Prostate Cancer Reduces Endurance Exercise Capacity in the Rat: Possible Roles of Reduced Cardiac Mass and Function

Prostate cancer is the most commonly diagnosed non‐skin cancer in men. Exercise intolerance is common in prostate cancer patients; particularly those subject to androgen deprivation therapy. Whether prostate cancer itself reduces exercise capacity is unknown. Objective We used a preclinical rat prostate tumor model to test the hypothesis that untreated prostate cancer reduces endurance exercise capacity. Methods Sixteen male Copenhagen rats performed an initial treadmill test to exhaustion. The rats' prostates were subsequently injected with either prostate carcinoma cells (R‐3327 AT‐1 cell line) in Matrigel (cancer, n=9) or Matrigel only (sham, n=7) and the treadmill tests were repeated eight weeks post‐surgery. Following the final treadmill test, left ventricle contractility (left ventricle Δpressure/Δtime) was measured under anesthesia and the heart and gastrocnemius muscles were then dissected and weighed. Results Average prostate tumor mass in the cancer group was 9.8±2.6 g (range: 0.2 to 19.5 g). Initial times to exhaustion were not significantly different between groups (sham: 29.8±1.3, cancer: 28.6±2.5 min, p=0.710). Time to exhaustion at eight weeks post‐surgery was reduced compared to initial values for both groups but the eight‐week time to exhaustion was significantly lower in the cancer group (13.3±1.4 min) compared to the sham group (19.7±2.1 min, p=0.019). Left ventricle Δpressure/Δtime was not significantly different between groups, but within the cancer group prostate tumor mass was significantly inversely correlated to left ventricle Δpressure/Δtime (−0.71, p=0.047). Total body mass was not significantly different between groups (p=0.363) but heart (↓12%, p=0.021), left ventricle (↓16%, p=0.003) and gastrocnemius (↓9%, p=0.005) muscle mass were significantly lower in the cancer group compared to the sham group. Within the cancer group heart (r=−0.74, p=0.22) and left ventricle (r=−0.85, p=0.004) mass, but not gastrocnemius muscle mass (r=−0.15, p=0.696), were inversely correlated with prostate tumor mass. In other words, within the cancer group the rats with the largest prostate tumors had the lowest cardiac contractility, the smallest heart mass, and, more specifically, the smallest left ventricle mass. Conclusion We found that untreated prostate cancer reduced endurance exercise capacity in rats. Although multiple mechanisms likely contributed to the reduced exercise capacity in rats with prostate cancer, reductions in cardiac muscle function and mass, as well as reductions in gastrocnemius muscle mass, likely played an important role. Support or Funding Information American Cancer Society (RSG‐14‐150‐01‐CCE to BJB)