Metastatic castration-resistant prostate cancer remains a challenging condition to treat. Among the available therapeutic options, the androgen receptor signaling inhibitors abiraterone acetate plus prednisone (AA) and enzalutamide (Enza), are currently the most used first-line therapies in clinical practice. However, validated clinical indicators of prognosis in this setting are still lacking. In this study, we aimed to evaluate a prognostic model based on the time of metastatic disease presentation (after prior local therapy [PLT] or de-novo [DN]) and disease burden (low volume [LV] or high-volume [HV]) at AA/Enza onset for mCRPC patients receiving either AA or Enza as first-line.
A cohort of consecutive patients who started AA or Enza as first-line treatment for mCRPC between January 1st, 2015, and April 1st, 2019 was identified from the clinical and electronic registries of the 9 American and European participating centers. Patients were classified into 4 cohorts by the time of metastatic disease presentation (PLT or DN) and volume of disease (LV or HV; per the E3805 trial, HV was defined as the presence of visceral metastases and/or at least 4 bone metastases of which at least 1 out the axial/pelvic skeleton) at AA/Enza onset. The endpoint was overall survival defined as the time from AA or Enza initiation, respectively, to death from any cause or censored at the last follow-up visit, whichever occurred first.
Of the 417 eligible patients identified, 157 (37.6%) had LV/PLT, 87 (20.9%) LV/DN, 64 (15.3%) HV/PLT, and 109 (26.1%) HV/DN. LV cohorts showed improved median overall survival (59.0 months; 95% CI, 51.0-66.9 months) vs. HV cohorts (27.5 months; 95% CI, 22.8-32.2 months; P = 0.0001), regardless of the time of metastatic presentation. In multivariate analysis, HV cohorts were confirmed associated with worse prognosis compared to those with LV (HV/PLT, HR = 1.87; p = 0.029; HV/DN, HR = 2.19; P = 0.002).
Our analysis suggests that the volume of disease could be a prognostic factor for patients starting AA or Enza as first-line treatment for metastatic castration-resistant prostate cancer, pending prospective clinical trial validation.
Journal of translational medicine. 2023 Feb 03*** epublish ***
Pier Vitale Nuzzo, Filippo Pederzoli, Calogero Saieva, Elisa Zanardi, Giuseppe Fotia, Andrea Malgeri, Sabrina Rossetti, Loana Valenca Bueno, Livia Maria Q S Andrade, Anna Patrikidou, Ricardo Pereira Mestre, Mikol Modesti, Sandro Pignata, Giuseppe Procopio, Giuseppe Fornarini, Ugo De Giorgi, Antonio Russo, Edoardo Francini, SPARTACUSS Investigators
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA., Cancer Risk Factors and Lifestyle Epidemiology Unit-ISPRO, Florence, Italy., Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy., Division of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy., Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy., Instituto D'Or de Pesquisa e Ensino, Salvador, State of Bahia, Brazil., Department of Medical Oncology, Gustave Roussy Institute, Villejuif, France., Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland., Oncology Unit, ASST Cremona, Cremona, CR, Italy., Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST), Meldola, Italy., Department of Surgical, Oncological, and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy., Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134, Florence, Italy. .