Racial Variation in Membranous Urethral Length and Postprostatectomy Urinary Function.

Urinary incontinence remains a significant post-prostatectomy sequalae. While many patient and technical factors have been found to contribute to post-prostatectomy incontinence, the impact of anatomical differences by races has not been studied . Shorter preoperative membranous urethral length (MUL) on prostate MRI has been associated with higher risk of post-prostatectomy incontinence. We compared MUL in Asian and non-Asian men and their post-prostatectomy urinary function using the Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP). We found that MUL was significantly shorter for Asian vs. non-Asian men (7.9mm, 95% confidence interval [CI] 7.5-8.3 vs. 10.9mm, 95%CI 10.2-11.7 - mean difference 3.0mm, 95%CI for mean difference 2.15-3.87; p<0.01) and that Asian men had significantly worse EPIC-CP urinary score ≥12 months post-prostatectomy (3.82; 95%CI 2.47-5.17 vs. 1.95; 95%CI 1.11-2.79 - mean difference: 1.87; 95% CI for mean difference is 0.32-3.42; p=0.022). Confirmatory studies are needed to explore racial differences in MUL and its effect on post-prostatectomy urinary incontinence.

The United States Preventive Services Task Force infographic states that 19% of men will experience persistent urinary incontinence after prostate cancer treatment [1]. Approximately 60 000 men undergo radical prostatectomy (RP) in the United States annually; thus, approximately 11 400 men will experience post-RP urinary incontinence this year [2]. Post-RP incontinence may limit a physically active lifestyle, cause embarrassment and depression, and may not respond to corrective therapy. The risk of post-RP incontinence varies according to the definition and methodology applied, as well as the surgical technique and surgeon experience. Although technical modifications to decrease post-RP incontinence have been described, there is no technique that eliminates its occurrence. Therefore, better patient selection may be the most practical way to attenuate the occurrence of post-RP incontinence.

Older patient age and shorter membranous urethral length (MUL) are associated with worse post-RP incontinence [3]. A systematic review by Mungovan et al [4] suggested that longer preoperative MUL is positively associated with return of post-RP continence. However, most of the evidence on MUL arises from studies on men of European descent. Hu et al [5] recently demonstrated that Asian-American men have significantly worse urinary continence within 12 mo after RP in comparison to their non-Asian counterparts; however, the contributory factors remain unknown. We hypothesized that Asian men may have worse post-RP urinary function because of shorter MUL in comparison to non-Asian men. Therefore, we aimed to assess differences in MUL between Asian and non-Asian men and to evaluate whether these differences were associated with worse urinary function after RP.

We identified 274 men with localized prostate cancer who underwent prostate magnetic resonance imaging (MRI) compliant with Prostate Imaging-Reporting and Data System version 2.1 technical recommendations at our institution before robotic RP performed by a single surgeon (J.C.H.) between June 2015 and June 2020. Thirty-six men who self-identified as “Asian” and for whom follow-up information was available were included (Supplementary Fig. 1). We subsequently age-matched these men randomly to 36 non-Asian men to compare MUL and Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) urinary function outcomes [6]. The EPIC-CP urinary incontinence score ranges from 0 to 12, with higher scores indicating worse function.

After undergoing training with a fellowship-trained uroradiologist (D.J.M.), measurements were performed by two blinded raters (S.P.B., A.R.; urology residents) on sagittal small field-of-view T2-weighted preoperative prostate MRI scans (Supplementary Fig. 2) [7]. Final MUL measurements were made by averaging the measurements recorded by the two raters. For eight men (11.1%) for whom MUL measurements differed by >20% between the two raters, the uroradiologist’s independent measurement was used in the final analysis.

There were no significant differences in age, body mass index (BMI), prostate-specific antigen, RP pathology, nerve-sparing status, or prostate volume by race (Table 1). The median follow-up was 12 mo for both Asian and non-Asian men. The inter-reader agreement k value was 0.92. MUL was significantly shorter for Asian (7.9 mm, 95% confidence interval [CI] 7.5–8.3) than for non-Asian men (10.9 mm, 95% CI 10.2–11.7), with a mean difference of 3.0 mm (95% CI 2.15–3.87; p < 0.01).

