Patient selection for PRRT rechallenge in neuroendocrine tumors: impact of initial response duration on outcomes

Abstract Background Patient selection for rechallenge peptide receptor radionuclide therapy (re-PRRT) in neuroendocrine tumors (NET) remains poorly defined. As re-PRRT is increasingly considered in clinical practice, identifying patients most likely to benefit has become a critical yet unresolved question. This study evaluated the efficacy and safety of re-PRRT and aimed to identify pragmatic factors associated with retreatment benefit. Materials and methods This retrospective study included 37 patients with neuroendocrine tumors (NET). Kaplan–Meier estimates were used to evaluate progression-free survival (PFS) following initial (i-PRRT) and re-PRRT. Baseline laboratory parameters were compared between treatment courses, and SSTR-targeted PET metrics (SUV mean , SUV max , and SSTR-positive tumor volume) were assessed at baseline and follow-up. Univariable Cox regression identified prognostic factors for PFS. Adverse events were graded according to CTCAE v5.0. Results Median PFS was 32 months after i-PRRT and 17 months after re-PRRT, with disease progression observed in 20/37 patients. Longer PFS following initial therapy was associated with improved outcome after retreatment (per month, HR 0.96, 95% CI 0.93–0.999; p < 0.05). In an exploratory analysis, patients with an initial PFS exceeding 24 months demonstrated a longer median PFS after re-PRRT than those with shorter initial PFS (19 vs. 4 months; log-rank p = 0.02). Higher baseline CRP was significantly associated with shorter PFS after i-PRRT (per mg/dl, HR 8.8, 95% CI 1.2–58.6; p < 0.05), whereas no such association was observed for re-PRRT (per mg/dl, HR 0.79, 95% CI 0.13–3.8; p = 0.8). Instead, higher baseline LDH was significantly associated with shorter PFS following re-PRRT (per U/l, HR 1.007, 95% CI 1.000–1.014; p < 0.05). No PET-derived baseline parameter correlated with PFS. RECIST indicated predominantly stable disease across treatment courses, although responses were less favorable at retreatment. No grade ≥ 3 toxicities were observed during re-PRRT. Conclusion Re-PRRT represents a feasible treatment option for selected NET patients. Duration of disease control following initial PRRT was associated with outcome after re-PRRT and may represent a clinically relevant marker for patient selection. The exploratory 24-month threshold requires prospective validation before clinical implementation.