Obesity and weight gain after prostate cancer diagnosis significantly increased the risk of cardiovascular disease (CVD) and all-cause mortality and possibly prostate cancer-specific mortality (PCSM), as well, a large retrospective review suggested.

Obesity at the time of diagnosis was associated with 23%-24% higher CV and all-cause mortality and a trend toward higher PCSM. The risk of dying of prostate cancer increased by 65% in men who gained more than 5% of their body weight after prostate cancer diagnosis, and all-cause mortality was 27% higher.

Perhaps counterintuitively, however, the hazard for all-cause mortality also increased with weight loss, as reported online in the Journal of Clinical Oncology.

“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,” Ying Wang, PhD, of the American Cancer Society in Atlanta, and coauthors concluded. “This may be especially important given evidence that survivors of prostate cancer may be more prone to weight gain compared with men in the general population. 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.”

“Further studies are needed to determine whether intentional weight loss provides health benefits among overweight and obese survivors of prostate cancer,” they added. “Clinicians should be vigilant about identifying moderate weight loss or gain in survivors of prostate cancer because both have poor prognostic implications.”

The findings added to a large volume of evidence linking body weight and weight gain to worse outcomes in prostate cancer, said the authors of an accompanying editorial. Unlike most prior studies, which focused on weight and weight change before or near the time of prostate cancer diagnosis, the current study contributed information about the impact of postdiagnostic weight and weight change.

“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,” concluded Catherine H. Marshall, MD, of the Sidney Kimmel Comprehensive Cancer Center, and Corinne E. Joshu, PhD, of the Bloomberg School of Public Health, both at Johns Hopkins University in Baltimore.

“Furthermore, it emphasizes the increasing need to consider shared risk factors for both cancer and CVD for best management of both diseases.”

Background and Study Design

As Marshall and Joshu pointed out, most studies to date focused on obesity before prostate diagnosis or during the first year after diagnosis. Wang and colleagues noted that “survivors cannot change prediagnosis behaviors, and the initial hardships of a cancer diagnosis and primary treatment may influence body weight and make efforts toward modifying weight around the time of diagnosis difficult.”

In contrast, obesity and weight gain in the postdiagnosis period (>12 months after diagnosis) might be more easily modified and more relevant to recommendations for cancer survivors, the authors continued. Two previous studies focusing on the effects of body mass index (BMI) or weight gain in the postdiagnosis period yielded conflicting results with regard to mortality.

Wang and colleagues expanded the scope of their investigation to include the relationships between obesity and weight gain in the postdiagnosis period and subsequent cause-specific and all-cause mortality. For their analysis, they used data for 86,402 men who participated in the Cancer Prevention Study II Nutrition Cohort, of whom 11,788 had diagnoses of nonmetastatic prostate cancer during 1992 to 2013.

Within all the patients with prostate cancer diagnoses, investigators compiled two cohorts on the basis of postdiagnostic BMI data (n=8,330) and weight change (n=6,942).

Investigators defined normal weight as BMI 18.5 to <25, overweight as BMI 25 to <30, and obese as BMI ≥30. Weight change was determined by the difference between postdiagnosis weight and at the next biennial follow-up survey. Weight gain ≥5% was defined as moderate, 3% to <5% as small, and ± <3% as maintenance. Weight loss of 3%-5% was defined as small and ≥5% as moderate.

To reduce the potential for bias, Wang and colleagues excluded deaths occurring within 4 years after the first postdiagnostic survey in the BMI cohort and 4 years after the second postdiagnostic survey in the weight change cohort.

Key Findings

The data showed that 86.7% of the men were 65 or older, 92.6% had T1 or T2 disease at diagnosis, 53% had Gleason score 2-6, and 24.8% had Gleason score 7. In the BMI cohort, 36% had healthy weight, 49% overweight, and 16% were obese.

During follow-up, 3,855 deaths occurred in the BMI group (500 attributed to prostate cancer) and 3,973 in the weight change group (375 from prostate cancer). Additionally, 1,155 participants died of CVD in the BMI group and 881 in the weight-change group.

As compared with the healthy-weight group, obese men had a hazard ratio of 1.28 for PCSM (95% CI 0.96 to 1.67), 1.24 for for CVD mortality (95% CI 1.03-1.49), and 1.23 for all cause mortality (95% CI 1.11-1.35). Postdiagnostic weight gain >5% was associated with a PCSM hazard ratio of 1.65 as compared with the stable-weight group (95% CI 1.25-2.25) and an all-cause mortality hazard of 1.27 (95% CI 1.12-1.45). Weight gain was not associated with CVD mortality.

Small weight loss was associated with a 15% increase in the hazard for all-cause mortality (95% CI 1.02-1.31), and men who lost >5% of body weight had a 30% higher all-cause mortality hazard (95% CI 1.16-1.46).