Association between maximal urethral length preservation and postoperative continence after robot-assisted radical prostatectomy: a meta-analysis and systematic review

Abstract

Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle–Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68–5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13–3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.

INTRODUCTION

Prostate cancer is one of the most common malignant tumors in men and a leading cause of cancer-related death in men globally.1,2,3 Radical prostatectomy (RP), which removes the entire prostate gland and seminal vesicles, is the gold standard treatment for localized prostate cancer.4 With the development of minimally invasive technology, the urinary incontinence (UI) rate after RP has been significantly reduced. However, the return to continence can be a slow process, and approximately 10% of patients still have UI 12 months after robot-assisted RP (RARP).5

The complex mechanism underlying the development of postoperative UI remains incompletely understood. However, it is widely accepted that UI primarily results from damage to the pelvic floor structures supporting the urethra. Therefore, preserving the periurethral structures during surgery is crucial. Various surgical techniques have been proposed to achieve this goal, including bladder neck preservation and reconstruction, rhabdosphincter preservation, periurethral structure preservation, and nerve-sparing surgery.6

Recent studies have highlighted preservation of the full length of the functional urethra, anatomically located between the verumontanum and the prostatic apex, as a critical component in maintaining urinary continence.7,8,9 While maximal urethral length preservation (MULP) has shown promise in improving short-term continence rates after RP, its long-term efficacy remains uncertain. Concerns regarding MULP include the risk of positive surgical margins due to incomplete resection at the prostate apex. As far as we know, few meta-analyses or systematic reviews evaluated the prognostic value of MULP. This meta-analysis was performed to assess the relationship between MULP and postoperative UI after RARP.

PATIENTS AND METHODS

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.10 The requirements for ethical approval and patient consent were waived because all data were extracted from previously published studies. The protocol for the overarching project was registered in the Prospective Register of Systematic Reviews (PROSPERO; Registration No. CRD42024526158).

Search strategy and selection criteria

We conducted a meta-analysis of studies published before December 31, 2023. Eligible studies included randomized trials and cohort studies assessing the effects of MULP on postoperative UI after RP. A comprehensive literature review of the PubMed, Web of Science, Embase, and the Cochrane Library databases was performed using the following keywords: ((maximal urethral length) OR (urethral length) OR (full functional-length urethral)) AND (preservation) AND ((robot-assisted radical prostatectomy) OR (robotic radical prostatectomy) OR (robot-assisted laparoscopic radical prostatectomy)). The MULP technique typically involved meticulous dissection of the prostate apex to expose and preserve an additional length of the intraprostatic urethra. Two authors (HYW and YPF) independently reviewed articles and unanimously decided on their inclusion. The initial results underwent title or abstract assessment, followed by full-text assessment for selected publications.

All the studies included in this meta-analysis met the following four inclusion criteria. (1) The study patients consented to RARP, and documentation of MULP performance was available; (2) the study reported follow-up data on postoperative UI and investigated the association between MULP and the continence rate; (3) the measurement of the urinary continence status was specified; and (4) in the case of duplicate studies, the most recent report was included in the meta-analysis.

The exclusion criteria included (1) review articles, case reports, letters to editors, or editorial comments; (2) noncomparative studies reporting the outcome of MULP; (3) incomplete data regarding the postoperative urinary continence status; or (4) studies published only as abstracts and reports from meetings. No language or publication status restrictions were imposed.

Literature quality evaluation

The Newcastle–Ottawa Scale (NOS) was used to assess the quality of each included study.11 The NOS is a three-part assessment instrument designed for observational studies, such as case–control and cohort studies. The NOS consists of three factors: selection, comparability, and outcome. A study was considered of poor quality if it scored less than 5 on the NOS.

Outcomes and data extraction

The primary outcome of this meta-analysis was postoperative UI, including early UI (1 month after RARP) and late UI (12 months after RARP). The secondary outcomes were a positive surgical margin (PSM) of the pathological specimens and, when available, the PSM rate at the prostate apex.

All data were extracted from the included studies by one author and verified by a second author (HYW and YPF). Other extracted data included the first author’s name, publication year, study time frame, country, study type (retrospective or prospective), total number of patients, and definition of UI. For dichotomous data, such as the rate of UI, the number of events and total number of patients were extracted. Where data could not be obtained from the literature, the related data were considered missing.

