Omission of Chemoradiation in Locally Advanced Rectal Adenocarcinoma: Evaluation of PROSPECT in a National Database

J Surg Oncol. 2024 Sep 30. doi: 10.1002/jso.27839. Online ahead of print.

Abstract

Background and objectives: The PROSPECT trial showed noninferiority of neoadjuvant chemotherapy (NAC) with selective chemoradiation (CRT) versus CRT alone. However, trial results are often difficult to reproduce with real-world data. Pathologic outcomes and overall survival (OS) were evaluated by neoadjuvant strategy in locally advanced rectal adenocarcinoma patients in a national database.

Methods: The 2012-2020 National Cancer Database was queried for clinical T2N1 and T3N0-1 rectal adenocarcinoma patients with definitive resection. Patients were categorized by neoadjuvant treatment with CRT alone, NAC alone, and NAC with CRT. Outcomes included R0 resection, pathologic complete response (PCR), and OS.

Results: Of 18 892 patients, 16 126 (85.4%) received CRT, 1018 (5.4%) NAC, and 1748 (9.3%) NAC with CRT. Patients with NAC alone or NAC with CRT were more likely to have stage-III disease, private insurance, and academic facility treatment (all p < 0.001). NAC alone had lower adjusted odds of an R0 resection (OR 0.72; 95%CI 0.54-0.95) and PCR (OR 0.77; 95%CI 0.64-0.93). NAC with CRT demonstrated improved OS (HR 0.71; 95%CI 0.61-0.82), with no difference between NAC and CRT alone. Among patients who received adjuvant chemotherapy, no differences in OS were seen.

Conclusions: Patients who received NAC alone had worse pathologic outcomes. NAC had similar OS to CRT and NAC with CRT showed improved OS.

Keywords: chemoradiation; locally advanced rectal adenocarcinoma; neoadjuvant therapy; overall survival; pathologic complete response.