Temporal changes in survival in men with <i>de novo</i> metastatic prostate cancer: nationwide population-based study

<b>Background:</b> There have been large changes in the pattern of detection, work-up and treatment of men with prostate cancer during the last two decades. Therefore, we aimed to investigate temporal changes in survival in men with metastatic prostate cancer. <b>Methods:</b> Population-based cohort study in Prostate Cancer data Base Sweden of 13,709 men with <i>de novo</i> metastatic prostate cancer diagnosed between 1998 and 2015. Overall survival in four calendar periods were compared by the use of Kaplan–Meier analyses and Cox regression models including age at diagnosis, <i>T</i> stage and serum levels of prostate-specific antigen (PSA). <b>Results:</b> Between 1998–2001 and 2010–2015, median survival increased with 6 months for all men. The largest increase in survival was 14 months in men age 60–69 at diagnosis and in multivariable analysis risk of death decreased for men diagnosed in 2010–2015 compared to 1998–2001, hazard ratio (HR) 0.77 (95% CI: 0.68–0.86). The median PSA at date of diagnosis decreased with 46% from 181 ng/mL in 1998 to 98 ng/mL in 2015. <b>Conclusions:</b> There was an increase in survival among men with <i>de novo</i> metastatic prostate cancer in Sweden between 1998 and 2015. This increase was due to a decreased cancer extent indicated by lower PSA levels with ensuing longer lead times and speculatively also due to an increased use of chemotherapy in the latest time period. Given the increasing use of systemic treatment for advanced prostate cancer, our results are likely heralding larger increases in survival in men with metastatic prostate cancer in the near future.**背景：** 过去二十年间，前列腺癌男性患者的检测流程、诊疗评估与治疗方案均发生了显著变革。为此，本研究旨在探讨转移性前列腺癌男性患者生存率的时间变化趋势。 **方法：** 本研究基于瑞典前列腺癌数据库（Prostate Cancer data Base Sweden）开展人群队列研究，纳入1998年至2015年间确诊的13709例初诊（de novo）转移性前列腺癌男性患者。采用Kaplan–Meier分析（Kaplan–Meier analysis）与Cox回归模型，对比四个日历周期的总生存率，校正变量包括诊断年龄、T分期（T stage）以及血清前列腺特异性抗原（prostate-specific antigen，PSA）水平。 **结果：** 1998–2001年至2010–2015年期间，所有患者的中位生存期延长了6个月。其中，诊断时年龄为60~69岁的患者生存期增幅最大，达14个月。多变量分析显示，与1998–2001年相比，2010–2015年确诊患者的死亡风险显著降低，风险比（hazard ratio，HR）为0.77（95%置信区间（confidence interval，CI）：0.68~0.86）。确诊时的中位PSA水平从1998年的181 ng/mL下降至2015年的98 ng/mL，降幅达46%。 **结论：** 1998年至2015年间，瑞典初诊转移性前列腺癌男性患者的生存率有所提升。该生存率提升的原因可能包括：一是肿瘤负荷降低（表现为PSA水平下降），从而延长了先导时间（lead times）；二是近期化疗使用量增加（推测机制）。鉴于晚期前列腺癌系统性治疗的应用日益广泛，本研究结果预示未来转移性前列腺癌男性患者的生存率或将实现更大幅度的提升。