Predicting Tumor Regrowth in Patients Undergoing Non-Operative Management after Total Neoadjuvant Therapy

Total neoadjuvant treatment (TNT) has become the standard of care for locally advanced rectal cancer (LARC), leading to increased rates of complete clinical response and expanding the potential for organ preservation through non-operative management (NOM) protocols. Despite these advances, tumor regrowth remains a concern, necessitating vigilant surveillance to ensure early detection. However, adherence to surveillance protocols is often suboptimal, and the factors influencing tumor regrowth during NOM have not been well defined. This study aims to identify predictors of tumor regrowth in patients undergoing NOM after TNT.

We conducted a retrospective review of patients with LARC who completed TNT at a single institution between 2019 and 2024. Patients who achieved sustained complete clinical response (cCR) for at least 12 months, as well as those who experienced tumor regrowth following cCR, were included. Patients with suspected regrowth who subsequently underwent surgery and were found to have a pathologic complete response (pCR) were excluded. Univariate analyses were performed to compare demographic, histopathologic, biochemical, clinical, radiological, and treatment-related factors between patients who experienced tumor regrowth and those who did not. The primary objective of our study was to identify predictors of tumor regrowth.

Among 137 patients with LARC, 44 patients (32.1%) achieved cCR following completion of TNT. Of these, 10 patients experienced tumor regrowth and subsequently underwent surgery, with histopathology revealing a pCR in 2 cases. Currently, 11 patients remain in their first year of NOM, and 3 patients were lost to follow-up. In total, 20 patients sustained cCR. A total of 28 patients (25% female) with a mean age of 62.4 years (± 13) were included in the univariate analysis. No statistically significant differences were observed in demographic, histopathologic, biochemical, clinical, radiological, or treatment-related factors between patients who experienced tumor regrowth and those who did not (Table 1).

This study did not identify any predictors of tumor regrowth in patients undergoing NOM after TNT. The limited number of events severely restricted the power to detect statistically meaningful associations. Nevertheless, this area warrants further investigation to better tailor surveillance strategies and optimize NOM recommendations.