ASCO 2009-PATIENTS WITH ADVANCED COLORECTAL CANCER MAY NOT NEED UPFRONT SURGERY

June 1, 2009 (Orlando, Florida) — Most patients with metastatic colorectal cancer can safely avoid surgery on their primary tumors. According to data presented here at the American Society of Clinical Oncology (ASCO) 45th Annual Meeting, patients with asymptomatic surgically incurable colorectal cancer do not need immediate surgery to remove their tumor unless they are having complications.

Primary tumor resection in patients who present with synchronous metastatic colorectal cancer is of uncertain benefit. "But even though there is no proven benefit for survival, such operations are frequently done," said lead author Philip Paty, MD, an attending surgeon and vice chair of clinical research at Memorial Sloan-Kettering Cancer Center in New York City. "The rational is that it prevents future complications, such as bleeding, perforation, or obstruction."

Surgical removal of the primary tumor at the time of diagnosis is still common in patients with metastatic colorectal cancer, but with the advent of new and more effective chemotherapeutic agents, it is unclear whether surgery is still warranted.

In this study, Dr. Paty and colleagues sought to determine the frequency of complications in patients with synchronous stage IV colorectal cancer who received up-front modern combination chemotherapy without prophylactic surgery.

The retrospective study was conducted at Memorial Sloan-Kettering. Using a prospective institutional database, the researchers identified 233 consecutive patients from 2000 to 2006 with synchronous metastatic colorectal cancer and an unresected primary tumor. The patients in this group also received oxaliplatin- or irinotecan-based triple-drug chemotherapy (FOLFOX, IFL, or FOLFIRI) with or without bevacizumab (Avastin) as their initial treatment. Patients who underwent subsequent surgery, radiotherapy, and/or endoluminal stenting to manage primary tumor complications were then identified.

Of 233 patients, the vast majority (217 or 93%) never required surgical palliation of their primary tumor. "Ten patients developed an obstruction but were treated without surgery, [for example, with] a stent or radiation," said Dr. Paty.

Sixteen patients did require emergency surgery for primary tumor obstruction or perforation, and 47 patients eventually underwent an elective colon resection at the time of metastasectomy. An additional 8 patients had an elective colon resection during a laparotomy for hepatic artery infusion-pump placement.

The researchers noted that the use of bevacizumab, the location of the primary tumor in the rectum, and the metastatic disease burden were not associated with an increased rate of intervention. Also, the necessity of emergency intervention did not correlate with overall survival.

"We observed that 93% never required colon surgery to treat complications from the primary tumor," said Dr. Paty.

This is now the routine practice at his institution, he explained, but there is still individualized selection for up-front surgery. "Our study is not revolutionary, in that many surgeons are practicing this policy, but there is just not a lot of published data."

There are 2 important advantages to this practice, said Nicholas Petrelli, MD, who was approached by Medscape Oncology for an independent comment.

"You can start chemotherapy sooner and the patient avoids having to undergo surgery," said Dr. Petrelli, medical director of the Helen F. Graham Cancer Center in Wilmington, Delaware. "I think that Dr. Paty is onto something."

Dr. Petrelli emphasized that more data are needed, and noted that the results of NSABP-C-10, a phase 2 trial designed to evaluate the treatment of this population with chemotherapy rather than up-front therapy to remove the primary tumor, may provide such data.

"We have almost completed patient accrual," said Dr. Petrelli, "and the results of that trial will support whether or not this should become the standard of care."

Dr. Paty and Dr. Petrelli have disclosed no relevant financial relationships. Coauthors Leonard Saltz and Nancy Kemeny report having a consulting/advisory role or receiving research funding from Pfizer, Genentech, Sanofi-Aventis, Bristol Myers, Amgen, and Imclone.

American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract CRA4030. Presented June 1, 2009.