Identifying Optimal Neoadjuvant Strategy Based on Pathological Complete Response Rates in Local Advanced Rectal Cancer: A Systematic Review and Network Meta-Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiation therapy (CRT) have an enhanced prognosis Watch and wait is appropriate treatment strategy after patients achieving clinical complete response, but the proportion is small. We aimed to identify optimal neoadjuvant strategy based on pCR rates in LARC by network meta-analysis. <h3>Materials/Methods</h3> This network meta-analysis (NMA), based on phase II and phase III studies, involving patients with LARC, indirectly compared seven strategies including short course radiotherapy (SCRT) + immediate surgery, SCRT + delayed surgery, SCRT + consolidation chemotherapy + surgery, induction chemotherapy + long course chemoradiotherapy (LCCRT) + surgery, LCCRT + consolidation chemotherapy + surgery, LCCRT + delayed surgery and standard neoadjuvant chemoradiotherapy. Studies were identified through PubMed, EMBASE, the Cochrane Library, and abstracts found in ASTRO and ASCO. The primary endpoint pathological complete response (pCR) with odds risk (OR) were pooled according to frequentist network meta-analytical techniques. <h3>Results</h3> Fifteen trials, involving 4424 patients met our eligibility criteria. For LARC patients, the pCR-NMA was based on all 15 trials. In terms of pCR, all other treatments performed significantly better than SCRT + immediate surgery. SCRT + consolidation chemotherapy + surgery, LCCRT + consolidation chemotherapy + surgery, and LCCRT + delayed surgery performed significantly better than SCRT + delayed surgery. SCRT + delayed surgery performed significantly better than SCRT +immediate surgery (OR 0.07, 95% CI 0.01–0.29). SCRT + consolidation chemotherapy + surgery performed significantly better than standard neoadjuvant LCCRT (OR 2.2, 95% CI 1.1–5.0). Interestingly, SCRT + consolidation chemotherapy + surgery had superior trends to the remaining six treatment models. By direct and indirect comparison, we obtained a ranking of the pCR rates achieved by these treatment modalities:SCRT + consolidation chemotherapy + surgery > LCCRT + consolidation chemotherapy + surgery > LCCRT + delayed surgery > induction chemotherapy +LCCRT + surgery > standard neoadjuvant LCCRT > SCRT + delayed surgery > SCRT + immediate surgery. <h3>Conclusion</h3> Evidence from this study suggests that SCRT + consolidation chemotherapy may yield higher pCR rates compared to other treatment modalities in LARC patients at this stage.