Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry

This prospective, noninterventional analysis of patient record data from the multicenter PCR of men with mCRPC was conducted to gain a greater understanding of real-world outcomes in a broad group of patients treated for mCRPC to optimize future treatment of patients with this disease. We focused on the characteristics and clinical outcomes of patients, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases, who received their first treatment for mCRPC during participation in the PCR. The data for the PCR were collected at 199 centers specializing in the treatment of prostate cancer by both oncologists and urologists in a range of settings (including hospitals, private clinics, outpatient departments, and universities) in 16 countries: Austria, Belgium, France, Germany, Israel, Italy, Luxembourg, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Turkey, and the UK. Patient enrollment took place between 2013 and 2016. At the start of the PCR, abiraterone acetate and enzalutamide were not routinely available in the mCRPC setting in all 16 countries. The study duration was 5.5 years, with a maximum patient follow-up of 3 years, and was designed specifically to include more than one line of therapy where applicable. The study end date was 9 July 2018.

Men aged ≥ 18 years with a histologically or cytologically confirmed diagnosis of prostate adenocarcinoma with mCRPC (disease progression despite testosterone < 50 ng/dL and/or androgen deprivation therapy and/or history of orchiectomy), enrolled at any time after diagnosis, under surveillance according to routine clinical practice, or who initiated a systemic treatment for mCRPC (as required) following baseline data collection at enrollment, were eligible. The PCR included patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, “abiraterone”), enzalutamide, docetaxel, other chemotherapy, and radium-223. Only treatment groups with adequate numbers of patients (> 50) for reliable analysis were included. Patients treated with other chemotherapy or radium-223 were excluded because the numbers were too low.

Treatment outcomes were duration of initial therapy and reasons for stopping initial mCRPC therapy. Appropriate treatment gaps for classifying subsequent therapy were 30 days for abiraterone or enzalutamide and 60 days for docetaxel, which included any prolonged, temporary treatment discontinuation. Efficacy outcomes were OS at 3 years after enrollment and time to progression. Criteria for disease progression on treatment (date of recording progression/assessment) were met if: (1) there was evidence of radiographic progression by investigator’s assessment (Prostate Cancer Working Group 2 and Response Evaluation Criteria In Solid Tumors guidelines were recommended by the protocol); (2) there was evidence of clinical progression by investigator’s assessment (date of the patient visit); (3) first-line mCRPC treatment was stopped because of progression (date treatment stopped); or (4) new mCRPC treatment was started because of progression (date new treatment began). The treatment effects for time to progression with the therapies of interest were compared for the entire analysis population. We compared treatment outcomes in the whole analysis population with those in subgroups of patients with baseline cardiovascular disease requiring treatment (including at least one of the following co-morbidities: hypertension, angina pectoris, history of myocardial infarction, arrhythmia, thromboembolic disease, transient ischemic attack, cerebrovascular accident, and/or other cardiovascular event), diabetes mellitus, or visceral metastases (defined as lesions in the liver and/or lung). These patient subgroups are typically under-represented in clinical studies. Adverse events were collected only for those patients receiving abiraterone, as a regulatory requirement.

We used observational methodology to capture data. The treating physician made treatment decisions at his or her discretion, per routine clinical practice, and only data available from clinical practice were collected. We collected prior disease history and management data at study inclusion and clinical data at study inclusion and prospectively every 3 months during routine follow-up (at least every 3 months per protocol) over the 3-year study period, with clinical-trial levels of monitoring quality (see Supplementary Fig. S1). Because docetaxel is administered through a maximum number of cycles (typically 6–10 cycles as appropriate), outcomes influenced by duration of docetaxel treatment should not be compared with those of abiraterone or enzalutamide. Cause of death data were not collected.

To ensure a patient population representative of that seen in clinical practice and to reduce selection bias, the protocol stated that all consecutive patients meeting the eligibility criteria at a participating site and who agreed to participate according to local regulations were enrolled in the PCR, irrespective of their treatment.

Of more than 3000 men included in the PCR, data from patients who were being treated with abiraterone, enzalutamide, or docetaxel as first-line mCRPC therapy and who had not received previous systemic mCRPC treatment were included in this analysis. The PCR was designed to generate data for informative purposes. Thus, this sample size was determined by pragmatic considerations, to provide data from a large population that is representative of patients with mCRPC in the Europe/Middle East region.

We only used descriptive statistics to present observed data from routine clinical practice. To manage confounding, we used propensity score methods for the comparative effectiveness analyses. We did not apply missing data imputation methods; thus, there were no sensitivity analyses, and subgroups were constructed based on medical criteria (i.e., treatment received, co-morbidities).

At the end of study, 3003 patients were evaluated, 1874 (62.4%) of whom had received no previous mCRPC treatment; of these, 1654 (88.3%) started a treatment documented in the PCR (abiraterone, enzalutamide, docetaxel, other chemotherapy, radium-223, trial medication). Abiraterone, enzalutamide, or docetaxel as first-line mCRPC therapy was received by 754, 227, and 602 patients, respectively, with a median follow-up of 18.6 months. The number of patients and study flow are presented in the Supplementary Material (Fig S2).