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Metabolic syndrome and its pharmacologic treatment are associated with the time to castration-resistant prostate cancer

Abstract

Background

Metabolic syndrome and its pharmacologic treatment can potentially influence the progression of prostate cancer in men receiving androgen deprivation therapy (ADT). We aimed to evaluate the association between metabolic syndrome and its pharmacologic treatment with time to castration-resistant prostate cancer (CRPC).

Methods

We identified 409 men with metastatic castration-sensitive prostate cancer receiving first line ADT from 1996 to 2014 at our institution. Information concerning metabolic syndrome, statin use, aspirin use, and metformin use at initiation of ADT was collected from medical records. Time to CRPC was defined as the duration between initiating ADT and diagnosis of CRPC based on the Prostate Cancer Working Group 3 definition. Flexible parametric survival models were used to calculate hazard ratios (HR, and 95% confidence intervals, CI) of the association between metabolic conditions and time from ADT initiation to CRPC.

Results

During a median follow-up of 59 months, 87% (N = 356) men progressed to CRPC. Median time to CRPC was 19 months. Fifty-six percent of men met the definition of metabolic syndrome. Controlling for demographic and prostate cancer-specific variables, metabolic syndrome was associated with shorter time to CRPC (HR 1.41, 95% CI 1.09–1.81). Importantly, in men with metabolic syndrome, statin use was associated with a slower progression to CRPC (HR 0.70, 95% CI 0.49–0.98).

Conclusions

Our study suggests that metabolic syndrome is a risk factor for earlier progression from castration-sensitive to castration-resistant prostate cancer and raises the possibility that treatment, such as statin use, may slow the time to progression.

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Fig. 1: Cumulative incidence of CRPC by metabolic syndrome.
Fig. 2: Cumulative incidence of CRPC by metabolic syndrome and statin use.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Dr. Sweeney for critical review of the manuscript, Junaid Nabi and Grace Shaw for administrative assistance.

Funding

JHG was supported by a scholarship from Kaohsiung Municipal Siaogang Hospital. ASK is supported by the DiNovi Family Foundation. AP is supported by William Casey and the Swedish Society for Medical Research. LAM and KLP are supported by the Prostate Cancer Foundation.

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Contributions

Conception and design JHG, KLP, ASK, LAM; acquisition of data MP, JHG; analysis and interpretation of data All authors; drafting of the manuscript All authors; critical revision of the manuscript for important intellectual content All authors; statistical analysis JHG, AP; obtaining funding ASK; administrative, technical, or material support ASK; supervision LAM, ASK. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Jiun-Hung Geng.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki. The study was approved by the institutional IRB (Protocol No: 2018P002714). All participants provided written informed consent.

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Geng, JH., Plym, A., Penney, K.L. et al. Metabolic syndrome and its pharmacologic treatment are associated with the time to castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 25, 320–326 (2022). https://doi.org/10.1038/s41391-022-00494-w

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