Abstract
BACKGROUND: The majority of patients with newly diagnosed metastatic prostate cancer (PC) initially respond to androgen deprivation therapy (ADT) and are classified as metastatic castration-sensitive PC (mCSPC). Following months to years of ADT, the disease tends to become resistant to ADT. Recent randomized phase-III trials demonstrated a survival benefit with the addition of upfront docetaxel to ADT in mCSPC. Following its implementation in routine care, this combined treatment strategy requires more detailed evaluation in a real-world setting. AIM: To assess the real-world outcome and safety of upfront docetaxel treatment in mCSPC. METHODS: A multicenter retrospective cohort study in the Southeast Health Care Region of Sweden was performed. This region includes approximately 1.1 million citizens and the oncology departments of Linköping, Jönköping, and Kalmar. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. The primary endpoint was progression-free survival (PFS) at 12 mo, and the secondary endpoints were PFS at 24 mo, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalizations. Exploratory analyses on potential prognostic parameters were performed. RESULTS: Ninety-four patients were eligible and formed the study cohort. PFS at 12 and 24 mo was 75% (95%CI: 66-84) and 58% (46-70), respectively. OS at 12 and 24 mo was 93% (87-99) and 86% (76-96). A total of 91% of patients (n = 86) were given docetaxel according to the standard protocol of 75 mg/m(2) every 3 wk (6 cycles), while 9% (n = 8) received a modified protocol of 50 mg/m(2) every 2 wk (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate Cox regression analyses show that baseline PSA > 180 vs < 180 and the presence of distant metastases vs locoregional lymph node metastases were only negative prognostic factors (HR 2.86, 95%CI: 1.39-5.87, P = 0.0041 and 3.36, 95%CI: 1.03-10.96, P = 0.045). Following multivariate analysis, statistical significance remained for PSA (2.51, 95%CI: 1.21-5.19, P = 0.013) but not for metastatic status (2.60, 95%CI: 0.78-8.65, P = 0.12). Febrile neutropenia was recorded in 21% (n = 20) of patients, and 26% (n = 24) had at least one episode of unplanned hospitalization under and up to 30 d after the treatment course. CONCLUSION: Results from this study support the implementation of upfront docetaxel plus ADT as part of the standard of care treatment strategy in mCSPC.