European Urology

Letters to the Editor published online

I have read the paper of Schröder et al [1]. I am afraid that I disagree with the conclusion that the study did not show noninferiority of delayed endocrine treatment (DET) to early endocrine treatment (EET) applied to men with T2-T3 pN1-3 M0 prostate cancer due simply to statistical power. I think that the problem of prostate cancer management in this study is much more complicated and relates to versatility of phenotypes and patient age.

The age range in this study was huge: It was 46.0–79.2 yr in the DET group and 52.2–76.8 yr in the EET group [1]. Bellmunt has noticed, for example, that ageing can be associated with changes that might affect how chemotherapy acts [2]. The range of tumour grade is also wide in this study. Why only World Health Organisation (WHO) grading was used? Maybe Gleason grading would show some differences between analysed groups [3].

Therapy-resistant and therapy-sensitive tumours manifest distinct patterns of association with stemness/differentiation pathways, suggesting that prostate cancers can develop within genetically distinct programs [4]. Why are some of the prostate cancers clinically significant but others are not? It seems that the key is proteins involved in control of regenerative potential and cell senescence. Cells from organisms with renewable tissues can permanently withdraw from the cell cycle in response to diverse stresses. This response, termed cellular senescence, is controlled by the tumour-suppressor proteins and constitutes a potent anticancer mechanism. Senescent cells acquire phenotypic changes that may contribute to ageing and to certain age-related diseases, including late-life cancer [5]. It seems that late-life prostate cancer is a good example: Is this a cancer or a physiologic feature of senescence? Is each prostate cancer that may affect an elderly man actually a cancer or is it a physiologic feature of senescence? Who should be treated and how?

Maybe a cancer definition in these particular cases of early onset prostate cancer and late-life prostate cancers should be reevaluated. New definitions for such different cancers probably would help to resolve the problem of the heterogeneous population of prostate cancer patients. Definition based on biologic properties (ie, active gene pattern and protein expression) will better reflect disease then “crude” pathologic findings, which can be misleading in those particular cases. It seems that comparing late-life prostate cancers with their early onset counterparts can lead to inappropriate conclusions.
Conflicts of interest: The author has nothing to disclose.