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Epidemiology

Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy

British Journal of Cancer volume 129, pages 1988–2002 (2023)Cite this article

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Abstract

Background

Previously suggested modifiable risk factors for prostate cancer could have resulted from detection bias because diagnosis requires a biopsy. We investigated modifiable risk factors for a subsequent cancer diagnosis among men with an initially negative prostate biopsy.

Methods

In total, 10,396 participants of the Health Professionals Follow-up Study with an initial negative prostate biopsy after 1994 were followed for incident prostate cancer until 2017. Potential risk factors were based on previous studies in the general population. Outcomes included localised, advanced, and lethal prostate cancer.

Results

With 1851 prostate cancer cases (168 lethal) diagnosed over 23 years of follow-up, the 20-year risk of any prostate cancer diagnosis was 18.5% (95% CI: 17.7–19.3). Higher BMI and lower alcohol intake tended to be associated with lower rates of localised disease. Coffee, lycopene intake and statin use tended to be associated with lower rates of lethal prostate cancer. Results for other risk factors were less precise but compatible with and of similar direction as for men in the overall cohort.

Conclusions

Risk factors for future prostate cancer among men with a negative biopsy were generally consistent with those for the general population, supporting their validity given reduced detection bias, and could be actionable, if confirmed.

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Fig. 1: Risk (cumulative incidence) of total and lethal prostate cancer among men with negative biopsy in the Health Professionals Follow-up Study, 1994–2017.

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Data availability

Information regarding procedures for obtaining and accessing HPFS data is described at https://www.hsph.harvard.edu/hpfs/for-collaborators/.

Code availability

All code is available in conjunction with the study data.

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Acknowledgements

We thank the participants and staff of the HPFS for their valuable contributions. The authors would like to acknowledge the contribution to this study from central cancer registries supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR) and/or the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program. Central registries may also be supported by state agencies, universities, and cancer centres. Participating central cancer registries include the following: Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Hawaii, Idaho, Indiana, Iowa, Kentucky, Louisiana, Massachusetts, Maine, Maryland, Michigan, Mississippi, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, Seattle SEER Registry, South Carolina, Tennessee, Texas, Utah, Virginia, West Virginia, Wyoming.

Funding

This study was supported by the Zhu Family Center for Global Cancer Prevention and by the US National Cancer Institute (U01 CA167552, R03 CA226942). PLN, KLP, LAM and KHS are Prostate Cancer Foundation Young Investigators. ELG is funded as an American Cancer Society Clinical Research Professor (grant CRP-23-1014041).

Author information

Author notes

  1. These authors contributed equally: Xiaoshuang Feng, Yiwen Zhang.

  2. These authors jointly supervised this work: Lorelei A. Mucci, Konrad H. Stopsack.

Authors and Affiliations

  1. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    Xiaoshuang Feng, Yiwen Zhang, J. Bailey Vaselkiv, Kathryn L. Penney, Edward L. Giovannucci, Lorelei A. Mucci & Konrad H. Stopsack

  2. Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France

    Xiaoshuang Feng

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Ruifeng Li & Edward L. Giovannucci

  4. Department of Radiation Oncology, Brigham and Women’s Hospital/Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    Paul L. Nguyen

  5. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Kathryn L. Penney

  6. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Konrad H. Stopsack

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  1. Xiaoshuang Feng
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Contributions

LAM and KHS conceived the study idea and designed the study. XF, YZ, JBV, RL, ELG, LAM and KHS contributed to the methodology. XF, YZ, JBV and RL contributed to the data extraction. XF, YZ, and RL performed the statistical analysis. XF, YZ, PLN, KLP, ELG, LAM and KHS interpreted the analysis. XF and KHS drafted the manuscript. All authors critically revised the manuscript. LAM and KHS supervised the project. All authors gave final approval for the version to be submitted. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

Corresponding author

Correspondence to Konrad H. Stopsack.

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Competing interests

KLP reports research grants/funding from Janssen. PLN reports research funding from Astellas, Bayer, and Janssen; consulting for Nanocan, Boston Scientific, Bayer, Janssen, Novartis, and Blue Earth; and equity in Nanocan. LAM reports grants/funding from Bayer, AstraZeneca, and Janssen; has provided expert testimony for Bayer. The remaining authors declare no competing interests.

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The study protocol was approved by the institutional review board at the Harvard T.H. Chan School of Public Health, and participating cancer registries, as required.

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Feng, X., Zhang, Y., Vaselkiv, J.B. et al. Modifiable risk factors for subsequent lethal prostate cancer among men with an initially negative prostate biopsy. Br J Cancer 129, 1988–2002 (2023). https://doi.org/10.1038/s41416-023-02472-y

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