Neoadjuvant short-course radiotherapy with consolidation chemotherapy for locally advanced rectal cancer: a systematic review and meta-analysis

Background: Short-course radiotherapy with consolidation chemotherapy (SCRT-CCT) has emerged as a promising alternative to the long course chemoradiotherapy (LCRT) regimen in locally advanced rectal cancer management. The systematic review and meta-analysis is aimed at summarizing current evidence on SCRT-CCT and comparing it to LCRT. Material and methods: Electronic databases of MEDLINE, Web of Science, and Cochrane library were searched using a predefined search strategy returning 3314 articles. This review included 11 studies (6 randomized trials and 5 non-randomized studies) on SCRT-CCT regimen based on seven different cohorts. Weighted arithmetic means and forest plots were generated to determine summary estimates. Results: The probability of achieving pathological complete response (pCR) was higher with SCRT-CCT compared to LCRT (risk ratio [RR] = 1.75, 95% confidence interval [CI]: 1.41–2.19). No statistically significant difference in 3-year overall survival (OS) was observed between the two groups (RR= 1.06, 95% CI: 0.98–1.14). The weighted arithmetic mean of 3-year OS and pCR was 83.6% versus 80.9%, and 24.5% versus 13.6% for SCRT-CCT and LCRT, respectively. R0 resection and T-downstaging rates ranged from 69.2–100% to 47–75% for SCRT-CCT, and 71–92.3% and 41–75% for LCRT, respectively. The regimens had similar compliance, postoperative, and late toxicity, however, acute toxicity rates varied primarily due to differences in treatment protocols. Conclusions: This review highlights the ability of SCRT-CCT to produce improved tumor response with comparable OS, R0 resection, and T-downstaging at the cost of increased acute toxicity. However, heterogeneity in treatment protocols across studies makes it difficult to provide definitive conclusions regarding the regimen. Several ongoing trials are expected to provide further evidence confirming the findings of RAPIDO trial and detail appropriate SCRT-CCT protocols to improve oncological outcomes, minimize toxicity, and determine its effectiveness as the standard-of-care for locally advanced rectal cancer patients.