The study was approved by the institutional review board of the authors' institutions (Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee/Ref no: CRE-2015.481). And permission to access the medical records through the inter-hospital computer network was granted by the aforementioned review board. Furthermore, the principles of the Helsinki Declaration were followed. Informed consent has been exempted by the review board as most of the patients in this study were dead when the data was collected.
Study Population and Treatment
In early 2011, AA was approved by the local health authority for use in patients with mCRPC who had received prior chemotherapy, and subsequently in 2012, also for chemo-naïve patients. The present review included mCRPC patients who were started on AA in 6 oncology centers between August 2011 and December 2014. All patients had metastatic prostate cancer which had progressed despite achieving castration-level of testosterone. Enzalutamide, another AR pathway targeted agent, was not accessible during the study period and only be commercially available since October 2015 in our locality. Patients with visceral disease who were medically unfit for, or who declined, chemotherapy, and treated with AA within the period were also included. Patients were treated with 1 g AA once daily in combination with 5 mg prednisone twice a day until disease progression, death or unacceptable toxicity. Clinical and biochemical follow-up with serum prostate-specific antigen (PSA), blood counts, liver and renal profile were regularly undertaken during the treatment period. Serum lactate dehydrogenase (LDH) was not a mandatory parameter to be regularly examined during the treatment. Regular imaging assessment was not mandatory unless clinical suspicion or biochemical progression was evident. Continuation of AA beyond disease progression and post-AA treatments were at the discretion of individual oncologists based on several factors including patient's preference, medical condition or affordability, physician's preference and availability of alternative treatment options.
Data Collection and Outcomes Measures
The electronic clinical records of the patient cohort were retrieved by the inter-hospital computer network. The definition of clinical, biochemical and radiological progressive disease was according to the Prostate Cancer Clinical Trials Working Group (PCWG-2) criteria. Overall survival (OS) and progression-free survival (PFS) were defined as time from first dose of AA to death, and to the first event of clinical, radiographic or PSA progression or death, respectively. Patients who had transient serum PSA level upsurge but not to the extent of biochemical progression (PCWG-2 criteria) followed by a drop, were defined as having PSA flare. PSA doubling time (PSA-DT) was calculated by determining the regression slope of the log PSA against time based on 3 consecutive PSA measurements prior to AA. Patients who had reduction or withdrawal of WHO class II or III analgesics according to the WHO analgesics ladder during or after AA was regarded as having improvement in pain control. Treatment-related toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) 4.02 toxicity scale.
Statistical analysis was performed using the Statistical Package for the Social Sciences (Windows version 220.127.116.11; SPSS Inc, Chicago, US). The updated database as at 1 May 2015 was used for analysis. Kaplan-Meier plots of OS and PFS were obtained for subsets of patients segregated by various potential prognosticators. The log-rank test was employed to assess the difference in outcome between subsets. The variables were also subject to multivariate analyses using the Cox proportional hazards regression model. P values ≤ 0.05 were considered significant. The hazard ratio (HR) and the corresponding 95 % confidence interval were calculated.
BMC Urol. 2016;16(12) © 2016 BioMed Central, Ltd.