Temporal changes in cause‐specific death in men with localised prostate cancer treated with radical prostatectomy: a population‐based, nationwide study

Abstract Background and Objective Changes in diagnostic work‐up, histopathological assessment, and treatment of men with prostate cancer during the last 20 years have affected the prognosis. The objective was to investigate the risk of prostate cancer death in men with clinically localised prostate cancer treated with radical prostatectomy in Sweden in 2000–2010. Methods Population‐based, nationwide, study on men with clinically localised prostate cancer treated with radical prostatectomy in the period 2000–2010. Cox regression analyses were used to assess differences in risk of prostate cancer death according to calendar period for diagnosis and stratified on risk category. Results The study included 19 330 men with a median follow‐up of 12.4 years. Men diagnosed in 2007–2008 and 2009–2010 had a significantly lower risk of prostate cancer death compared to men diagnosed in 2000–2002. The reduced risk of prostate cancer death was restricted to men with intermediate‐risk prostate cancer with no differences observed in men with low‐ or high‐risk prostate cancer. Conclusion During the study period, the risk of prostate cancer death decreased in the total population of men with localised prostate cancer treated with radical prostatectomy. The decrease was restricted to men with intermediate‐risk prostate cancer.


INTRODUCTION
To inform on treatment options knowledge of the natural history of the disease at hand as well as the effect of interventions are imperative. The natural history of localised prostate cancer is best known in men diagnosed in the 1970s and 1980s, 1,2 while outcomes following curatively intended treatment have primarily been studied in randomised controlled trials in men diagnosed in the 1990s and 2000s. [3][4][5][6] 2.1. Statistical methods Follow-up was calculated with the reverse Kaplan-Meier method.
All tests were two-sided and the significance level was set to p < 0.05. Statistical analysis was performed with R version 4.0.0 (R Foundation for Statistical Computing).

RESULTS
The study includes 19 330 men diagnosed with localised prostate cancer in 2000-2010 who underwent primary radical prostatectomy within 6 months from diagnosis. The median follow-up was 12.4 years, ranging from 9.1 to 17.2 years. During the study period the proportion of men aged 65 years or above increased, as did the proportion of men with clinical stage T1 and men with Gleason scores ≤ 6, Table 1 The cumulative incidence of prostate cancer and nonprostate cancer death is depicted in Figure 1. Overall, cumulative prostate cancer deaths following 9 years remained unchanged with 1.7% (95% CI 1.2%-2.1%) of men diagnosed in 2000-2002 compared with 1.4% (95% CI 1.1%-1.8%) of men in 2009-2010. In the same period, the nonprostate cancer deaths declined from 7.8% (95% CI 6.8%-8.8%) to 5.9% (95% CI 5.2%-6.5%).
In univariable Cox regression analyses lower risk of prostate cancer death was seen in men diagnosed in later calendar periods, men with higher education level and men diagnosed in hospitals performing the highest annual number of prostatectomies, Limitations of this study include the use of data from the original histopathological reports of diagnostic prostate biopsies without centralised review and that we were unable to assess the impact on the outcome of each change that occurred during the study period.
Strengths of our study include a large nationwide, population-based cohort of men with comprehensive data from several high-quality healthcare registers. [18][19][20] We chose to only include men treated with radical prostatectomy to try and reduce biases caused by changes in treatment strategies. Besides changes in surgical technique, changes in case-mix, work-up, and histopathological assessment of biopsies likely also affected outcome. During the study period, an increasing proportion of men with very low-risk prostate cancer were managed by active surveillance 25 and more men with high-risk prostate cancer and high comorbidity underwent radical prostatectomy (Table S1).
This could be the reason why we did not detect any changes in the risk of prostate cancer death in these risk categories.  34 In recent years "very low-risk prostate cancer" has been included as a fourth risk group accounting also for the prostate volume. 35  searcher should contact the corresponding author who will direct the demand for data to the PCBaSe reference group who will then provider the access described above.