Safety and efficacy of a sandwich total neoadjuvant therapy strategy for low-risk distal locally advanced rectal cancer: results from the TESS phase II trial

This prospective phase II multicenter study evaluated a novel sandwich total neoadjuvant treatment (TNT) strategy for patients with relatively low-risk distal locally advanced rectal cancer (LARC). The regimen consisted of two cycles of capecitabine and oxaliplatin (CapeOx) administrated before, during, and after radiotherapy, followed by surgery or a watch-and-wait strategy, and two cycles of adjuvant capecitabine chemotherapy. The primary endpoint was the clinical complete response (cCR) rate. All 98 patients completed radiotherapy, and 88.8% received six cycles of neoadjuvant chemotherapy. In the intention-to-treat analysis, 46.9% of patients achieved cCR, 7.1% achieved near-clinical complete response (near-cCR), and 45.9% had non-clinical complete response (non-cCR). In the observed population, the complete response (CR), pathological complete response (pCR), and sphincter-preservation (SP) rates were 61.2%, 46.4%, and 79.6%, respectively. The local regrowth-free survival, local recurrence-free survival, distant metastases-free survival, and overall survival rates were 89.5%, 100%, 92.9%, and 96.9%, respectively. Overall, this sandwich TNT strategy achieved high rates of cCR, pCR, CR, and SP, with favorable survival outcomes and acceptable toxicity, suggesting a promising organ-preserving treatment approach for selected patients with distal LARC. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03840239.