Prioritizing Chemotherapy in Total Neoadjuvant Therapy Improves pCR Rate in Locally Advanced Rectal Cancer in Countries with Limited Radiotherapy Access: A Randomized Controlled Trial.

backgroundNeoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer (LARC) is frequently delayed in resource-limited settings due to restricted access to radiotherapy. Total neoadjuvant therapy (TNT), which starts with chemotherapy, may offer a practical alternative. This randomized trial compared TNT with the conventional NCRT‑first approach.

methods202 patients with LARC were randomized to receive either TNT (neoadjuvant chemotherapy followed by NCRT, then surgery) or conventional treatment (NCRT followed by adjuvant chemotherapy and surgery). The primary endpoint was pathological complete response (pCR); treatment-related toxicity and overall survival (OS) were predefined secondary outcomes.

resultsA total of 202 patients with LARC (101 per arm) were enrolled and analyzed. The TNT group achieved a significantly higher pCR rate than the conventional group (55.4% vs. 42.57%, p = 0.023). Sphincter preservation, resection margins, and surgical complications were similar between groups. Among treatment-related toxicities, thrombocytopenia was less frequent in the TNT group (5.0% vs. 12.87%, p = 0.048), whereas dysuria was more common (15.8% vs. 5.94%, p = 0.024); other adverse events were comparable. OS remained an exploratory secondary endpoint and did not differ significantly between groups at the time of analysis (p = 0.109).

conclusionTNT may represent a feasible and well-tolerated treatment strategy, particularly in settings where access to radiotherapy is delayed. The improvement in pCR supports its potential oncologic value; however, survival outcomes remain immature and require confirmation in larger studies with longer follow-up.