In a 5-year follow-up of the phase II OPRA trial reported in the Journal of Clinical Oncology, Verheij et al found that many patients receiving total neoadjuvant therapy for rectal adenocarcinoma remained free of the need for total mesorectal excision.
Study Details
In the U.S. multicenter trial, 324 patients with stage II/III rectal cancer were randomly assigned to receive total neoadjuvant therapy with induction chemotherapy followed by chemoradiation (n = 158) or chemoradiation followed by consolidation chemotherapy (n =166).
Patients achieving complete or near-complete response were offered a watch-and-wait strategy. Total mesorectal excision was recommended for those with an incomplete response. The primary endpoint was disease-free survival, and the secondary endpoint was total mesorectal excision–free survival.
Key Findings
Median follow-up was 5.1 years. The 5-year disease-free survival rates were 71% (95% confidence interval [CI] = 64%–79%) in the induction chemotherapy/chemoradiation group and 69% (95% CI = 62%–77%) in the chemoradiation/consolidation chemotherapy group (P = .68).
In restaging at 8 weeks after total neoadjuvant therapy, total mesorectal excision was recommended for 28% of the induction chemotherapy/chemoradiation group and 24% of the chemoradiation/consolidation chemotherapy group. Among patients who were put on a watch-and-wait approach, regrowth occurred in 44% of the induction chemotherapy/chemoradiation group and 29% of the chemoradiation/consolidation chemotherapy group. Overall, 5-year total mesorectal excision–free survival was 39% (95% CI = 32%–48%) in the induction chemotherapy/chemoradiation group and 54% (95% CI = 46%–62%) in the chemoradiation/consolidation chemotherapy group (P = .012).
Among 81 patients with regrowth, regrowth occurred in 94% within 2 years and in 99% within 3 years. Disease-free survival at 5 years was similar among patients who underwent total mesorectal excision after restaging (64%, 95% CI = 53%–78%) and those on a watch-and-wait plan who underwent total mesorectal excision after regrowth (64%, 95% CI = 53%–78%; P = .94).
The investigators concluded: “Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter [a watch-and-wait phase], most cases of tumor regrowth occur in the first 2 years.”
Julio Garcia-Aguilar, MD, PhD, of the Colorectal Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
