Surgical Salvage After Rectal Cancer Recurrence Ups Survival

ORLANDO—One in four patients with resected rectal cancer who later underwent surgical salvage for recurrence at a single site were still alive at 5 years, according to a subanalysis of a large, randomized Intergroup study presented at the 38th Annual Meeting of the American Society of Clinical Oncology (abstract 507). "Approximately 27% of the patients have long-term survival and appear to be cured," said Michael J. O’Connell, MD, director, Allegheny Cancer Center, Allegheny General Hospital, Pittsburgh.

This is believed to be the only study to date to look specifically at the role of surgical salvage after potentially curative surgical resection in a large series of rectal cancer patients. The analysis is based on data from Intergroup 0114, a randomized study of four adjuvant fluorouracil (5-FU)-based chemotherapy regimens combined with radiotherapy following resection of T3, T4, and node-positive rectal cancer. Six cooperative groups enrolled 1,792 patients.

Previously, investigators in INT 0114 reported that, with 8.9 years of follow-up, there were no statistically significant outcome differences between treatment groups. About 42%, or 715 patients, experienced recurrence; another 10% died with no evidence of malignant disease.

More recently, investigators conducted a subset analysis to determine the impact of salvage therapy in the 500 evalu-able patients who had recurrence in a single organ or site (about 71% of the recurrent patients in INT 0114). Most commonly, the recurrence was in the liver, lungs, or tissues around the resection site. Most recurrences were detected by chest x-rays or CT scans (70% to 80%).

Of those 500 patients with a solitary site of recurrence, 171 (34%) underwent further surgery, and of that group, approximately 27% had long-term disease-free survival out to 5 years.

"The flat plateau phase of these curves suggests that 25% to 30% of the patients have been cured," said Dr. O’Connell, who presented the results on behalf of lead investigator Joel E. Tepper, MD.

This substudy illustrates some of the patterns of surgical salvage after primary therapy in North America, Dr. O’Connell said. For example, it shows that a high percentage of patients with rectal cancer present with a solitary site of recurrence and that about one third of these patients receive a surgical procedure with curative intent.

Other findings from the trial include:

n Survival after recurrence was not strongly dependent on whether the site of first recurrence was liver, lung, or local. Long-term disease-free survival remained around 25% for patients grouped according to those recurrence sites. Survival appeared slightly better among patients who had lung or liver metastases, but that difference was not statistically significant. However, survival was lower in patients who had tumor resected from other sites (P < .04).

n Patients with single-site recurrence had better survival than patients with recurrences at multiple sites. Furthermore, 5-year survival was significantly higher for the patients having surgical resection of liver, lung, or local recurrences, compared with those who did not (P = .0001).

n Time to recurrence and initial stage were not prognostic factors in this study.

n The role of additional adjuvant therapy in patients who have a recurrence remains uncertain; 59 patients did receive further treatment, but there was no suggestion that more chemotherapy or radiotherapy affected survival after recurrence. Dr. O’Connell noted that "caution must be exercised with interpretation of these nonrandomized data."

In light of these data, follow-up care after potentially curative therapy for rectal cancer might include imaging studies every 6 months for the first 2 years, then annually for 5 years, Dr. O’Connell said. "The vast majority of these recurrences are within the first 2 years following resection, although there is a continuing lower incidence beyond that period of time," he said. He stressed that this is not an evidence-based recommendation but, rather, his own personal preference.

Elin R. Sigurdson, MD, PhD, surgical oncologist with Fox Chase Cancer Center, said that the findings confirm that there is a role for surgery in the management of metastatic disease. However, she said, it remains "very important" to seek molecular markers that show which patients are at risk for failure.

"Based on the numbers from this study, we are following 1,700 patients aggressively to salvage approximately 40 patients," Dr. Sigurdson said.