Review of Neoadjuvant Chemotherapy Alone in Locally Advanced Rectal Cancer

Currently, the standard management of locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy followed by resection. Despite the significant improvement in local recurrence, survival benefits are not gained due to distant failure and radiotherapy-associated toxicity. Compliance to adjuvant chemotherapy after preoperative chemoradiotherapy is also poor. Neoadjuvant chemotherapy alone followed by surgery may be an alternative. The objective of this review is to determine the efficacy of neoadjuvant chemotherapy alone in operable LARC.

Electronic databases searched (from database inception-December 2013) were Medline, PubMed, Embase, Scopus, Cochrane library, and the Clinical Trials Register. Specific journals were also hand searched. The selection criteria were studies published in English investigating stage II-III non-metastatic rectal cancer patients treated with neoadjuvant chemotherapy (oral, intravenous or rectal route) followed by curative resection. The primary outcome measure was tumour response. Secondary outcome measures included acute toxicity, operative morbidity, R0 resection, local recurrence, overall survival (OS) and disease-free survival (DFS).

One randomised phase III trial, six single-arm phase II trials and one retrospective case series study were eligible for inclusion. Six studies administered fluoropyrimidine-based multiple agent regimens and two studies administered fluorouracil-based monotherapy. The studies with multiple agents and stronger chemotherapy regimens (intravenous and/or oral) followed by delayed surgery showed better tumour response rates. The overall objective response rate was good and ranged from 62.5 to 93.7 %. Pathological complete response ranged from 3.8 to 33.3 %. The R0 resection and compliance rates were also high ranging from 90 to 100 % and 72 to 100 %, respectively. Grade 3-4 toxicities ranged from 2.3 to 39 %. Four- to 5-year OS and DFS ranged from 67.2 to 91 % and 60.5 to 84 %, respectively.

This review demonstrates that neoadjuvant chemotherapy could be affectively administered in LARC and could provide a good alternative to chemoradiotherapy in moderate-risk rectal cancers without compromising short- and long-term outcomes.