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

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.

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.

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.

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.