Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm.
To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM).
PubMed search from 2000 to 2022.
Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel.
Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022.
Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months).
From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]).
Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.
JAMA network open. 2023 Nov 01*** epublish ***
Brandon A Mahal, Lucia Kwak, Wanling Xie, James A Eastham, Nicholas D James, Howard M Sandler, Felix Y Feng, Meryem Brihoum, Karim Fizazi, Christopher Sweeney, Praful Ravi, Anthony V D'Amico
Department of Radiation Oncology, University of Miami, Miami, Florida., Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts., Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Institute of Cancer Research, London, United Kingdom., Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, California., Department of Radiation Oncology and Urology, University of California, San Francisco., Unicancer, Urogenital Tumor Study Group (GETUG), Paris, France., Institute Gustave Roussy, Department of Cancer Medicine, University of Paris-Saclay, Villejuif, France., South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia., Department of Medicine, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts., Department of Radiation Oncology, Brigham and Women's Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts.