Urinary Outcomes of Minimally Invasive Treatments for Prostate Cancer—A Systematic Review by Young Academic Urologists’ Urotechnology Working Group

Abstract

Introduction:

Minimally invasive treatments (MITs) have emerged as viable treatment options for carefully selected patients with localized disease. Their major advantage is that MITs enable the preservation of nearby healthy prostate tissue and critical structures such as the urethral sphincter and neurovascular bundles without compromising oncologic outcomes. The aim of the current review is to describe the impact of different MITs for prostate cancer (PCa) on urinary continence.

Materials and Methods:

A systematic literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Inclusion criteria were as follows: all clinical trials conducted and related to the urinary outcomes (UO) of PCa MITs. Exclusion criteria were as follows: any reviews, articles, conference abstracts, articles whose subject fell outside the scope of this review, or any articles published more than 5 years ago.

Results:

In the course of the last 5 years, a total of 114 articles on MITs of PCa have been published. Among them, only 36 dealt with the UO for MITs. Brachytherapy, cryoablation, and high-intensity focused ultrasound (HIFU) seem to be the most widely used technologies, whereas irreversible electroporation, focal brachytherapy, focal cryoablation, and multi-parametric magnetic resonance imaging-ultrasound-guided (mpMRI-US-guided) HIFU seem to be the safest techniques in terms of UO.

Conclusion:

The use of MITs for treating PCa is a fast-growing option that can help preserve functional parameters and urinary continence close to their normal levels. It should be noted that although there are currently limited data available on all MITs for the treatment of PCa, the ones that have been extensively studied have shown promising results.

Introduction

Minimally invasive treatments (MITs) (new modalities that have been developed as minimally invasive procedures with the aim of providing equivalent oncologic safety, reduced toxicity, and improved functional outcomes)¹ have emerged as viable treatment options for carefully selected patients with localized disease. In those patients, MITs enable the preservation of nearby healthy prostate tissue and critical structures such as the urethral sphincter and neurovascular bundles without compromising oncologic outcomes. According to the European Association of Urology guidelines, MITs are recommended as a treatment option for low- and intermediate-risk prostate cancer (PCa) within a clinical trial setting or well-designed prospective cohort study and not recommended for high-risk patients.¹

Despite being a technique that is only just evolving, some of the MITs show favorable oncologic outcomes (comparable with radical prostatectomy in the short- and medium-term follow-up),² whereas some results remain controversial (e.g., the high rate of repeated interventions or the low rate of re-biopsy in patients).³ However, according to its secondary goal of reducing the toxicity rate after cancer treatment, most MITs continue to show promising results. In 2018, the European Section of Urotechnology reported the outcomes of MITs, the urinary continence rate was around 90% to 100%.⁴ The most common early complications were urinary retention (8%–10% of patients) and urinary tract infections (17%–20% of patients).

Another comprehensive systematic review included almost 6000 patients and showed promising midterm oncologic outcomes. Hopstaken et al. reported that clinically significant PCa in the treatment area varied from 0% to 60% depending on the modalities used.⁵ In their analyses, 95% to 100% of patients remained pad-free after treatment. No significant changes between pre- and post-treatment continence rates were observed regardless of the ablative technique used.

The goal of the current article is to summarize the currently available data on MIT urinary outcomes (UO) and to discuss the possible limitations and advantages of different techniques.

Materials and Methods

This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines.

We performed a systematic literature search using the Medline (PubMed) database with the following query: (“prostate cancer”) AND (“minimally invasive” OR “focal therapy” OR “tumor ablation” OR “ablation techniques” OR photochemotherapy OR brachytherapy OR “focal ablation” OR cryoablation OR cryotherapy OR cryosurg* OR hemiablat* OR HIFU OR “high-intensity focused ultrasound” OR IRE OR “irreversible electroporation” OR nanoknife OR “laser interstitial thermother*” OR LITT OR PDT OR “photodynamic therap*” OR RFA OR “Radiofrequency ablation” OR “therapeutic ultrasound” OR TULSA OR “partial prostatectomy”) AND (“urinary outcomes” OR “functional outcomes”) NOT (“radical prostatectomy” OR salvage OR recurrent). The year and country of publication were not used as criteria when retrieving the data.

