For adults whose stage T3 or greater rectal cancer shows a pathological complete response to neoadjuvant chemoradiation and resection, perioperative adjuvant therapy was associated with significantly improved outcomes, according to the results of two observational cohort studies of the National Cancer Database.
In the first study, Fahima Dossa, MD, of the University of Toronto, and her associates compared 667 patients with T1 to 2N+ or T3 to 4N0/+ rectal adenocarcinoma who received adjuvant chemotherapy with 667 patients who did not. They used propensity-score matching to account for measurable differences between groups that might influence the receipt of adjuvant treatment. They also conducted a subgroup analysis to determine if treatment effects depended on whether patients initially had node-positive disease.
After a median follow-up of 3.1 years (interquartile range, 1.9-4.4 years), adjuvant therapy was associated with significantly improved overall survival (hazard ratio, 0.44; 95% confidence interval, 0.28-0.70), Dr. Dossa and her coinvestigators said. However, the effect was limited to patients with pretreatment, node-positive disease (HR, 0.24; 95% CI, 0.10-0.58).
“Although this study suggests a beneficial effect of adjuvant treatment on survival in patients with pathologic[al] complete response, these results are limited by the presence of potential unmeasured confounding in this nonrandomized study,” Dr. Dossa and her associates wrote in JAMA Oncology. A pathological complete response signifies a good prognosis in locally advanced rectal cancer, and any additional survival benefit from adjuvant chemotherapy has to be weighed against the risk of chemotoxicity, they stressed. (In their study, 5-year overall survival rates were 95% in the adjuvant group and 88% in the observation-only group).
In the second study, Patricio M. Polanco, MD, of the University of Texas, Dallas, and his associates also used propensity-score matching to compare 741 patients with clinical TNM stages T1 to 2N+ or T3 to 4N0/+ rectal adenocarcinoma who received adjuvant chemotherapy with 741 patients who underwent observation only. Once again, after a median follow-up of 3.2 years, adjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.50; 95% CI, 0.32-0.79). Estimated 5-year overall survival rates were 95% and 88%, respectively (P = .05). Subgroup analyses showed that adjuvant chemotherapy had the strongest apparent effect in the setting of stage T3/T4 and node-positive disease.
Current U.S. guidelines recommend treating stage T3 or higher or node-positive rectal cancer with neoadjuvant chemoradiation therapy plus 6 months of perioperative chemotherapy. Each of these studies attempted to address the lack of evidence clearly supporting adjuvant chemotherapy for these patients, the researchers noted.
Dr. Fossa and her associates reported no specific funders or conflicts of interests. Dr. Polanco disclosed support from the VA North Texas New Investigator Program, Department of Veterans Affairs. He and his associates reported no conflicts of interest.
SOURCES: Dossa F et al. JAMA Oncol. 2018 Apr 19. doi: 10.1001/jamaoncol.2017.5597; Polanco PM et al. JAMA Oncol. 2018 Apr 19. doi: 10.1001/jamaoncol.2018.0231.