||6R01CA184075-06 Interpret this number
||Fred Hutchinson Cancer Center
||PALS: Prostate Cancer Active Lifestyle Study
DESCRIPTION (provided by applicant): Epidemiologic data have consistently shown that obesity is associated with an increased risk of prostate cancer (PCa) progression, but identification of causal mechanisms has been challenging. One potential link between obesity and PCa progression is impaired glucose regulation, a mechanism for which there are several types of supportive evidence. The Diabetes Prevention Program (DPP) is an established lifestyle intervention with long-term success. Thus, the DPP offers a novel strategy to test its ability to improve PCa outcomes and yield insights on biological pathways through which obesity may modify PCa progression. Men on Active Surveillance (AS), where men with low risk PCa are monitored with blood tests, physical exams and surveillance prostate biopsies represent an ideal population to study the effects of a lifestyle intervention. Despite the nomenclature of low risk, 50% of these patients will experience disease progression requiring active treatment. Obesity may be one of the major factors leading to disease conversion from low to high risk. We hypothesize that a lifestyle intervention in men with PCa on AS will lead to improved markers of glucose regulation. To test this hypothesis we propose a 6-month randomized trial in 200 overweight/obese (BMI > 25 kg/m2) men with PCa who have elected AS. Patients will be randomized to either a lifestyle intervention (structured diet/exercise program based on the DPP); or control (oral and written information based on U.S. general dietary/physical activity guidelines). The study will address the following specific aims: 1. To test whether the DPP lifestyle intervention (vs. control) improves serum fasting glucose; 2. To test whether the DPP lifestyle intervention (vs. control) improves serum biomarkers of glucose regulation (insulin, C-peptide, insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGF-BP3) and adiponectin); 3. To test whether the DPP lifestyle intervention decreases the levels of insulin receptor or insulin-like growth factor-1 receptor (IGF-1R) in PCa tissue epithelium on follow-up prostate biopsy; 4. To test whether PCa patients randomized to the DPP lifestyle intervention sustain the lifestyle changes for at least 6 months after the end of the intervention
period. We will also evaluate the DPP lifestyle intervention effects on health-related quality of life and on pathologic features of the surveillance prostate biopsies. This study will address two of the most common diagnoses in men today: obesity and prostate cancer. With the growing recognition that many men with PCa may not require active treatment and can rather be monitored through AS protocols, it becomes imperative to identify modifiable risk factors for reducing the rate of disease progression in these men. Findings from this study may have wide reaching implications in improving both the overall and disease-specific outcomes in men diagnosed with clinically localized PCa, and provide a treatment alternative of an active lifestyle
for active surveillance.
Randomized trial evaluating the role of weight loss in overweight and obese men with early stage prostate Cancer on active surveillance: Rationale and design of the Prostate Cancer Active Lifestyle Study (PALS).
, Neuhouser M.L.
, Beatty S.J.
, VanDoren M.
, Lin D.W.
, Porter M.
, Gore J.L.
, Gulati R.
, Plymate S.R.
, Wright J.L.
Contemporary clinical trials, 2019 Jun; 81, p. 34-39.