PET imaging and radionuclide therapy in neuroendocrine prostate cancer: a systematic review

Neuroendocrine prostate cancer (NEPC) is a rare cancer subtype with significant prognostic implications. This systematic review aims to explore the current landscape of positron emission tomography (PET) imaging and radionuclide therapy in this rare entity.

The Scopus and PubMed online databases were systemically reviewed to identify relevant studies on the topic of interest.

A total of 60 studies reporting such evidence in 102 patients were retrieved. A total of 179 PET/CT examinations were performed across all NEPC patients, with [¹⁸F]Fluorodeoxyglucose ([¹⁸F]FDG) being the most frequently utilized radiotracer (45% of NEPC patients), followed by [⁶⁸Ga]Ga-DOTA-peptides (22%), [⁶⁸Ga]Ga-prostate specific membrane antigen ([⁶⁸Ga]Ga-PSMA) (18%), and other PET tracers (15%). Single-modality PET/CT imaging was mostly employed to evaluate NEPC extent, detect unusual metastatic sites, assess therapy response, and guide for biopsy sites in cases of hormone-secreting NEPC. Multimodal PET/CT utilizing dual- or triple-tracer approaches was employed for collective NEPC interpretation, assessment of heterogeneity, therapy response assessment, and determination of radionuclide therapy eligibly. For treatment, 16 [¹⁷⁷Lu]Lu-DOTATATE cycles, administered to 7 patients, produced effective disease control in all patients. One patient received both [¹⁷⁷Lu]Lu-PSMA and [¹⁷⁷Lu]Lu-DOTATATE, achieving partial response, while another patient receiving 4 [¹⁷⁷Lu]Lu-PSMA cycles also showed a partial response.

The multimodal molecular imaging approach appears to be the most effective for NEPC evaluation and determination of radionuclide therapy eligibility. [¹⁷⁷Lu]Lu-based therapies seem to be a compelling treatment approach to be pursued in eligible cases, although larger studies are needed to confirm the current findings.