ArticleUrologic oncology2023
Determinants of widespread metastases and of metastatic tropism in patients with prostate cancer: A genomic analysis of primary and metastatic tumors.
Article in Urologic oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 8 citations in OpenAlex.
- Neoadjuvant intraprostatic immunotherapy for high-risk localized prostate cancer.Nature reviews. Urology · 2026Review
- Case - A rare ocular recurrence of prostate cancer Adenocarcinoma metastasis to the vitreous.Canadian Urological Association journal = Journal de l'Association des urologues du Canada · 2026Article
- Review
- Prostate Cancer Liver Metastasis: An Ominous Metastatic Site in Need of Distinct Management Strategies.Journal of clinical medicine · 2024Review
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11 authors at 5 institutions in 1 country.
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Abstract
introductionEmerging evidence suggests that metastasis is better described as a spectrum of disease rather than a binary state. A greater understanding of the genomic features that determine extent and location of metastatic spread may inform risk stratification and monitoring. Here, we identify genomic alterations from primary prostate carcinomas that are predictive of wide-spread metastatic potential.
methodsGenomic and clinical data from 1,312 patients with primary prostate carcinoma were extracted from the MSK-MET cohort through cBioPortal. Metastatic site counts and overall survival (OS) data were publicly available and used as the primary outcomes. Primary tumor samples were profiled using the MSK-IMPACT targeted sequencing platform. We focused on 58 genes frequently altered in prostate cancer. Cox proportional hazard analyses defined hazard ratios (HRs) and 95% confidence intervals (CIs) for overall mortality in patients with different metastatic outcomes.
resultsOut of the 1,312 patients in our cohort, 939 (71%) developed metastases, of whom 113 (8.6%) had metastases to 5 or more distinct anatomical sites (defining wide-spread metastases, WSM). Bone was the most common site of metastasis (36%), and 80% of patients with liver metastases had 4 or more additional sites of metastasis. Among patients with metastasis, increasing number of metastatic sites was associated with increased risk of death (HR: 1.8, 95%CI: 1.63-1.99, P < 0.001). Alterations in the following genes were enriched in tumors from patients with WSM vs. others: TP53 (40% vs. 20%, P < 0.0001), FOXA1-amplification (8% vs. 3%, P = 0.02), AR-amplification (4.4% vs. 1%, P = 0.01), RB1-deletion (5.3% vs. 0.7%, P = 0.001), and BRCA2-deletion (4.4% vs. 0.7%, P = 0.01). Univariable survival analysis showed all these alterations were predictive of OS (P < 0.05). On multivariable analysis, only TP53 mutations, and FOXA1 and AR amplifications were independent prognostic factors. FOXA1 (n = 37) and AR (n = 13) amplifications were mutually exclusive and patients with these experienced very poor OS (HR: 3.57, 95%CI:2.26-5.6, P < 0.001].
conclusionsWe identified genomic alterations (TP53 mutations, FOXA1/AR amplification, RB1/BRCA2 deletion) from primary prostate carcinomas that are predictive of wide-spread metastases and poor outcome.
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