Statistical analyses

R software version 4.1.2 (The R Foundation for Statistical Computing, Vienna, Austria) was used for the statistical analysis and to create forest plots for this meta-analysis. The impact of MULP on the outcomes of UI and PSM was assessed using the odds ratio (OR) with the 95% confidence interval (CI). The statistical significance of the OR was determined by the Z-test and the corresponding P value. Heterogeneity among the included studies was assessed using the I² test with the corresponding P value. A fixed-effects model was applied if I² < 50%; otherwise, a random-effects model was employed to minimize the effect of heterogeneity. A sensitivity analysis was performed to assess the reliability and stability of the meta-analysis results. Publication bias was assessed using funnel plots and Egger’s regression test. P < 0.05 was deemed statistically significant in all tests.

RESULTS

Search results and study selection

The search process, as outlined in the flow diagram (Figure 1), yielded a total of 130 articles from the database search. After removing duplicates, 75 records underwent initial screening based on the title and abstract. Subsequently, 67 studies were excluded during the abstract review because they did not meet the predefined inclusion criteria. Of the remaining eight studies that underwent full-text evaluation, two were excluded because of the absence of a control group treated by RARP without MULP. Consequently, six articles were included in the final data analysis.12,13,14,15,16,17 No relevant reviews or meta-analyses of the effect of MULP on UI post-RP were found, and no unpublished studies meeting the criteria were obtained.

Figure 1.

Flow diagram of study selection.

Study characteristics

The characteristics of the six studies meeting the inclusion criteria are detailed in Table 1. Three studies13,15,16 were conducted in the USA, one12 in Greece, one14 in Korea, and one17 in Germany. All six studies were single-center studies with sample sizes ranging from 90 to 580 (total of 1869 participants). Two studies13,15 defined urinary continence as the absence of pad usage postoperatively, while three others14,16,17 defined it as the use of one pad or no pad. One study assessed continence based on both pad usage and questionnaires.12 Additionally, two studies assessed the preoperative continence status of patients and excluded those who were incontinent before RARP.12,13

Table 1.

Summary of included studies

Study	Type	Country	Time frame	Continence definition	Patient (n)
Sfoungaristos et al.12 2013	Prospective	Greece	2008–2012	Number of pads and questionnaires	244
Hamada et al.13 2014	Prospective	USA	2011–2013	No pad	90
Heo et al.14 2020	Retrospective	Korea	2014–2017	0–1 pad	571
Ko et al.15 2020	Retrospective	USA	NA	No pad	580
Nunez Bragayrac et al.16 2020	Retrospective	USA	2014–2016	0–1 pad	242
Hoeh et al.17 2023	Retrospective	Germany	2014–2019	0–1 pad	142

NA: not available

The results of the quality assessment of the articles are shown in Table 2. All the studies included in the analysis scored 7 or 8 points on the NOS, indicating medium to high quality. Following the quality assessment, no studies were disqualified because of lack of reliability.

Table 2.

Quality evaluation of included cohort studies using the Newcastle–Ottawa Scale

Studies	Type of study	Selection				Comparability	Outcome			Total
		1	2	3	4		1	2	3
Sfoungaristos et al.12 2013	Cohort study	1	1	1	1	2	0	1	1	8
Hamada et al.13 2014	Cohort study	1	1	1	1	2	0	1	1	8
Heo et al.14 2020	Cohort study	1	1	1	0	2	0	1	1	7
Ko et al.15 2020	Cohort study	1	1	1	0	2	0	1	1	7
Nunez Bragayrac et al.16 2020	Cohort study	1	1	1	0	2	0	1	1	7
Hoeh et al.17 2023	Cohort study	1	1	1	0	2	0	1	1	7

Selection: (1) representativeness of the exposed cohort; (2) selection of the unexposed cohort; (3) exposure verification; and (4) demonstration that the result of interest was not present at the beginning of the study; comparability: comparability of cohorts based on design or analysis; outcome: (1) result evaluation; (2) follow-up was long enough for results to occur; and (3) adequacy of cohort follow-up

