Associations of Outdoor Air Pollution With Cause-specific Mortality in Metastatic Prostate Cancer: A cohort study.

BACKGROUND

Cardiovascular disease is an important competing cause of death in men with metastatic prostate cancer, and ambient air pollution may increase cardiovascular vulnerability. We evaluated associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with all-cause, cardiovascular, and prostate cancer-specific mortality, including joint associations with androgen deprivation therapy (ADT).

METHODS

We analyzed 33,384 men from 11 US state registries diagnosed with metastatic prostate cancer during 2000-2015 and followed through 2018. Residential PM2.5 and NO2 concentrations at diagnosis were assigned using 1-km exposure models. Multivariable Cox models estimated all-cause mortality, and inverse-probability-weighted Cox models assessed cause-specific mortality.

RESULTS

Each interquartile-range increase in PM2.5 was associated with higher cardiovascular mortality (HR 1.04, 95% CI 1.02-1.07; p-trend=0.008). Cardiovascular mortality was also higher in the fourth and fifth PM2.5 quintiles versus the first (HR 1.18 and 1.21, respectively). Higher NO2 was associated with prostate cancer-specific mortality in the highest quintile (HR 1.07, 95% CI 1.01-1.13). In joint analyses, ADT-treated men with high versus low PM2.5 exposure had higher cardiovascular mortality (HR 1.19, 95% CI 1.05-1.34), without clear evidence of effect modification (p-interaction=0.051).

CONCLUSIONS

In men with metastatic prostate cancer, higher PM2.5 exposure was associated with cardiovascular mortality, particularly among ADT-treated patients, supporting further study of environmental exposures and systemic therapy in cardiooncology.

WHAT THIS STUDY ADDS: Men with metastatic prostate cancer receiving androgen deprivation therapy may be particularly vulnerable to cardiovascular complications. In this large population-based cohort, higher residential PM2.5 exposure was associated with increased cardiovascular mortality, including among men receiving ADT. Although we found no clear evidence that ADT modified the effect of PM2.5, the joint exposure pattern suggests that environmental air pollution may contribute to cardiovascular vulnerability in patients already exposed to cardiometabolic effects of systemic therapy. These findings extend environmental epidemiology to a clinically high-risk cancer population.