Discussion
tumor, CRPC, occult extra-prostatic disease, toxicity, occult metastatic disease, prostate, prostate HDR, prostate cancer
TUMOR, DISEASE, RECURRENT DISEASE, METASTATIC DISEASE, PROSTATE, SECONDARY, PROSTATE CANCER, CANCER RELAPSE
As a primary outcome, the ROASDTER trial investigates the feasibility and safety of a novel salvage strategy that combines Lu-177 PSMA RLT with HDR brachytherapy in patients with proven radiorecurrent ILF with no signs of metastatic disease. By adding Lu-177 PSMA RLT as a systemic therapy early in the course of cancer relapse, occult metastatic disease may be treated early, potentially reducing rates of systemic progression, which is the most frequent pattern of relapse in this setting [Given the physical and biological characteristics of Lu-177 PSMA RLT, we hypothesize this may have an improved toxicity profile compared with other salvage therapy options. Specifically, in a comprehensive meta-analysis of salvage therapy options, there were lower severe genitourinary (GU) toxicity rates amongst the radiation salvage options compared with the non-radiation options. The severe GU toxicity rates for SBRT, LDR brachytherapy, and HDR brachytherapy were 5.6%, 9.1%, and 9.6%, respectively, while the severe GU toxicity rates for cryotherapy, RP and HIFU were 15%, 21%, and 23%, respectively [As a secondary outcome, this trial investigates disease control associated with a standard salvage treatment option, involving two fractions of prostate HDR brachytherapy, in the PSMA-PET era. Most of the salvage data in the literature precedes PSMA PET use and the ROADSTER trial may provide a new benchmark by using PSMA PET as a screening tool to select patients with lower likelihood of having any occult extra-prostatic disease at the time of diagnosing the ILF. This “stage migration” effect may allow for patients who are included in the trial to have a more favourable recurrence-free survival, with adequate treatment of their ILF site. Moreover, PSMA PET and MR data together may allow for more accurate definition of the recurrent disease in the prostate at the time of HDR prostate brachytherapy boost with a focused boost to the lesion and better OAR sparing [Additional outcomes in ROADSTER trial include translational studies, assessing the effects of Lu-177 PSMA RLT and HDR brachytherapy on the radiorecurrent prostate cancer. Tissue, blood, and urine biospecimens will be collected at during the study. These biospecimens will be interrogated to characterize effects on tumor and normal tissue radiation injury and immune activation and to assess for potential biomarkers of response or toxicity after Lu-177 PSMA RLT and HDR brachytherapy.While out of scope for the current trial protocol, which is focused on safety and feasibility endpoints, our practice for men receiving salvage brachytherapy includes long term biochemical and clinical monitoring. Future plans will include examination of long-term disease control and side effects in this population.While there are several Lu-177 PSMA RLT trials ongoing for patients with CRPC, there are only a few studies that are incorporating Lu-177 PSMA RLT in metastatic castrate sensitive prostate cancer (CSPC): (NCT04720157; NCT04443062; NCT05079698; NCT04343885; and NCT03828838) [In summary, the ROADSTER trial is a randomized phase I/II trial investigating safety, feasibility and early efficacy of a novel salvage treatment strategy involving Lu-177 PSMA RLT in conjunction with whole prostate HDR brachytherapy with a focused boost. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy. Access to MR and PSMA PET imaging will allow for localization of the recurrent disease within the prostate, guidance of focal boost delivery at the time of HDR brachytherapy and the precision acquisition of tissue biospecimens from involved and uninvolved prostate for translational science correlative studies.