Non-Whole-Gland High-Intensity Focused Ultrasound vs Whole-Gland High-Intensity Focused Ultrasound for Management of Localized Prostate Cancer: 1-Year Oncological and Functional Outcomes

Abstract

Objective:

The aim of the study was to compare the oncological and functional outcomes in localized prostate cancer patients who received non-whole-gland high-intensity focused ultrasound (HIFU) with those in patients who received whole-gland HIFU therapy.

Patients and Methods:

Eighty-six patients from September 2012 to January 2017 in our center were retrospectively analyzed. Oncological outcomes included histological absence of prostate cancer, biochemical disease-free survival (BDFS) as well as the absence of lesions suspected for harboring prostate cancer in multiparametric magnetic resonance imaging (mpMRI). Regarding functional outcomes, we determined international prostate symptom score (IPSS), pad-free rate, pad-free and leakage-free rates as well as international index of erectile function-5 (IIEF-5).

Results:

Of the 86 patients, 25 patients who underwent non-whole-gland HIFU and 61 patients who underwent whole-gland HIFU were enrolled in our 1-year follow-up study. There were no significant differences in histological absence of prostate cancer (p = 0.655), BDFS (p = 0.820), prostate-specific antigen (PSA) nadir (p = 0.453), and absence of suspicious lesions in mpMRI (p = 0.633) between non-whole-gland HIFU group and whole-gland HIFU group. However, compared with the whole-gland HIFU, the non-whole-gland HIFU group had fewer IPSS at 1 month (8.64 ± 3.63 vs 10.85 ± 6.10), a longer time to PSA nadir (5.04 ± 2.07 vs 3.83 ± 1.65), less temporary urine retention rate (20.0% vs 44.3%), less complication rate especially urinary tract strictures (4% vs 26.2%), whereas pad-free rate, pad-free and leakage-free rates, and IIEF scores were comparable.

Conclusion:

Non-whole-gland HIFU is a promising type of treatment for localized prostate cancer with satisfactory oncological results with less impairment of functional outcomes and complications compared with whole-gland HIFU, but it requires longer follow-up and larger samples of randomized control trials.

Introduction

There is a great debate about the treatment options for prostate cancer, with disagreement on whether patients with localized tumor ought to undergo deferred treatment or radical interventions, and on the most suitable type of management. Immediate radical interventions burden patients with more risks of treatment-related side effects, especially urinary incontinence, and to some extent are more likely to constitute overtreatment compared with active surveillance.¹ Nevertheless, those who choose active surveillance face uncertainty of tumor control and anxieties about subsequent series of psychological problems such as emotional distress.² On the contrary, the latest European Association of Urology (EAU) guidelines have further specified that active surveillance can not only be considered for patients with low-risk tumor but can also be expanded to selected patients with favorable intermediate-risk localized prostate cancer (Gleason score 3 + 4), despite carrying increased risk of metastases.³ Hence, we are more puzzled how to balance morbidity of treatment and quality of life and, at the same time, avoid overtreatment for low- and intermediate-risk localized cases. There is need to explore new concepts of treatment to help both urologists and oncologists make better clinical decisions.

Transrectal high-intensity focused ultrasound (HIFU) therapy, as an alternative therapy, is increasingly used as primary treatment for localized prostate cancer, for which radical prostatectomy and definitive radiotherapy have been considered as constituting gold standard management for a long time. Moreover, HIFU is now used as salvage therapy for recurrent disease.⁴ There is already evidence that the chances for overall survival and metastasis-free survival up to 5 years are the same for both patients who have undergone whole-gland HIFU treatment and radical prostatectomy.⁵ However, with the emergence of radiographic technologies such as multiparametric magnetic resonance imaging (mpMRI) helping to distinguish clinically significant from clinically insignificant prostate cancer, and the concept of precision medicine on the contrary, there are already some cohort studies that have focused on the use of hemiablation as the non-whole-gland HIFU for prostate cancer treatment.^6
–8 Ahmed and colleagues,^9,10 have advanced the theory of index lesion and carried out a study of focal ablation targeting the index lesion in multifocal localized prostate cancer, which may corroborate the thesis that metastatic phenotypes have only monoclonal origins, and that secondary lesions are not attributed to prostate-specific antigen (PSA) biochemical failure.^11,12 However, it is unclear and scarcely reported whether the oncological and functional outcomes of non-whole-gland HIFU and whole-gland HIFU are distinct. The aim of our study is to primarily compare the 1-year oncological and functional outcomes between non-whole-gland HIFU and whole-gland HIFU for the primary treatment of localized prostate cancer, to establish how HIFU may be best integrated into our clinical practice.

