Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

• Published in: Annals of surgical oncology 2020-10, Vol.27 (11), p.4319-4336
• Main Authors: Hoendervangers, S., Burbach, J. P. M., Lacle, M. M., Koopman, M., van Grevenstein, W. M. U., Intven, M. P. W., Verkooijen, H. M.
• Format: Article
• Language: English
• Subjects: Antineoplastic Combined Chemotherapy Protocols; Bibliographic data bases; Chemoradiotherapy; Chemotherapy; Clinical trials; Colorectal Cancer; Humans; Magnetic resonance imaging; Medicine; Medicine & Public Health; Meta-analysis; Neoadjuvant Therapy; Neoplasm Recurrence, Local - drug therapy; Oncology; Oxaliplatin; Pancreatic Neoplasms; Radiation therapy; Randomized Controlled Trials as Topic; Rectal Neoplasms - drug therapy; Rectal Neoplasms - pathology; Rectum; Surgery; Surgical Oncology; Survival; Systematic review; Toxicity; Treatment Outcome
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-020-08615-2

Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.