For patients with operable rectal cancer, there is no clear role for adjuvant chemotherapy, according to an analysis of the PROCTOR and SCRIPT trials from the Dutch Colorectal Cancer Group. The findings were presented by Anne J. Breugom, MD, of Leiden University Medical Center in the Netherlands, at the 2013 European Cancer Congress.1
“The role of adjuvant chemotherapy after preoperative radiotherapy or chemoradiation followed by total mesorectal excision surgery is still under discussion,” she said.
A Cochrane review2 showed a significant reduction in the risk of death (17%) among patients undergoing postoperative chemotherapy as compared to the observation arm and a 25% reduction in the risk of disease recurrence. However, many of those trials did not evaluate contemporary strategies, Dr. Breugom pointed out.
“The aim of this study, which includes data from both the PROCTOR study and the SCRIPT study, is to investigate the additional value of postoperative chemotherapy with respect to overall survival and the risk of disease recurrence,” she said.
PROCTOR/SCRIPT was a multicenter randomized trial of 470 patients with stage II or III rectal adenocarcinoma, 238 of whom received adjuvant chemotherapy and 232 underwent observation. Patients included 177 from PROCTOR, randomly assigned to observation or to postoperative chemotherapy (fluorouracil [5-FU]/leucovorin) with or without preoperative radiotherapy followed by total mesorectal excision, and 292 from SCRIPT, randomly assigned to observation or to postoperative chemotherapy (capecitabine) after preoperative radiotherapy or chemoradiation followed by total mesorectal excision.
Approximately three-quarters of the patients had stage III disease, and essentially all had R0 resections. More than 82% had received neoadjuvant radiotherapy, and approximately 13% received chemoradiation. Three-quarters of patients completed their chemotherapy.
Outcomes Similar on All Endpoints
At a median follow-up of 4 years, overall survival was not significantly different between the arms (hazard ratio [HR] = 0.878, P = .527). Five-year overall survival was 74.4% with chemotherapy and 75.9% with observation. Ten-year survival was 65.1% and 55.8%, respectively, but at 10 years, fewer than 15 patients were at risk in either group, she said.
Disease-free survival was also similar (HR = 0.835, P = .247): 67.4% for chemotherapy and 66.1% for observation, at 3 years; 62.0% and 58.4% at 5 years; and 55.6% and 43.5% at 10 years.
There was a hint that tumors ≥ 10 cm may benefit from chemotherapy (HR = 0.552; P = .028), but overall a disease-free survival advantage was lacking, she emphasized.
No Rationale for Adjuvant Chemotherapy
“Currently, there is no indication to administer adjuvant chemotherapy as a standard treatment,” Dr. Breugom concluded.
She acknowledged the study was underpowered, which reflected poor accrual. “If there is an effect after long-term follow-up, this effect will be small,” she predicted.
A meta-analysis is currently in progress that will include the 470 patients of PROCTOR/SCRIPT, the 113 patients from CHRONICLE (who are receiving capecitabine /oxaliplatin), and 634 from an Italian study evaluating adjuvant 5FU/leucovorin).
She added that identification of molecular biomarkers in tumor material from the study’s patients could offer prognostic or predictive information about the benefits of adjuvant chemotherapy in rectal cancer patient subgroups. ■
Disclosure: Dr. Breugom reported no potential conflicts of interest.
1. Breugom AJ, van den Broek CBM, van Gijn W, et al: The value of adjuvant chemotherapy in rectal cancer patients after preoperative radiotherapy or chemoradiation followed by TME-surgery: The PROCTOR/SCRIPT study. 2013 European Cancer Congress. Abstract 1. Presented September 28, 2013.
2. Petersen SH, Harling H, Kirkeby LT, et al: Postoperative adjuvant chemotherapy in rectal cancer operated for cure. Cochrane Database Syst Rev 3:CD004078, 2012.
David Sebag-Montefiore, MD, Professor of Clinical Oncology at the University of Leeds and St. James’s Institute of Oncology in the United Kingdom, was the invited discussant of the PROCTOR/SCRIPT study. He noted that in this 470-patient study, the disease-free and overall survival hazard ratios...