Background: Among patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy and undergo nonoperative management (NOM), a subset experience tumor regrowth and require salvage surgery. We sought to identify clinicopathologic factors associated with tumor regrowth to assist in patient selection for NOM.
Methods: Patients treated for rectal cancer at a single National Cancer Institute (NCI)-designated Comprehensive Cancer Center in whom NOM was pursued based on cCR or near-cCR were identified. Patients were stratified based on whether they developed tumor regrowth during follow-up. Tumor and treatment details were compared to identify factors affecting regrowth-free survival (RFS).
Results: Among 125 patients, 26 (20.8%) experienced local regrowth and 8 (6.4%) experienced distant metastasis at a median follow-up of 35 months. Extramural vascular invasion (EMVI) and clinically positive pelvic sidewall lymph nodes (PSW) were associated with worse RFS (hazard ratio [HR] 2.48, 95% confidence interval [CI] 1.08-5.72, p = 0.03; HR 2.77, 95% CI 1.16-6.61, p = 0.002). Among 107 patients eligible for post hoc endoscopic evaluation, those with cCR (n = 80) at first endoscopic re-evaluation had trended towards higher RFS than those with near-cCR (n = 27; HR 2.12, 95% CI 0.95-4.75, p = 0.07), with a significant difference in patients without regrowth at 1 year (HR 5.58, 95% CI 1.23-25.32, p = 0.03).
Conclusions: Rectal cancer patients with high-risk magnetic resonance imaging (MRI) features, namely EMVI and positive PSW nodes, are more likely to experience tumor regrowth despite an excellent clinical response. Patients with a near-complete endoscopic response may also be at higher risk of later regrowth. The decision to attempt NOM should be carefully weighed against the increased risk of tumor regrowth.
Keywords: Neoadjuvant therapy; Nonoperative management; Rectal cancer; Regrowth; Watch and wait.
© 2025. Society of Surgical Oncology.