Assessment of Neuroendocrine Features Using 99mTc-Octreotide Scintigraphy in Patients with Metastatic Castration-Resistant Prostate Cancer: Does it Predict Response to 177Lu-PSMA Radioligand Therapy?

PURPOSE: Neuroendocrine differentiation is a recognized phenotypic change in advanced prostate cancer. Neuroendocrine-like cells may lack androgen receptor or prostate-specific membrane antigen expression, potentially contributing to treatment resistance. This study evaluated octreotide scan positivity as a surrogate marker of neuroendocrine differentiation and its association with response to 177Lu-prostate-specific membrane antigen radioligand therapy in patients with metastatic castration-resistant prostate cancer. MATERIALS AND METHODS: Thirty-six patients with metastatic castration-resistant prostate cancer who were candidates for 177Lu-prostate-specific membrane antigen radioligand therapy were enrolled. Whole-body octreotide scintigraphy was performed after intravenous administration of 750 MBq of 99mTc-octreotide. Abnormal uptake was classified as mild, moderate, or severe relative to liver uptake. All patients subsequently received standard 177Lu-prostate-specific membrane antigen radioligand therapy and were followed for treatment response after at least two treatment cycles. RESULTS: Of the 36 enrolled patients, 8 who died within 2 months after the first treatment cycle were excluded from response assessment; therefore, 28 patients were included in the final response analysis. Among these 28 patients, 19 (67.9%) responded to treatment and 9 (32.1%) did not. Eight patients (28.6%) had negative octreotide scans, whereas 20 (71.4%) had positive scans, all showing mild uptake. Positive scans were observed in 13 of 19 responders (68.4%) and 7 of 9 non-responders (77.8%). No significant association was observed between octreotide scan positivity and treatment response (P = 1.00). CONCLUSION: Octreotide scan positivity was relatively common in patients with metastatic castration-resistant prostate cancer but was not significantly associated with response to 177Lu-prostate-specific membrane antigen radioligand therapy. Larger studies are needed to confirm these findings.