Inclusion criteria were as follows: all clinical trials conducted in English and related to the UO of PCa primary MITs.

Exclusion criteria were as follows: any reviews, articles, conference abstracts, articles whose subject fell outside the scope of this review, or any articles published more than 5 years ago.

Two people (A.A. and C.A.) screened and included into the review studies reporting any UO of PCa MITs. The first step was for A.A. and C.A. to undertake a title review and exclude any inappropriate publications: reviews, comments, conference abstracts, and articles in languages other than English.

After that, A.A. and C.A. performed independent abstract reviews according to the inclusion and exclusion criteria. After abstract and title revision, A.A. manually removed any duplicates. At the final stage, A.A. and C.A. independently performed a full-text review of the relevant articles. We excluded articles where the authors provided no required data.

We tried to resolve disagreements through debate; if we could not reach a consensus, the third person would make the final decision (M.T.).

We extracted the following information from the included articles: year of publication, intervention, the total number of patients, median follow-up, number of patients with urinary incontinence (UI) at first and final follow-up, mean baseline International Prostate Symptom Score (IPSS), mean IPSS at final follow-up, and others. Results are presented in Table 1.

Table 1.

Urinary Outcomes of Minimally Invasive Treatments for Prostate Cancer

Study/LE	Year of publication	Intervention	Total number of patients, n	Median follow-up, months	Number of patients with UI at first follow-up, n (%)	Number of patients with UI at final follow-up, n (%)	Mean baseline IPSS	Change of mean IPSS at final follow-up compared with baseline
Langley et al.⁶/2b	2018	LDR brachytherapy	597	107	7 (0.5)	—	4	−2.0
D’hulst et al.⁷/2b	2018	LDR brachytherapy	159	71 ± 29^a	—	—	—	—
Hoffman et al.⁸/2b	2020	LDR brachytherapy	87	74	9 (11)	3 (5)	—	—
Winoker et al.⁹/2b	2019	LDR brachytherapy	105	80.3 ± 55.8^a	—	3 (2.9)	23.6	−7.6
Winoker et al.¹⁰/2b	2019	LDR brachytherapy	222	119	—	—	6.4	+2.3
Viktorin-Baier et al.¹¹/2b	2020	LDR brachytherapy	1291	37.1	—	—	5.76	+1.23
Yaxley et al.¹²/2b	2022	LDR brachytherapy	297	142	22 (7.4)	—	—	—
Matsuoka et al.¹³/2b	2022	Focal LDR brachytherapy	51	68	—	0 (0)	—	—
Prada et al.¹⁴/2b	2020	Focal HDR brachytherapy	50	32	—	—	8.2	6.7
Hass et al.¹⁵/2b	2022	Focal HDR brachytherapy	37	20	—	—	7.1	−0.1
Barqawi et al.¹⁶/2b	2018	Cryoablation(whole-gland ablation)	167	14	—	—	—	−4.0
Barqawi et al.¹⁶/2b	2018	Cryoablation(hemigland ablation)	29	14	—	—	—	−4.5
Shah et al.¹⁷/2b	2019	Cryoablation(focal ablation)	69	27.8	4 (6)	0 (0)	—	—
Mercader et al.¹⁸/2b	2020	Cryoablation (whole-gland ablation)	177	60 ± 32.9^a	9 (5)	3 (1.7)	—	—
