PALS: Prostate Cancer Active Lifestyle Study

 描述(由申请人提供)：流行病学数据一直表明肥胖与前列腺癌(PCA)进展的风险增加有关，但确定原因机制一直是具有挑战性的。肥胖和前列腺癌进展之间的一个潜在联系是血糖调节受损，这一机制有几种类型的支持证据。糖尿病预防计划(DPP)是一种长期成功的既定生活方式干预措施。因此，DPP提供了一种新的策略来测试其改善PCa结果的能力，并对肥胖可能影响PCa进展的生物学途径提供见解。主动监测(AS)，通过血液测试、体检和监视前列腺活检对低风险前列腺癌患者进行监测，是研究生活方式干预效果的理想人群。尽管有低风险的命名，但这些患者中有50%将经历需要积极治疗的疾病进展。肥胖可能是导致疾病从低风险转变为高风险的主要因素之一。我们假设，对患有前列腺癌AS的男性进行生活方式干预将导致血糖调节标志物的改善。为了验证这一假设，我们提出了一项为期6个月的随机试验，对象为200名超重/肥胖(BMI&GT；25公斤/平方米)患有前列腺癌的男性。患者将被随机分为生活方式干预组(基于DPP的结构化饮食/锻炼计划)或对照组(基于美国一般饮食/体力活动指南的口头和书面信息)。本研究将针对以下具体目标：1.测试DPP生活方式干预(与对照组)是否改善空腹血糖；2.测试DPP生活方式干预(与对照组)是否改善血糖调节的血清生物标志物(胰岛素、C-肽、胰岛素样生长因子-1(IGF-1)、IGF-BP3和脂联素)；3.测试DPP生活方式干预是否降低前列腺癌组织上皮中胰岛素受体或胰岛素样生长因子-1受体(IGF-1R)的水平；4.测试随机接受DPP生活方式干预的PCA患者在干预结束后是否持续生活方式改变至少6个月 句号。我们还将评估DPP生活方式干预对健康相关生活质量的影响以及对监测前列腺活检的病理特征的影响。这项研究将解决当今男性最常见的两种诊断：肥胖和前列腺癌。随着人们越来越认识到许多患有前列腺癌的男性可能不需要积极的治疗，而是可以通过AS方案进行监测，因此确定可改变的危险因素以降低这些男性的疾病进展率变得势在必行。这项研究的发现可能对改善被诊断为临床局限性前列腺癌的男性的总体和疾病特异性结果具有广泛的影响，并提供一种积极生活方式的治疗选择。 进行主动监视。

 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.