Neoadjuvant chemotherapy without radiation as a potential alternative treatment for locally advanced rectal cancer: A meta-analysis

Abstract

BACKGROUND Neoadjuvant chemoradiotherapy (Neo-CRT) is the current standard strategy for treating locally advanced rectal cancer. However, it delays the administration of optimal chemotherapy and increases toxicity. AIM To compare the feasibility and efficacy of neoadjuvant chemotherapy (Neo-CT) and Neo-CRT for patients with locally advanced rectal cancer. METHODS The Cochrane, EMBASE, and PubMed databases were searched for relevant articles using MESH terms and free words. The hazard ratio of overall survival and the risk ratio (RR) for the pathological complete response, the sphincter preservation rate, and treatment-related adverse events were analyzed. RESULTS A total of 19 studies of 60870 patients were included in the meta-analysis. There was no significant difference in overall survival [hazard ratio = 1.09, 95% confidence interval (CI) = 0.93–1.24; P = 0.19] or the pathological complete response (RR = 0.79, 95%CI = 0.61–1.03; P = 0.086) between the Neo-CT and Neo-CRT groups. As compared to the Neo-CRT group, the incidences of anastomotic fistula (RR = 0.49, 95%CI = 0.35–0.68; P = 0.000) and temporary colostomy (RR = 0.69, 95%CI = 0.58–0.83; P = 0.000) were significantly lower in the Neo-CT group, with a simultaneous increase in the sphincter preservation rate (RR = 1.07, 95%CI = 1.01–1.13; P = 0.029). However, there was no significant difference in the tumor downstaging rate, overall complications, and urinary complications. CONCLUSION Neo-CT administration can lower the incidences of anastomotic fistula and temporary colostomy and increase the sphincter preservation rate as to compared to Neo-CRT and could provide an alternative to chemoradiotherapy for locally advanced rectal cancer.

GRECCAR 14 – a multicentric, randomized, phase II–III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol

“…neoadjuvant CRT n = 12 135) [23], there were no significant differences between groups in terms of pCR [odds ratio (OR) = 0.62], N downstaging rate (OR = 1.20), R0 resection rate (OR = 1.24) or local relapse rate (OR = 1.12). Another meta-analysis of 60 870 patients in 19 studies [24] found no significant difference in overall survival (p = 0.19) or pCR (p = 0.086) between the NACT and neoadjuvant CRT groups. However, the incidences of anastomotic fistula (p = 0.001) and temporary colostomy (p = 0.001) were significantly lower in the NACT group, with a simultaneous increase in the sphincter preservation rate (p = 0.029).…”

“…The UK National Institute for Health and Care Excellence changed their guidelines on the inescapable role of radiotherapy due to improvements in initial MRI staging and TME standardization [21], similar to the changes in the ASTRO guidelines for tumours with good prognosis [22]. Following this, research has questioned the usefulness of radiotherapy after induction chemotherapy even for LARC [23,24].…”

Effect of Neoadjuvant Therapy on the Functional Outcome of Patients With Rectal Cancer: A Systematic Review and Meta-Analysis

“…When it comes to optimising the neoadjuvant regimen, the FOWARC study showed that the FOLFOX regimen (oxaliplatin þ leucovorin þ fluorouracil) could not only reduce the possible harm brought by radiotherapy but also have a considerable prognosis [81]. The feasibility of replacing neoadjuvant CRT with neoadjuvant chemotherapy was also supported by data and illustrations from Wu et al [82]. Moreover, it is vital to optimise the surgical approach.…”

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

“…Pelvic radiation has traditionally played an essential role in neoadjuvant therapy for locally advanced rectal cancer (LARC) in the past, either as neoadjuvant concurrent chemoradiotherapy (nCCRT) or neoadjuvant short course radiotherapy (nSCRT)[ 1 - 3 ]. However, its efficacy has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials[ 4 - 6 ] and a systematic review[ 7 ]. Consequently, the use of neoadjuvant systemic therapy alone without radiation has emerged as one of the alternatives in contemporary guidelines for patients with certain genetic mutations who achieved a complete clinical response after immunotherapy or patients with a good response (> 20%) after chemotherapy[ 8 ].…”