Follow-up of colorectal cancer patients after resection with curative intent—the GILDA trial

Abstract

Purpose: Surgery remains the primary treatment of colorectal cancer. Data are lacking to delineate the optimal surveillance strategy following resection. A large-scale multi-center European study is underway to address this issue (Gruppo Italiano di Lavoro per la Diagnosi Anticipata—GILDA).

Methods: Following primary surgery with curative intent, stratification, and randomization at GILDA headquarters, colon cancer patients are then assigned to a more intensive or less intensive surveillance regimen. Rectal cancer patients undergoing curative resection are similarly randomized, with their follow-up regimens placing more emphasis on detection of local recurrence. Target recruitment for the study will be 1500 patients to achieve a statistical power of 80% (assuming an alpha of 0.05 and a hazard-rate reduction of >24%).

Results: Since the trial opened in 1998, 985 patients have been randomized from 41 centers as of February 2004. There were 496 patients randomized to the less intensive regimens, and 489 randomized to the more intensive regimens. The mean duration of follow-up is 14 months. 75 relapses (15%) and 32 deaths (7%) had been observed in the two more intensive follow-up arms, while 64 relapses (13%) and 24 deaths (5%) had been observed in the two less intensive arms as of February 2004.

Conclusions: This trial should provide the first evidence based on an adequately powered randomized trial to determine the optimal follow-up strategy for colorectal cancer patients. This trial is open to US centers, and recruitment continues.

Introduction

Colorectal cancer remains one of the leading causes of cancer death in the western world. The American Cancer Society (ACS) estimates the lifetime risk of colorectal cancer to be 1 in 17 for males and 1 in 18 for females. The ACS predicts that 146,940 Americans will develop colorectal cancer in 2004, and that 56,730 will die of the disease. Despite advances in surgical technique and adjuvant therapy, overall 5-year survival rate has only reached 62% [1].

In an effort to improve survival, surgical salvage of colorectal cancer relapse has been attempted. The long-term disease-free survival of some of these patients has led authors to recommend intensive surveillance routines after initial curative surgery in an attempt to identify recurrence at a stage when resection is feasible. Patients with a history of colorectal cancer are also at risk to develop new primary colorectal cancers. The risk of development of such new primary lesions has been estimated to be as high as 0.35% per year [2]. This has prompted many medical societies to recommend increased surveillance, emphasizing endoscopy, to identify these new primary lesions at a curable stage.

Follow-up strategies have evolved without clinical trials to demonstrate effectiveness. As a consequence, there is little consensus on the optimal follow-up of colon and rectal cancer. Even among specialist groups such as the members of the American Society of Colon and Rectal Surgeons (ASCRS) there is little consistency. A survey of the ASCRS members revealed that, among those surgeons who follow their own colon cancer patients, 31% advocate obtaining liver function tests every 3 months during the first post-operative year, while 26% recommend not routinely obtain those tests at all. Follow-up CT scans are recommended twice a year by 10% of surgeons twice in the first year, while 53% would not recommend any routine CT scan. Even the commonly accepted practice of surveillance colonoscopy within the first 12 months after curative resection is not carried out in a uniform manner. While 70% of ASCRS surgeons would perform one colonoscopy within that first year after surgery, 18% would perform colonoscopy at 6 month intervals, and 4% would not schedule any routine endoscopy in the first 12 months [3].

The Mario Negri Institute, which has had experience with a large-scale randomized study of follow-up for breast cancer [4], developed the GILDA trial in an attempt to rationalize colorectal cancer follow-up. This trial, unlike any previously published study on the topic, appears to be able to accrue enough patients to provide adequate statistical power and thereby reach meaningful conclusions about the benefit of such follow-up regimens. This ongoing trial remains interested in recruiting further institutions to enroll patients. The Saint Louis Department of Veterans Affairs Hospital has obtained institutional approval for GILDA, and has enrolled two patients as the first US participating center. Full English language translations of all GILDA protocols, quality of life tests, data sheets and related material are available in either hard copy or electronic format from the authors (e-mail to [email protected]).