Abstract
Introduction: Prostate cancer (PCa) is the second leading cause of cancer mortality in US males, with metastatic disease (mPCa) comprising 5% of cases. This represents an incurable and uniformly lethal disease. Thus, novel therapeutic approaches are needed. Cytoreductive surgery in the metastatic setting has become commonplace for renal cell carcinoma, and definitive local radiotherapy has been employed in the oligometastatic setting for prostate cancer via the STAMPEDE trial. This study further explores the use of definitive local treatment via pelvic radiotherapy or radical prostatectomy along with androgen deprivation therapy (ADT) vs. ADT alone in the setting of metastatic prostate cancer.
Methods: The 2019 National Cancer Database (NCDB) was queried to conduct a retrospective cohort analysis of cT1-4N0-3M1 PCa who received local therapy in conjunction with ADT vs. ADT alone. Clinicopathologic variables were compared between the two groups using Wilcoxon signed rank and Chi-square for continuous and categorical variables, respectively. Overall survival (OS) analysis was performed using Cox Proportional Hazards and the Kaplan-Meier method. Comparisons were made between local therapy + ADT vs. ADT alone and between radical prostatectomy + ADT vs. radiation therapy + ADT vs. ADT alone.
Results: A total of n=36,635 patients with cM1 were identified, with 3197 (8.7%) patients receiving local therapy + ADT. Among local therapy + ADT, 2884 (90.2%) patients received radiation therapy + ADT, and 313 (9.8%) received radical prostatectomy + ADT. The median follow-up was 2.8 years. Kaplan-Meier analysis showed significant improvement in 5-year OS for patients who received local therapy + ADT vs. ADT alone. For ADT alone, 5-year OS was 31.3% (CI= 30.7-31.8%) vs. 54.2%. (CI= 52.4-56.1%) for local therapy +ADT. Furthermore, comparing the type of local therapy on Kaplan-Meier analysis: radical prostatectomy + ADT showed better 5-yr OS, 74.0% (CI= 67.5-79.1%) vs. 52.2% (CI= 50.2-54.2%) for radiation therapy +ADT (p<0.001).
Conclusion: Definitive local treatment, in addition to ADT, may improve 5-year OS for well-selected patients with metastatic prostate cancer. Patient outcomes are significantly improved for those treated with radical prostatectomy vs. radiation therapy. These findings support multimodal treatment for metastatic prostate cancer, and further studies are needed to optimize criteria for patient selection and choice of definitive localized therapy in this setting.