Clinical Trial on the Effectiveness of TUMT Compared to PAE in Reducing Severe LUTS in Men with BPH

The TUMT-PAE-1 trial is a randomised clinical trial aiming to compare the effectiveness of transurethral microwave thermotherapy (TUMT) with prostatic artery embolisation (PAE) in reducing urinary symptoms caused by prostate gland enlargement. The assessment will be done by patient reported and functional outcome measures. The primary purpose is to evaluate the urinary symptoms six months after the procedure, measured by the International Prostate Symptom Score (IPSS).

One fourth of men older than 70 years have moderate to severe lower urinary tract symptoms (LUTS) that impair their quality of life (QOL). This is most frequently caused by benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) is still regarded as the gold standard for surgical treatment of BPH. However, TURP is only an option for patients fit for general anesthesia and can result in complications. Consequently, several less invasive procedures have been developed, as prostatic artery embolization (PAE) and transurethral microwave thermotherapy (TUMT).

The objective of this clinical trial is to assess if transurethral microwave thermotherapy (TUMT) is non-inferior to prostatic artery embolization (PAE) in reducing lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). The primary aim is to compare LUTS 6 months after the TUMT and PAE procedures, measured by the International Prostate Symptom Score (IPSS). Both treatments have previously been shown to reduce LUTS with a similar post-procedure outcome in mean IPSS. However, the previous studies differed in baseline characteristics thus it is currently unknown if they perform equally well. Secondary objectives include comparison of patient reported and functional outcomes at short- and long-term follow-up. The trial importantly includes analysis of patient-reported outcome measures of satisfaction with treatment, quality of life, incontinence, erectile and ejaculatory function, as well as evaluation of uroflowmetry, prostate volume, prostate specific antigen, catheter dependency, side effects, hospital admissions and re-treatment rate.

This study is designed as a multi-centre, non-inferiority, open label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments using the randomisation module in REDCap. The primary outcome is expected to be evaluated by a 95% confidence interval against the predefined threshold of +3 points in IPSS for inferiority. Secondary outcomes will be presented descriptively and assessed by students T-test, Chi-squared test and linear mixed models. The patient reported outcomes will be obtained by standardized validated surveys and functional outcomes, side effects and re-treatment rates will be measured at 1 month, 3 months, 6 months, 1 year, 2 years and 5 years post procedure. Assuming a difference in mean IPSS after treatment of 1 point with an standard deviation (SD) of 5 and a non-inferiority margin set at the border for a clinically non-meaningful difference of 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% drop-out the study will include 220 patients. An interim analysis will be performed for every 50 cases.

TUMT and PAE are minimally invasive procedures performed in an outpatient setting that have been shown to reduce LUTS in a similar magnitude. To date there are no randomised clinical trials comparing PAE to TUMT, which is problematic as the most prominent problem with minimally invasive BPH treatment is the lack of proper selection of candidates for a specific procedure. Non-inferiority of TUMT to PAE is expected, with analysis of the secondary outcomes, the investigators aspire to contribute to a better understanding of patient selection for either treatment.

Eligibility Criteria:
Inclusion Criteria:

* Ability to understand and the willingness to sign an informed consent.
* Diagnosis of LUTS secondary to BPH refractory to/contraindicated for medical treatment or not patient preference.
* Severe urinary symptoms on IPSS (IPSS score ≥ 20).
* Bladder outlet obstruction (BOO) is defined by Qmax ≤ 15ml/sec, based on uroflowmetry.
* Prostate volume at minimum 50 ml measured by TRUS or MR.
* Men with prostate cancer in Active Surveillance or Watchful Waiting who have LUTS due to a large BPH component are allowed.
* Indwelling catheter or intermittent catheter is allowed. In this case baseline IPSS is 35 points.

Exclusion Criteria:

* Active bladder cancer (patients with pTa low-grade tumors are allowed).
* Previous pelvic radiation for cancer treatment.
* Bladder stones (inclusion is allowed after removal).
* Current urethral strictures or bladder neck contracture.
* Neurogenic LUTS.
* Symptomatic urinary tract infection at the time of intervention.
* Documented bacterial prostatitis in the last year.
* Severe atheromatous disease or other pathology preventing catheter-based intervention (as rated on CT angiography by an interventional radiologist).
* Allergy to iodinated contrast media.
* Renal failure defined as estimated glomerular filtration rate (eGFR) \< 35ml/min.
* High bleeding risk (spontaneous international normalized ratio (INR) \> 1.6).
* Contraindication to conscious sedation (if requested by the patient).
* Prostate median lobe defined by treating physician.
* Urethral colliculus to bladder neck length \<35mm.