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Clinical and genomic characterization of de novo prostate cancer presenting with PSA ≥100 ng/mL
Abstract   Peer reviewed

Clinical and genomic characterization of de novo prostate cancer presenting with PSA ≥100 ng/mL

Tara Al-Saleem, Ann Tierney, Miles Hsu, Martin W. Schoen, Isla Garraway, Kara N. Maxwell, Heena Desai, Candace Haroldsen, Matthew Rettig, Kyle William Robinson, …
Journal of clinical oncology, v 44(16_suppl), pp e17024-e17024
01 Jun 2026
DOI: https://doi.org/10.1200/JCO.2026.44.16_suppl.e17024

Abstract

e17024Background: In the era of PSA screening for prostate cancer, presentation with PSA ≥100 ng/mL is rare. We sought to identify predictors of PSA ≥100 at diagnosis and to evaluate the prognostic role of tumor genomics in Veterans presenting with PSA ≥100 versus < 100 within the Department of Veterans Affairs (VA), where enrolled Veterans have relatively equal access to care. Methods: We conducted a retrospective cohort study of Veterans with de novo prostate cancer using the merged VA Multi-Omics Analysis Platform for Prostate Cancer and Sequencing (MAPP-SEQ) and Rate Elements Skewing Outcomes Linked to Veteran Equity in Prostate Cancer (RESOLVE PCa) databases. Veterans were included if they were diagnosed from 1999-2004 and staged in the VA Central Cancer Registry. Veterans were stratified by PSA at diagnosis ( < 100 vs ≥100 ng/mL). Among Veterans with available next-generation sequencing (NGS) performed within 6 months of diagnosis, tumors were classified into the Somatic Tumor Risk Assessment for Overall Survival-Prostate (STRATOS-P) genomic system as favorable (SPOP or no other alterations), intermediate (BRCA2, PTEN, CDK12, LYN, MYC, RAD21, CCND1, FGF19, FGF3, FGF4, AR, TP53), or unfavorable (RB1, PRCK1, FGFR1, or TP53+PTEN) gene classes (Table). We also examined metastatic sites at presentation, volume of bone metastases (mets), and sociodemographic variables. Metastatic burden across increasing PSA strata (100-200, 201-500, 501-1000, > 1000 ng/mL) was assessed. Results: A total of 273,097 Veterans with de novo prostate cancer were included, of whom 11,575 (4.4%) presented with PSA ≥100 ng/mL. No sociodemographic, rurality, service-connection, or insurance variables were independently associated with PSA ≥100 at diagnosis. Veterans with PSA ≥100 had a higher likelihood of bone mets and lower overall survival (OS) compared to Veterans with PSA < 100 (Table). In a subset of 3,020 Veterans with volume of metastatic disease data, increasing PSA was associated with higher volume disease. Among 1118 patients with NGS available, tumor gene class provided additional prognostic stratification beyond PSA alone. Unfavorable gene class demonstrated similar OS in both PSA < 100 and PSA ≥100 groups, while favorable gene class in PSA ≥100 remained inferior to PSA < 100 disease (Table). Conclusions: In a nationwide cohort of Veterans with prostate cancer, sociodemographic variables were not associated with PSA > 100 at time of presentation of prostate cancer. However, presentation with PSA ≥100 is associated with higher metastatic burden and inferior survival. Further work is needed to understand how genomic classification may refine prognosis beyond PSA. OutcomePSA <100PSA ≥100Mean OS (mos)44.633.7Bone mets (%)1.760.2Favorable genomics OS (mos)51.536.7Intermediate genomics OS (mos)41.432.1Unfavorable genomics OS (mos)25.526.8

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