Rectal cancer surgery timing after neoadjuvant therapy: balancing downstaging and perioperative outcomes

AIM OF THE STUDY: Neoadjuvant therapy (NAT) and Total Mesorectal Excision (TME) improves oncological outcomes in locally advanced rectal cancer (LARC). We aimed to define the optimal timing for rectal resection and TME after NAT, balancing pathologic Complete Response (pCR) and downstaging with the fewest complications. METHODS: Stage I-III rectal cancer surgery preceded by NAT were retrieved from a retrospective collaborative of 81 centers in Italy 2018-2021. Logistic regression (LR) examined the independent association between postoperative outcomes (pCR, downstaging, intra- and postoperative complications, incomplete resection) and NAT protocols: chemoradiotherapy (nCRT) and short-course radiotherapy (S-CRT) stratified for timing (<8w; 8-12w; >12w) between NAT completion and surgery. RESULTS: Overall, 1428 patients were included: 1042 received nCRT, 187 SCRT, 125 long-course RT, and 74 others. Different timing of nCRT were not associated with any of the outcomes. Time interval >12w for S-CRT was significantly and independently associated with pCR (OR 4.99, 95 %CI 1.4-18), but with similar downstaging, intra- and post-operative complications, and incomplete resection. LR predicting for pCR found a significant association with ASA≥3 (OR 0.67, 95 %CI 0.5-0.9) and with S-CRT <8 weeks (OR 0.31, 95 %CI 0.13-0.74), while no variables were found to be associated with downstaging and intraoperative complications. Postoperative complications were associated with male, ASA≥3, and medium-low rectal cancer, while incomplete resection with ASA≥3, and BMI. CONCLUSION: Unlike previous literature, the timing of nCRT was not associated with pCR, downstaging, intra- and postoperative complications, or incomplete resection. Timing >12 weeks between SCRT completion and TME showed improved pCR with similar downstaging, intra- and post-operative complications, and incomplete resection.