Modes of Failure Following Metastasis Directed Therapy in Patients with Oligometastatic Hormone Sensitive Prostate Cancer: A Multi-institutional Analysis

Purpose/Objective(s): Early data suggest that metastasis directed therapy (MDT) in oligometastatic prostate cancer (OPCa) is able to improve progression-free survival (PFS), improve overall survival (OS), and delay time to androgen deprivation therapy (ADT). However, many men have metastatic disease progression and their clinical course is not well characterized. Therefore, we aim to report oncologic outcomes, patterns of failure, and modes of progressors in a multi-institutional cohort of patients with OPCa treated with MDT using stereotactic ablative radiation therapy (SABR). The hypothesis was differences exist in modes of failure and classes of progressors related to patient characteristics. Materials/Methods: Oligometastatic disease was defined as ≤5 lesions. All patients were treated with SABR. Survival analysis was conducted for PSA failure (per PCa Working Group 2), time to next intervention (TTNI), distant metastasis-free survival (DMFS), OS, and biochemical PFS (bPFS) using the Kaplan-Meier method, log-rank test, and multivariate Cox regression analysis (MVA). Descriptive patterns of failure and modes of progressors were reported. Results: A total of 474 lesions were treated in 258 patients with a median follow-up of 25.2 months (interquartile range = 14.4 – 37.0). ADT was administered during MDT in 130 patients (50.4%). Median time to PSA failure was 15.7 months (95% CI = 13.9 – 23.4), TTNI was 28.6 months (95% CI = 24.6 – 42.9), and DMFS was 19.1 months (95% CI = 14.8 – 27.8). On MVA, bPFS was associated with N1 at diagnosis (hazard ratio [HR] = 1.84; 95% CI = 1.1 – 3.2), M1 at diagnosis (HR = 0.36; 95% CI = 0.2 – 0.9), initial PSA (HR = 1.001; 95% CI = 1.0007 – 1.002), use of ADT during MDT (HR = 0.36; 95% CI = 0.23 – 0.59), and pre-SABR PSA (HR = 1.02; 95% CI = 1.0 – 1.04). Initial MDT sites were bone (62.0%), lymph node (27.5%), or mixed pattern of metastasis (10.5%). Among the patients with recurrence, pattern of failure favored bone recurrence with 44.2% (50/113 patients) recurring in bone and 24.8% (28/113 patients) recurring in multiple locations including ≥1 bone lesion. Patients initially treated for bone metastases recurred again in bone 87.8% (72/82 patients) or shifted to node 12.2% (10/82 patients). Patients initially treated for nodal metastases recurred again in a node only 64.5% (20/31 patients) or shifted to bone 35.5% (11/31 patients). Modes of progressors were defined as three classes: [Class I] 40.9% of patients had long term control for >18 months post-MDT, [Class II] 28.1% of patients were oligoprogressors (≤3 lesions at recurrence) or 7.9% of patients had PSA failure with no metastatic disease, and [Class III] 23.1% of patients were polyprogressors (>3 lesions). Conclusion: Following MDT of OPCa, patterns of failure appeared to shift to bone recurrence rather than nodal recurrence. Most men treated with MDT either had long-term control (Class I) or were oligoprogressors (Class II), possibly making them amenable to repeat MDT. These findings have implications for future clinical trial design.