ESMO 2016: Longer Interval Between Preoperative Chemoradiotherapy and Surgery Urged in Locally Advanced Rectal Cancer
A longer waiting interval from the end of preoperative chemoradiotherapy to surgery increases the rate of pathologic complete response and yields a higher proportion of patients achieving tumor downstaging in patients with locally advanced rectal cancer, according to new findings from a prospective, randomized trial presented by Evans et al at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstract 452O).
Greater tumor downstaging and regression could impact the rates of sphincter preservation and achieve improved local control, according to Jessica Evans, MBBS, MRCS, of the Colorectal Surgery Department at the Royal Marsden Hospital NHS Foundation Trust. Dr. Evans and colleagues conducted this prospective, randomized, multicenter trial designed to determine whether a 6- or 12-week interval between neoadjuvant chemoradiotherapy and surgery is optimal in patients with locally advanced rectal cancer to allow greater rectal cancer downstaging and tumor regression.
This study enrolled 237 patients with locally advanced rectal cancer to receive chemoradiotherapy followed by surgery. Following chemoradiotherapy, 122 patients were randomized to a cohort with a planned 6-week interval, and 115 patients were randomized to another cohort with a 12-week interval between chemoradiotherapy and surgery.
12-Week Cohort and Tumor Downstaging
Differences were observed between the two cohorts in the proportion of patients achieving downstaging of their tumors and in the pathologic complete response rates. A greater proportion (58%) of patients in the 12-week interval cohort had tumor downstaging compared with 43% of patients in the 6-week interval cohort (P = .019).
An improved rate of pathologic complete response was also observed with a longer interval; the pathologic complete response rate was 20% in the 12-week vs 9% for the 6-week cohort (P < .05). Additionally, more patients in the 12-week interval cohort achieved magnetic resonance imaging (MRI) tumor regression grade of 1 or 2 (52% in the 12-week arm vs 34% in the 6-week arm; P < .05).
Conclusions
The authors advised that a longer (12-week) interval after chemoradiotherapy prior to surgery results in significantly greater tumor downstaging, improved pathologic complete response rates, and greater MRI tumor regression grade. Since obtaining a pathologic complete response and improved MRI tumor regression grade after the neoadjuvant treatment is an accepted surrogate measure of disease-free survival, undertaking surgery before maximal regression may be disadvantageous in patients with locally advanced rectal cancer. The authors recommend that the adoption of a change in the standard from surgery at 6 to 8 weeks to surgery at 12 to 14 weeks can only be safely undertaken if MRI evaluation of response or progression is still undertaken at 4 to 6 weeks.
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