Ethical Matters
This study was approved by the Research Ethics Committee of the Faculty of Medicine at the University of Tokyo (approval number: 2021259NI). The need for informed consent was waived by the committee, because of the retrospective nature of the study. Data were obtained from medical chart, and patient identifying information was anonymized before analysis.
Population
Patients who had been treated from April 2016 to March 2020, and who had (a) serum PSA levels ≤ 20 ng/ml, (b) clinically significant PC (csPC), which was defined as those with at least one core with a Gleason score of 3+4, or a score of 6 with a maximum cancer core length ≥ 4 mm, had been located using magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) elastic fusion image-guided transperineal prostate biopsy and 12-cores transperineal systematic biopsy, (c) life expectancies longer than 10 years, (d) no metastasis, (e) no bilateral cancers with Gleason scores ≥ 7, (f) no severe anal strictures, and (g) no previous history of treatment for PCa, and those who underwent FT with high-intensity focused ultrasound (HIFU) and RARP were included in the present study. FT was performed at the Department of Urology, Tokai University Hachioji Hospital, Tokyo, Japan. RARP was performed at Tokai University Hospital, Kanagawa, Japan. The treatment results for FT used in this study have been published previously [14]. After treatment, PSA levels and the urinary function domain of the Expanded Prostate Cancer Index Composite (EPIC) [15] were measured every 3 months.
Treatments
The surgical procedure of RARP was performed transperitoneally using a six-port technique based on a previously established method [16]. Expert surgeons with a cumulative total of more than 100 patients were included in this study. The urethral catheter was removed 5 days after surgery after confirming the absence of leakage from the urinary bladder anastomosis using cystourethrography. After urethral catheter removal, pelvic floor muscle exercises were initiated to improve urinary continence.
HIFU is an extracorporeal ablative technology that delivers ultrasonic energy to pinpoint only millimeter-wide foci. Only minor temperature changes are observed outside the focal zone, making it an attractive modality for FT [17]. The detailed protocol for FT with HIFU has been described previously [18]. The recorded localization of each mpMRI-visible csPCa was converted to the treatment planning screen of TRUS image on the HIFU work station, and treatment range was determined. The treatment planning was set for the accurate recognition and treatment of the target lesion. The treatment range included at least a double treatment volume for the target lesion. Intra-operative US images are available during treatment. Based on the appearance of the popcorn phenomena in the target area, which indicates effective treatment, energy output can be adjusted intra-operatively from 24W to 48W. The urethral catheter was removed within 24 hours after treatment.
Outcomes
Oncological Outcomes
The oncological outcome was the FFS. In the RARP group, biochemical failure was defined as a PSA level ≧0.20 ng/ml [1]. Based on previous studies, biochemical failure in the FT group was defined as a more than 2.0 ng/ml increase from the PSA nadir after treatment (Phoenix ASTRO definition) [1, 19]. PSA levels were measured in both groups before and every 3 months after treatment.
Functional Outcomes
The EPIC [20] was used to evaluate the quality of life (QOL). The EPIC score was measured in the RARP group before and 1, 3, 6, and 12 months after the treatments. Urinary functions were evaluated using the urinary function domain of the EPIC 12 months after treatment [18, 21, 22].
Statistical Analysis
Statistical Analysis Methods
Background factors were summarized for all collected data. Biochemical failure, urinary function, and win ratio analyses were performed after propensity score matching. We also conducted subgroup analyses according to the age classification (<70/≥70 years old) and the D'Amico risk classification (low/intermediate/high). All analyses were performed using SAS software (ver. 9.4, SAS Institute Inc., Cary, NC, USA). Statistical significance was set at a two-sided 5% level.
Propensity Score Matching
To mitigate the differences in background factors, we performed propensity score matching using logistic regression with risk classification, preoperative PSA level, T classification, Gleason score, PSA density, and age. Using the nearest neighbor method, we performed 1:1 matching to match the FT group. The caliper was set at 0.2 to the standard deviation of the logit of the propensity score. Patients outside the matching range were excluded. Data were considered balanced if the absolute value of the standardized difference after matching was <0.1.
Analysis of FFS and QOL
For FFS, annual survival rates and 95% confidence intervals (CIs) were calculated using the Kaplan–Meier method, and a log-rank test was used to compare survival curves between the groups. The hazard ratio (HR) of the FT group to the RARP group was estimated using Cox regression analysis. The median urinary function domain of the EPIC at 12 months post-treatment was compared between the groups using the Wilcoxon rank-sum test.
Win Ratio Analysis
Win ratios were calculated, with FFS as the first priority and the urinary function domain of the EPIC as the second priority. First, all possible pairs of patients who underwent FT and RARP were identified. Second, each pair was compared for FFS to determine wins and losses. The overview diagram for determining the winner is shown in Figure 1. Tie pairs were then moved to the urinary function domain of EPIC comparisons to determine wins and losses. Patients with higher scores were judged as winners. Finally, pairs that did not have a result of win or loss in all outcomes were classified as "tie" and were not included in the win ratio calculation. A win ratio > 1.0 suggested a higher comprehensive outcome in the FT group than in the RARP group.