Review and Updates on Approaches to Neoadjuvant Chemotherapy in Rectal Cancer

Abstract

The currently established standard of care treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant fluorouracil and oxaliplatin. The body of evidence that supports this treatment has grown over the last 20 years. However, recent advances and ongoing studies seek to further evaluate the role of neoadjuvant chemotherapy with and without radiation and total neoadjuvant therapy (TNT). In this article, we review the current literature as well as investigate the emerging role of TNT for patients with LARC and comment on updates utilizing combination neoadjuvant chemotherapy in early-stage rectal cancer. Evidence for the current standard of neoadjuvant CRT comes from well-established randomized phase III trials as well as emerging evidence on merits of TNT. There is a growing body of literature including retrospective analysis and ongoing clinical trials that look at upfront induction chemotherapy in addition to CRT prior to surgical resection leading to more effective delivery of systemic therapy and increases in response to treatment. Neoadjuvant combination chemotherapy is also being investigated in early-stage low rectal tumors to see if rates of local excision will increase compared to radical excision. Current evidence continues to support neoadjuvant CRT as the standard treatment for LARC. There is an increasing body of evidence to support TNT in LARC as an effective treatment strategy that better ensures delivery of systemic therapy leading to higher rates of complete response (CR) and is encouraging for the development of non-operative protocols. There is ongoing evaluation looking at the benefit of novel sensitizers added to neoadjuvant therapy and ongoing investigation into upfront combination chemotherapy with selective use of radiation in upper rectal cancers.