Introduction

New prostate cancer (PCa) cases in the U.S. are estimated to be over 300,000 annually [1]. Increasingly, patients are opting for active surveillance (AS) rather than immediate aggressive treatment due to concerns about treatment toxicity [2]. Indeed, estimates suggest roughly 60% of low-risk and 10–20% of intermediate-risk patients are electing AS [2]. While the risk of metastases and death on AS are very low, 20–50% or more of patients on AS experience an upgrade in grade group (GG) or disease stage over time [3]. AS involves close monitoring and repeat periodic biopsies looking for disease progression—typically in the form of higher-grade disease on repeat biopsy (i.e., grade reclassification). Identifying non-toxic treatments, such as lifestyle interventions, that can delay progression is crucial.

Risk factors associated with increased risk of PCa progression on AS in various studies include Black race, older age, higher prostate-specific antigen (PSA) density, genetic or hereditary factors, obesity, poor diet, poor overall metabolic health, and lack of physical activity (PA); however, results are conflicting [4]. In regards to PA, some evidence suggests regular PA may be associated with improved PCa outcomes, including reduced risk of advanced PCa, slower progression, improved survival after diagnosis, PCa-specific survival and lessened treatment side effects [5, 6]. The incorporation of PA also supports muscle and bone health, which is important in that many treatments—especially for advanced PCa—can negatively impact these factors. Proposed mechanisms by which PA may mediate better outcomes and decreased side effects of treatment include enhancing immune function, modulating hormone levels, and reducing inflammation. Moreover, regular PA can boost energy levels, stabilize moods, and improve physical function; therefore, making it an essential component of cancer care [7].

Conflicting results in AS and PA studies

Despite some evidence to suggest benefits of PA in PCa [6], there are limited and conflicting data on whether PA affects progression in AS. Some studies show no correlation, others indicate that active patients had higher PSA levels than sedentary patients, and yet others demonstrate that higher levels of PA were linked with a lower risk of PCa reclassification [7].

Higgins et al. address some of these limitations in a prospective cohort study involving 828 patients with GG 1 PCa on AS. Patients were followed for a median of 6.4 years, during which 21% underwent grade reclassification [8]. The authors used multivariable competing risk proportional hazards regression model to test whether increased PA was associated with grade reclassification, defined as a more aggressive grade than at first biopsy. PA ≥ 3 metabolic equivalent of task (MET) hours per week were associated with a significantly decreased risk of grade reclassification to GG3 or higher. Specifically, 3 to <9, 9–18, and ≥18 MET-hours/week were associated with 82%, 74%, and 69% lower risk of grade reclassification, respectively. While this study nicely provides further evidence for the potential benefit of PA, an important finding was that PA levels as low as 3–<9 MET hours/week were associated with a lower risk of grade reclassification, which is below the current general guideline recommendation, and higher levels were not associated with greater reductions.

Failure to meet PA guideline recommendations

The current American Cancer Society guidelines recommend patients with PCa engage in 150–300 min per week of moderate aerobic activity, or 75–150 min per week of vigorous aerobic activity, along with strength training at least 2 days per week, which would translate to a minimum of ~9 MET hours/week [9]. These recommendations are tailored to a patient’s health status, cancer stage, and treatment. Several factors can and do influence the likelihood that a patient with PCa will perform PA, such as comorbidities, psychological distress, socioeconomic factors, and lack of access to safe or supportive environments [10]. Overall, while there is evidence and a general understanding of the benefits of exercise among patients and clinicians, adherence to recommended guidelines is relatively low. Thus, based upon the data from Higgens et al, for patients on AS, perhaps the goal should not be perfection (i.e., meet guidelines), but rather to be good enough (i.e., moderate physical activity such as brisk walking, dancing, gardening, etc., >3 MET hours/week). Of course, this all assumes that the association they saw with more PA and lower grade reclassification is causative (i.e., the PA caused the lower reclassification), which we know is not necessarily true (i.e. association does not mean causation). Therefore, future studies should focus on testing whether PA indeed causes reduced grade reclassification and if so, then identifying the minimum number of MET hours required to produce a positive effect. These studies may require diverse approaches, including patient-specific exercise programs that incorporate PA into survivorship care plans and improved patient education and motivational support to help bridge the gap between clinical advice and real-world adherence. Additionally, more prospective studies are needed to assess longitudinal changes in objective daily activity and not just baseline and to develop personalized PA interventions. As shown by Higgins et al., even modest increases in PA, below traditional guideline thresholds, may be associated with significant benefits for PCa patients on AS, underscoring the importance of future research to improve and make programs more accessible [8].

Conclusion

PA may play an essential role in PCa progression and overall outcomes. Therefore, implementing targeted interventions that promote PA guidelines could help decrease disease progression in patients on AS as well as those undergoing treatment. However, further research in this area is desperately needed to conclusively prove whether PA does impact PCa progression using consistent definitions of disease progression. Furthermore, with activity trackers (i.e., FitBit), it is now possible to longitudinally track objective PA much more closely and thus have a more comprehensive assessment of PA. Finally, additional opportunities for research include examining PA intensity and its impact in various stages of PCa to determine when in the natural history of PCa it can have the most impact and assessing its impact on PCa progression across diverse patient populations.