Problems of success and problems of failure: recurrent disease after cytoreductive surgery and intraperitoneal chemoperfusion.

Abstract

Peritoneal carcinomatosis is an all-too-frequent mode of dissemination of colorectal carcinoma. Natural history studies have shown that peritoneal carcinomatosis is uniformly fatal, with median survival of approximately 6 months. 1 For more than a decade, a handful of centers have pursued aggressive cytoreductive surgery combined with intraperitoneal chemotherapy for this disease. Several phase II single institution trials showed survival of peritoneal carcinomatosis from colorectal carcinoma well in excess of a year. Although more than doubling the survival time in comparison with historical controls represents a significant accomplishment in this group of patients, the results were treated with a healthy degree of skepticism. Strict selection criteria, variation in intraperitoneal chemotherapy, and the vagueness of what represents “cytoreductive surgery” made many of our colleagues, particularly those in medical oncology, reticent to refer patients for such an aggressive therapy. To bring cytoreductive surgery and intraperitoneal chemotherapy into the mainstream, a randomized trial was sorely needed. Conducting a randomized trial involving patients with peritoneal carcinomatosis is a difficult undertaking. However, investigators from the Netherlands Cancer Institute in Amsterdam succeeded where other institutions had failed. A report on their prospective randomized trial was published in the Journal of Clinical Oncologylast year. 2 In their study, over a 3-year period, 105 patients were randomized to receive “standard treatment” with fluorouracil and leucovorin, with or without palliative surgery, or the same chemotherapy with aggressive cytoreduction and intraperitoneal hyperthermic chemotherapy with mitomycin c. With a mean follow-up of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the cytoreduction and chemoperfusion arm (P .032). Treatment morbidity in this study was similar to that at other centers, and the mortality rate was 8%. Furthermore, an exciting finding of this trial was a Kaplan-Meier estimate of 5-year survival in the range of 20%, which confirmed the results of several of the single-institution phase II trials. 3–5 This study also confirmed the universal finding that the prognosis following cytoreductive surgery and intraperitoneal hyperthermic chemotherapy is closely related to the completeness of the cytoreduction. Critics of this randomized trial could argue with the fact that this study used a fluorouracilbased chemotherapy rather than more active oxaliplatinand irinotecan-based regimens. However, this randomized trial clearly succeeds where the previous phase II trails failed, making cytoreductive surgery and intraperitoneal hyperthermic chemotherapy a standard treatment for selected patients with peritoneal carcinomatosis from colorectal carcinoma.