Patients and Methods

Patient preparation

Eighty-six localized prostate cancer patients without metastases verified through bone scan, pelvic CT, or MRI scan from September 2012 to January 2017 were enlisted in our retrospective study. Of these patients, 25 underwent the primary non-whole-gland HIFU therapy, including 13 hemiablations and 12 zonal ablations. All other patients were treated with a whole-gland HIFU. Patients were informed of all possible treatment options and were counseled about possible risks. Prostate cancer was detected by systematical transrectal ultrasound-guided, random biopsy of 12 cores in all patients. When the MRI scan showed suspicious areas within the prostate, additional targeted fusion biopsies were performed through either a transperineal or transrectal approach to increase detection rate. Seven patients in our study received androgen deprivation therapy, which had no statistical significance in non-whole-gland and whole-gland group.

Transrectal high-intensity focused ultrasound procedure

Under general anesthesia, all patients received a single-shot antibiotic prophylaxis. After sterile placement of transurethral Foley catheter patients are positioned in a lateral posture. Before insertion of the transducer, the prostate and rectum are examined, and the anal sphincter is gradually and carefully stretched. Nonresistant movement is indispensable for procedure. In our scheme, to ensure accuracy and reduce bias, the prostate is divided into 24 zones, as shown in Figure 1. In the past we mostly used the whole-gland HIFU therapy in our clinic. We also applied three types of non-whole-gland HIFU ablations—hemiablation, zonal ablation, and target ablation—based on patient-specific treatment plans (Fig. 2). It must be pointed out that in this series only salvage cases were treated by targeted ablation. This was planned on the basis of preoperative mpMRI and real-time transrectal ultrasonography images during HIFU and confirmed by fusion biopsies. Taking the safety distance between the rectum, nerve bundle, sphincter, and apex of prostate into account, therapeutic range is contoured precisely through real-time three-dimensional ultrasonic planning at the console. As a landmark alleviating treatment planning we used an indwelling catheter. In a whole-gland HIFU ablation it was left in situ during the treatment of the left lobe, and removed during the treatment of the right lobe and the urethral area of the prostate.

FIG. 1.

Diagrammatic depiction of zones of prostate in HIFU treatment from the transverse base, middle, and apex plane, respectively. HIFU = high-intensity focused ultrasound.

FIG. 2.

Diagram of four different HIFU treatments for prostate cancer in our center. (A) Diagram of whole-gland HIFU treatment. Blue solid edge: prostate; green circle: urethra; red pentagram: lesion; vertical lines: therapeutic range. (B) Diagram of Hemiablation treatment. (C) Diagram of zonal ablation treatment. (D) Diagram of targeted HIFU treatment. Blue dotted edge: incised prostate; blue pentagram: recurrent lesion.

Follow-up procedure

As a follow-up procedure, patients who underwent the HIFU therapy were subjected to serum PSA level tests quarterly during the first year. Biochemical disease-free survival (BDFS) at 12 months was defined using the Phoenix criteria (PSA nadir +2 ng/mL). Scheduled mpMRI comprising T2-weighted, diffusion-weighted, and dynamic contrast-enhanced sequences was used to identify the tumor location and possible local invasion after HIFU procedure at 6 and 12 months, and a final score determined using the Prostate Imaging Reporting and Data System (PI-RADS) developed by the European Society of Urological Radiology (ESUR). After HIFU procedure, lesion on MRI scored PI-RADS ≥3 was deemed to be suspicious. Our primary oncological outcome was histological absence of prostate cancer at 12 months. However, in our research, systematic postoperative prostate biopsy at 12 months was not a routine procedure because most patients refused repeated biopsies except PSA or mpMRI showed clinical evidence of further recurrence. Thus, we only performed control prostate biopsies when there were biochemical or imaging signs of recurrence. Functional assessments were mainly carried out according to the following parameters: an international prostate symptom score (IPSS) questionnaire was used to estimate the lower urinary tract symptom preoperatively and postoperatively; continence status was defined as “pad-free” or “pad-free and leakage free”; the international index of erectile function-5 (IIEF-5) score was used to assess sexual function, including erectile confidence, ability for penetration, maintaining and completing intercourse as well as achieving sexual satisfaction.

