But losing weight may also increase all-cause mortality risk

After a diagnosis of prostate cancer, weight gain and obesity may significantly increase the risks of cardiovascular disease (CVD), all-cause mortality, and – perhaps – prostate cancer-specific mortality (PCSM) in men, according to results from a large, retrospective study published in the Journal of Clinical Oncology. Surprisingly, researchers also found losing weight post-diagnosis may also increase hazards for all-cause mortality.

“Current evidence supports the link between obesity and risk of advanced prostate cancer, potentially through alterations in hormones, adipocytes, and inflammatory factors. As these factors are also implicated in tumor progression pathways, it is important to understand the potential consequences of obesity and weight gain on long-term survival after a prostate cancer diagnosis,” wrote Alyssa N. Troeschel, MPH, of the Rollins School of Public Health and the Laney Graduate School, Emory University, Atlanta, GA, and colleagues.

They included 11,788 men enrolled in the Cancer Prevention Study II Nutrition Cohort who had been diagnosed with nonmetastatic prostate cancer between 1992 and 2013. All were followed through December 2016. In all, 86.7% of men were age 65 years or older, 92.6% had T1 or T2 disease at diagnosis, 53% had Gleason scores of 2-6, and 24.8% had Gleason scores of 7.

At approximately 2-year intervals, men self-reported their current weight, and researchers obtained postdiagnosis BMI data from the first survey these men completed between 1 and less than 6 years post-diagnosis. Changes in weight were derived from calculating the difference between the first and second surveys.

In all, 3,855 deaths from all causes occurred (500 from PCSM, and 1,155 from CVD mortality). For PCSM, postdiagnosis obesity—defined as 30 kg/m2 or greater—had a hazard ratio of 1.28 (95% CI: 0.96-1.67) compared with healthy weight—defined as a BMI of 18.5 to ˂25.0 kg/m2. For all-cause mortality and CVD mortality, hazard ratios were higher (HR: 1.23; 95% CI: 1.11-1.35 and HR: 1.24; 955 CI: 1.03-1.49, respectively).

Men who were overweight also had a higher HR of PCSM (1.23; 95% CI: 1.00-1.50), but not of CVD or all-cause mortality.

In those with lower-risk tumors, the BMI/mortality outcome association was stronger, particularly for PCSM. In men with lower-risk tumors, obesity after diagnosis was associated with a higher risk of PCSM (HR: 1.58; 95% CI: 1.13-2.22). This was not true in those with high-risk tumors (HR: 1.00; 95% CI: 0.63-1.58).

For their analysis of the effects of weight gain, Troeschel and fellow researchers included 2,973 deaths (375 from PCSM and 881 from CVD mortality). They found that weight gain after diagnosis of more than 5% of body weight was association with a higher risk of PCSM (HR: 1.65; 95% CI: 1.21-2.25) compared with stable weight, as well as a higher risk of all-cause mortality (HR: 1.27; 95% CI: 1.12-1.45). Weight gain was not, however, associated with a higher risk of death from CVD.

Interestingly, a weight loss of 3% to 5% of their body weight (HR: 1.15; 95% CI: 1.02-1.31) and of >5% of body weight (HR: 1.30; 95% CI: 1.16-1.46) were also associated with higher risk of all-cause mortality. Increased risks did not occur, however, among those who gained 3%-5%.

“Our results do not support promotion of weight loss among survivors of prostate cancer, although the observed positive association between weight loss and all-cause mortality is likely a result of underlying disease rather than a true causal relationship,” stressed the authors. “Future studies are needed to determine whether intentional weight loss provides health benefits among overweight and obese survivors of prostate cancer.”

Study limitations include bias caused reverse causation by exclusion of patients with follow-up ending within 4 years of postdiagnosis surveys, selection bias, self-reported BMI, and the inability to separate the direct effect effects between BMI and weight change.

“Survivors of prostate cancer are advised to maintain a healthy weight and avoid weight gain, and our findings provide additional evidence to follow these recommendations,” concluded Troeschel and colleagues. “Clinicians should be vigilant about identifying moderate weight loss or gain in survivors of prostate cancer because both have poor prognostic implications.”

In an accompanying article, Catherine H. Marshall, MD, of the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, and Corinne E. Joshu, MPH, PhD, of Johns Hopkins Bloomberg School of Public Health, noted that while these results add to mounting evidence that links body weight and weight gain to worse outcomes in men with prostate cancer, Troeschel and colleagues focused on the effects of weight and changes in weight after a prostate cancer diagnosis.

Importantly, they noted, these researchers also focused on the effects of post-diagnostic obesity and found it to be associated with a significantly higher risk of CVD-related mortality.

“Androgen deprivation therapy, the primary treatment for advanced prostate cancer, has also been associated with an increased risk of cardiovascular risk factors and mortality in some studies,” wrote Marshall and Joshu. “In sensitivity analyses where these men were removed, obese men still had a significantly higher risk of cardiovascular and all-cause mortality. Although this association has been reported for men without prostate cancer, it is still important to keep in mind with regard to men with prostate cancer, because CVD is now the leading cause of noncancer death in men with prostate cancer.”

These results call attention to the deleterious effects of obesity and weight gain on outcomes in men with nonmetastatic prostate cancer, stressed Marshall and Joshu, and should be studied further.

“This study highlights the importance of considering prostate cancer–specific outcomes, as well as CVD outcomes, in men with prostate cancer and highlights areas for future research, including the impact of intentional weight loss and potential roles of fitness and body composition among men with prostate cancer. Furthermore, it emphasizes the increasing need to consider shared risk factors for both cancer and CVD for best management of both diseases,” they concluded.

  1. Obesity in men diagnosed with nonmetastatic prostate cancer may increase the risks of mortality due to cardiovascular disease, all-cause mortality, and—potentially—prostate cancer-specific mortality.

  2. Weight loss after a diagnosis of nonmetastatic prostate cancer may also increase risks of all-cause mortality.

E.C. Meszaros, Production Editor, BreakingMED™

The Cancer Prevention Study II was funded by the American Cancer Society and the Laney Graduate School, Emory University.

Troeschel had no relevant relationships to disclose.

Marshall reported having a consulting/advisory role for McGraw-Hill Education, Bayer; receiving research Funding from Conquer Cancer Foundation/Bristol-Myers Squibb; and receiving travel, accommodations, and expenses from Dava Oncology, Bayer.

Marshall was also supported, in part, by the National Institutes of Health Cancer Center and the American Cancer Society. Joshu reported no conflicts of interest.

Cat ID: 25

Topic ID: 78,25,730,914,795,25,518,917