(Cost-)effectiveness of focal therapy versus radical therapy (standard of care) in the treatment of men with intermediate-risk prostate cancer: study protocol for the ENFORCE focal randomised controlled trial.

backgroundIntermediate-risk prostate cancer (PCa) is currently managed with radical whole-gland therapies, such as radical prostatectomy (RP) or radiotherapy (RT). While effective, these treatments can significantly impact quality of life (QoL), particularly in relation to urinary incontinence and erectile dysfunction. Focal therapy poses a promising alternative for whole-gland treatment in this specific patient population; however, current evidence has primarily been limited to phase I and II studies. Robust prospective evidence is needed to determine whether focal therapy can be considered a safe alternative for management of intermediate-risk PCa. The objective of this randomised controlled trial (RCT) is to evaluate the oncological effectiveness, QoL and cost-effectiveness of focal therapy compared with radical treatment as standard of care.

methodsThis ENFORCE focal study is designed as a multicentre RCT with six participating centres that perform focal therapy in the Netherlands. Patients are included after receiving informed consent and are thereafter 1:1 randomised between focal therapy, consisting of high-intensity focused ultrasound, irreversible electroporation or transurethral ultrasound ablation and radical treatment, consisting of RT or RP. A total of 356 patients will be enrolled. This study has two co-primary endpoints, oncological effectiveness at 36 months (non-inferiority) and QoL at 12 months (superiority) both of which must be met to demonstrate overall trial success. Follow-up will be at least 3 years, with a maximum of 5 years to gain information regarding long-term outcomes. The set follow-up visits are 6 weeks, 3 months, 6 months, 12 months and yearly thereafter. At the follow-up visits, clinical data will be collected, and questionnaires regarding QoL and costs will be administered. Furthermore, at 9 months and 18 months, prostate-specific antigen will be monitored in alignment with European guidelines on follow-up after RP and RT. Primary analyses will be conducted using intention-to-treat analyses. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Research Ethical Committee Oost-Nederland (NL83913.091.23, primary approval in December 2023; last approved version 10 July 2025). The results will be submitted for publication in peer-reviewed medical journals, and data will be accessible.

trial registrationNCT06223295.