Bossier et al.¹⁹/2b	2020	Cryoablation(whole-gland ablation)	40	41	16 (40)	7 (17)	—	—
Bossier et al.¹⁹/2b	2020	Cryoablation(hemigland ablation)	26	27	7 (28)	4 (17)	—	—
Shah et al.²⁰/2b	2021	Cryoablation (focal ablation)	49	6	—	—	8	−1.0
Thakker et al.²¹/2b	2022	Cryoablation (focal ablation)	100	6	—	—	—	−2.1
Fernández-Pascual et al.²²/2b	2022	Cryoablation (focal ablation)	75	25	0 (0)	0 (0)	12	0
von Hardenberg et al.²³/2b	2018	mpMRI-US-guided HIFU	24	12	1 (4)	1 (4)	6	−2.0
Lei et al.²⁴/2b	2019	HIFU (whole-gland ablation)	61	12	8 (13.1)	2 (3.3)	5.2	+0.16
		HIFU(hemigland ablation)	13	12	1 (7.7)	1 (7.7)	4.69	+0.23
		HIFU(focal ablation)	12	12	1 (8.3)	1 (8.3)	5.08	−0.91
Sivaraman et al.²⁵/2b	2020	mpMRI-US-guided HIFU	52	12	3 (5.1)	—	3.6	+2.2
Sivaraman et al.²⁵/2b	2020	US-guided HIFU	88	3	14 (15.9)	—	5.8	+2.4
Shoji et al.²⁶/2b	2020	mpMRI-US-guided HIFU	90	12	—	0 (0)	6	−1.0
Westhoff et al.²⁷/2b	2021	mpMRI-US-guided HIFU	48	38	—	—	—	—
Ghai et al.²⁸/2b	2021	mpMRI-US-guided HIFU	44	5	0 (0)	0 (0)	3.5	+2.5
Hong et al.²⁹/2b	2022	HIFU (focal ablation)	163	17	4 (2.5)	—	—	—
Lovegrove et al.³⁰/2b	2020	HIFU (focal ablation)	355	12	15 (5.2)	10 (4.7)	9.47	−0.03
Oderda et al.³¹/2b	2022	Targeted microwave ablation	11	6	—	—	6.4	+4.5
Rastinehad et al.³²/2b	2019	Nanoparticle-based photothermal therapy	16	12	—	—	8	0
Collettini et al.³³/2b	2019	Irreversible electroporation	30	12	2 (6.7)	1 (3.5)	—	—
Enikeev et al.³⁴/2b	2020	Irreversible electroporation	12	12	—	—	—	−5.0
Blazevski et al.³⁵/2b	2020	Irreversible electroporation	81	36	7 (8.6)	1 (1.2)	—	—
Scheltema et al.³⁶/2b	2022	Irreversible electroporation	229	60	—	1 (1)	—	—
Hatiboglu et al.³⁷/2b	2020	TULSA	29	6	3 (10)	0 (0)	9.3	−3.3
Klotz et al.³⁸/2b	2021	TULSA	115	12	3 (3)	3 (3)	7.0	−1.0
Hatiboglu et al.³⁹/2b	2021	TULSA	29	24	3 (10)	0 (0)	9.3	−3.6
Rabinowitz et al.⁴⁰/2b	2023	TULSA	45	6	—	6 (13.3)	—	—
Kaouk et al.⁴¹/2b	2022	Partial prostatectomy	9	1.5	0 (0)	0 (0)	—	—
Sood et al.⁴²/2b	2022	Partial prostatectomy	88	25	—	0 (0)	—	—

Mean value ± SD.

HDR = high-dose rate; HIFU = high-intensity focused ultrasound; IPSS = International Prostate Symptom Score; LDR = low-dose rate; SD = standard deviation; TULSA = transurethral ultrasound ablation; UI = urinary incontinence; US = ultrasound.

The quality of the selected clinical studies was assessed using the Oxford Center for Evidence-Based Medicine: Level of Evidence (LE). The LE is presented in Table 1.

Results

A total of 36 articles were included in our review. Eight articles reported the UO for low-dose-rate prostate brachytherapy (LDRBT); two—for high-dose-rate brachytherapy (HDRBT); seven—for cryoablation; eight—for high-intensity focused ultrasound (HIFU); four—for irreversible electroporation (IRE) of the prostate, one—for targeted microwave ablation (TMA); one for nanoparticle-based photothermal therapy; four—for transurethral ultrasound ablation (TULSA); and two—for partial prostatectomy.

