High intensity focused ultrasound for the treatment of localized prostate cancer: Efficacy and impact on sexual function

Introduction: Since 1999, a therapeutic device using High Intensity Focused Ultrasound (HIFU) technology has been marketed in Europe for the treatment of localized prostate cancer. Clinical and technical development was designed to provide a minimally invasive alternative for these patients. The purpose of this study was to evaluate the efficacy of HIFU therapy for localized prostate cancer and its impact on sexual function. Material and Methods: HIFU technology is based on a convergent beam of high intensity ultrasound that creates a sudden and sharp increase in temperature (85°C to 100°C) in the tissues at the focal point. This leads to a precise lesion in the tissue, adjustable from 19 to 24 mm in height and 2 mm in diameter. Successive displacements of the focal point are computer-driven, allowing treatment of a defined volume. All patients were treated with the ABLATHERM® device (EDAP SA, France); they were treated using the device prototypes between 1993 to 1999 and then with the marketed machine. The treatment procedure was improved from 2000 onwards with the combination of transurethral resection of the prostate (TURP) in order to reduce post-treatment catheter time. A nerve-sparing procedure was also tested in 2002. The selected population included 120 patients considered to be potentially curable with clinical stage T1-T2 prostate cancer and an initial PSA < 10 ng/ml (group 1). A larger group of 167 patients with an initial PSA < 30 ng/ml was also considered (group 2). All patients were not candidates for surgery due to their age or comorbidities. In the two groups, clinical failure was defined by the need for administration of an adjuvant prostate cancer treatment (hormone deprivation or external radiation). Disease progression, or biochemical failure, was strictly defined as any evidence of residual cancer on follow-up biopsies (regardless of the PSA level), or 3 successive increases of the PSA level (with negative follow-up biopsies), with a velocity > 0.75 ng/ml/year. Disease-free survival rates were calculated using the Kaplan-Meier method. Survival rates were compared using the log-rank test. The impact of HIFU treatment on sexual function was assessed by a questionnaire in 70 patients who underwent standard HIFU treatment and in 28 patients in whom a nerve-sparing procedure was performed. Results: Patient baseline characteristics (± SD) were, in group 1 and group 2 respectively: mean age: 71.2 (± 5.34) years and 71.8 (± 5.11) years; clinical stage: T1 for 61 patients and T2 for 59 patients in group 1, and T1 for 77 patients, T2 for 85 patients and T3 for 5 patients in group 2; mean initial PSA level: 5.67 (± 2.47) ng/ml and 9.30 (± 6.01) ng/ml; Gleason score: 2-6 for 77 patients and 7-10 for 43 patients in group 1, and 2-6 for 98 patients, 7 for 44 patients, and 8-10 for 25 patients in group 2; mean prostate volume: 33. 6 (± 16.5) mi and 34.4 (± 16.7) mi, respectively. Mean follow-up was 27 months (range: 3-96 months) in group 1, and 23 months (range: 3-90 months) in group 2. In group 1, a residual cancer was diagnosed in 17 patients, but only 6 patients needed adjuvant treatment due to a significant rise of the PSA level (hormone deprivation: n=2, external radiation: n=4), leading to a clinical success rate of 95%. Similarly, in group 2, 36 patients presented with positive follow-up biopsies, and 21 of them required adjuvant treatment (hormone deprivation: n=10, external radiation: n=11), leading to a clinical success rate of 87.5%. The disease-free survival rates (previously defined on the combined biopsy and PSA criteria) were 76.9% and 66% in group 1 and 2, respectively. In addition, the disease-free survival rate in group 2 was stratified according to the initial prognosis risk level: 85% in low-risk patients (i.e. patients with clinical stage T1-T2a and PSA < 10 ng/ml and Gleason score < 7), 67.5% in intermediate-risk patients (i.e. clinical stage T2b or PSA 10-20 ng/ml or Gleason score = 7), and 42% in high-risk patients (i.e. clinical stage T2c or PSA > 20 ng/ml or Gleason score > 7). In the overall population, 70 patients had normal sexual function prior to HIFU treatment; 25 patients (36%) still had erections allowing sexual intercourse with penetration after treatment. A nerve-sparing procedure was also performed in 28 potent patients: 43% of these patients had persistent erections allowing sexual intercourse with penetration after treatment, indicating that this nerve-sparing procedure still needs to be improved. Conclusion: The efficacy results observed after HIFU treatment are similar to those observed after other non-surgical treatments for prostate cancer. After complete HIFU treatment of the gland, more than 1/3 of patients still reported erections allowing sexual intercourse with penetration; these results must be interpreted for an elderly population (mean age: 72 years). A nerve-sparing procedure is currently being perfected and tested.