Outcomes

The outcomes of urinary continence after RARP are presented in Table 3. With respect to early continence (1 month after RARP), data from 5 studies involving 1727 patients showed that 61.9% (475/767) of patients who underwent MULP were continent, compared with 39.4% (378/960) who did not undergo MULP (Z = 3.62, P = 0.003, OR = 3.10, 95% CI: 1.68–5.73; Figure 2a). Similarly, data from 4 studies involving 1537 patients showed that 92.0% (674/733) of patients who underwent MULP were continent 12 months after RARP, compared with 86.7% (697/804) who did not undergo MULP, indicating a significant improvement in late continence (12 months after RARP) with MULP (Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13–3.90; Figure 2b). Regarding oncology outcomes, MULP did not increase the overall PSM rate (Z = 0.29, P = 0.770, OR = 1.08, 95% CI: 0.66–1.75; Figure 2c) or the PSM rate at the prostate apex (Z = −1.15, P = 0.251, OR = 0.77, 95% CI: 0.50–1.20; Figure 2d).

Table 3.

Functional and oncological outcomes

Study	Total		1-month continence		12-month continence		PSM rate		Apical PSM rate
	MULP, n (%)	Control, n (%)	MULP, n (%)	Control, n (%)	MULP, n (%)	Control, n (%)	MULP, n (%)	Control, n (%)	MULP, n (%)	Control, n (%)
Sfoungaristos et al.12 2013	129 (100.0)	115 (100.0)	58 (45.0)	24 (20.9)	95 (73.6)	79 (68.7)	25 (19.4)	19 (16.5)	0 (0)	0 (0)
Hamada et al.13 2014	60 (100.0)	30 (100.0)	36 (60.0)	3 (10.0)	0 (0)	0 (0)	6 (10.0)	6 (20.0)	6 (10.0)	2 (6.7)
Heo et al.14 2020	305 (100.0)	266 (100.0)	224 (73.4)	174 (65.4)	301 (98.7)	260 (97.7)	45 (14.8)	48 (18.0)	23 (7.5)	32 (12.0)
Ko et al.15 2020	225 (100.0)	355 (100.0)	125 (55.6)	100 (28.2)	211 (93.8)	315 (88.7)	45 (20.0)	30 (8.5)	8 (3.6)	10 (2.8)
Nunez Bragayrac et al.16 2020	48 (100.0)	194 (100.0)	32 (66.7)	77 (39.7)	0 (0)	0 (0)	9 (18.8)	50 (25.8)	3 (6.3)	15 (7.7)
Hoeh et al.17 2023	74 (100.0)	68 (100.0)	0 (0)	0 (0)	67 (90.5)	43 (63.2)	20 (27.0)	16 (23.5)	0 (0)	0 (0)

MULP: maximal urethral length preservation; PSM: positive surgical margin

Figure 2.

Forest plot of the association between MULP and (a) early continence (1 month after RARP), (b) late continence (12 months after RARP), (c) PSM rate, and (d) apical PSM rate. MULP: maximal urethral length preservation; PSM: positive surgical margin; RARP: robot-assisted radical prostatectomy; CI: confidence interval.

Sensitivity analysis and publication bias

High heterogeneity was observed in the association between MULP and early continence (I² = 77.5%, P = 0.001). Upon exclusion of the study by Heo et al.,14 the recalculated OR was 4.29 (95% CI: 1.88–9.81, P < 0.001), with no remaining heterogeneity (I² = 35.5%, P = 0.199). Similarly, exclusion of the study by Ko et al.15 reduced the high heterogeneity in the association between MULP and PSM (I² = 72.8%, P < 0.01) to no heterogeneity (I² = 0, P = 0.481), with a recalculated OR of 0.87 (95% CI: 0.64–1.16, P = 0.337).

The funnel plot analysis showed no significant asymmetry, indicating no substantial publication bias in the results (Figure 3). Egger’s test could not be performed because of insufficient statistical power with <10 studies.

Figure 3.

Funnel plot of studies assessing publication bias of the relationship between MULP and (a) early continence (1 month after RARP), (b) late continence (12 months after RARP), (c) PSM rate, and (d) apical PSM rate. MULP: maximal urethral length preservation; PSM: positive surgical margin; RARP: robot-assisted radical prostatectomy.