Statistical analyses

Statistical description and analysis of quantitative data were performed using the mean ± standard deviation and t-test, respectively. Statistical analysis of enumeration data was performed using χ² test. All statistical analyses were carried out using the Statistical Package for Social Science (SPSS version 21.0) software. p < 0.05 was set to be statistically significant.

Results

Baseline demographics

Of the 86 patients included in this analysis, a group of 25 patients were subjected to non-whole-gland HIFU treatment, of which 13 underwent hemiablation and 12were treated by zonal ablation. All basic characteristics of the 86 patients are listed in Table 1. Although we have indicated the results from both hemiablation and zonal ablation in the non-whole-gland HIFU group, all statistical results were derived from the comparison carried out between the entire non-whole-gland HIFU and the whole-gland HIFU group. There were no significant differences concerning the parameters of age (p = 0.058), PSA (p = 0.290), Gleason score (p = 0.308), risk classification (p = 0.099), and clinical T stage (p = 0.255) before treatment between the two groups. Nonetheless, the prostate volumes before treatment in non-whole-gland group were greater than those observed in the whole-gland group (p = 0.000). This is in accordance with the preoperative prostate volume reduction rate (p = 0.000), as 36% of the patients underwent the transurethral resection of prostate or thulium laser enucleation of prostate in the non-whole-gland HIFU group, which was <83.6% of whole-gland HIFU group.

Table 1.

Clinical Baseline Characteristics of Prostate Cancer Patients with Non-Whole-Gland High-Intensity Focused Ultrasound and Whole-Gland High-Intensity Focused Ultrasound

Variables	Non-whole-gland HIFU		Whole-gland HIFU	p
Variables	Hemiablation	Zonal ablation	Whole-gland HIFU	p
N	13	12	61
Age (year)	70.54 ± 8.38	68.67 ± 6.93	73.16 ± 7.65	0.058
Pre-PSA (ng/mL)	8.54 ± 8.43	8.23 ± 4.96	6.70 ± 5.97	0.290
Prostate volume (mL)	37.30 ± 8.86	40.25 ± 10.86	30.32 ± 9.40	0.000
Pre-PVR (%)	7 (53.8)	2 (16.7)	51 (83.6)	0.000
ADT	1 (7.7)	0 (0.0)	6 (9.8)	0.642
Clinical T stage				0.255
T_1c (%)	8 (61.5)	11 (91.7)	36 (59.0)
T_2a (%)	4 (30.8)	0 (0.0)	12 (19.7)
T_2c (%)	1 (7.7)	1 (8.3)	13 (21.3)
Gleason score				0.308
≤6 (%)	3 (23.1)	4 (33.3)	23 (37.7)
7a (%)	5 (38.4)	6 (50.0)	15 (24.6)
7b (%)	3 (23.1)	2 (16.7)	13 (21.3)
≥8 (%)	2 (15.4)	0 (0.0)	10 (16.4)
Risk group (D'Amico)				0.099
Low (%)	2 (15.4)	2 (16.7)	15 (24.6)
Intermediate (%)	8 (61.5)	10 (83.3)	34 (55.7)
High (%)	3 (23.1)	0 (0.0)	12 (19.7)

ADT = androgen deprivation therapy; HIFU = high-intensity focused ultrasound; Pre-PSA = preoperative prostate-specific antigen; Pre-PVR = preoperative prostate volume reduction.

Oncological outcomes

Among the 25 patients subjected to the non-whole-gland HIFU, preoperative and postoperative PSA levels at 3, 6, and 12 months were 8.39 ± 6.84, 2.08 ± 1.70, 1.44 ± 1.06, and 2.13 ± 1.37 (ng/mL), respectively (Table 2). In the whole-gland HIFU group PSA levels were 6.70 ± 5.97, 1.18 ± 1.50, 1.46 ± 1.89, and 1.79 ± 1.85, respectively (Fig. 3A, B). PSA kinetics indicated that the PSA decreasing rates by 3 and 6 months from baseline were comparable between these two groups, while a significant difference in PSA levels could be found at 3 months (p = 0.026). No difference was observed in terms of PSA nadir (p = 0.453), whereas PSA nadir was reached markedly earlier in the whole-gland HIFU group compared with patients in the non-whole-gland HIFU group (3.83 ± 1.65 vs 5.04 ± 2.07 months; p = 0.006). Twenty of 25 patients (80.0%) in non-whole-gland HIFU group showed a histological absence of prostate cancer at 12 months, which was comparable with 52 of 61 patients (85.2%) in whole-gland HIFU group (p = 0.655). There was no remarkable difference observed in non-whole-gland and whole-gland HIFU group according to the BDFS (96.0% vs 91.8%; p = 0.820). No mpMRI measurable prostate cancer occurred in 20 (80%) patients of non-whole-gland HIFU group, which was also comparable with 53 (86.8%) patients of whole-gland HIFU group (p = 0.633). Nine patients from the whole-gland HIFU group and five patients from the non-whole-gland HIFU group who had a histologically confirmed relapse at 12 months after primary HIFU treatment were treated by salvage HIFU with appropriate energy adjustment. All the results regarding oncological efficacy are summarized in Table 3.

