Leveraging Age and Comorbidity to Optimize Treatment Selection in Men with Recurrent Prostate Cancer
Abstract
Rationale: Men with recurrence of prostate cancer after surgery or radiation therapy as evidenced by rising prostate specific antigen (PSA) levels are generally offered androgen deprivation therapy (ADT) to treat their disease. However, timing of ADT is very controversial; it is unclear if it is better to start ADT very early after the return of PSA or to wait until later time points such as higher PSA values or spread of disease. Furthermore, ADT causes a number of major side effects, including an increased risk of diabetes and cardiovascular events such as heart attacks and sudden cardiac death. Men who have other major medical conditions (“comorbidities”) are at particularly high risk of developing such complications related to ADT, and many of them are unlikely to live long enough to benefit from treatment. Though it may be advisable for such men to delay treatment with ADT, no strong guidelines exist that recommend against immediate ADT for these men. Objective: To use a nationally representative dataset of men with recurrent prostate cancer across six Department of Veterans Affairs (VA) medical centers to characterize the impact of age, comorbidities, and tumor-related variables on (1) long-term risks of dying of prostate cancer vs. other causes; (2) the timing of ADT; and (3) the benefits of early ADT vs. delayed/no ADT to improve survival. We expect that these data will show that older and sicker men are treated indiscriminately with early ADT despite high likelihood of dying of causes other than prostate cancer and despite no benefit from early ADT. Aims: Aim 1: To determine the impact of age, comorbidity, and tumor-related variables on long-term risks of death from cancer and death from other causes in men with recurrent prostate cancer. Aim 2: To characterize patterns of care in terms of timing of ADT (early ADT vs. delayed/no ADT) in men with recurrent disease by age, comorbidity, and tumor-related variables. Aim 3: To compare effectiveness of early ADT vs. delayed/no ADT in reducing cancer and all-cause death in men with varying ages, comorbidity, and tumor-related variables. Applicability of Research: This research will help patients with recurrent prostate cancer after surgery or radiation therapy to make better decisions regarding when to start ADT. Data from this study will support a more individualized approach to care, where men who are at high risk for cancer death and low risk of dying of causes other than prostate cancer would be counseled to receive early intervention with ADT, while men at low risk of prostate cancer death and at high risk of dying of causes other than prostate cancer would be counseled to avoid early ADT. This type of tailored approach is critical for older and sicker men, since side effects of ADT are worse in these patients and treatment with early ADT may not be as effective as it is in younger and healthier patients. Indeed, the goal of our proposal is to develop a personalized medicine approach that tailors the right treatment to the right patient at the right time. Contribution to Field of Prostate Cancer Research: This study will provide insight into whether early initiation of ADT in older and/or sicker men results in lower rates of death from cancer and all causes. It will also characterize how physicians take age, comorbidity, and tumor-related variables into account when making decisions regarding timing of ADT. It will also provide information on long-term risk of death from cancer or other causes associated with age, presence of other major medical conditions, and tumor-related variables. Overall, this information will allow doctors to better personalize timing of ADT based on a patient’s individual characteristics. It will also inform development of treatment guidelines regarding timing of ADT.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710486
Entities
People
- Timothy Daskivich
Organizations
- Cedars-Sinai Medical Center
- United States Army