Brachytherapy

Low-dose-rate brachytherapy is an MIT involving permanently implanting radioactive seeds into the prostate. These seeds contain isotopes with a low therapeutic dose of radiation and a prolonged half-life period; Iodine-125 (I-125), Palladium-103 (103Pd-), and Cesium-131 isotopes are commonly used for LDRBT.⁴³ The radioactive energy spreads over weeks and months, damaging the cancer focus and preventing its progression. Unlike LDRBT, HDRBT does not involve permanent seed implantation. During this procedure, the isotope with a higher dose of radiation (such as Iridium-192 [IR-192]) is introduced into the patient’s body temporarily for several minutes.

The work of Langley et al. presents the long-term outcomes for LDRBT.⁶ A total of 597 patients were included in this study, and the median follow-up was 8.9 years. At 3 months after the implantation of the seeds, 99% of the assessed patients remained pad-free, at 12 months—97%, and at 5 years—100%. Severe incontinence disorders were witnessed in only 7 of the 207 (<0.5%) assessed patients—they had grade 2 stress UI according to the International Continence Society score. Such symptoms were observed in the first 3 years after intervention. After that period, all these patients showed regression in terms of their symptoms.

In the Hoffman et al. study, 87 patients underwent the LDRBT monotherapy with a median follow-up of 74 months.⁸ The authors estimated continence according to the Expanded Prostate Cancer Index Composite (EPIC-26) UI domain. Three (4%) of those 87 patients showed symptoms of urinary leakage at a baseline; 6 months after the intervention, 9 (11%) patients had such symptoms; and at 1-, 3- and 5-year follow-up, the number of patients reporting urinary leakage was 2 (2%), 2 (3%), and 3 (5%), respectively.

Winoker et al. assessed the UO for LDRBT in patients with severe lower urinary tract symptoms (LUTS).⁹ A total of 105 patients with the baseline IPSS 20–35 were followed up for 80.3 ± 55.8 months. The mean pretreatment IPSS was 23.6 ± 3.0. Fifteen of those 105 (14.3%) patients showed a deterioration in IPSS (mean increase 6.7, p = 0.001); 23 (21.9%) showed no significant difference in IPSS (mean decrease 0.6, p = 0.216); and 67 (63.8%) of patients showed some improvements in terms of IPSS (mean decrease 13.2, p = 0.001). So, the overall mean IPSS change for 105 patients was—7.6 ± 9.3 (from 23.6 ± 3.0 at the baseline to 16.0 ± 8.7 at final follow-up), p = 0.001. At the final follow-up, 3 of the 105 (2.9%) patients had objective UI (they used at least one pad daily); at the same time, 8 patients (7.7%) reported a subjective UI in the follow-up questionary: 3 of them had urge UI, 2 had stress UI, and 3 had mixed UI.

The same study group also assessed the 10-year outcomes for LDRBT.¹⁰ The authors included 222 patients with a median follow-up of 119 months. The IPSS increase was +2.3 (from baseline 6.4 to 8.7 at final follow-up, p = 0.0001). There were no statistically significant differences in IPSS increase between patients who underwent LDRBT monotherapy and those who underwent LDRBT + external beam radiation therapy (p = 0.56).

Victorin-Baier et al. performed the largest study of LDRBT functional outcomes.¹¹ They included 1291 patients with a median follow-up of 37.1 months. The authors reported an overall mean increase of IPSS from 5.76 to 6.99. The IPSS increase was the highest at the first 6 weeks—6 months after seed implantation—and then this value decreased up to 3 years after treatment. After a 3-year follow-up, the mean IPSS remained stable.

In the study of Yaxley et al., the authors assessed the UO for 297 patients who underwent LDRBT with a median follow-up of 11.8 years.¹² Only 22 men (7.4%) with ≥10 years of follow-up required a pad for stress or urge UI.

Focal LDRBT demonstrated a more favorable impact on UO than total LDRBT. The study of Matsuoka et al. included 51 patients with a median follow-up of 5.7 years.¹³ All participants remained continent at the end of observation.

Prada et al. reported a change in IPSS in patients who underwent focal HDRBT.¹⁴ The mean decrease of IPSS in 50 patients with a median follow-up of 32 months was 1.5. The International Continence Score (ICQ-SF) remained 0 in all the participants during the follow-up period.

