (PCI)
• During surgery • Tumor distribution (13 abdominal pelvic regions) •Tumor nodule size (0-3 points)
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Pathology/Surgery Factors Associated with Survival
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
Optimal Cytoreductive Surgery
Residual visible tumor nodules
• CC0 - none
• CC1 - <2.5mm
• CC2 - 2.5 mm-2.5cm
• CC3 - >2.5cm
Peritoneal Mesothelioma
TNM staging system
• Most common system used for staging cancer
• T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)
Peritoneal Mesothelioma
TNM staging system
• Most common system used for staging cancer • T stage – size or depth of tumor (1-4)
• N stage – presence of lymph nodes with cancer (0-2)
• M stage – presence of metastasis to organs (0- 1)
• For colon cancer
• Stage I = T1/2, N0, M0
• Stage II = T3/4, N0, M0
• Stage III = N1/2, M0
• Stage IV = M1
Peritoneal Mesothelioma
Survival Stratified by T Stage Based on PCI
• T1 = PCI 1-10
• T2 = PCI 11-20
• T3 = PCI 21-30
• T4 = PCI 30-39
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Peritoneal Mesothelioma
Survival Stratified by Nodal Stage
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Survival Stratified by M stage
• M1 = extraabdominal disease (e.g. chest/skin)
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Overall survival stratified by TNM staging system
52 patients
Peritoneal Mesothelioma
T1 N0 M0
T2-3 N0 M0
T4 or N1 or M1
166 patients
76 patients
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Combining TNM Stage with Histology and Optimal Surgery
HR CI
Sarcomatoid vs. epitheloid 5.5 2.9-10.5
Incomplete vs. complete CRS 2.0 1.2-3.2
Stage II vs. I 3.3 1.2-9.4
Stage III vs. I 5.9 2.1-17.2
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Summary
• Appears to stratify patients for prognosis
–Patients who do poorly
• High volume disease
• Extra-abdominal disease
• Non-epitheloid histology
–Patients who do ‘well’
• Low volume disease
• Node negative
– Selected patients undergoing CRS
Peritoneal Mesothelioma
Yan TD, et al. Cancer. 2011 May 1;117(9):1855-63
Conclusions
• Surgery offers good long term outcomes for selected patients with favorable tumors
• Surgery is high risk
• We need comparative studies that demonstrate how much surgery and intraperitoneal chemotherapy may benefit patients
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
• My medical oncology collaborator, Andrea Cercek, MD
Peritoneal Mesothelioma
Thank You
• Mesothelioma Applied Research Foundation and Lee Krug, MD
• My medical oncology collaborator, Andrea Cercek, MD
• The patients who allow us to study their tumors
Peritoneal Mesothelioma