**Carlo Cattrini 1,2,\*, Davide Soldato 1,3, Alessandra Rubagotti 3,4, Linda Zinoli 3, Elisa Zanardi 1,3, Paola Barboro 3, Carlo Messina 5, Elena Castro 6, David Olmos <sup>2</sup> and Francesco Boccardo 1,3**


Received: 22 September 2020; Accepted: 1 October 2020; Published: 3 October 2020

**Simple Summary:** In randomized trials, both chemotherapy and androgen-receptor signaling inhibitors provided significant survival benefits in patients with metastatic prostate cancer (mPCa). However, it is largely unknown to what extent these therapeutic advances have impacted the general, real-world survival of patients with de novo mPCa. Here, we analyzed more than 26,000 patients included in the U.S. Surveillance, Epidemiology, and End Results (SEER) database to describe potential recent improvements in overall and cancer-specific survival. We found that patients diagnosed in the latest years showed a modest reduction in the risk of death and cancer-specific death, compared with those diagnosed in 2000–2003 and 2004–2010. Although our analysis was not adjusted for many confounders, the overall population of patients diagnosed in 2011–2014 only showed a survival gain of 4 months. Patients' ineligibility or refusal of anticancer treatments, insurance issues, intrinsic disease aggressiveness, or prior unavailability of drugs in a hormone-sensitive setting might contribute to these disappointing results.

**Abstract:** The real-world outcomes of patients with metastatic prostate cancer (mPCa) are largely unexplored. We investigated the trends in overall survival (OS) and cancer-specific survival (CSS) in patients with de novo mPCa according to distinct time periods. The U.S. Surveillance, Epidemiology, and End Results (SEER) Research Data (2000–2017) were analyzed using the SEER\*Stat software. The Kaplan– Meier method and Cox regression were used. Patients with de novo mPCa were allocated to three cohorts based on the year of diagnosis: A (2000–2003), B (2004–2010), and C (2011–2014). The maximum follow-up was fixed to 5 years. Overall, 26,434 patients were included. Age, race, and metastatic stage (M1) significantly affected OS and CSS. After adjustment for age and race, patients in Cohort C showed a 9% reduced risk of death (hazard ratio (HR): 0.91 (95% confidence interval [CI] 0.87–0.95), *p* < 0.001) and an 8% reduced risk of cancer-specific death (HR: 0.92 (95% CI 0.88–0.96), *p* < 0.001) compared with those in Cohort A. After adjustment for age, race, and metastatic stage, patients in Cohort C showed an improvement in OS and CSS compared with Cohort B (HR: 0.94 (95% CI 0.91–0.97), *p* = 0.001; HR: 0.89 (95% CI 0.85–0.92), *p* < 0.001). Patients with M1c disease had a more pronounced improvement in OS and CSS compared with the other stages. No differences were found between Cohorts B and C. In conclusion, the real-world survival of de novo mPCa remains poor, with a median OS and CSS improvement of only 4 months in the latest years.

**Keywords:** prostatic neoplasms/mortality; prostatic neoplasms/epidemiology; SEER Program