Hass et al. reported the long-term outcomes for focal HDRBT.¹⁵ A total of 37 patients with a median follow-up of 20 months were included in the study. After the procedure, no significant increase in IPSS was registered during the first 6 months, then it decreased to the baseline level: the mean IPSS at baseline, 6 months, 1- and 2-year follow-ups was 7.1, 7.7, 7.0, and 7.0, respectively. The ICIQ score remained stable too: at baseline—1.4, at 6 months—1.5, at 1 year—1.8, and at the 2-year follow-up—1.7. Also, the respective score for patients with an ICIQ score of 0 at the baseline did not increase at any of the follow-ups.

Summary

The available studies evaluate the mean change of IPSS ±2.0 at 4–5 years after treatment. The greatest change in IPSS was observed in patients with severe LUTS—the decrease was 7.6. Immediately after the procedure, 0.5% to 11% of patients showed symptoms of urinary leakage. However, 1 year after treatment, only 2.9% to 5% of them remained incontinent. It presents brachytherapy as a continence-safe treatment with relatively low rates of stress, urge, and mixed UI.

Cryoablation

Cryoablation induces cell death by rupturing cell membranes following a rapid temperature change.⁴² ^,44 The current options for cryoablation include whole-gland ablation, hemigland ablation, and focal ablation of the cancer foci. Currently, most studies on cryoablation discuss focal options, whereas whole-gland ablation is not that frequent because of the high complication rate. A few studies of total cryoablation with long follow-ups started in the early 2010s were included in the review.

Mercader et al. observed a decrease in the number of patients with UI during follow-up after whole-gland cryoablation.¹⁸ The study included 177 patients with a mean follow-up of 60 months, 9 patients (5%) had UI right after treatment, whereas at the end of follow-up, only 3 (1.7%) retained symptoms of UI.

In the Barqawi et al.¹⁶ study, the authors compared the following two options: 167 patients underwent whole-gland cryoablation, whereas 29 underwent hemigland ablation. The median follow-up was 14 months. The mean decrease of IPSS was 4.0 in the whole-gland group and 4.5 in the hemigland group. The most frequent complications in the early postoperative period were urinary retention and urgency—27.7% of patients suffered these complications. Bossier et al. compared the prevalence of UI in patients undergoing whole-gland ablation and hemigland ablation.¹⁹ A total of 40 patients with a median follow-up of 41 months were assigned to the whole-gland ablation group (40% had UI symptoms), and 26 patients (28% had UI symptoms) with a median follow-up of 27 months were assigned to the hemigland ablation group. At the final follow-up, only 17% of patients in both groups had any UI. Early and 1-year urinary continence rates were 60% and 83% in the whole-gland ablation groups compared with 72% and 83% in the hemigland ablation group.

In 2019, Shah et al. estimated the rate of UI in patients who underwent focal cryoablation. A total of 69 patients with a median follow-up of 27.8 months were enrolled. After treatment, four of them had UI, but at the end of the follow-up, all the patients were incontinence-free.¹⁷ In their next study, Shah et al. obtained similar results.²⁰ They included 49 patients after focal cryoablation with a median follow-up of 6 months in their study. The mean IPSS decrease was 1.0. Thakker et al. included 100 patients who underwent focal cryoablation. The mean decrease of IPSS was 2.1 at the 6-month follow-up; the mean changes in IPSS for men with baseline mild, moderate, and severe LUTS were +0.9 (p = 0.06), −4.2 (p = 0.001), and −11.1(p = 0.001), respectively.²¹ In the study of Fernandez-Pascual et al., 75 patients with a median follow-up of 12 months were enrolled.²² At the final follow-up, all patients remained continent, and the IPSS remained at baseline.

Summary

In the available studies, the most favorable outcomes were observed in patients who underwent a focal ablation—UI rate was up to 6%, and most patients showed stable IPSS results (with a weak tendency for improvement). Whole-gland cryotherapy showed the most unfavorable outcomes in terms of UI—up to 40% patients reported urinary leakage. However, hemigland and whole-gland ablation outcomes were similar in the late postoperative period (up to 17% of patients had some kind of urinary leakage). Still, right after treatment, hemigland ablation seems to be more favorable.

