Molecular landscape of prostate cancers with clival metastases
Issued Date
2026-04-01
Resource Type
ISSN
10837159
eISSN
1549490X
Scopus ID
2-s2.0-105033170808
Pubmed ID
41782345
Journal Title
Oncologist
Volume
31
Issue
4
Rights Holder(s)
SCOPUS
Bibliographic Citation
Oncologist Vol.31 No.4 (2026)
Suggested Citation
Likasitwatanakul P., Blinka S.M., Zarka J.G., Gebrael G., Weg E., Longoria O., Moore J.A., Sharp A., De Bono J., Sternberg C.N., Agarwal N., Swami U., Orme J.J., Schweizer M.T., Sloan L., Hwang J.H., Antonarakis E.S. Molecular landscape of prostate cancers with clival metastases. Oncologist Vol.31 No.4 (2026). doi:10.1093/oncolo/oyag074 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115937
Title
Molecular landscape of prostate cancers with clival metastases
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Corresponding Author(s)
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Abstract
Background 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. Patients and methods 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). Results 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. Conclusion 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.