ArticleThe oncologist2026
Genomic and transcriptomic correlates of deep prostate-specific antigen response in patients with metastatic androgen pathway modulation-sensitive prostate cancer.
Article in The oncologist, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDespite advances in metastatic androgen pathway modulation-sensitive prostate cancer (mAPMS) treatment, outcomes remain heterogeneous. Achieving a post-treatment undetectable prostate-specific antigen (PSA) is a strong prognostic marker. We aimed to identify genomic and transcriptomic determinants of PSA response in a real-world clinical-genomic cohort. PATIENTS AND
methodsPatients with mAPMS who underwent DNA (Tempus xT) and, in a subset, RNA (Tempus xR) sequencing were identified from the Tempus Lens database. Inclusion required stage IV disease within 90 days of sample collection and obtained within 12 months before or 3 months after treatment initiation. Patients with PSA at 6 months (n = 525) were classified as PSA-Low (<0.1 ng/mL, n = 240) or PSA-High (≥0.1 ng/mL, n = 285). Overall survival (OS) was assessed by 6-month landmark analysis with delayed-entry adjustment. Logistic and Cox models were adjusted for clinical variables. Sensitivity analyses used a relative definition of >95% PSA decline from baseline.
resultsBaseline PSA was lower in PSA-Low versus PSA-High patients (24 vs 36 ng/mL, P = .01). SPOP (17% vs 11%) and ZFHX3 (2.5% vs 6%) alterations differed between groups, but neither persisted after adjustment. Using the relative definition, ZMYM3 and JAK1 alterations were independently associated with failure to achieve a deep PSA response. Expression of PSMA, TROP2, B7-H3, and STEAP1 did not differ between groups. PSA-Low status was independently associated with improved OS, as was deep relative response.
conclusionDeep PSA response at 6 months correlates with improved OS in mAPMS. Integrating molecular markers with PSA response may inform treatment intensification or de-escalation strategies.
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