Pathological Response and Specimen Quality Following Long-Course Chemoradiotherapy for Rectal Cancer with a Six vs. Twelve Week Delay: Data From the STARRCAT Randomised Controlled Trial

Long-course chemoradiotherapy (CRT) is used to down-stage locally-advanced rectal cancer (LARC) prior to resection. An interval period prior to surgery allows for tumour shrinkage to facilitate surgical removal. The optimal time interval remains unclear, with little high-quality evidence to guide clinical decisions about when to operate. This study explores the pathological outcomes from a pilot randomised controlled trial comparing an interval of 6 weeks versus 12 weeks between CRT and surgery. Thirty one patients were recruited from seven UK centres between June 2012 and May 2014. Photographs were taken of the specimens and assessed by a blinded histopathologist for the quality of the mesorectal dissection. Rates of pathological complete response (pCR), down-staging, and circumferential resection margin (CRM) involvement were determined. Response was also assessed using novel tumour cell density (TCD) assessment where the slides from the resected specimen and baseline biopsy were scanned at 400x magnification, the tumour area selected and 285 to 315 data-points analysed by a blinded expert to describe the percentage of different tissue components. The work was partly funded by a PathSoc Career Development Fellowship and is presented on behalf of the STARRCAT Trial Investigators. Twenty three patients underwent surgery (10 from the 6-week arm and 13 from the 12-week arm). The mesorectal fascial plane was intact in 7 specimens from the 6-week arm (70%) and 8 from the 12-week arm (62%). Three patients at 6-weeks and two patients at 12-weeks showed a pCR. Only one patient (from the 12-week arm) had an involved CRM. TCD was 0.3% for the 6-week arm and 4.3% for the 12 week arm (p=0.12). In this small randomised trial, rates of mesorectal quality, CRM status, pCR and TCD were similar following either a 6 or 12 week interval after CRT. Further studies are now needed to clarify whether a longer interval does facilitate on going down-staging.