High-intensity focused ultrasound

HIFU is an MIT method based on direct tumor heating by high-intensity ultrasound (US).^45,46 Similar to cryoablation, HIFU may be used for whole-gland, hemigland, or focal ablation.

Lei et al. included all of the above techniques in their comparison²⁴: 61 patients—whole-gland ablation group, 13—hemigland, and 12—focal. The median follow-up was 12 months. The number of patients with UI remained stable at the baseline level for hemi- and focal ablation, whereas in the whole-gland ablation group, the number of patients with UI decreased (6 of 8 patients became pad-free). The mean change of IPSS was +0.16, +0.23, and −0.91 for patients who underwent whole-gland, hemigland, and focal ablation, respectively.

Sivaraman et al.²⁵ compared UO for patients after US-guided (88 patients included) and MRI-guided focal HIFU (52 patients included). The follow-up period was 3 months. The mean increase of IPSS was 2.4 and 2.2 (p = 0.8) for US- and MRI-guided HIFU. However, the number of patients with urinary leakage was significantly higher in the US-guided HIFU group (15.9% vs 5.1%, respectively, p = 0.04).

Other included studies showed similar results. Shoji et al. reported the absence of patients with UI at the 12-month follow-up, and IPSS decreased to 1.0.²⁶ In Ghai et al.’s study, there were also no cases of UI, and IPSS showed an increase of 2.5.²⁸ Hardenberg et al. reported three (12.5%) cases of UI at the 1-year follow-up: two patients used only one pad, and one patient required two pads.²³ The mean decrease of IPSS in their study was 2.0. In the study of Hong et al., there were only four (2.5%) cases of UI in the early postoperative period.²⁹ The study of Westhoff et al. stands out from the crowd. The authors reported that 25% of the 48 patients with a median follow-up of 38 months had a clinically meaningful impairment of urinary continence at their final follow-up.²⁷ Most patients associated their treatment regret with such impairment (regret was determined as >40/100 in Clark’s validated scale).

The HIFU Evaluation and Assessment of Treatment (HEAT) study evaluated functional outcomes after a primary and secondary focal HIFU.³⁰ Following the initial focal HIFU treatment, the average change in IPSS was −0.03 (p = 0.02), with no further decrease observed. The proportion of patients maintaining leak-free continence fell from 77.9% to 72.8% (p = 0.06), whereas the percentage of those who were pad-free declined from 98.6% to 94.8% (p = 0.07) over a period of 1–2 years, respectively.

Summary

The available data demonstrate that whole-gland HIFU has an increased risk of UI after treatment (up to 13%–16%). Focal HIFU is associated with a lower rate of UI (4%–8%). However, mpMRI-US fusion guidance may allow for the reduction of this rate up to 5.1% during the early postoperative period.

Other modalities

Targeted microwave ablation

TMA is a focal treatment technique based on tissue thermal damage induced by microwaves. As opposed to HIFU, the TMA is independent of thermal conductivity or tissue impedance of the medium, and so, the coagulative necrosis induced by TMA is more predictable and controllable than HIFU.⁴⁷ However, TMA was developed for treating hepatocellular carcinoma and is not widely used for treating urologic malignancies, so only one study was identified.

A total of 11 patients with a median follow-up of 6 months were included in the initial study of Oderda et al.³¹ The authors reported an increase in median IPSS to approximately 4.5. However, those changes were insignificant (p = 0.39). After procedure, one (9%) patient reported urgency; during the 6-month follow-up period, the urgency developed in two patients (18%).

Nanoparticle-based photothermal therapy

Nanoparticle-based photothermal therapy is a focal treatment technology based on heat production by nanoshell particles. After drug intravenous insertion, the particles are stored in the tissue and absorb light at wavelengths of high tissue transparency and heat those tissues, destroying them. Our analysis included only one initial study since nanoparticle-based photothermal therapy is still a relatively new procedure.

