Nuzzo et al. Journal of Translational Medicine (2023) 21:75 https://doi.org/10.1186/s12967-022-03861-2 RESEARCH © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Open Access Journal of Translational Medicine Clinical impact of volume of disease and time of metastatic disease presentation on patients receiving enzalutamide or abiraterone acetate plus prednisone as frst-line therapy for metastatic castration-resistant prostate cancer Pier Vitale Nuzzo 1 , Filippo Pederzoli 1 , Calogero Saieva 2 , Elisa Zanardi 3 , Giuseppe Fotia 4 , Andrea Malgeri 5 , Sabrina Rossetti 6 , Loana Valenca Bueno 7,8 , Livia Maria Q. S. Andrade 7,8 , Anna Patrikidou 9 , Ricardo Pereira Mestre 10 , Mikol Modesti 10 , Sandro Pignata 6 , Giuseppe Procopio 11 , Giuseppe Fornarini 3 , Ugo De Giorgi 12 , Antonio Russo 13 and Edoardo Francini 14* on behalf of the SPARTACUSS Investigators Abstract Background 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. Methods 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. Results 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 *Correspondence: Edoardo Francini edoardo.francini@unifi.it Full list of author information is available at the end of the article