Androgen-responsive POSLUMA-guided Intra-prostatic Boost (ARPEGGIO)

Prostate cancer is commonly treated with a combination of hormone therapy and radiation therapy. Hormone therapy, or androgen deprivation therapy (ADT), lowers testosterone levels and often shrinks or weakens prostate cancer before radiation begins. However, after hormone therapy starts, it can become harder for doctors to tell exactly where active cancer remains inside the prostate using standard imaging (typically an MRI). This study is being conducted to determine whether a newer imaging test can better identify which parts of the cancer are still active and may benefit from more focused radiation treatment.

All participants in this study will receive six months of ADT, which is part of standard care for intermediate- and high-risk prostate cancer. In addition, participants will undergo PSMA PET/CT scans, a type of imaging that highlights prostate cancer cells, as well as MRI scans. These scans will be performed at three time-points: before hormone therapy begins, approximately eight weeks after starting hormone therapy (before radiation planning), and again at 24 weeks (at the end of all treatment) to see how the cancer has responded to treatment.

Radiation therapy will begin shortly after the eight-week imaging scan. Participants will receive high-precision radiation (stereotactic body radiation therapy/SBRT) to the prostate over about two weeks. Based on the imaging results, doctors may give an extra "boost" of radiation to small areas that still show signs of active cancer. If the scans show that the cancer has responded well to hormone therapy, some patients may not need this extra boost. This approach is designed to deliver the strongest treatment where it is needed while limiting radiation to healthy tissue in order to minimize side effects.

The main goal of the study is to understand whether doctors can confidently use the mid-treatment PSMA PET/CT scan to guide radiation planning. Researchers will also monitor changes in PSA blood levels, imaging findings, treatment side effects, and patient-reported quality of life, including urinary, bowel, and sexual symptoms. Additionally, doctors participating in the study will provide feedback on how easy or difficult it is to define radiation target areas using the different scans.

Participation in this study lasts about 6 months, and all treatments provided are commonly used in prostate cancer care, with the incorporation of PSMA PET scans being the experimental component. While participants may or may not directly benefit, the results obtained from this study may help improve how radiation therapy is planned and delivered for future patients with prostate cancer, with the goal of maintaining treatment effectiveness while reducing side effects.