• Stéphane Oudard, Igor Latorzeff, Armelle Caty, Laurent Miglianico, Emmanuel Sevin, Anne Claire Hardy-Bessard, Remy Delva, Frédéric Rolland, Loic Mouret, Franck Priou, Philippe Beuzeboc, Gwenaelle Gravis, Claude Linassier, Philippe Gomez, Eric Voog, Xavier Muracciole, Christine Abraham, Eugeniu Banu, Jean-Marc Ferrero, Alain Ravaud, Ivan Krakowski, Jean-Léon Lagrange, Gaël Deplanque, David Zylberait, Laurence Bozec, Nadine Houede, Stéphane Culine, and Reza Elaidi.
• Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris, France.
• JAMA Oncol. 2019 May 1; 5 (5): 623-632.

ImportanceAndrogen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting.ObjectiveTo assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease.Design, Setting, And ParticipantsThis open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used.InterventionsPatients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year).Main Outcomes And MeasuresThe primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life.ResultsOverall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life.Conclusions And RelevanceCompared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.Trial RegistrationFrench Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166.

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