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Should a History of Extraperitoneal Disease Be a Contraindication to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Metastases?

Baratti, Dario, M.D.1; Kusamura, Shigeki, M.D., Ph.D.1; Iusco, Domenico, M.D., Ph.D.2; Cotsoglou, Christian, M.D.3; Guaglio, Marcello, M.D.1; Battaglia, Luigi, M.D.1; Virzì, Salvatore, M.D.2; Mazzaferro, Vincenzo, M.D., Ph.D.3,4; Deraco, Marcello, M.D.1

doi: 10.1097/DCR.0000000000001156
Original Contributions: Colorectal Cancer
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BACKGROUND: Survival improvements have been reported in selected patients affected by colorectal peritoneal metastases who were undergoing cytoreductive surgery with intraperitoneal hyperthermic chemotherapy. Treatment of peritoneal metastases associated with extraperitoneal disease is still controversial.

OBJECTIVE: We assessed the prognostic impact of a history of extraperitoneal disease that was curatively treated either at the same time as or before the onset of peritoneal metastases.

DESIGN: We reviewed 2 prospective databases. Peritoneal involvement was scored by Peritoneal Cancer Index.

SETTINGS: Our study was conducted in 2 high-volume peritoneal malignancy management institutions.

PATIENTS: A total of 148 patients with peritoneal metastases were included. In 27 patients, extraperitoneal disease involving the liver (n = 23), lung (n = 1), both lung and liver (n = 2), or inguinal lymph nodes and liver (n = 1) was curatively treated either simultaneously with peritoneal metastases (n = 22) or before their onset (n = 5).

INTERVENTIONS: All of the macroscopic tumors were removed by means of peritonectomy procedures and visceral resections. Microscopic residual disease was treated by mitomycin C/cisplatin-based hyperthermic intraperitoneal chemotherapy.

MAIN OUTCOME MEASURES: Overall survival was the primary outcome measure.

RESULTS: After a median follow-up of 34.6 months (95% CI, 22.6–65.7 mo), 5-year survival of patients treated for both peritoneal and extraperitoneal disease versus peritoneal metastases alone was 16.5% versus 52.0% (p = 0.019). After multivariate analysis, reduced survival correlated with extraperitoneal disease (p = 0.001), Peritoneal Cancer Index >19 (p = 0.004), and peritoneal residual disease >2.5 mm (p = 0.018). Three prognostic groups were defined, and median survival was not reached for group 1 (Peritoneal Cancer Index ≤19 and no extraperitoneal disease), reached in 27.0 months for group 2 (Peritoneal Cancer Index ≤9 and extraperitoneal disease), and reached in 11.6 months for group 3 (Peritoneal Cancer Index >19 and no extraperitoneal disease or Peritoneal Cancer Index >9 and extraperitoneal disease).

LIMITATIONS: The main study limitation is its observational nature.

CONCLUSIONS: A history of extraperitoneal disease is associated with poorer prognosis. However, survival benefit may be obtained in selected patients with limited peritoneal involvement. See Video Abstract at

1 Peritoneal Malignancy Program, Istituto Nazionale Tumori, Milan, Italy

2 General Surgery Unit, Bentivoglio Hospital, Azienda Unità Sanitaria Locale di Bologna, Bologna, Italy

3 Gastrointestinal Surgery and Liver Transplantation Unit, Istituto Nazionale Tumori, Milan, Italy

4 Department of Oncology and Onco-Hematology, University of Milan, Milan, Italy

Funding/Support: None reported.

Financial Disclosure: None reported.

Marcello Deraco and Vincenzo Mazzaferro equally contributed to this article.

Presented at the 11th International Symposium on Regional Cancer Therapies, Chandler, AZ, February 13 to 15, 2016.

Correspondence: Dario Baratti, M.D., Istituto Nazionale Tumori, via Giacomo Venezian, 1, 20133 Milano, Italy. E-mail:

© 2018 The American Society of Colon and Rectal Surgeons