Long-course chemoradiation in carcinoma rectum; is it really worth it? Perspectives from a developing nation

Abstract

Introduction: Colorectal cancer is the third most common cancer worldwide by incidence, and second most common cause of cancer‐associated mortality. Total mesorectal excision (TME) with negative margins including a negative CRM is the primary goal to avoid locoregional recurrences and improve survival in carcinoma rectum. Tumour excision may not always be possible in treating locally advanced disease and the likelihood of R1‐2 resection is high. Primary aim of preoperative long‐course chemoradiation is tumour shrinkage and improving R0 resection rate. However, the optimal fractionation in relation to radiotherapy is still controversial. Methods: Between January 2017 and December 2018, histologically proven rectal adenocarcinomas in mid‐lower rectum, with clinical stage II and III planned for an open or laparoscopic abdominal surgery were randomly allocated 1:1 to receive either short‐course radiotherapy (5X5) over one week or long‐course chemo‐radiotherapy (LCRT, 50.4Gy/28 fractions) over six weeks. The patients in the SCRT arm received two cycles of chemotherapy (oxaliplatin 130 mg/m2 D1, capecitabine 1000 mg/m2 BD D1‐D14 every 3 weeks for 2 cycles) followed by surgery at 6‐8 weeks from radiotherapy completion. The patients in the LCRT arm received capecitabine 1650 mg/m2 in two daily divided doses during radiotherapy, followed by surgery at 8‐12 weeks. Patients in both arms were planned for adjuvant chemotherapy. The primary goal was to evaluate whether SCRT is a non‐inferior alternative to LCRT. Results: Ninety patients were recruited in the study; 45 in each arm. The final number of patients in the analysis was 41 patients in the SCRT arm (Mean age 43.95 years617.35, 70.2% males, 29.3% females) and 44 patients in LCRT arm (Mean age 41.52 years617.37, 68.2% males, 31.8% females). Baseline features were similar in terms of histopathological differentiation (most common moderately‐differentiated adenocarcinoma; 46.3% SCRT, 45.5% LCRT, P= .991), staging (most common stage IIIB; 56.1% SCRT, 70.5% LCRT), T stage (most common cT4; 53.6% SCRT, 72.7% LCRT), node positivity (65.9% SCRT, 86.4% LCRT), location of tumour (most in lower rectum; 75.6% SCRT 81.8% LCRT, P= .484). Time to surgery was 44.80 days66.60 in SCRT and 73.02 days612.06 in LCRT. Type of surgery was an anterior resection (51.2% in SCRT, 47.7% in LCRT) or an abdomino‐perineal resection (48.8% SCRT, 52.3% LCRT). CRM positivity was higher in LCRT (6.8 %, 2.4%in SCRT). Pathological complete response was higher in LCRT (11.4%, 2.4% in SCRT). Sphincter preservation rates were similar (51.2% SCRT, 50% LCRT,P=.91). There were no significant differences in downstaging after neoadjuvant therapy (P =.12), type of surgery (P= .75), ypT stage (P= .11), ypNstage (P= .73), yp composite stage (P =.34), sphincter preservation rate (P =.91), pCR (P= .11), CRM positivity (P = .34), R0 resection (P =.34) and tumour downstaging (P= .89). Patient delay during radiotherapy was higher in LCRT(72.7%, zero delay in SCRT, P