Impact of Web-Based Lifestyle Interventions on Prostate Cancer Prognosis

项目总结 前列腺癌是美国男性中最常见的被诊断出的癌症，超过 预计2015年将有220,800例新诊断病例。虽然很大比例的新病例似乎在临床上 前列腺癌是一种惰性肿瘤，仍然是美国男性癌症死亡的第二大原因。 防止最初局限于局部的前列腺癌发展为致命疾病是一个关键的优先事项。证据来自 我们小组和其他人建议前列腺癌诊断后的生活方式因素可能会阻止非转移 前列腺癌不会成为致命的疾病。我们最近根据生活方式制定了11个因素的评分 诊断后的做法与前列腺癌死亡风险的降低密切相关(未发表)。 4-7分和8-11分(对0-3分)的男性得分分别为48%(HR=0.52，95%CI=0.32，0.84)和75%(HR=0.25；95%CI=0.09)， 0.69)分别降低前列腺癌死亡风险。基于这些令人信服的数据，我们制定了一种生活方式 通过互联网为前列腺癌患者提供计划，最终目标是改善临床 将生活方式干预作为辅助治疗纳入标准的前列腺癌患者的结果 前列腺癌管理。在这项提案中，我们旨在解决关键问题-是否可以访问 基于互联网的生活方式计划(旨在增加锻炼+/-改善饮食质量)影响前列腺癌 生物学和降低前列腺癌进展的风险？我们建议进行为期2年的3-ARM(基于网络的 以锻炼为目标的干预与基于网络的干预(以锻炼为目标+饮食与日常护理)随机 加州大学旧金山分校150名选择手术的前列腺癌患者的对照试验 弗朗西斯科。男性将在根治性前列腺切除术前8周进行登记，并完成后续评估 术后6个月、1年、2年。被分配到干预部队的男子将获得为期两年的网络- 基于术后生活方式计划和针对干预措施量身定做的短信(例如，锻炼或锻炼+ 饮食)和Fitbit。我们将检验锻炼与锻炼+饮食与日常护理的效果：1)经过验证的FDA- 经批准的预后评分，译码，在活检(干预前)和前列腺摘除(初始8- 周干预期)组织；2)肿瘤及正常组织中肿瘤相关通路的表达 来自活检和前列腺切除术；3)术后可检测到的PSA和前列腺癌复发的风险 4)术后6个月、1年和2年的性功能和排尿功能。 做手术。这项研究将提供关于可持续互联网的影响的关键转换数据 干预前列腺癌男性患者的前列腺癌生物学和临床结果。这些数据将 支持使用生活方式干预作为前列腺癌的辅助治疗。这项建议的优点 包括我们新颖、基于证据的干预；高度相关的初步数据；创新的预测 生物标记物成果；以及经验丰富的多学科团队，具有出色的记录。

PROJECT SUMMARY Prostate cancer is the most commonly diagnosed cancer among men in the United States (US), with more than 220,800 new diagnoses expected in 2015. While a large proportion of new cases appear to have clinically indolent tumors, prostate cancer remains the second-leading cause of cancer death among men in the US. Preventing progression of initially localized prostate cancers to lethal disease is a key priority. Evidence from our group and others suggests that lifestyle factors after prostate cancer diagnosis may prevent non-metastatic prostate cancer from becoming lethal disease. We recently developed an 11-factor score based on lifestyle practices after diagnosis that is strongly associated with reduced risk of prostate cancer death (unpublished). Men with 4-7 and 8-11 points (vs. 0-3) had a 48% (HR= 0.52, 95%CI=0.32, 0.84) and 75% (HR=0.25; 95% CI=0.09, 0.69) lower risk of prostate cancer death, respectively. Based on these compelling data, we developed a lifestyle program delivered via the Internet for prostate cancer patients, with the ultimate goal of improving clinical outcomes in men with prostate cancer by incorporating a lifestyle intervention as adjuvant therapy to standard prostate cancer management. In this proposal, we aim to address the critical question – does access to an Internet-based lifestyle program (designed to increase exercise +/- improve diet quality) impact prostate biology and reduce risk of prostate cancer progression? We propose to conduct a 2-year 3-arm (web-based intervention targeting exercise vs. web-based intervention targeting exercise + diet vs. usual care) randomized controlled trial among 150 prostate cancer patients opting for surgery at the University of California, San Francisco. Men will be enrolled eight weeks before radical prostatectomy and complete follow-up assessments 6 months, 1 year, and 2 years post-surgery. Men assigned to the intervention arms will receive a two-year web- based lifestyle program post-surgery and text messaging tailored to the intervention (i.e., exercise or exercise + diet) and Fitbits. We will examine the effect of exercise vs. exercise + diet vs. usual care on: 1) a validated, FDA- approved prognostic score, Decipher, measured in biopsy (pre-intervention) and prostatectomy (post-initial 8- week intervention period) tissue; 2) mRNA expression of cancer-related pathways in tumor and normal tissue from biopsy and prostatectomy; 3) detectable PSA post-surgery and risk of prostate cancer recurrence at 2- years after radical prostatectomy; and 4) sexual and urinary function at 6 months, 1 year, and 2 years post- surgery. This study will provide critical translational data on the effect of a sustainable Internet-based intervention on prostate tumor biology and clinical outcomes in men with prostate cancer. These data will support the use of lifestyle interventions as adjuvant therapy for prostate cancer. Strengths of this proposal include our novel, evidence-based, intervention; highly relevant preliminary data; innovative prognostic biomarker outcome; and experienced multi-disciplinary team with outstanding track record.