SAN FRANCISCO—Colorectal cancer patients who start adjuvant chemotherapy within four weeks of surgery have a significantly lower risk of recurrence compared with patients who initiate chemotherapy eight or 12 weeks after surgery, researchers reported here at the Gastrointestinal Cancers Symposium.
The message was clear, said Richard M. Goldberg, MD, Associate Director of Clinical Research at the University of North Carolina Lineberger Comprehensive Cancer Center, who chaired the session in which the data were presented. “Treat your patient as soon as you can, because outcomes are better with treatment started at four weeks than later.”
Although adjuvant chemotherapy is standard for patients with locally advanced or high-risk colorectal cancer, the importance of treatment timing has not been fully explored.
“Two common clinical assumptions are that chemotherapy should commence as soon as practical after surgical resection, and that chemotherapy offered beyond three months may not provide benefit,” said the study's lead author, James J. Biagi, MD, Associate Professor and Acting Head of Oncology at Queen's University Cancer Research Institute in Ontario.
Because these assumptions are unlikely to be tested in a randomized controlled trial, Dr. Biagi and colleagues performed a systematic literature review and meta-analysis to evaluate the true impact of chemotherapy timing.
Examining both the published literature and abstract presentations, the team identified nine studies that examined the time between surgery and chemotherapy and treatment benefit. Based on a meta-analysis of those data, which included more than 14,000 patients, Dr. Biagi and his colleagues estimated that there was a 15% increased risk of disease recurrence and a 12% increased risk of death at five years for every four weeks of treatment delay, beyond the initial four weeks after surgery.
Modeled a Hypothetical Patient Using Adjuvant! Online
To illustrate the impact of that increased risk, the researchers modeled a hypothetical patient using Adjuvant! Online.
For a 65-year-old male in good general health with T3N2 disease, the estimated five-year overall survival rate would be 45% with no chemotherapy and 60% with fluorouracil-based chemotherapy.
If those estimates were based on receiving chemotherapy at four weeks, then the patient's estimated five-year survival rate would decrease to 55% if chemotherapy started at eight weeks and 50% if it started at 12 weeks.
Looking at this at a population level, Dr Biagi noted that there were 140,000 new cases of colorectal cancer in the United States in 2009. If one assumes that 35% of those cases were Stage III, then 49,000 individuals would be eligible for adjuvant chemotherapy.
If one arbitrarily assumes that half of them are able to start adjuvant chemotherapy four weeks after surgery but instead were delayed to eight weeks, that would put 1,225 lives at risk at five years.
Despite the drop in benefit with increased time between surgery and chemotherapy, there may be some remaining benefit for patients treated after three months, Dr. Biagi said. For example, his hypothetical patient had a 45% overall survival rate with no chemotherapy but a 50% overall survival with chemotherapy starting at 12 weeks.
“This would suggest that there may actually be some benefit to chemotherapy beyond that arbitrary three-month window,” he said.
“Our analysis suggests a significant adverse association between time to adjuvant chemotherapy and survival in colorectal cancer. We believe the level of evidence from our study, with the knowledge that this relationship will not be subjected to prospective assessment, provides sufficient proof of an adverse association. We think, based on these results, that clinicians and jurisdictions should make efforts to optimize logistics that minimize time to adjuvant chemotherapy,” he concluded.
“I think what we see from this study is that we need to start tracking this a little bit better in clinical trials and that control it better,” said the study's Discussant, Johanna Bendell, MD, Associate Director of Drug Development and Director of Gastrointestinal Cancer Research at Sarah Cannon Research Institute. “And we also need to encourage coordinated care within the health care systems.”
The Gastrointestinal Cancers Symposium is cosponsored by the American Society of Clinical Oncology, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.