Real World Evaluation of Upfront Docetaxel in Metastatic Castrate Sensitive Prostate Cancer

Abstract Background: Recent randomised phase III trials demonstrate survival benefit for the addition of upfront docetaxel to androgen deprivation therapy (ADT) in metastatic castrate sensitive prostate cancer (mCSPC). Following its implementation in routine care, this combined treatment strategy needs further evaluation in a real world setting.Methods: A multicentre retrospective cohort study in the South East Health care region of Sweden was conducted. All patients given upfront docetaxel for mCSPC from July 2015 until December 2017 were included. Primary endpoint was progression free survival (PFS) at 12 months and secondary endpoints were PFS at 24 months, overall survival (OS), treatment intensity, adverse events, and unplanned hospitalisations. Exploratory analyses on potentially prognostic parameters were performed.Results: 94 patients were eligible and formed the study cohort. PFS at 12 and 24 months were 75% (95% CI 66-84) and 58% (46-70). OS at 12 and 24 months were 93% (87-99) and 86% (76-96). 91% (n=86) initiated docetaxel according to the standard protocol of 75 mg/m2 every 3 weeks (6 cycles), whereas 9% (n=8) received a modified protocol of 50 mg/m2 every 2 weeks (9 cycles). The average overall dose intensity for those commencing standard treatment was 91%. Univariate cox regression analyses revealed that baseline PSA >180 vs <180 and presence vs absence of distant metastases were 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, the statistical significance remained for PSA (2.51, 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) and 26% (n=24) had at least one episode of unplanned hospitalisation under and up to 30 days after the treatment course. Conclusions: The outcome and safety profile of upfront docetaxel in addition to androgen deprivation therapy in metastatic castrate sensitive prostate cancer appear similar in real world and randomised controlled populations. Further implementation of this treatment strategy is encouraged.