Prognostic Value of the Largest Lesion Size for Progression-Free Survival in Patients with NET Undergoing Salvage PRRT with [(177)Lu]Lu-DOTATOC

SIMPLE SUMMARY: Peptide receptor radionuclide therapy (PRRT) using radionuclide-labeled somatostatin analogues is based on the overexpression of somatostatin receptors on neuroendocrine tumors and is shown to have a good safety profile and efficacy in different types of metastatic neuroendocrine tumors. As this therapy is usually not curative, most patients experience disease progression after initial PRRT. In these cases, retreatment with PRRT, also called salvage PRRT, can be a treatment option, but little is known about the efficacy and possible risk factors. In this retrospective study that included 32 patients, we found that the size of the largest lesion is a significant predictor of disease progression after salvage PRRT. This risk factor is easy to obtain and can help identify patients who may benefit from intensified follow-up strategies. ABSTRACT: (1) Background: retreatment with radionuclide-labeled somatostatin analogues following disease progression after initial treatment cycles is often referred to as salvage peptide receptor radionuclide therapy (salvage PRRT). Salvage PRRT is shown to have a favorable safety profile in patients with metastatic neuroendocrine tumors (NETs), but numerous questions about the efficacy and prognostic or predictive factors remain to be answered. The purpose of this study was to evaluate two parameters that have shown prognostic significance in progression-free survival (PFS) in initial PRRT treatment, namely the size of the largest lesion (LLS) and the De Ritis ratio (aspartate aminotransferase (AST)/alanine aminotransferase (ALT)), as prognostic factors in the context of salvage PRRT. In addition, the PFS after initial PRRT was evaluated as a predictor of the PFS following salvage PRRT. (2) Methods: retrospective, monocentric analysis in 32 patients with NETs (gastroenteropancreatic, 23; unknown primary, 7; kidney, 1; lung, 1) and progression after initial PRRT undergoing retreatment with [(177)Lu]Lu-DOTATOC. The prognostic values of LLS, the De Ritis ratio, and PFS after initial treatment cycles regarding PFS following salvage PRRT were evaluated with univariable and multivariable Cox regression. PFS was defined as the time from treatment start until tumor progression according to RECIST 1.1 criteria, death from any cause or start of a new treatment due to progression of cancer-related symptoms (namely carcinoid syndrome). (3) Results: progression after salvage PRRT was observed in 29 of 32 patients with median PFS of 10.8 months (95% confidence interval (CI), 8.0–15.9 months). A higher LLS (hazard ratio (HR): 1.03; p = 0.002) and a higher De Ritis ratio (HR: 2.64; p = 0.047) were associated with shorter PFS after salvage PRRT in univariable Cox regression. PFS after initial PRRT was not associated with PFS following salvage PRRT. In multivariable Cox regression, only LLS remained a significant predictor. (4) Conclusions: the size of the largest lesion is easy to obtain and might help identify patients at risk of early disease progression after salvage PRRT. Validation is required.