Clival metastases are a rare and clinically aggressive manifestation of advanced prostate cancer, associated with cranial nerve palsy and poor survival. The molecular features of prostate cancers giving rise to clivus metastases remain unknown.
We performed a multi-center retrospective study across six institutions, identifying prostate cancer patients with radiographically confirmed clival metastases and available next-generation sequencing (NGS) data. Baseline characteristics and clinical outcomes were collected. Genomic alterations from tissue- and/or blood-based assays were aggregated at the patient level and compared with a publicly available metastatic castration-resistant prostate cancer (mCRPC) cohort (SU2C/PCF).
Fifty-nine patients with clival metastases contributed 87 molecular assays. More than half of patients had Gleason grade group 5 cancer and presented with de novo metastatic (M1) disease. The median interval from initial prostate cancer diagnosis to clival metastasis was 71.4 months (95%CI 42.0-101.7), while median overall survival following clival involvement was only 15.3 months (95%CI 6.9-22.8). Compared with the SU2C/PCF mCRPC cohort, clival metastases showed significant enrichment of BRAF and CHEK2 alterations, as well as homologous recombination repair (HRR) with relative depletion of AR-related, PI3K pathway, and G2-M pathway alterations.
Prostate cancers giving rise to clival metastases exhibit a distinct molecular profile enriched for DNA damage-repair and RAF kinase alterations, suggesting unique metastatic biology and potential therapeutic vulnerabilities.
The oncologist. 2026 Mar 04 [Epub ahead of print]
Pornlada Likasitwatanakul, Steven M Blinka, Jabra G Zarka, Georges Gebrael, Emily Weg, Ossian Longoria, Joseph A Moore, Adam Sharp, Johann de Bono, Cora N Sternberg, Neeraj Agarwal, Umang Swami, Jacob J Orme, Michael T Schweizer, Lindsey Sloan, Justin H Hwang, Emmanuel S Antonarakis
Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, ; USA., Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, ; USA., Department of Oncology, Mayo Clinic, Rochester, MN, 55905, ; USA., Division of Oncology, University of Utah Huntsman Cancer Institute, Salt Lake City, UH, 84112, ; USA., Department of Medical Oncology, Weill Cornell Medicine and the Englander Institute for Precision Medicine, New York, NY, 10021, USA., The Institute of Cancer Research, London, SM2 5GP, ; United Kingdom., Department of Radiation Oncology, University of Minnesota-Twin Cities, Minneapolis, MN, 55455, ; USA., Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA, 98195, ; USA.