Purpose: Metastatic prostate cancer is incurable and a standard treatment is life-long, palliative, hormone therapy. Improving treatments for Veterans with metastatic prostate cancer is therefore an unmet need.
Background: The approach to metastatic prostate cancer is evolving in response to improvements in androgen suppressive therapies, demonstration that stereotactic body radiotherapy (SBRT) offers control of metastatic sites in excess of 95%, and improved imaging. Retrospective data from the West LA VA suggests Veterans with metastatic prostate cancer with 5 or fewer metastasis have improved outcomes as compared to those with > 5 metastases. This raises the question if a multimodal approach with aggressive, early treatment of newly diagnosed metastatic prostate cancer could be attempted with curative intent.
Methods: We will conduct a single arm phase 2 trial in 28 Veterans with newly diagnosed M1a,b prostate cancer and 1 to 5 radiographically visible metastases staged by NaF or PSMA PET-CT. Treatments include radical prostatectomy and adjuvant fractionated radiotherapy, metastasis directed SBRT, and complete ADT: leuprolide, abiraterone acetate, apalutamide for a total of six months systemic therapy. The primary endpoint is the percent of Veterans achieving a PSA < 0.05 ng/mL six months after recovery of testosterone to ≥ 150 ng/dL, a surrogate for disease control. Secondary endpoints include biochemical progression, radiographic progression, cancer specific survival, health-related quality of life. Prior to treatment, Veterans undergo a radiographic directed biopsy of a metastatic lesion to confirm metastatic disease and obtain metastatic tumor tissue for correlative genomic studies. Genomic analyses to investigate molecular correlates to lethal primary prostate tumors and the emergence of metastases will use the pretreatment tissue from directed biopsies of metastases and the radical prostatectomy specimens.
Conclusions: Accrual will proceed over five years at the VA West LA and Long Beach Medical Centers. It is anticipated that determination of the primary endpoint for each patient will take place within 18 months of his initiation of therapy.
Implications: The treatment approach to Veterans with oligometastatic prostate cancer could pivot from palliation toward cure. The correlative analyses could identify genomic features of potentially lethal primary tumors and may elucidate the proximal mechanistic drivers of metastasis.