Original article
The risk of prostate cancer mortality and cardiovascular mortality of nonmetastatic prostate cancer patients: A population-based retrospective cohort study

https://doi.org/10.1016/j.urolonc.2018.02.016Get rights and content

Highlights

  • Men were more likely to die from non-prostate cancer related outcomes.

  • We did not observe an association between androgen deprivation therapy and cardiovascular disease mortality after adjustment for age and risk groups.

  • The analyses showed a high proportion of prostate cancer specific mortality among men on androgen deprivation therapy, older men and men with a high-risk tumor.

Abstract

Purpose

To assess the risk of prostate cancer (PCa) specific mortality (PCSM) compared to cardiovascular disease mortality (CVDM), or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age.

Patients and methods

This retrospective population-based cohort study identified 1,908 nonmetastatic PCa patients in the cancer registry Zurich and Zug, diagnosed between 2000 and 2009 living in the City of Zurich. Multiple imputation methods were applied to handle missing PCa information. Fine and Gray competing risk regression analysis was used to estimate subdistribution hazard ratios for the outcomes PCSM, CVDM, or OCM

Results

Ten years after diagnosis the cumulative probability of PCSM and CVDM was 16.4% and 10.0%, respectively. We observed an increased adjusted risk of PCSM in men treated with androgen deprivation therapy (ADT) compared to surgery, but could not observe an association between ADT and CVDM. The probability of PCSM was significantly higher for patients on active surveillance or watchful waiting, compared to surgery. Age and PCa risk categories were positively associated with risk of PCSM, whereas there was no evidence for an association with CVDM or OCM based on risk groups.

Conclusions

Overall, men with PCa were more likely to die from non-PCa related outcomes. Nevertheless, the analyses showed a high proportion of PCSM among men on ADT, older men and men with a high-risk tumor. However, further research is needed to understand comprehensively the benefits of the respective treatments.

Introduction

Prostate cancer (PCa) is the most common male cancer in Switzerland; about 1,000 cases annually are registered in the Canton of Zurich [1]. The number of incident cases increased in the last decade [2], mainly due to the increasing number of men having a PCa screening examination, namely a PSA (prostate-specific antigen) test [3]. Therefore, more men are diagnosed earlier, but usually with a low-risk tumor [4]. In contrast, the number of men dying from PCa decreased over the last decades. Men with a low-risk tumor have a higher risk of dying from other causes than of PCa [5]. Hence, for some men there is overtreatment [6] of PCa with an unneeded effect on quality of life through severe adverse effects like incontinence or impotence [7], [8]. Accordingly, the challenge is to identify those men who have a higher risk of dying from PCa and those who are more likely to die of other causes.

In Switzerland, the leading causes of death in men are cancer (30%) and cardiovascular diseases (CVD, 31%) [9]. Studies have shown that PCa patients treated with androgen deprivation therapy (ADT) might have an excess risk of dying from CVD [10], [11], such that we, in addition to death of other causes, included death from CVD in our analysis. For Switzerland, it is currently unclear in which way treatment affect long-term survival of PCa patients. In contrast to several other countries, Switzerland has a universal health insurance system, which provides equal access and state-of-the-art treatment options for all patients, which might affect treatment outcomes and survival compared with other countries. To our knowledge, this is the first study in Switzerland that assesses the risk of PCa-specific mortality (PCSM) compared to cardiovascular disease (CVDM) or other-cause mortality (OCM) of men with nonmetastatic PCa according to PCa risk groups, primary treatment, and age.

Section snippets

Study population

The epidemiological Cancer Registry Zurich and Zug is the largest cancer registry in Switzerland covering roughly 1.6 million inhabitants. The Registry was established in 1980 to register every cancer patient living in the canton of Zurich (since 2011, the canton of Zug is also included). The Registry is almost complete. Using the flow method, Lorez et al. [12] have shown that in Zurich 89.6% of all cancer sites are captured within 3 years of diagnosis and 97% after 5 years. In addition, the

Results

Mean age at diagnosis was 71.3 years (standard deviation = 9.7, median = 71.0). Table 1 shows the baseline characteristics of the patients and the proportion of causes of death by age, risk, and treatment groups after multiple imputations. About 20% of patients were 80 years or older at time of diagnosis and 11% were younger than 60 years. More than 50% of men were diagnosed with a high-risk tumor. About half of men underwent surgery and 34% were on WW or AS. Among the deaths observed in the

Discussion

In this study among 1,908 PCa patients of a Swiss cancer registry, we observed that PCSM was the leading single cause of death only for men>79 years, men having a high-risk tumor and men treated with ADT.

Overall, the estimated 10-year cumulative probability of death was lowest for PCSM. This indicates that men with PCa were more likely to die from other causes than PCa. We observed a higher adjusted risk of PCSM in men treated with ADT compared to surgery, but did not observe an association of

Conclusion

Overall, in the City of Zurich, men with nonmetastatic PCa were more likely to die from non-PCa related causes. PCSM was the leading single cause of death only for men>79 years old, men with a high-risk tumor and men treated with ADT. The reasons that lead to treatment decisions of physicians and patients are not completely clear yet. Further research that takes other factors such as comorbidities but also medical guidelines or health insurance systems into account, is needed to understand

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