DIABETES or hypertension may be associated with poorer prostate cancer-specific survival among smokers with castration-resistant prostate cancer (CRPC), according to a secondary analysis of a multicentre trial.
The association was particularly evident among patients treated with enzalutamide, highlighting a potential relationship between metabolic comorbidities and outcomes during advanced prostate cancer treatment.
Diabetes is an important metabolic comorbidity among people with cancer, but its potential influence on treatment outcomes in CRPC remains incompletely understood.
Researchers used data from the ENABLE study for prostate cancer, an investigator-initiated, multicentre randomised controlled trial comparing enzalutamide with abiraterone plus prednisolone.
The secondary analysis investigated whether diabetes, hypertension, and smoking status were associated with survival.
A total of 178 patients had been randomised and treated. Smoking information was available for 161, including 84 patients without a smoking history and 77 with a smoking history.
Researchers subsequently assessed outcomes according to whether patients had diabetes or hypertension and whether they received enzalutamide or abiraterone plus prednisolone.
Smoking status alone was not associated with significant differences in survival outcomes.
However, among patients with a smoking history, those with diabetes or hypertension experienced significantly poorer prostate cancer-specific survival than smokers without either condition.
Multivariable analysis found that the presence of diabetes or hypertension independently predicted poorer prostate cancer-specific survival within this group.
Treatment-specific analysis also identified a significant difference between smokers with and without diabetes or hypertension among patients receiving enzalutamide.
This association was not observed in the abiraterone plus prednisolone group.
The findings raise the possibility that metabolic health could influence outcomes among some patients receiving androgen receptor signalling inhibitors.
Diabetes and cancer frequently coexist, making it important to understand whether glycaemic and cardiovascular comorbidities influence cancer prognosis or treatment response.
However, the findings should be interpreted cautiously. This was a retrospective secondary analysis of trial data, and the subgroup of smokers was relatively small.
Diabetes and hypertension were also considered together in the principal comparison, meaning the study does not establish the independent effect of diabetes alone.
The results therefore do not demonstrate that diabetes causes poorer survival or that one prostate cancer treatment should be selected over another on the basis of diabetes status.
Further prospective research could determine whether improved management of metabolic comorbidities affects treatment outcomes in CRPC and clarify the mechanisms underlying the observed association.
Reference
Fukagai T et al. Prognostic impact of diabetes or hypertension in smokers with CRPC receiving enzalutamide or abiraterone. Int J Clin Oncol. 2026. doi:10.1007/s10147-026-03178-w.
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