48: Intermittent Androgen Deprivation Therapy Plus Comprehensive Stereotactic Radiotherapy for Oligometastatic Prostate Cancer (CROP)

Purpose/Objective(s)The standard treatment for metastatic prostate cancer is systemic therapy. This prospective phase I/II study assessed the utility of SBRT to all tumor sites plus intermittent androgen deprivation therapy (ADT) in patients with hormone sensitive oligometastatic prostate cancer. Endpoints included incidence of SBRT induced late toxicities and clinical outcomes including cumulative incidences of developing biochemical progression, new metastases, restarting ADT, castration resistant prostate cancer (CRPC), and overall survival (OS).Materials/MethodsSynchronous and metachronous metastatic disease presentations were eligible if there were ≤ 5 metastases, with ≤ 3 metastases in any one organ system. Conventional scans (CT/bonescan +/- MRI) were used to stage patients at baseline, although novel PET imaging was optional. SBRT was delivered to all sites of disease, including the prostate if not previously treated. SBRT dose was site dependent but was generally 30-35 Gy in 5 fractions for lymph nodes and non-spine bone lesions, 24-28 Gy in 2 fractions for spine, and 35 Gy in 5 fractions to the prostate. ADT was started prior to or immediately after SBRT and was continued for 1 year before moving to an intermittent approach. ADT was to be restarted when the PSA reached ≥ 10 ng/mL or earlier if clinically indicated (development of new metastases or rapidly rising PSA). Toxicity (CTCAE v4.0) and PSA measurements were collected every 4 months during follow-up. Conventional scans were performed at a minimum of once per year, but more frequent imaging was allowed at the discretion of the physician. Time zero was start of ADT or SBRT, whichever was earlier.Results92 patients with 158 metastases were accrued with a median age of 74 years. Median follow-up time was 37 months. Median baseline PSA was 8.5 ng/mL (range 0.78 – 179.8). 39 (42%) patients had Gleason score of 8-10. 32 (35%) patients had synchronous disease presentation. 14 (15%) patients were staged with PET imaging. 5 (5%) patients developed late grade 3 GU toxicity and 6 (7%) patients developed a late SBRT induced bone fracture. There were no grade 4/5 toxicities. Median PSA nadir was 0.02 ng/mL. 50% of patients reached a PSA nadir of ≤ 0.02 ng/mL, while 92% of patients reached a PSA nadir of < 1 ng/mL. The cumulative incidence (CI) of biochemical progression (PSA nadir + 2 ng/mL) was 54% at 4 years. The 4-year CI of developing new metastases and local failure of irradiated sites was 42.8% and 7%, respectively. The 4-year CI of restarting ADT and developing CRPC was 62% and 25%, respectively. OS was 79% at 4 years.ConclusionThe incidence of grade ≥ 3 toxicity was low when combining SBRT with intermittent ADT for hormone sensitive oligometastatic prostate cancer. With > 3 years of median follow-up, outcomes are promising compared to historical results of using ADT alone, particularly with regards to the development of CRPC. Further work will be done to identify potential predictors of clinical outcomes. The standard treatment for metastatic prostate cancer is systemic therapy. This prospective phase I/II study assessed the utility of SBRT to all tumor sites plus intermittent androgen deprivation therapy (ADT) in patients with hormone sensitive oligometastatic prostate cancer. Endpoints included incidence of SBRT induced late toxicities and clinical outcomes including cumulative incidences of developing biochemical progression, new metastases, restarting ADT, castration resistant prostate cancer (CRPC), and overall survival (OS). Synchronous and metachronous metastatic disease presentations were eligible if there were ≤ 5 metastases, with ≤ 3 metastases in any one organ system. Conventional scans (CT/bonescan +/- MRI) were used to stage patients at baseline, although novel PET imaging was optional. SBRT was delivered to all sites of disease, including the prostate if not previously treated. SBRT dose was site dependent but was generally 30-35 Gy in 5 fractions for lymph nodes and non-spine bone lesions, 24-28 Gy in 2 fractions for spine, and 35 Gy in 5 fractions to the prostate. ADT was started prior to or immediately after SBRT and was continued for 1 year before moving to an intermittent approach. ADT was to be restarted when the PSA reached ≥ 10 ng/mL or earlier if clinically indicated (development of new metastases or rapidly rising PSA). Toxicity (CTCAE v4.0) and PSA measurements were collected every 4 months during follow-up. Conventional scans were performed at a minimum of once per year, but more frequent imaging was allowed at the discretion of the physician. Time zero was start of ADT or SBRT, whichever was earlier. 92 patients with 158 metastases were accrued with a median age of 74 years. Median follow-up time was 37 months. Median baseline PSA was 8.5 ng/mL (range 0.78 – 179.8). 39 (42%) patients had Gleason score of 8-10. 32 (35%) patients had synchronous disease presentation. 14 (15%) patients were staged with PET imaging. 5 (5%) patients developed late grade 3 GU toxicity and 6 (7%) patients developed a late SBRT induced bone fracture. There were no grade 4/5 toxicities. Median PSA nadir was 0.02 ng/mL. 50% of patients reached a PSA nadir of ≤ 0.02 ng/mL, while 92% of patients reached a PSA nadir of < 1 ng/mL. The cumulative incidence (CI) of biochemical progression (PSA nadir + 2 ng/mL) was 54% at 4 years. The 4-year CI of developing new metastases and local failure of irradiated sites was 42.8% and 7%, respectively. The 4-year CI of restarting ADT and developing CRPC was 62% and 25%, respectively. OS was 79% at 4 years. The incidence of grade ≥ 3 toxicity was low when combining SBRT with intermittent ADT for hormone sensitive oligometastatic prostate cancer. With > 3 years of median follow-up, outcomes are promising compared to historical results of using ADT alone, particularly with regards to the development of CRPC. Further work will be done to identify potential predictors of clinical outcomes.