Stereotactic Ablative Radiotherapy (SABR) May Reduce the Need for Long-Term Androgen Deprivation Therapy (ADT) in Patients with Oligometastatic Prostate Cancer

Abstract

We hypothesized that using SABR to treat men with 1-5 prostate adenocarcinoma metastases may reduce the need for long-term ADT. Men with 1-5 nodal, skeletal, or visceral prostate adenocarcinoma metastases were treated with SABR on a prospective clinical trial (NCT01859221) or registry. Active prostate disease was treated with standard radiotherapy. ADT was recommended but not required. Follow-up imaging was not required without PSA progression. Biochemical progression-free survival (bPFS) was defined as a PSA rise ≥2 ng/mL after SABR, clinical-PFS (cPFS) as new metastases on radiographic/clinical assessment, castrate-resistant-PFS (CRPC-PFS) as PSA/clinical progression despite continuous ADT, and widespread progression-PFS as ≥6 new metastases. Outcomes were assessed using the Kaplan Meier method from the start of the first course of SABR. Additional courses of SABR were considered at the time of oligoprogression. Metastasis site control was calculated from the start date of each course of SABR and censored at time of last imaging/biochemical assessment or widespread progression. Univariate analysis was performed using log-rank test. 37 men (29 clinical trial and 8 prospective registry) received SABR to 102 metastases (62 non-spine bone, 22 spine, 17 lymph node, and 1 lung). 95% had hormone sensitive disease. Doses ranged from 18-50 Gy in 1-10 fractions (50 Gy/10, 64% and 50Gy/5, 30%). 6 patients had synchronous primary disease. 32% had 1 metastasis, 32% had 2 metastases, and 34% had 3-5 metastases. 9 patients (24%) declined ADT, 15 (41%) stopped ADT after 6-12 months, and 13 (35%) remained on long-term continuous or intermittent ADT (≥24 months). Median follow-up was 3.6 years (1.7-5.2 years). 3-year metastasis site control was 97%. There was a trend towards improved 3-year bPFS survival in men who received upfront long-term ADT compared with no/short-term ADT (51% versus 14%, p = 0.08). However, long-term ADT did not appear to improve OS (80% versus 86%, p = 0.33), CRPC-PFS (61% versus 78%, p = 0.5), widespread-PFS (51% versus 61%, p = 0.74), or cPFS (38% versus 41%, p = 0.86). Of the 24 patients who initially declined or received short-term ADT, the median time to next therapy was 1.8 years (0.6-5.2), and 63% remain alive without clinical or 46% without biochemical progression and 21% remain off therapy. Only 1 grade 3+ toxicity (lumbar radiculopathy) was attributed to SABR. Oligometastatic prostate cancer caries a favorable long-term prognosis and SABR resulted in excellent metastasis site control with low morbidity. The majority of men declined upfront long-term ADT with no apparent impact on clinical disease control, progression to CRPC, or survival. These results warrant further validation including assessment on the impact on quality of life.