Rastinehad et al. enrolled 16 patients with a median follow-up of 12 months.³² Median IPSS between baseline and the 3-month follow-up was not significantly different (p = 0.06). Urinary quality of life (QoL) at baseline, 1 month, 3 months, 6 months, and 12 months was 2, 2, 1, 1, and 2, respectively, with no statistical difference between baseline and the 3-month follow-up (p = 0.33).

Irreversible electroporation

Irreversible electroporation (IRE) is a focal treatment technology that utilizes pulsatile electrical currents to ablate tissue. IRE works by applying short, intense electric pulses creating nanopores in the cell membrane. This disturbs the osmotic balance, leading to cell destruction.⁴⁸

Collettini et al. included 30 participants in their study.³³ At a baseline, 29/30 participants were pad-free and leak-free. At 6- and 12-month follow-ups, 28 of them remained pad-free, whereas 25 participants remained leak-free. At 24-month follow-up, 12/12 reached patients were pad-free and leak-free. Enikeev et al. assessed the changes in participants’ IPSS after IRE.³⁴ During a 12-month follow-up, none of the 12 patients reported any progression of LUTS, and 3/12 participants noted an improvement in urination reflected in an IPSS decrease (the mean decrease was 5.0). Blazevski et al. included in their study 81 patients with a median follow-up of 36 months.³⁵ At 6 weeks after treatment, seven (8.6%) patients had symptoms of UI and required at least one pad, but at 12 months after treatment, only one (1.2%) patient continued to use pads. Similar results were demonstrated in the study of Scheltema et al.³⁶ The authors enrolled in their study 229 patients with a median follow-up of 60 months. At 12 months after the intervention, only one (1%) patient was incontinent.

Transurethral ultrasound ablation

MRI-guided TULSA is an MIT based on MRI-guided and controlled transurethral ablation of the prostate by targeted US.^48,49 Similar to HIFU, this technique promises to directly ablate cancer focus independently of its localization (e.g., TULSA may be more preferred for anterior tumors or in patients with large prostate than HIFU).

In the initial study of Hatiboglu et al., 29 patients with a median follow-up of 6 months were included.³⁷ At 1-month follow-up, three participants used at least a pad per day, including one patient who used two pads a day. At the 3-month visit, one patient required a pad per day. At 6 months postintervention, all patients were pad-free. The mean IPSS at baseline, 1-month, 3-month, and 6-month follow-ups was 9.3, 15.0, 6.3, and 6.0, respectively. In the second study with a longer follow-up (24 months), all patients remained pad-free.³⁹ The mean IPSS was 5.2 and 5.7 at the 12- and 24-month follow-ups, respectively.

In the Klotz et al. study, which included 115 patients with a follow-up period of 12 months, 3 patients were incontinent after treatment.³⁸ The median IPSS changed as follows: at baseline—7.0, at 1-month follow-up—14.0, at 3 months—8.0, and at the 6- and 12-month follow-ups—6.0. In Rabinowitz et al.’s study, 45 patients with a median follow-up of 6 months were enrolled.⁴⁰ The authors aimed to define optimal ways of improving bladder drainage. In 26 patients, the indwelling urethral catheter was used for bladder drainage; in 19 patients, the suprapubic tube was used for that purpose. There was no significant difference between IPSS at baseline and 6 months after treatment, regardless of urinary management strategy.

The incontinence rates at 6 months were similar between groups (2/19 [10.5%] for suprapubic drainage and 4/26 [15.4%] for urethral catheter drainage).

Partial prostatectomy

Partial prostatectomy is an MIT based on a less traumatic than on a radical prostatectomy operation technique.⁵⁰ The rationale for partial prostatectomy is still being discussed: a transperitoneal approach and endotracheal anesthesia are still needed for this intervention, so partial prostatectomy should not be considered “a truly MIT.” However, we decided to include this technique in our review since it aims to minimize the surgical volume significantly compared with radical prostatectomy.

Initial studies have made use of robotic surgical systems for this aim. In the study of Kaouk et al., nine patients underwent this procedure. A median follow-up was 6 weeks, at the final visit all patients were continent.⁴¹ In the study of Sood et al., 88 patients with a median follow-up of 25 months were included.⁴² At 12 months after treatment, all the patients were continent (0–1 pads), with 90.9% of patients using 0 pads. The median time to urinary continence was 1 month.

