Background
toxicity, prostate, Prostate cancer, prostate cancer deaths, prostate cancer
DISEASE, PROSTATE CANCER RECURRENT, DNA DAMAGE, PROSTATE, PROSTATE CANCER, PROSTATE CANCER
Prostate cancer is a major male health issue, with over 1.4 million new cases of prostate cancer diagnosed and 375,000 new prostate cancer deaths in 2020 worldwide [There are several potentially curative treatment options for patients with ILF, including salvage radical prostatectomy (RP), as well as prostate directed ablative therapies such as cryotherapy, high intensity focused ultrasound (HIFU), and salvage radiotherapy options such as stereotactic body radiation therapy (SBRT), low dose rate (LDR) brachytherapy or high dose rate (HDR) brachytherapy. In a recent meta-analysis comparing these options, the chances of recurrence-free survival (RFS) were similar, with approximately half of patients with durable disease control with the different salvage techniques [Prostate-specific membrane antigen positron emission tomography (PSMA PET) has been used more recently as a tool to detect prostate cancer recurrence after radiation treatments. In this setting, PSMA PET has been shown to change the management plan in a majority of patients when compared to the management plan based on conventional imaging alone [Lu-177 PSMA RLT emits beta particles with a maximum energy of 497 keV, which limits the range of these particles in tissue to less than 2 mm [We hypothesized that a theragnostic combination targeting PSMA may improve outcomes and reduce toxicity in men with suspected ILF after definitive radiotherapy. Specifically, use of a diagnostic PSMA-targeting agent will improve our ability to select men with a high probability of ILF. The use of a PSMA-targeting RLT would then allow the selective treatment of the site of ILF as well as potential extra-prostatic disease not detectable even with the diagnostic PSMA PET imaging. In ROADSTER, we aim to assess safety and feasibility of adding Lu-177 PSMA RLT in combination with HDR brachytherapy for ILF after definitive radiotherapy. A randomized phase I/II design will be used to provide a contemporaneous cohort of men treated with our institutional standard salvage therapy of two fractions of HDR. Translational endpoints will include acquisition of liquid and tissue biospecimens for the assessment of response biomarkers and assessment of DNA damage and immune activation among the two cohorts.