In this retrospective cohort study, weight gain from 5 years before prostatectomy to 1 year after was associated with a nearly two-fold increased risk of prostate cancer recurrence. This association remained significant even among physically active men. Further, there appeared to be a linear association between weight change and recurrence, suggesting that risk of recurrence increased with increasing weight gain, and decreased with increasing weight loss.
Obesity and weight gain may influence risk of prostate cancer recurrence through several mechanisms, including metabolic, hormonal, and inflammatory pathways. Obese men tend to have higher insulin and leptin levels and lower androgen levels (23
). These metabolic and hormonal changes may differ throughout the natural history of weight change. The consequences of these adipose-mediated metabolic and hormonal changes may influence prostate cancer differently depending on when they occur during the natural history of prostate cancer carcinogenesis: before disease is present, early in the natural history, or after detection or treatment. We focused on the time frame when the tumor is present, but not yet diagnosed, and cancer cells are escaping from the primary tumor before the prostatectomy. We thus addressed the influence of weight change on the ability of those cancer cells to escape, survive and proliferate. Future studies should address whether weight change in the years following prostatectomy influences recurrence independent of weight change circa diagnosis and surgery.
While weight gain from young adulthood to middle age is not associated with or inversely associated with prostate cancer incidence in most (28
) but not all studies (38
), only one previous study has addressed weight gain and prostate cancer recurrence. Strom and colleagues evaluated annual weight gain from age 25 to time of diagnosis; they reported an unadjusted two-fold increased risk of recurrence among men with an annualized average weight gain >1.5 kg/yr (8
). Because only an unadjusted analysis was reported, it is unclear whether weight gain was a risk factor for recurrence independent of obesity and/or pathologic characteristics. In our study the positive association between weight gain and recurrence was independent of pathological tumor characteristics as well as cigarette smoking status, physical activity level, weight and height.
In our study, obesity 1 year after surgery appeared to be associated with an increased risk of recurrence; an association that was attenuated among physically active men. Obesity in middle age has been extensively studied for prostate cancer incidence and mortality, and obesity at time of surgery for risk of prostate cancer recurrence. Specifically, obesity in middle age has been associated with a higher incidence of advanced stage and higher grade prostate cancer, a higher risk of death from prostate cancer, and obesity at diagnosis has been associated with higher case fatality in men with prostate cancer (22
). In contrast, obesity has been observed to be either not associated or inversely associated with risk of early stage and low grade disease (22
). Our findings for obesity at 1 year after surgery, while not statistically significant, are consistent with those from studies reporting a positive association between obesity at the time of surgery and recurrence (2
), including for a prior study conducted in prostate cancer patients of the one surgeon (5
) and of multiple surgeons at Johns Hopkins Hospital (6
We also evaluated whether the associations for weight change and obesity were modified by physical inactivity. We assessed these interactions because this potential modifier
may also influence metabolic, hormonal and inflammatory pathways (23
). While we found suggestions that physical activity differentially influenced the associations of obesity and weight change with recurrence, these findings were not statistically significantly different.
We evaluated obesity, physical activity, and weight change in a cohort of men with prostate cancer who underwent radical prostatectomy performed by the same surgeon. Obesity is associated with worse stage/grade at time of diagnosis (22
), which is, in turn, a strong predictor of recurrence. Thus in our analysis, we adjusted for pathologic stage and grade, so that the independent effects of obesity and of weight gain could be detected. Because all men had to be healthy enough to undergo surgery, the prevalence of obesity was much lower in our sample than in the US population. Despite this select group of patients of a single surgeon, we expect that our findings are generalizable across the range of BMI and weight change present in our study. Because these men had clinically-localized disease, we had low power to perform sub-group analyses by stage and grade. Although obesity is associated with PSA in men without a diagnosis of prostate cancer, previous work found no difference in the performance of PSA as a predictor of biochemical recurrence by weight status (40
). Adjustment for pre-surgery PSA level did not change our inferences. We asked the men to report their leisure time physical activity using a single question; this measure was not validated and may not capture the full range of activity in all men. Our measures were retrospective, so may be subject to recall bias.
Obesity and weight gain in adulthood have been associated with numerous adverse health outcomes. Our study suggests that weight gain may also increase the risk of prostate cancer recurrence among men who have undergone radical prostatectomy to treat clinically-localized prostate cancer. Thus, by avoiding weight gain, men with prostate cancer may both prevent recurrence and improve overall well-being.