FIG. 3.

PSA kinetics and functional outcomes of prostate cancer patients under non-whole-gland HIFU and whole-gland HIFU. (A) PSA kinetics of non-whole-gland HIFU at preoperative 0 month, postoperative 3, 6, and 12 months. (B) PSA kinetics of whole-gland HIFU at preoperative 0 month, postoperative 3, 6, and 12 months. (C) IPSS is affected at 1, 3, and 12 months after non-whole-gland HIFU treatment, in contrast with preoperation (*p < 0.05). (D) IPSS is affected at 1, 3, and 12 months after whole-gland HIFU treatment, in contrast with preoperation (*p < 0.05). (E) Effect on erectile function of non-whole-gland HIFU treatment using IIEF-5 questionnaire at preoperative 0 month, postoperative 3 and 12 months. (F) Effect on erectile function of whole-gland HIFU treatment using IIEF-5 questionnaire at preoperative 0 month, postoperative 3 and 12 months. IIEF-5 = international index of erectile function-5; IPSS = international prostate symptom score; PSA = prostate-specific antigen.

Table 2.

The Prostate-Specific Antigen Kinetics of Prostate Cancer Patients with Non-Whole-Gland High-Intensity Focused Ultrasound and Whole-Gland High-Intensity Focused Ultrasound

PSA (ng/mL)	Non-whole-gland HIFU		Whole-gland HIFU	p
PSA (ng/mL)	Hemiablation	Zonal ablation	Whole-gland HIFU	p
At 0 months	8.54 ± 8.43	8.23 ± 4.96	6.70 ± 5.97	0.290
At 3 months	1.85 ± 1.65	2.34 ± 1.80	1.18 ± 1.50	0.026
At 6 months	1.14 ± 1.03	1.75 ± 1.04	1.46 ± 1.89	0.934
At 12 months	1.86 ± 1.23	2.42 ± 1.49	1.79 ± 1.85	0.358

Bold value means p < 0.05.

PSA = prostate-specific antigen.

Table 3.

Elementary Tumor Control Outcomes of Prostate Cancer Patients with Non-Whole-Gland High-Intensity Focused Ultrasound and Whole-Gland High-Intensity Focused Ultrasound

Variables	Non-whole-gland HIFU		Whole-gland HIFU	p
Variables	Hemiablation	Zonal ablation	Whole-gland HIFU	p
PSA nadir (ng/mL)	1.06 ± 1.06	1.58 ± 1.15	1.06 ± 1.52	0.453
Time to PSA nadir (month)	4.62 ± 1.56	5.50 ± 2.50	3.84 ± 1.66	0.006
PSA decreasing rate at 3 months (%)	75.4 ± 16.9	71.2 ± 19.6	79.0 ± 23.7	0.285
PSA decreasing rate at 6 months (%)	83.4 ± 15.3	70.4 ± 36.6	74.9 ± 29.2	0.743
Histological absence of prostate cancer (%)	11 (84.6)	9 (75.0)	52 (85.2)	0.655
BDFS (%)	12 (92.3)	12 (100.0)	56 (91.8)	0.820
No mpMRI measurable prostate cancer (%)	11 (84.6)	9 (75.0)	53 (86.8)	0.633

Bold value means p < 0.05.

BDFS = biochemical disease-free survival (%); mpMRI = multiparametric magnetic resonance imaging.

