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Following prostatectomy the treatment of biochemically-relapsing prostate cancer patients consists in salvage prostate bed radiotherapy combined with hormone therapy. Following local salvage treatment, most relapses are metastatic. At the metastatic stage novel androgen-receptor targeting agents such as abiraterone acetate are now routinely used. To further reduce the metastatic risk, we conducted an open-label, multicenter, single-arm, phase II trial (NCT01780220) to evaluate the efficacy and safety of the addition of abiraterone acetate to salvage prostate bed radiotherapy combined with goserelin in biochemically-relapsing prostate cancer patients and determined if the presence of circulating tumor cells could predict for the risk of relapse following treatment.  

We hypothesized that combined abiraterone, goserelin and prostate bed radiotherapy  would increase biochemical-relapse free survival above 70% at 3 years. We recruited men who had an history of adenocarcinoma of the prostate treated by surgery, and who had a rising of their serum PSA above or equal to 0.2 ng/mL, at least 6 months after radical prostatectomy. All patients were treated by prostate bed salvage radiotherapy (66 Gy in 33 f) and by abiraterone acetate plus prednisone plus LH-RH agonist for 6 months in total. Primary outcome consisted in biochemical recurrence-free survival (bRFS), in which recurrence was defined by a re-elevation of serum PSA ≥0.5 ng/ml. Secondary outcomes consisted in alternative biochemical recurrence-free survival (alt-bRFS) using an alternative PSA cut-off defined as ≥0.2 ng/ml, metastasis-free survival and overall survival. Circulating tumor cells (CTC) were detected using the CellsearchTM system (cut-off for positivity ≥ 5 CTC) prior to treatment.

We enrolled 46 patients, of which 78% were considered at high-risk according to EAU guidelines for stratification. The median follow-up was 47 months. The experimental regimen showed good outcomes with 3-year rates of bRFS and alt-bRFS rate at 97.8% and 84.8%, respectively.  Severe acute or late toxicities related to radiotherapy were scarce as expected. Rate of hepatic cytolysis of all grades, was surprisingly high with abiraterone acetate treatment (50% of patients), including cases of grades 3-4 (18% of patients). CTC were detected in 5 (11%)  patients, which was not associated to baseline characteristics, such as PSA doubling time (p =0.892), PSA level (p =0.975), or ISUP group (p =0.991). Detecting circulating tumor cells at baseline was significantly associated to poorer bRFS (p =0.008) and alt-bRFS (p =0.04). 

The addition of abiraterone acetate to salvage radiotherapy and LHRH agonist resulted in high rates of biochemical relapse-free survival. Adverse effects were manageable, but a close surveillance of liver toxicity is advised. CTC detection at baseline could represent a promising prognostic factor of oncological outcomes following salvage treatment.