Randomized controlled trial of 8 weeks’ vs 12 weeks’ interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer

Abstract

Aim The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks’ interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. Method This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3‐4N0M0, TxN+M0) rectal cancer were randomized into 8‐ and 12‐week interval groups. All the patients received long‐course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5‐fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end‐point was pCR. Secondary end‐points were sphincter preservation, postoperative morbidity and mortality. Results Two‐hundred and fifty‐two patients (n = 125 in the 8‐week group, n = 127 in the 12‐week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8‐week group and 23.6% (n = 30) in the 12‐week group (P = 0.021). Sphincter‐preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12‐week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). Conclusion Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2‐fold increase in pCR rate without any difference in mortality and morbidity.

How to measure tumour response in rectal cancer? An explanation of discrepancies and suggestions for improvement

“…When comparing 7 versus 11 weeks interval, there was no difference in complete response rates, tumour stage or TRG in a French study including 265 rectal cancer patients [31]. In two Turkish randomised trials [30,32] including a total number of 657 patients, comparing classic intervals (between 6 and 8 weeks) with prolonged intervals (10 weeks and 12 weeks respectively) there was an increase in pathological complete response and downstaging, but not in TRG.…”

“…Unfortunately, there is a huge variation in timing within and between different studies, which makes comparisons very difficult. Moreover, results from randomised clinical trials focussing on this interval are conflicting [30][31][32]. When comparing 7 versus 11 weeks interval, there was no difference in complete response rates, tumour stage or TRG in a French study including 265 rectal cancer patients [31].…”

Machine Learning for Predicting Pathological Complete Response in Patients with Locally Advanced Rectal Cancer after Neoadjuvant Chemoradiotherapy

“…Two randomized trials by Akgun et al [32] and Terzi et al [33] have demonstrated that pCR rates are higher for long intervals (> 8 weeks) than for short intervals, although both intervals have exhibited similar rates in postoperative mortality and morbidity. However, the GRECCAR-6 trial revealed no significant difference between long (11 week) and short intervals (7 weeks) with respect to pCR occurrence, although greater complications and difficulties in surgery were observed for participants with an 11-week interval [34].…”

Adjuvant Chemotherapy in Elderly Colorectal Cancer Patients

“…This approach (scRT and CAPOX followed by surgery) can be considered a new reference treatment in high-risk rectal cancer. Neo-adjuvant chemotherapy has been added as one treatment option in recent guidelines [124] and is used increasingly, especially to facilitate organ preservation after both conventional CRT and short-course RT [125][126][127][128][129].…”