Discussion

The review collected all the available data about UO for PCa MITs over the last 5 years. In the context of our review, MITs include all organ-sparing techniques that result in little to no collateral damage to surrounding organs, in contrast to radical prostatectomy or external beam radiotherapy. Unlike radical treatments, MITs have a minimal impact on QoL. However, in this review, we aimed to compile all available data on the UO of MITs to enable a direct comparison of different techniques. We analyzed in total 38 articles, most of them on cryoablation (7), low-dose brachytherapy (8), and HIFU (8). These techniques are widely spread and well-studied. Studies on related technologies (such as IRE, TMA, nanoparticle-based photothermal therapy, partial prostatectomy, or TULSA) are still being pioneered, and some are still under development.

The IPSS is a widely assessed parameter. It permits the clinician to estimate the severity of LUTS. Many studies reported a significant impairment of IPSS during the first 6 weeks after surgical intervention. One year after treatment, the IPSS usually returned to the baseline and remained stable at this level. Patients with moderate-to-severe LUTS (IPSS ≥8) tended IPSS decrease at 1 year and later follow-ups compared with baseline. At the same time, in patients with mild LUTS (IPSS <8), the IPSS tended to increase slightly. These changes amount to the anticipated adverse events: tissue ablation performed for PCa treatment destroys the prostate structures and eliminates the mechanical obstruction in the prostatic urethra. However, in patients with intact prostatic volumes (without benign prostatic hyperplasia), the ablation may impair the native gland configuration. This impact on LUTS is true for radical prostatectomy too.⁵¹

Other modalities used to evaluate urinary function were ICQ-SF, EPIC-26, and other questionnaires. They are commonly used to estimate treatments related to urinary toxicity. The authors of original research studies used one of them to report the presence of UI in patients and to classify UI into urgent, stress, and mixed. Unfortunately, UO are only widely reported for brachytherapy, cryoablation, and HIFU; the data regarding other techniques are still lacking. In a departure from that, IRE, TULSA, focal brachytherapy, focal cryoablation, and mpMRI-US-guided HIFU seem to be the safest techniques in terms of urinary toxicity. However, subsequent studies are still needed to confirm this assumption.

Among the main limitations of the current work are limited UO data, which are usually considered to be a secondary outcome, whereas most of the studies focus on oncologic outcomes. However, the main goal of MITs is to decrease the rate of sexual and urinary toxicity and to propose well-tolerated treatment strategies with a minimal impact on QoL. One more limitation of our study is the inclusion of both types of studies in which patients underwent whole-gland ablation and patrial-gland ablation. It is obviously that patients who underwent whole-gland therapies are at higher risk of urinary complications than those treated with focal therapies. However, many of the included studies have two and more patient groups, which differ by the ablation volume or technique. Because a few of those studies are single center, the authors suppose that it makes the comparison of different ablation volumes more visual. Another limitation is the absence of uniformity in reporting incontinence. For this reason, the results for UI rate are rather varied and it is difficult to compare them side-by-side. We see this as a key basis for improvement—it is necessary to unify and consolidate all the outcome measures to enhance further any efforts to assess the efficacy and safety of MITs.

Conclusion

The use of minimally invasive techniques for treating PCa is a fast-growing option that can help preserve functional parameters and urinary continence close to their normal levels. Although focal ablation may be the safest choice in terms of urinary toxicity, it is important to discuss all treatment options with the patient on an individual basis. It should be noted that although there are currently limited data available on all MITs for PCa, the ones that have been extensively studied have shown promising results.

Footnotes

Authors’ Contributions

M.T. conducted an article conceptualization writing and editing; A.A. and C.A. performed the article writing, editing, systematic search, and table and PRISMA preparation; A.M., J.G.R., S.P., E.C., I.R.B., K.-F.K., S.R., P.P., L.B., A.V., and P.D.B. participated in article editing and consulting; H.F., D.E., and G.E.C. participated in article editing, conceptualization, and supervision.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Supplementary Material

Supplementary Figure S1

Abbreviations Used

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