Castrate Sensitive Prostate Cancer

The purpose of this study is to characterize the reduction in PSMA-avid tumor volume and metastasis-directed radiotherapy treatment intensity facilitated by PET PSMA-response adapted SABR for poly-metastatic castration sensitive prostate cancer.

The investigators have used national VHA data to demonstrate real-world efficacy of abiraterone and enzalutamide in Veterans with mCRPC. In the real-world that is the VHA, the investigators have successfully estimated g values that accurately predict OS and the use of this metric in other settings should now be explored. In the egalitarian system that is the VHA the treatment of prostate cancer is excellent and uniform across the US. The choices made are clearly personalized, given not all men received all therapies and that younger Veterans were treated more aggressively. But with survivals that rival those in registration trials that enroll optimally fit individuals usually not encumbered by the co-morbidities that afflict many Veterans, the outcomes are testimony to the fact that for this common malady of older Veterans with whom VA physicians have broad experience the care administered is unsurpassed. Importantly this care at least as regards Veterans with mCRPC demonstrates that given equal access to health care, all men with prostate cancer fare comparably well. As our sophistication in categorizing cancers molecularly has increased this study will look to better examine any emerging differences across study participants.

This study consists of two home-based exercise programs: a stationary exercise bicycle intervention (Arm A), and a walking intervention (Arm B). The study will enroll 24 patients who are starting ADT (Androgen Deprivation Therapy)/ARSI (Androgen-Receptor Signaling Inhibitors) therapy for newly diagnosed metastatic castrate-sensitive prostate cancer (mCSPC). All participants will be asked to complete 1-2 training sessions at UVA prior to starting the exercise. All participants will be asked to complete aerobic and strength testing before and after the exercise program. Participants will be asked to answer questionnaires throughout the program. The at-home exercise will last for 12 weeks.

Prostate cancer remains the most common malignancy in men in Europe. Over the last two decades, the treatment landscape for both localized and metastatic prostate cancer has been revolutionized. For patients with metastatic castration-sensitive prostate cancer (mCSPC), the primary treatment objectives are to delay progression to metastatic castration-resistant prostate cancer (mCRPC) and to improve overall survival (OS). Although patients with PC may initially respond to androgen deprivation therapy (ADT), progression to castration resistance occurs in 10-20% of patients within 5 years. Primary ADT has been the standard of care for over 50 years. However, recent advancements have shifted treatment from ADT monotherapy for all mHSPC/mCRPC patients to more intensive approaches, which include combinations of ADT with new androgen receptor pathway inhibitors (ARPIs), chemotherapy, or both, tailored to tumor characteristics such as metastatic burden. In clinical practice, a reduction in prostatic specific antigen (PSA) levels from baseline is commonly used to monitor disease control, particularly in the castration sensitive phase (both early and metastatic). For patients with mCSPC, a decrease in PSA levels signifies that the treatment is effective. Moreover, the depth, time and duration of this PSA reduction are linked to better clinical outcomes, including OS. Although more patients achieved an optimal PSA response with intensified ADT (with ARPI or docetaxel), those with a suboptimal response have a significantly worse survival rate. Several key studies have demonstrated that achieving undetectable PSA (≤0.2 ng/mL) is associated with better OS, irrespective of subgroups. This study aims to evaluate patient survival based on PSA response and to describe baseline characteristics among patients with or without PSA response. Specifically, patients will be divided into two groups based on the achievement of PSA values ≤ 0.2 ng/dl, and overall survival (OS) and progression free survival (PFS) for each group will be evaluated. Clinical and laboratory information at baseline will be compared between the two groups. Baseline characteristics considered are histology, Gleason score, stage of disease, presence of genetic alterations, PSA values, sites and number of metastases, de novo or metachronous disease, high/low risk disease, high/low volume disease.