DISCUSSION

In this meta-analysis, we observed a significant improvement in urinary continence following RARP with MULP. Notably, our data indicated that MULP not only enhanced early continence (1 month after RARP) but also late continence (12 months after RARP), a finding that has not been clearly reported in prior studies. One major concern regarding MULP is its potential to increase PSM rates, which could compromise local tumor control.18 However, our results showed no increase in either the total PSM rate or the PSM rate at the apical margin in surgical specimens, indicating that MULP is both effective and safe in RARP.

The relationship between urethral length and postprostatectomy urinary continence has been a longstanding area of interest.19,20 In 2002, Coakley et al.7 suggested that a longer magnetic resonance imaging (MRI)-measured membranous urethra could predict more rapid recovery of continence after radical retropubic prostatectomy (RRP). Lee et al.21 found that patients without overlap of the prostatic apex with the membranous urethra on MRI experienced earlier return of urinary continence after RRP. Although a subsequent study on RARP by the same group found that variations in the prostatic apex shape did not affect postoperative continence recovery, the membranous urethral length remained an independent protective factor of early return of continence.22 Additionally, a recent meta-analysis revealed that a longer preoperative MRI-measured membranous urethral length is significantly associated with a higher rate of continence in men undergoing RARP.23 These findings suggest that preserving the urethral length during surgery could be an effective strategy for preventing UI after RP.

In 2004, van Randenborgh et al.24 first reported the MULP technique in a retrospective cohort of 1013 patients undergoing RRP, demonstrating that MULP significantly improved postoperative continence without compromising tumor control. This technique involves retracting the base of the prostate craniodorsally to expose an intraprostatic segment of the membranous urethra and carefully dissecting the apical tissue of the prostate. Rather than simply transecting the urethra at the prostate apex, this approach allows for the preparation of a longer urethral stump for vesicourethral anastomosis. This is particularly beneficial for patients with a long intraprostatic membranous urethra. Importantly, MULP preserves the rhabdosphincter located between the verumontanum and the distal edge of the prostatic apex.25,26 Moreover, a longer urethral stump facilitates vesicourethral anastomosis and reduces bladder descent. Two studies included in the present analysis employed neurovascular bundle preservation or urethral reconstruction simultaneously, with MULP further enhancing the urinary continence rate based on these techniques.13,17 This suggests effective integration of MULP with other surgical methods.

There was slight variation in the definition of urinary continence across the reviewed studies: no pad (two studies13,15), no pad or one pad (three studies14,16,17), and a combination of pad usage and questionnaires (one study12). The definition of urinary continence, particularly post-RP, has long been contentious. Additionally, none of the included studies reported pad weight gain or mean pad weight gain per pad, which might offer a more objective reflection of the continence status than the self-reported pad count.27 Another important consideration is the extent of the preserved urethral length, which can vary among surgeons even within the same MULP procedure. Although two studies measured the preserved urethral length intracorporeally during surgery, the imaging-assessed urethral length before and after surgery was not documented.13,16 Therefore, further studies are needed to comprehensively assess the impact of MULP on continence recovery.

This meta-analysis has several limitations to consider. First, the intermediate-term continence rate (3–6 months) after RARP could not be evaluated because of the insufficient number of studies. Second, because of the lack of related data, some factors that may have had an impact on postoperative continence (e.g., tumor location and T stage) were not analyzed. Third, most of the included studies involved patients from Europe and the USA; representation of Asian populations was insufficient. It has been reported that in general, Asian men have a significantly shorter membranous urethral length.28 This discrepancy may partly explain why the study by Heo et al.,14 which was based on data from Korean patients, contributed the most to the heterogeneity in the analysis of early continence. Finally, although our findings suggest a functional benefit provided by MULP, most studies included in this meta-analysis were retrospective. Further support for these results is warranted through more prospectively designed studies. The oncological safety of MULP also requires further investigation, particularly regarding long-term biochemical recurrence and survival outcomes.

CONCLUSION

Our study provides convincing evidence that MULP enhances both the early and late rates of urinary continence after RARP without compromising oncological outcomes. To overcome the limitations of the current meta-analysis, future studies with larger sample sizes and standardized methodologies are needed.

AUTHOR CONTRIBUTIONS

TYX substantially contributed to the study design and was the major contributor to the writing of the manuscript. ZLL collected the data and contributed to the study design. HYW and YPF contributed to the data interpretation and analysis. YNN designed the study and revised the manuscript. All authors read and approved the final manuscript.

COMPETING INTERESTS

All authors declare no competing interests.