A longer waiting interval from the end of preoperative chemoradiotherapy to surgery increases the rate of pathological complete response (pCR) and yields a higher proportion of patients achieving tumour downstaging in patients with locally advanced rectal cancer, according to new findings from a prospective, randomised trial presented at the ESMO 2016 Congress in Copenhagen, Denmark on 9 October, 2016.
Greater tumour downstaging and regression could impact the rates of sphincter preservation and achieve improved local control according to Jessica Evans, Colorectal Surgery, Royal Marsden Hospital NHS Foundation Trust, London, UK. Dr. Evans and colleagues conducted this prospective, randomised, multicentre trial that was 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 tumour regression.
This study enrolled 237 patients with locally advanced rectal cancer to receive chemoradiotherapy followed by surgery. Following chemoradiotherapy, 122 patients were randomised to a cohort with a planned 6-week interval and 115 patients were randomised to another cohort with a 12-week interval between chemoradiotherapy and surgery.
The majority of patients in the 12-week cohort achieved tumour downstaging
Differences were observed between the two cohorts in the proportion of patients achieving downstaging of their tumours and in the pCR rates. A greater proportion (58%) of patients in 12-week interval cohort had tumour downstaging compared with 43% of patients in the 6-week interval cohort (p = 0.019).
An improved rate of pCR was also observed with a longer interval; the pCR rate was 20% in the 12-week versus 9% for the 6-week cohort (p < 0.05). Additionally, more patients in the 12-week interval cohort achieved magnetic resonance tumour regression grade of 1 or 2 (mrTRG 1-2 rate); the mrTRG 1-2 rate in the 12-week arm was 52% versus 34% in the 6-week arm (p < 0.05).
The authors advised that a longer, 12-week interval, after chemoradiotherapy prior to surgery results in significantly greater tumour downstaging, improved pathological complete response rates, and greater magnetic resonance tumour regression grade. Since obtaining a pathological complete response and mrTRG 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 6-8 weeks to 12-14 weeks can only be safely undertaken if MRI evaluation of response or progression is still undertaken at 4-6 weeks.
Results of a prospective randomised control 6 vs 12 trial: Is greater tumour downstaging observed on post treatment MRI if surgery is delayed to 12-weeks versus 6-weeks after completion of neoadjuvant chemoradiotherapy?
J. Evans, J. Bhoday, B. Sizer, P. Tekkis, R. Swift, R. Perez, D. Tait, G. Brown
This study was funded by the Biomedical Research Centre and Ms Jessica Evans supported by the Royal College of Surgeons of England Research Fellowship.