Abstract Background: Prostate cancer is among the most common causes of cancer-related mortality for males globally. A major challenge lies in distinguishing indolent from potentially fatal disease at the time of diagnosis. Hypertension is associated with an increased risk of developing prostate cancer. However, evidence suggests that antihypertensive medication usage could be associated with better outcomes for patients with prostate cancer. Despite this, the underlying tumour biology of hypertension in patients with prostate cancer has not been characterised. Materials and Methods: We analysed 466 patients with intermediate-to-high risk prostate cancer receiving radiotherapy and androgen deprivation therapy, of whom 248 patients had tumour gene expression profiling. High-risk prostate cancer was defined as Cambridge Prognostic Group (CPG) 4 or 5, or having a Gleason score ≥ 8. Multivariate survival analysis, including age and initial prostate specific antigen levels as covariates, was used to determine the relationship between hypertension status at diagnosis with prostate cancer, prostate cancer risk groups, and metastatic disease. Differential gene expression was performed for hypertension status at diagnosis with prostate cancer and metastatic disease. Immune and stromal cell estimation scores, and Hallmark gene sets, were inferred using patient tumour gene expression profiles. Results and Discussion: Hypertension status at diagnosis with prostate cancer was not associated with metastatic disease. When classifying by Gleason score risk, hypertension had significantly better outcomes for metastatic disease in high-risk patients (HR = 0. 43, p-value = 0. 009), but not in low- and intermediate-risk patients (HR = 1. 86, p-value = 0. 18; p-interaction = 0. 022). However, when classifying by CPG risk, hypertension was not associated with metastatic disease in high-risk patients or low- and intermediate-risk patients. 142 genes were differentially expressed for hypertension status at diagnosis of prostate cancer (p-value 0. 01), of which 4 were also differentially expressed in relation to metastatic disease (p-value 0. 01). Immune and stromal cell type estimation scores and Hallmark gene sets were not differentially expressed for hypertension status at diagnosis of prostate cancer. Conclusion: Hypertension was protective of metastatic disease in patients diagnosed with high-risk prostate cancer, but not in patients diagnosed with low- and intermediate-risk prostate cancer. Our ongoing analysis will aim to validate these findings in separate independent prostate cancer cohorts and to assess whether the observed associations are influenced by antihypertensive medication use prior to diagnosis. Using hypertension as a surrogate for antihypertensive medication usage, our analysis could potentially suggest antihypertensive medication as repurposed, preventative therapeutics for high-risk prostate cancer. Citation Format: Niamh Murphy, Emma Allott, Declan McKenna, Suneil Jain, Ross Murphy. Hypertension is significantly associated with better outcomes in high-risk patients with prostate cancer abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Innovations in Prostate Cancer Research and Treatment; 2026 Jan 20-22; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86 (2Suppl): Abstract nr B049.
Murphy et al. (2026) studied this question.