Functional outcomes

As presented in Table 4, IPSSs at 0, 1, 3, and 12 months in the non-whole-gland HIFU group were 4.88 ± 2.83, 8.64 ± 3.63, 5.44 ± 3.06, and 4.56 ± 2.16 and 5.20 ± 4.33, 10.85 ± 6.10, 6.21 ± 5.07, and 5.36 ± 4.36 in the whole-gland HIFU group, respectively. IPSSs of patients who received non-whole-gland HIFU therapy at 1 month were less than those of patients who received whole-gland HIFU (p = 0.042). Notably, IPSSs at 1 month were significantly higher than IPSS baseline scores for patients of both the non-whole-gland HIFU group and the whole-gland HIFU group. There were no differences noted at 3 and 12 months within each group (Fig. 3C, D). Postoperative temporary urine retention was found more frequently in the whole-gland HIFU group than in the non-whole-gland HIFU group (44.3% vs 20%; p = 0.035). However, the incidence of urinary tract infection in the non-whole-gland HIFU group was the same as in the whole-gland HIFU group (p = 0.297). When comparing erectile dysfunction of both groups, no significant difference in IIEF scores could be detected (IIEF score of the non-whole-gland group: 19.36 ± 3.56 at 0 month, 13.00 ± 4.90 at 3 months, 15.64 ± 4.91at 12 months vs 18.48 ± 3.65 at 0 month, 12.07 ± 4.48 at 3 months, 15.15 ± 4.57 at 12 months in the whole-gland group; Fig. 3E, F). Likewise, continence was also evaluated at 0, 3, and 12 months. Our findings showed that the proportion of the pad-free rates, as well as the pad-free and leakage-free rates of the whole-gland HIFU group, was not different from the patients in the non-whole-gland HIFU. With regard to postoperative complications, 16 patients in the whole-gland HIFU group displayed urinary strictures compared with only 1 patient in the non-whole-gland HIFU group (p = 0.040). Moreover, two patients from the whole-gland HIFU group suffered a vesicorectal fistula and one suffered an intra-abdominal abscess. Both, vesicorectal fistula and intra-abdominal abscess were not identified in the non-whole-gland HIFU group.

Table 4.

Elementary Functional Outcomes and Adverse Events of Prostate Cancer Patients with Non-Whole-Gland High-Intensity Focused Ultrasound and Whole-Gland High-Intensity Focused Ultrasound

	Non-whole-gland HIFU		Whole-gland HIFU	p
	Hemiablation	Zonal ablation	Whole-gland HIFU	p
IPSS
At 0 month	4.69 ± 2.29	5.08 ± 3.42	5.20 ± 4.33	0.691
At 1 month	8.62 ± 2.87	8.67 ± 4.44	10.85 ± 6.10	0.042
At 3 months	5.38 ± 3.45	5.50 ± 2.71	6.21 ± 5.07	0.389
At 12 months	4.92 ± 2.22	4.17 ± 2.12	5.36 ± 4.36	0.268
Temporary urinary retention (%)	2 (15.4)	3 (25.0)	27 (44.3)	0.035
Urinary tract infection (%)	1 (7.7)	0 (0.0)	9 (14.8)	0.297
Pad free (%)
At 0 month	13 (100.0)	12 (100.0)	60 (98.4)	1.000
At 3 months	12 (92.3)	11 (91.7)	53 (86.9)	0.763
At 12 months	12 (92.3)	11 (91.7)	59 (96.7)	0.704
Pad free and leakage free (%)
At 0 month	13 (100.0)	11 (91.7)	54 (88.5)	0.500
At 3 months	10 (76.9)	11 (91.7)	48 (78.7)	0.792
At 12 months	12 (92.3)	11 (91.7)	55 (90.2)	1.000
IIEF-5
At 0 month	18.92 ± 4.15	19.83 ± 2.89	18.47 ± 3.65	0.307
At 3 months	12.92 ± 4.75	13.08 ± 5.26	12.06 ± 4.47	0.395
At 12 months	15.53 ± 4.96	15.75 ± 5.08	15.15 ± 4.57	0.663
Urinary stricture (%)	1 (7.7)	0 (0.0)	16 (26.2)	0.040
Fistula (%)	0 (0.0)	0 (0.0)	2 (3.3)	0.898
Intra-abdominal abscess	0 (0.0)	0 (0.0)	1 (1.6)	1.000

Bold values mean p < 0.05.

IIEF-5 = international index of erectile function-5; IPSS = international prostate symptom score.

