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The obesity paradox in metastatic castration-resistant prostate cancer

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.

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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.

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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.

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Correspondence to Alberto Martini.

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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.

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Martini, A., Shah, Q.N., Waingankar, N. et al. The obesity paradox in metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis (2021). https://doi.org/10.1038/s41391-021-00418-0

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