Introduction & Objectives
Abiraterone acetate (AA) has established efficacy in mCRPC. AA withdrawal syndrome (AAWS) is characterized by a temporary decrease in PSA levels after AA cessation, and occurs in 6%-23% of patients, with variable clinical response. Its mechanism and clinical significance are still unclear. We report our center experience with AAWS in patients with mCRPC.

Materials & Methods
This is an observational, retrospective, single-center cohort study of patients with mCRPC treated with AA + prednisolone. Patients with AAWS, defined by any decrease in PSA level after AA discontinuation, were included. Clinical data and survival outcomes were collected from electronic medical records.

Results
Between January 2013 and July 2020 57 patients with mCRPC were treated with AA. Thirty-eight discontinued AA due to disease progression; 5 had AAWS criteria (13%). At diagnosis the median age of these 5 patients was 76 y (range 61-87) and median PSA was 14.3 (range 9-53); 3 patients already had metastatic disease. All developed bone metastases and 3 also visceral involvement. All were considered high-volume disease by CHAARTED criteria. During castration-sensitive phase (mCSPC), all patients were treated with continuous androgen blockade (median 21.0 months, range 12.8-124.5), and 1 with orchidectomy. Two patients had experienced withdrawal syndrome with bicalutamide. Three patients were previously treated with docetaxel (2 mCSPC, 1 mCRPC). The duration of response to AA (median of 6.6 months, range 3.0-16.8), and the magnitude of PSA reduction (78.8%, range 8.4%-91.7%) were variable. AAWS was associated with symptom improvement in 1 patient. Two patients started subsequent treatment immediately (docetaxel, cabazitaxel) while two started only upon PSA rise (AA rechallenge and docetaxel); the remaining patient is still responding 22.3 weeks after AA discontinuation. Prednisolone was stopped in 2 patients and switched to dexamethasone in the other 3. Four patients have died, 6.8 to 15.8 months after AA withdrawal.

Conclusions
AAWS is poorly understood, with variable presentation and evolution. We observed AAWS both in patients treated with AA in first line and patients previously exposed to docetaxel. It is unclear whether the response was due to AA discontinuation or to the steroid manipulation. Although AAWS may be associated with durable symptomatic and biochemical response, and allow for longer chemotherapy-free survival in some patients, its clinical role is still unclear.

Abiraterone acetate withdrawal syndrome in metastatic castration-resistant prostate cancer (mCRPC)