The Impact of Atorvastatin on Intraprostatic Biomarkers – Prognostic Value of 3LS-score – Follow-up of ESTO1-Trial

IF 4.8 2区医学 Q1 Biochemistry, Genetics and Molecular Biology

Neoplasia Pub Date : 2025-02-06 DOI:10.1016/j.neo.2025.101132

Eemil Lehtonen , Maiju Vertanen , Heimo Syvälä , Teemu Tolonen , Seppo Auriola , Teuvo Tammela , Aino Siltari , Teemu Murtola

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引用次数: 0

Abstract

Background

Prostate cancer (PCa) remains a global health burden, with limited reliable biomarkers beyond prostate-specific antigen (PSA). Statins have been associated with survival benefits in advanced Pca, potentially by modulating cholesterol metabolism and tumor biology. However, the causal mechanisms are not well understood. A distinct three-lipid signature (3LS) has previously been proposed as a prognostic biomarker for PCa.

Objective

This study investigates the effects of atorvastatin intervention on PCa tissue markers, long-term clinical outcomes, and the prognostic value of the 3LS derived from prostate tissue lipidome.

Methods

The ESTO1 trial randomized 158 statin-naïve PCa patients to receive high-dose atorvastatin (80 mg daily) or placebo before prostatectomy. Long term outcomes were assessed for 102 patients through medical records review. Prostate tissue samples were pathologically characterized, and lipidome quantified. Cox regression models were used to analyse clinical outcomes between the groups. The 3LS score was calculated by identifying the constituent lipids from the prostate lipidome.

Findings

Higher intraprostatic atorvastatin lactone concentrations were associated with reduced Ki67 expression and PSA levels. After a median follow-up of seven years, no significant differences were observed in biochemical recurrence, overall mortality, or initiation of hormonal therapy. However, the atorvastatin arm had a lower risk of major acute cardiovascular events (HR 0.11, 95% CI 0.01–1.01). The intraprostatic 3LS correlated with higher baseline tumor aggressiveness but did not predict subsequent outcomes.

Conclusion

Higher atorvastatin lactone concentrations in the prostate tissue were linked to improved pathological variables. Pre-surgery statin intervention reduced MACE risk but no impact on other clinical outcomes was observed. The 3LS from prostate tissue does not seem to be prognostic marker in localized Pca.

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来源期刊

Neoplasia 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

26 days

期刊介绍： Neoplasia publishes the results of novel investigations in all areas of oncology research. The title Neoplasia was chosen to convey the journal’s breadth, which encompasses the traditional disciplines of cancer research as well as emerging fields and interdisciplinary investigations. Neoplasia is interested in studies describing new molecular and genetic findings relating to the neoplastic phenotype and in laboratory and clinical studies demonstrating creative applications of advances in the basic sciences to risk assessment, prognostic indications, detection, diagnosis, and treatment. In addition to regular Research Reports, Neoplasia also publishes Reviews and Meeting Reports. Neoplasia is committed to ensuring a thorough, fair, and rapid review and publication schedule to further its mission of serving both the scientific and clinical communities by disseminating important data and ideas in cancer research.