Administrating Everolimus against neuroendocrine differentiated prostate cancer, a preliminary experience

Tatsuya Shimomura^1,*, Masaya Murakami^1,2, Kanako Kasai^1,2, Yu Imai^1,2, Yuzo Inaba^1,2, Takahiro Kimura¹
1 Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
2 Department of Urology, Fuji City General Hospital, Fuji, Japan
* Corresponding Author: Tatsuya Shimomura. Email: email

Canadian Journal of Urology https://doi.org/10.32604/cju.2026.076841

Received 27 November 2025; Accepted 20 April 2026; Published online 19 May 2026

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Abstract

Background: Neuroendocrine prostate cancer (NEPC) is a deadly condition, with a median overall survival of less than one year after diagnosis. Although clinical trials are ongoing, an established treatment strategy for NEPC has not yet been developed. A recent clinical trial, RADIANT-4, showed that treatment with everolimus significantly improved survival in patients with progressive neuroendocrine tumors of the lung or gastrointestinal tract. This study evaluated the efficacy of everolimus against neuroendocrine differentiated prostate cancer as an initial investigation. Methods: Five patients with neuroendocrine differentiated prostate cancer were treated with everolimus (10 mg daily). In our study, we examined the responses and changes over time of circulating neuroendocrine tumor markers, including neuron-specific enolase (NSE) and pro-gastrin-releasing peptide (pro-GRP). We also evaluated survival outcomes such as castration-resistant prostate cancer (CRPC)-free survival, overall survival (OS), and cancer-specific survival (CSS). Results: The median follow-up duration was 32 months. A decline in circulating neuroendocrine tumor markers was observed in all cases. The median decline rate of NSE was −0.417, and that of pro-GRP was −0.647 (p = 0.841). The median CRPC-free survival was 10 months (range: 3–NA). Median CSS and OS were both 32 months (range: 8–NA). Grade 3 adverse events (AEs) included hyperglycemia and pneumonitis. Grade 1 AEs included stomatitis (2 cases), paronychia, and pneumonitis. Conclusions: Everolimus demonstrated reductions in circulating neuroendocrine markers in this exploratory cohort of prostate adenocarcinoma with neuroendocrine differentiation; however, these findings are descriptive and do not establish treatment efficacy.