Discussion

Focal therapy in patients with low- and intermediate-risk localized prostate cancer is regarded as posing a challenge to the conventional notion that prostate cancer is a heterogeneity-abounded malignancy in every sense, including the clinical, spatial, morphological, and genetic diversity.^13,14 Good local tumor control is essential for the prognosis of prostate cancer patients.^15,16 How to achieve a good local control is an intractable problem, usually experienced in focal therapy. In our study, we have compared the local tumor control and functional results between non-whole-gland HIFU and whole-gland HIFU treatment, to establish the advantages and disadvantages of non-whole-gland treatment as a focal therapy.

Based on data analysis conducted in this study, the PSA at 3 months and time to PSA nadir for whole-gland HIFU are higher than those for non-whole-gland HIFU. However, there are no differences in PSA at 6 and 12 months, as well as the PSA nadir. These results confirm the widely held belief that benign prostate tissue can also contribute to PSA level, thus hindering PSA level to PSA nadir.¹⁷ Even a tiny tumor lesion that cannot be detected by the current image techniques contributes to a slight difference. The recovery of PSA to the same level at 12 months and BDFS at 12 months indicates that in spite of undergoing a non-whole-gland HIFU procedure, the tumor is not in progression, at least at the biochemical level. It can also be confirmed by imaging and repeated biopsies that the absence of prostate cancer in the non-whole-gland HIFU group at 12 months was comparable with that in the whole-gland HIFU group. Moreover, all the relapsed patients after the primary HIFU treatment could be treated using salvage HIFU. Non-whole-gland HIFU would not have increased the difficulties and decrease possibilities of salvage treatment, which were also identified by other reports.^18,19

No significant changes were observed in IPSSs for urinary function at 12 months compared with the baselines in both groups. However, a sharp increase in IPSS at 1 month was found within both groups, similar to other studies.^20,21 It is noteworthy that IPSS at 1 month was also higher in the whole-gland HIFU group than in the non-whole-gland HIFU group. Similarly, the incidence of urinary retention was higher in the whole-gland HIFU group. We speculate that it might be caused by longer operation time, greater energy transfer to the gland causing more edema and swelling. Erectile functions recovered to preoperative levels, though in the non-whole-gland HIFU group no negative impact on erectile functions could be observed. Yap and colleagues²² have pointed out that the only determinant of erectile function after HIFU therapy is the preoperative erectile function status. Furthermore, even though the incontinence rates are the same for both groups, severe complications such as urinary tract stricture and fistula formation were not observed in the non-whole-gland HIFU group. This observation suggests that the non-whole-gland concept might show a more favorable profile of adverse events.

Non-whole-gland HIFU may be regarded as an in-between concept in the range of active surveillance and radical treatment, for example, radical prostatectomy or external beam radiation therapy. It offers acceptable oncological control, causing less frequent adverse effects compared with the whole-gland HIFU regime. However, no significant differences have been discovered in the functional outcomes of the two types of management at 12 months. Meanwhile HIFU therapy as such may markedly reduce patients' psychological burden with low- and intermediate-risk prostate cancer. Therefore HIFU therapy may be the optimal concept for those patients who are unfit for major surgical interventions, or are reluctant to undergo active surveillance. Considering worries about side effects, especially the use of a non-whole-gland treatment strategy, might meet concerns best.

Retrospective design constitutes the predominant limitation in our study. Whole-gland HIFU was basically used in our center before 2014 wherever the lesion was located, and no matter how many lesions were present. In addition, HIFU device may be considered as a heterogeneity factor in our study, as FocalOne HIFU was introduced in our center in 2016. FocalOne HIFU might be different from the device used before 2016 at our clinic. Furthermore, only eight patients without the PSA biochemical recurrence and postoperative measurable mpMRI signs consented to have a rebiopsy during the follow-up process, and we consider the patients who did not undergo the rebiopsy without PSA recovery and suspicious lesions in MRI after HIFU treatment as histological absence of prostate cancer. This is a factor that could influence the oncological outcome in both groups. Hence, there is need for further prospective, randomized, multicenter, and comparative studies featuring active surveillance, non-whole-gland HIFU, and whole-gland HIFU, and even the radical prostatectomy and radiation, to reach more consensuses on patients' selection criteria, as well as a standardized follow-up scheme after focal ablation therapy.

Footnotes

Acknowledgments

The authors acknowledge Ms. Uta Roland, Ms. Sarah Gerner, Ms. Christiane Uder, Ms. Eva Maria Klotz, and Dr. Carola Wotzka for helping us with patients' data collection.

Author Disclosure Statement

There are no conflicts of interest to this work.

Abbreviations Used

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