Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Nov 24, 2021; 12(11): 1009-1022
Published online Nov 24, 2021. doi: 10.5306/wjco.v12.i11.1009
Real-world evaluation of upfront docetaxel in metastatic castration-sensitive prostate cancer
Jenny Isaksson, Henrik Green, Dimitrios Papantoniou, Linn Pettersson, Mats Anden, Johan Rosell, Elisabeth Åvall-Lundqvist, Nils Oskar Elander
Jenny Isaksson, Elisabeth Åvall-Lundqvist, Nils Oskar Elander, Department of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
Henrik Green, Division of Drug Research, Department of Biomedical and Clinical Sciences, Linköping University, Linköping 58185, Sweden
Dimitrios Papantoniou, Linn Pettersson, Department of Oncology, Ryhov County Hospital, Jönköping 55305, Sweden
Mats Anden, Department of Oncology, Kalmar County Hospital, Kalmar 39244, Sweden
Johan Rosell, Regional Cancer Center Southeast Sweden, Linköping University, Linköping 58185, Sweden
Author contributions: Isaksson J, Green H, Åvall-Lundqvist E and Elander NO designed the study; Isaksson J acquired the patient data with the help of Papantoniou D, Pettersson L and Anden M at the respective sites; Isaksson J, Green H, Rosell J and Elander NO analyzed the data; Isaksson J, Green H and Elander NO drafted the first version of the manuscript; all authors helped develop the methodology and perform the investigation, and all read and approved the final manuscript.
Institutional review board statement: The study was conducted in accordance with the Declaration of Helsinki and was approved by the Regional Ethics Review board in Linköping, Region Östergötland, Sweden, No. 2018/139–31.
Informed consent statement: Based on the retrospective and noninterventional nature of the study and the absence of publication of individual data, the ethics board did not consider it possible or necessary to obtain written informed consent.
Conflict-of-interest statement: None of the authors have any conflicts of interest to declare.
Data sharing statement: Additional data are available at reasonable request to the corresponding author.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Nils Oskar Elander, MD, PhD, Doctor, Department of Oncology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping University Hospital, Linköping 58185, Sweden. nils.elander@liu.se
Received: March 23, 2021
Peer-review started: March 23, 2021
First decision: July 27, 2021
Revised: August 9, 2021
Accepted: October 18, 2021
Article in press: October 18, 2021
Published online: November 24, 2021
Processing time: 241 Days and 1.1 Hours
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/m2 every 3 wk (6 cycles), while 9% (n = 8) received a modified protocol of 50 mg/m2 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.

Keywords: Prostate cancer; Chemotherapy; Docetaxel; Castration sensitive; Metastatic; Real world

Core Tip: Two recent trials reported impressive outcomes when upfront docetaxel is added to androgen deprivation therapy in metastatic castration-sensitive prostate cancer (mCSPC). This study presents the outcome and safety of this treatment strategy in a real-world context of all eligible patients in the southeast region of Sweden. While the treatment is toxic in terms of febrile neutropenia and unplanned hospitalizations, the outcome and long-term prognosis appear similar in real life and randomized controlled trial contexts. Further implementation of upfront docetaxel in mCSPC in routine care is encouraged.