Clinical Outcomes of Peptide Receptor Radionuclide Therapy in Japanese Patients with Metastatic Rectal Neuroendocrine Tumors

Background/Purpose: Rectal neuroendocrine tumors (NETs) with distant metastases are uncommon, and evidence supporting the effectiveness of peptide receptor radionuclide therapy (PRRT) in this population remains limited, particularly in Asian cohorts. This study aimed to evaluate the clinical role and real-world outcomes of PRRT in Japanese patients with somatostatin receptor-positive metastatic rectal NETs. Methods: We retrospectively analyzed 20 patients with metastatic rectal NETs who underwent PRRT at the University Hospital Basel (Switzerland) and Yokohama City University Hospital (Japan) between April 2015 and May 2023. The primary endpoint was progression-free survival (PFS), and secondary endpoints included disease control rate (DCR), overall response rate (ORR), overall survival (OS), and adverse events (AEs). Exploratory subgroup analyses were performed according to clinical characteristics, including changes in serum neuron-specific enolase (NSE). Results: The median PFS was 18.9 months (95% CI, 13.5–24.3), and the median OS was 30.3 months (95% CI, 18.9–41.7). The DCR was 80.0%, and the ORR was 15.0%. Treatment responses included partial response in 3 patients, stable disease in 13, progressive disease in 3, and not evaluable in 1. The most common AEs were lymphopenia and anemia, and no secondary malignancies were observed. No clinical factors were significantly associated with PFS; however, higher baseline NSE levels showed a trend toward shorter PFS. Patients with post-treatment declines in NSE showed more favorable treatment responses. Conclusions: PRRT may provide durable disease control with a favorable safety profile in Japanese patients with metastatic rectal NETs. However, these findings should be interpreted with caution given the small sample size and heterogeneous patient population. Baseline NSE elevation and early post-treatment declines may serve as potential prognostic indicators. These results are hypothesis-generating and warrant validation in larger, multicenter studies.