Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Clinical Research
  • Published:

The obesity paradox in metastatic castration-resistant prostate cancer

Prostate Cancer and Prostatic Diseases volume 25, pages 472–478 (2022)Cite this article

Subjects

Abstract

Objective

To test whether body mass index (BMI) amongst patients with metastatic castration-resistant prostate cancer (mCRPC) is associated with overall survival (OS) and cancer-specific survival.

Methods

Individual patient data from 1577 men with mCRPC treated with docetaxel and prednisone from the control arms of ASCENT2, VENICE, and MAINSAIL were considered. The role of BMI on survival outcomes was investigated both as a continuous and categorical variable (≤24.9 vs. 25–29.9 vs. ≥30 km/m2). BMI ≥ 30 kg/m2 was considered obese. Analyses were adjusted for age, PSA, ECOG performance status, number of metastases and prior treatment. The Cox semi-proportional hazard model was used to predict OS, whereas competing risks regression was used for predicting cancer-specific mortality (CSM). To exclude any possible effect attributable to higher doses of chemotherapy (titrated according to body-surface area), we checked for eventual interactions between BMI and chemotherapy dose (both as continuous-continuous and categorical-continuous interactions).

Results

The median (IQR) age for the patient population was 69 (63,74) years with a median (IQR) BMI of 28 (25–31) kg/m2. Median follow-up for survivors was 12 months. Of the 1577 patients included, 655 were deceased by the end of the studies. Regarding OS, BMI emerged as a protective factor both as a continuous variable (HR: 0.96; 95% CI: 0.94, 0.99; p = 0.015) and as a categorical variable (obesity: HR: 0.71, 95% CI: 0.53, 0.96; p = 0.027, relatively to normal weight). The protective effect of high BMI on CSM was confirmed both as a continuous (SHR: 0.94; 95% CI: 0.91, 0.98; p = 0.002) and as a categorical variable (obesity SHR: 0.65; 95% CI: 0.45, 0.93; p = 0.018). No interaction was detected between the BMI categories and the docetaxel dose at any level in our analyses (all p » 0.05).

Conclusions

Obese patients with mCRPC had better cancer-specific and overall survival as compared to overweight and normal weight patients. The protective effect of BMI was not related to receiving higher chemotherapy doses. Further studies aimed at elucidating the biological mechanism behind this effect are warranted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Kaplan–Meier survivor functions according to body mass index categories.
Fig. 2: Cumulative incidence functions for cancer-specific mortality according to body mass index categories.

Similar content being viewed by others

References

  1. Organization WH. Obesity https://www.who.int/topics/obesity/en/.

  2. Steele CB, Thomas CC, Henley SJ, Massetti GM, Galuska DA, Agurs-Collins T, et al. Vital Signs: trends in Incidence of Cancers Associated with Overweight and Obesity - United States, 2005-2014. MMWR Morb Mortal Wkly Rep. 2017;66:1052–8.

    Article  Google Scholar 

  3. Armstrong AJ, Halabi S, de Wit R, Tannock IF, Eisenberger M. The relationship of body mass index and serum testosterone with disease outcomes in men with castration-resistant metastatic prostate cancer. Prostate Cancer Prostatic Dis. 2009;12:88–93.

    Article  CAS  Google Scholar 

  4. Cushen SJ, Power DG, Murphy KP, McDermott R, Griffin BT, Lim M, et al. Impact of body composition parameters on clinical outcomes in patients with metastatic castrate-resistant prostate cancer treated with docetaxel. Clin Nutr ESPEN. 2016;13:e39–e45.

    Article  Google Scholar 

  5. Halabi S, Small EJ, Vogelzang NJ. Elevated Body Mass Index Predicts for Longer Overall Survival Duration in Men With Metastatic Hormone-Refractory Prostate Cancer. J Clin Oncol. 2005;23:2434–5.

    Article  Google Scholar 

  6. Park JM, Nam JS, Na W, Oh JJ, Lee S, Hong SK, et al. Prognostic value of body mass index in korean patients with castration-resistant prostate cancer. Korean J Urol. 2012;53:761–5.

    Article  Google Scholar 

  7. Vidal AC, Howard LE, de Hoedt A, Kane CJ, Terris MK, Aronson WJ, et al. Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int. 2018;122:76–82.

    Article  Google Scholar 

  8. Wu W, Liu X, Chaftari P, Cruz Carreras MT, Gonzalez C, Viets-Upchurch J, et al. Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: a retrospective review. PLoS One. 2015;10:e0122047.

    Article  Google Scholar 

  9. Freedland SJ, Wen J, Wuerstle M, Shah A, Lai D, Moalej B, et al. Obesity is a significant risk factor for prostate cancer at the time of biopsy. Urology. 2008;72:1102–5.

    Article  Google Scholar 

  10. Freedland SJ, Aronson WJ. Examining the relationship between obesity and prostate cancer. Rev Urol. 2004;6:73–81.

    PubMed  PubMed Central  Google Scholar 

  11. Vidal AC, Howard LE, Sun SX, Cooperberg MR, Kane CJ, Aronson WJ, et al. Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Prostate Cancer Prostatic Dis. 2017;20:72–8.

    Article  CAS  Google Scholar 

  12. Halabi S, Ou S-S, Vogelzang NJ, Small EJ. Inverse correlation between body mass index and clinical outcomes in men with advanced castration–recurrent prostate cancer. Cancer. 2007;110:1478–84.

    Article  Google Scholar 

  13. Lee JS, Lee HS, Ha JS, Han KS, Rha KH, Hong SJ, et al. Subcutaneous Fat Distribution is a Prognostic Biomarker for Men with Castration Resistant Prostate Cancer. J Urol. 2018;200:114–20.

