In this prospective study of physical activity among prostate cancer patients, we observed a strong inverse relation between walking pace after diagnosis and risk of prostate cancer progression. Men who walked briskly for three or more hours per week had the lowest risk of progression. There was also a suggestion of an inverse association for vigorous activity, but few men engaged in vigorous activity in this study population and this result was not statistically significant.
To our knowledge, only one other study has examined post-diagnostic physical activity in relation to clinical outcomes in prostate cancer survivors (2
). In that study, men who engaged in three or more hours per week of vigorous activity experienced a 61% reduced rate of prostate cancer–specific mortality compared to men who engaged in less than one hour per week (HR: 0.39; 95% CI: 0.18, 0.84; p
-trend: 0.03). Additionally, men who walked briskly after diagnosis experienced a 48% reduction in all-cause mortality (HR: 0.52; 95% CI: 0.39, 0.70, p-
trend: <0.001) and a non–statistically significant reduction in prostate cancer–specific mortality (HR: 0.66; 95% CI: 0.34, 1.29) compared to men who walked at an easy pace. Reverse causation is a concern when examining the relation between physical activity and prostate cancer-specific mortality, in that men with metastatic disease may reduce their physical activity as a result of their disease, creating a spurious association between decreased activity and poor prognosis. Thus, a particular strength of the current study is our outcome of prostate cancer progression, as this endpoint is far less susceptible to reverse causation given that the early indicators of progression occur prior to any symptoms.
Brisk walking may affect prostate cancer progression by reducing insulin resistance, decreasing bioavailable IGF-1, and increasing adiponectin levels. Circulating levels of insulin, bio–available IGF1, and adiponectin affect proliferation and apoptosis of prostate cancer cells in vitro
) and in vivo
), and have been associated with risk of advanced or fatal prostate cancer (28
). In the Physician’s Health Study, men in the highest quartile of pre-diagnostic C-peptide levels, a marker of insulin secretion, had a 2.38-fold increased risk of prostate cancer-specific mortality compared to men in the lowest quartile (HR: 2.38; 95% CI: 1.31, 4.30; p
-trend: 0.008) (28
). Among men with prostate cancer, men in the highest quintile of pre-diagnostic adiponectin had a 61% reduced risk of dying from prostate cancer compared to men in the lowest quintile (HR: 0.39; 95% CI: 0.17, 0.85; p
-trend: 0.02) (30
Further support for this mechanism comes from studies demonstrating reduced cell growth and increased apoptosis of prostate cancer cells cultured in serum from healthy men who engaged in regular aerobic exercise. Serum from exercising men had lower insulin and IGF1 and higher IGF binding protein-1 values compared to men who did not exercise; and addition of IGF1 to the exercisers’ serum removed its anti-proliferative, pro-apoptotic effect (7
Brisk walking may also affect prostate cancer progression by reducing inflammation. In a 12-month randomized controlled trial among elderly persons, walking “somewhat hard” was associated with lower circulating interleukin-6 (IL-6) (33
). IL-6 promotes cell proliferation and inhibits apoptosis of prostate cancer cells in vitro
), and high levels of IL-6 predicted a 73% increased risk of dying from prostate cancer among normal weight men (34
We acknowledge that our study has several limitations. First, we had limited power due to a small number of events, including only three prostate cancer deaths, and low participation in vigorous activity. However, our progression-based outcome is less susceptible to reverse causation compared to prostate cancer-specific mortality, as physical symptoms of prostate cancer progression that may cause a decrease in physical activity are unlikely to precede biochemical recurrence. Furthermore, many elderly prostate cancer patients are not capable of performing vigorous activities, and thus our findings for brisk walking are particularly relevant for designing future intervention studies.
Second, we cannot eliminate non-differential measurement error in our prospective physical activity assessment. Vigorous activities occur infrequently or sporadically in older persons and may be less accurately recalled than usual walking pace, which could partially explain the lack of a statistically significant association for vigorous activity. Third, we had no data on pre-diagnostic physical activity; however data from the Health Professionals’ Follow–up Study support an association between post-diagnostic activity and prostate cancer-specific mortality independent of pre-diagnostic activity (2
). Fourth, 24% of the men who completed the physical activity questionnaire were lost to follow-up. These men did not differ from the remaining men in terms of their clinical prognostic factors, age at diagnosis, BMI, vigorous activity, or usual walking pace; therefore, although loss of these men reduced our statistical power, it is unlikely to have biased our results. Lastly, the participants in our study were volunteers from a large population-based prostate cancer registry. The men who volunteered were younger at diagnosis, more likely to be white, and had better prognostic risk disease compared to the general CaPSURE population. Thus, our results may not be generalizable to non-Caucasian populations or populations with a different distribution of clinical prognostic factors.
In conclusion, we observed a statistically significant inverse association between brisk walking after diagnosis and risk of prostate cancer progression in men diagnosed with clinically localized prostate cancer. These results were based on a relatively small number of events among brisk walkers and thus further study is needed. However, our results are consistent with the only other study of physical activity after diagnosis and clinical outcomes in prostate cancer survivors, and suggest significant clinical benefits of brisk walking for men with prostate cancer.