Risk Factors for Regrowth After Nonoperative Management for Rectal Cancer

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.

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).

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).

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.