Aggressive Surgery and Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer

Abstract & Commentary

Synopsis: Peritoneal carcinomatosis from colorectal carcinoma is considered to be invariably fatal using standard surgical and chemotherapeutic approaches. Five-year disease-free survivals in approximately 25% of highly selected patients treated with aggressive surgery and intraperitoneal chemotherapy previously have been reported. This report from the Gustave Roussy Institute confirms the previous experience. Postoperative mortality was 9% and morbidity was significant, but both can be improved by patient selection. Half of the patients who relapsed did not have detectable disease in the peritoneal cavity. The role for postoperative intraperitoneal and systemic chemotherapy needs to be defined, but it seems unlikely that these results could have been obtained without first obtaining a minimal disease state through surgery. 

Source: Elias D, et al. Cancer. 2001;9:92:71-76.

In a prospective study, patients with peritoneal carcinomatosis (PC) from gastrointestinal primaries were recently documented to have mean survival times of 6.9 months, and this condition has generally been considered to be fatal.1 However, some highly selected patients have been reported to have prolonged (> 5 years) disease-free survivals following aggressive surgical debulking and intraperitoneal chemotherapy (IC).1 In the current report, Elias and colleagues treated 64 patients with PC from colorectal carcinoma from January 1993 to December 1999 on 2 separate protocols. Primary sites were colonic, rectal, and aggressive histology appendiceal tumors (46, 9, and 9 patients, respectively). All patients underwent maximal surgical debulking. Patients with liver or lymph node metastases were included if the malignant disease was grossly totally resected. Patients with lung metastases or disease in the para-aortic lymph nodes were excluded. Patients were entered into the study if complete tumor resection (residual disease < 1 mm) could be accomplished. The first protocol treated 37 patients by following the surgery with immediate intraperitoneal chemotherapy (EPIC) consisting of mitomycin C 10 mg/m2 on postoperative day 1 and 5-fluorouracil 500 mg/m2 on the next 4 days. Each drug remained in the peritoneal cavity for 23 hours and was drained for 1 hour before the next day’s drug was instilled. The second study of 27 patients was a phase I/II trial in which various approaches to maximize the distribution of IC and the addition of hyperthermia were explored. During this study, the doses of mitomycin C were modified and cisplatin was added in 6 patients. Data were collected prospectively and no patients were lost to follow-up. Median follow-up was 51.7 months (range, 8.1-89.3 months).

Surgery was extremely aggressive. The mean number of tumor bearing regions, resected organs, and bowel anastomoses were 7.9, 4.7, and 2.6, respectively. One fifth of the patients had colectomies and the median operating time was 444 minutes (range, 130-780 minutes). Approximately 10% of patients died during the postoperative period, 3 in each study. Four of these patients had large preoperative tumor burdens and 2 had preoperative risk factors (obesity, coagulopathy). Abdominal complications occurred in 45% of patients consisting of fistula formation, development of an abscess and/or the need for reoperation. Extra-abdominal complications occurred in approximately 55% of patients. The mean duration of hospitalization was approximately 4 weeks.

Overall and disease-free 5-year survivals for the entire group of patients were 27% and 18%, respectively. The presence of associated metastases and a large amount of peritoneal disease preoperatively were associated with significantly lower survivals (P = 0.04 and 0.019, respectively). Of the patients who developed tumor recurrence, one half remained tumor-free in the peritoneal cavity.

Comment by Michael J. Hawkins, MD

The use of aggressive surgical and IC techniques for the management of patients with advanced colorectal carcinoma metastatic to the peritoneal cavity continues to be a matter of debate. This study reports a high (10%) postoperative mortality and significant (66%) morbidity associated with this approach. The postoperative complication rate can no doubt be improved with experience and patient selection and the toxicity can be justified for patients with an otherwise terminal diagnosis. However, the toxicity and cost of this approach clearly requires the conduct of clinical trials to demonstrate what, if any, roll it has to play in the management of these very ill patients. All of the patients in these 2 studies were able to undergo excellent surgical reduction of their tumor burden and it seems unlikely that such results could be obtained without initial tumor debulking. It is hard to gauge from this report the degree to which immediate IC contributed to the high complication rate given the extensive nature of the surgeries performed. In addition, half of the patients relapsed only outside of the peritoneal cavity indicating that the role of systemic chemotherapy needs to be evaluated.

Nonetheless, at the present time it is difficult to decide upon a treatment course when one has a patient who is a good surgical risk with a minimal to moderate amount of disease that is limited to the peritoneal cavity that can likely be significantly debulked (debunked—I think). Systemic chemotherapy is clearly only palliative in this situation without surgery.2 Aggressive surgical debulking followed by either systemic chemotherapy alone or the combination of intraperitoneal chemotherapy followed by systemic chemotherapy is a logical choice for these patients and could form the basis for a randomized clinical trial.

References

1. Sadeghi B, et al. Cancer. 2000;88:358-363.

2. Sugarbaker P, et al. World J Surg. 1996;20:585-591.