Feasibility of treating neuroendocrine prostate cancer with anti-SSTR radioligands: A systematic review of imaging and treatment studies.

PURPOSE: To review clinical evidence on somatostatin receptor (SSTR) targeted imaging and SSTR directed radioligand therapy in neuroendocrine prostate cancer (NEPC).

METHODS

A PRISMA guided search of PubMed, Scopus, and Web of Science was performed on September 14, 2025. Two reviewers screened studies and extracted data. Risk of bias was appraised using Joanna Briggs Institute tools. Synthesis was descriptive.

RESULTS

Of 1937 records, 41 studies were included (4 prospective cohorts and 37 case reports or series). Case reports or series reported 80 patients with SSTR imaging. Cohort studies used 111In based SSTR scintigraphy (three cohorts) or 68Ga-DOTATATE PET/CT (one cohort) and reported SSTR uptake in a minority of patients with heterogeneity across metastatic sites. In patient level reports, SSTR imaging was positive in 61/80 cases (76.3%). Common tracers were 68Ga-DOTATATE (27/80), 68Ga-DOTANOC (17/80), 111In-octreotide or 111In-pentetreotide (14/80), and 18F-AlF-NOTA-octreotide (10/80). PSMA imaging was available in 27 cases; SSTR uptake was present in 11/14 PSMA negative cases. Ten patients in nine reports received SSTR directed PRRT, most often 177Lu-DOTATATE, with symptom benefit and imaging and/or biomarker improvement frequently described; toxicity reporting was limited.

CONCLUSION

SSTR expression in NEPC is heterogeneous. SSTR imaging can support phenotyping and selection for SSTR directed therapy in selected patients, including PSMA low disease, but prospective validation with standardized reporting is needed.