    Article  Google Scholar 

  14. Scher HI, Jia X, Chi K, de Wit R, Berry WR, Albers P, et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011;29:2191–8.

    Article  CAS  Google Scholar 

  15. Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Flechon A, Skoneczna I, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013;14:760–8.

    Article  CAS  Google Scholar 

  16. Petrylak DP, Vogelzang NJ, Budnik N, Wiechno PJ, Sternberg CN, Doner K, et al. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2015;16:417–25.

    Article  CAS  Google Scholar 

  17. LLC PDS. Project Data Sphere https://www.projectdatasphere.org/projectdatasphere/html/home.

  18. Albiges L, Hakimi AA, Xie W, McKay RR, Simantov R, Lin X, et al. Body Mass Index and Metastatic Renal Cell Carcinoma: clinical and Biological Correlations. J Clin Oncol. 2016;34:3655–63.

    Article  CAS  Google Scholar 

  19. McQuade JL, Daniel CR, Hess KR, Mak C, Wang DY, Rai RR, et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncol. 2018;19:310–22.

    Article  Google Scholar 

  20. Nguyen PL, Ma J, Chavarro JE, Freedman ML, Lis R, Fedele G, et al. Fatty acid synthase polymorphisms, tumor expression, body mass index, prostate cancer risk, and survival. J Clin Oncol. 2010;28:3958–64.

    Article  CAS  Google Scholar 

  21. Donnelly D, Bajaj S, Yu J, Hsu M, Balar A, Pavlick A, et al. The complex relationship between body mass index and response to immune checkpoint inhibition in metastatic melanoma patients. J Immunother Cancer. 2019;7:222.

    Article  Google Scholar 

  22. Wang Z, Aguilar EG, Luna JI, Dunai C, Khuat LT, Le CT, et al. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat Med. 2019;25:141–51.

    Article  CAS  Google Scholar 

  23. Desmedt C, Fornili M, Clatot F, Demicheli R, De Bortoli D, Di Leo A, et al. Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index. J Clin Oncol. 2020;38:2883–91.

    Article  CAS  Google Scholar 

  24. Utech AE, Tadros EM, Hayes TG, Garcia JM. Predicting survival in cancer patients: the role of cachexia and hormonal, nutritional and inflammatory markers. J Cachexia Sarcopenia Muscle. 2012;3:245–51.

    Article  Google Scholar 

  25. Banack HR, Kaufman JS. The obesity paradox: understanding the effect of obesity on mortality among individuals with cardiovascular disease. Prev Med. 2014;62:96–102.

    Article  Google Scholar 

  26. Banack HR, Kaufman JS. The “obesity paradox” explained. Epidemiology. 2013;24:461–2.

    Article  Google Scholar 

  27. Martini A, Parikh AB, Sfakianos JP, Montorsi F, Galsky MD, Oh WK, et al. Predicting toxicity-related docetaxel discontinuation and overall survival in metastatic castration-resistant prostate cancer: a pooled analysis of open phase 3 clinical trial data. Prostate Cancer Prostatic Dis. 2021. https://pubmed.ncbi.nlm.nih.gov/33531652/.

Download references

Acknowledgements

This publication is based on research using information obtained from www.ProjectDataSphere.org, which is maintained by Project Data Sphere, LLC. Neither Project Data Sphere, LLC nor the owner(s) of any information from the web site have contributed to, approved or are in any way responsible for the contents of this publication. EJG received salary support from NIH/NCI K08CA190770.

Author information

Authors and Affiliations

  1. Department of Urology, Vita-Salute San Raffaele University, Milan, Italy

    Alberto Martini & Francesco Montorsi

  2. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Alberto Martini, Qainat N. Shah, Nikhil Waingankar & John P. Sfakianos

  3. Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Che-Kai Tsao & Matthew D. Galsky

  4. Department of Oncology, Vita-Salute San Raffaele University, Milan, Italy

    Andrea Necchi

  5. Division of Endocrinology, Diabetes and Bone Disease, Tisch Cancer Institute at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Emily J. Gallagher

Authors
  1. Alberto Martini
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qainat N. Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nikhil Waingankar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John P. Sfakianos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Che-Kai Tsao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andrea Necchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francesco Montorsi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Emily J. Gallagher
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Matthew D. Galsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alberto Martini.

Ethics declarations

Competing interests

MDG has served as consultant for BioMotiv, Janssen, Merk, Dendreon, GlaxoSmithKline, Lilly, Astellas, Genetech, BMS, Novartis, Pfizer, EMD Serono, AZ, Seattle Genetics, Incyte, Aileron Therapeutics, Dracen, Inovio Pharmaceuticals, NuMab, has received research funding from Janssen, Merk, Dendreon, Novartis, BMS, AZ, Genentech/Roche, and owns stock of Rapt Therapeutics, outside the submitted work. AN has served as a consultant for Merck, Astra Zeneca, Janssen, Incyte, Roche, Rainier Therapeutics, Clovis Oncology, Bayer, and Astellas/Seattle Genetics, Ferring, Immunomedics. has received research funding from Merck, Ipsen, and Astra Zeneca. has received Travel expenses/Honoraria from Roche, Merck, Astra Zeneca, and Janssen.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martini, A., Shah, Q.N., Waingankar, N. et al. The obesity paradox in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 25, 472–478 (2022). https://doi.org/10.1038/s41391-021-00418-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41391-021-00418-0

This article is cited by

Search

Advanced search

Quick links