A multi-centre prospective development study evaluating focal therapy using high intensity focused ultrasound for localised prostate cancer: The INDEX study

Introduction: Focal therapy offers the possibility of cancer control, without the side effect profile of radical therapies. Early single centre prospective development studies using high intensity focused ultrasound (HIFU) have demonstrated encouraging genitourinary functional preservation and short-term cancer control. Large multi-centre trials are required to evaluate medium-term cancer control and reproduce functional recovery. We describe the study design of an investigator-led UK multi-centre, single arm trial using HIFU to deliver focal therapy for men with localised prostate cancer.

Methods: One-hundred and forty men with histologically proven localised low or intermediate risk prostate cancer (PSA < 15, Gleason ≤ 7, ≤ T2cN0M0) will undergo precise characterisation of the prostate using a combination of multi-parametric (mp)MRI and transperineal template prostate mapping (TPM) biopsies. Unilateral dominant tumours, the so-called index lesion, will be eligible for treatment provided the contra-lateral side is free of 'clinically significant' disease (as defined by Gleason ≥ 7 or maximum cancer core length ≥4 mm). Patients will receive focal therapy using HIFU (Sonablate 500®). Treatment effect will be assessed by targeted biopsies of the treated area and TPM biopsies at 36-months.

Results: Primary outcome is the absence of clinically significant disease based on 36-month post-treatment TPM biopsies. Secondary outcomes address a) genitourinary function using validated patient questionnaires (IPSS, IPSS-QoL, IIEF-15, EPIC-Urinary, EPIC-Bowel, FACT-P, EQ-5D), b) the predictive validity of imaging, and c) risk factors for treatment failure.

Conclusions: INDEX will be the first multi-centre, medium term follow-up trial to evaluate the outcomes of a tissue preserving strategy for men with localised prostate cancer using the TPM-ablate-TPM strategy.