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Are associations between obesity and prostate cancer outcomes following radical prostatectomy the same in smokers and non-smokers? Results from the SEARCH Cohort

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Abstract

Purpose

Obesity and smoking have been associated with poor prostate cancer (PC) outcomes. We investigated associations between obesity and biochemical recurrence (BCR), metastasis, castrate resistant-PC (CRPC), PC-specific mortality (PCSM), and all-cause mortality (ACM) and examined if smoking modified these associations.

Methods

We analyzed SEARCH Cohort data from men undergoing RP between 1990 and 2020. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between body mass index (BMI) as a continuous variable and weight status classifications (normal: 18.5 ≤ 25 kg/m2; overweight: 25–29.9 kg/m2; obese: ≥ 30 kg/m2) and PC outcomes.

Results

Among 6,241 men, 1,326 (21%) were normal weight, 2,756 (44%) overweight and 2159 (35%) obese; 1,841 (30%) were never-smokers, 2,768 (44%) former and 1,632 (26%) current-smokers. Among all men, obesity was associated with non-significant increased risk of PCSM, adj-HR = 1.71; 0.98–2.98, P = 0.057, while overweight and obesity were inversely associated with ACM, adj-HR = 0.75; 0.66–0.84, P < 0.001 and adj-HR = 0.86; 0.75–0.99, P = 0.033, respectively. Other associations were null. BCR and ACM were stratified for smoking status given evidence for interactions (P = 0.048 and P = 0.054, respectively). Among current-smokers, overweight was associated with an increase in BCR (adj-HR = 1.30; 1.07–1.60, P = 0.011) and a decrease in ACM (adj-HR = 0.70; 0.58–0.84, P < 0.001). Among never-smokers, BMI (continuous) was associated with an increase in ACM (adj-HR = 1.03; 1.00–1.06, P = 0.033).

Conclusions

While our results are consistent with obesity as a risk factor for PCSM, we present evidence of effect modification by smoking for BCR and ACM highlighting the importance of stratifying by smoking status to better understand associations with body weight.

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Data are available upon request within VA rules and policy requirements.

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Funding

No funding was received to assist with the preparation of this manuscript.

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Authors and Affiliations

  1. Durham VA Healthcare System, Durham, NC, USA

    Ivy T. Liu, Lin Gu, Amanda M. De Hoedt & Stephen J. Freedland

  2. San Francisco VA Medical Center, San Francisco, CA, USA

    Matthew R. Cooperberg

  3. Department of Urology, UCSF Medical Center, San Francisco, CA, USA

    Matthew R. Cooperberg

  4. Department of Urology, Oregon Health and Science University, Portland, OR, USA

    Christopher L. Amling

  5. San Diego VA Healthcare System, San Diego, CA, USA

    Christopher J. Kane

  6. Department of Urology, UC San Diego Health System, San Diego, CA, USA

    Christopher J. Kane

  7. Department of Surgery, Section of Urology, Augusta University—Medical College of Georgia, Augusta, GA, USA

    Zachary Klaassen & Martha K. Terris

  8. Charlie Norwood VA Medical Center, Augusta, GA, USA

    Martha K. Terris

  9. Caribbean VA Healthcare System, San Juan, PR, USA

    Lourdes Guerrios-Rivera

  10. Department of Surgery, University of Puerto Rico, San Juan, PR, USA

    Lourdes Guerrios-Rivera

  11. Department of Biological Sciences, North Carolina State University, Raleigh, NC, USA

    Adriana C. Vidal

  12. West Los Angeles VA Medical Center, Los Angeles, CA, USA

    William J. Aronson

  13. Department of Urology, UCLA Medical Center, Los Angeles, CA, USA

    William J. Aronson

  14. Department of Surgery, Division of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Stephen J. Freedland

  15. Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Ilona Csizmadi

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  1. Ivy T. Liu
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Contributions

ITL contributed to the writing of the original draft, review, and editing. LG contributed to the formal data analysis, interpretation, writing of the original draft, and review. AMH contributed to the data acquisition, writing and review, and project administration of the study. MRC, CLA, CJK, ZK, MKT, LGR, and WJA contributed to the data acquisition of the study. ACV contributed to the conceptualization, writing of the original draft, and review. SJF contributed to the acquisition of data, conceptualization, investigation, interpretation, writing of the original draft, review, and editing. IC contributed to the conceptualization, interpretation, methodology, supervision, writing of the original draft, review, and editing. All authors approved the final manuscript.

Corresponding author

Correspondence to Ivy T. Liu.

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The authors declare no potential conflict of interest that are relevant to the content of this article.

Ethical approval

This study was approved by the Durham VA IRB with waiver of informed consent and was conducted in accordance with recognized ethical guidelines (e.g., Declaration of Helsinki, CIOMS, Belmont Report, U.S. Common Rule).

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Liu, I.T., Gu, L., De Hoedt, A.M. et al. Are associations between obesity and prostate cancer outcomes following radical prostatectomy the same in smokers and non-smokers? Results from the SEARCH Cohort. Cancer Causes Control 34, 983–993 (2023). https://doi.org/10.1007/s10552-023-01747-2

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