Table 1

Preoperative characteristics and MRI measurements

	Asian	Non-Asian	p valuea
	(n = 36)	(n = 36)
Clinicopathologic characteristics
Mean age, yr (95% CI)	66.8 (64.7–69.0)	65.6 (62.6–68.6)	0.61
Mean body mass index, kg/m2 (95% CI)	25.9 (24.7–27.2)	26.7 (25.7–27.8)	0.33
Mean PSA ng/ml (95% CI)	10.3 (7.6–12.9)	8.6 (6.3–11.0)	0.35
Median Gleason grade group at RP (IQR)	3 (2–4)	2 (2–3)	1.0
Nerve-sparing status, n (%)			1.0
Complete	31 (86)	31 (86)
Partial	5 (14)	5 (14)
MRI measurements
Mean prostate volume, ml (95% CI)	50.4 (37.8–63.0)	41.5 (25.9–46.7)	0.20
Mean urethral measurements, mm (95% CI)
Membranous urethral length	7.9 (7.5–8.3)	10.9 (10.2–11.7)	<0.01
Infraprostatic urethral length	13.4 (12.5–14.3)	16.8 (15.7–17.9)	<0.01
Urethral stump	5.5 (4.8–6.4)	5.9 (5.3–6.5)	0.12

CI = confidence interval; IQR = interquartile range; MRI = magnetic resonance imaging; PSA = prostate-specific antigen; RP = radical prostatectomy.

Statistical tests performed: paired t test, Wilcoxon-Mann-Whitney test, χ2 test.

A generalized estimating equation ordinal regression model was constructed with EPIC-CP score as the dependent variable and covariables of race, age, and time following RP (3, 9, and ≥12 mo). Follow-up outcomes at ≥12 mo were pooled because urinary continence does not significantly improve after that time point [8]. There were no differences in EPIC-CP scores between Asian and non-Asian men at baseline, 3, or 9 mo. Asian men had significantly worse EPIC-CP urinary scores at ≥12 mo after RP (3.82, 95% CI 2.47–5.17 vs 1.95, 95% CI 1.11–2.79; mean difference 1.87; 95% CI 0.32–3.42; p = 0.022; Fig. 1). Our model demonstrated that Asian race is predictive of a higher EPIC-CP urinary score over time when compared to non-Asian race (parameter estimate 0.56, 95% CI 0.04–1.08; p = 0.034; Supplementary Table 1). Furthermore, we found that lower MUL (p = 0.03) and Asian race (p = 0.036) were each associated with increased EPIC-CP scores at 12 mo in an ordinal logistic model that included age and BMI (Supplementary Table 2).

Fig. 1

Urinary function recovery (Expanded Prostate Cancer Index Composite for Clinical Practice score) for Asian versus non-Asian men. The mean and error bar are presented for each time point.

Preoperative MUL is a prognostic risk factor for post-RP continence [3]. Current evidence shows that longer MUL has a significantly positive effect on overall time to continence recovery [4]. However, the role of racial variation and its association with MUL and post-RP continence recovery has not been explored; our study revealed that Asian men have shorter MUL compared to their non-Asian counterparts. We also compared urinary function recovery and found that Asian men have worse urinary function at >1 yr after RP. Our findings highlight the importance of patient selection to avoid urinary incontinence, particularly for Asian men. Moreover, we observed a significant difference in pelvic anatomy by race, a novel finding that may account for racial differences in post-RP urinary function outcomes.

One of the major principles in achieving post-RP urinary continence is preservation of a functional sphincter mechanism. Longer MUL facilitates this by increasing the urethra pressure profile and allowing preservation of a greater amount of urethral smooth muscle and rhabdosphincter [9]. Furthermore, Vis et al [9] showed that MUL-preserving techniques are associated with better continence rates at 3 and 12 mo after RP. Thus, preoperative assessment of MUL could maximize the potential of these surgical reconstructive techniques and help surgeons in planning a reconstructive approach.

To date, research on the role of race in post-RP incontinence has mostly focused on African American (AA) and White men. DeCastro et al [10] demonstrated that AA men were less likely to experience pad-free continence 12 mo after RP (60% vs 76.4%; p < 0.001). More recently, Hu et al [5] found that men of Asian ancestry have significantly worse urinary function within 12 mo of RP (odds ratio 0.76, 95% CI 0.59–0.98; p = 0.036) compared to non-Asian men. The present study demonstrates that Asian race was associated with shorter MUL and that both Asian race and shorter MUL are associated with worse urinary outcomes.

Our study is not without limitations. First, our sample comprises men of largely East-Asian ancestry (eg, Chinese and Korean); therefore, our broad categorization may not reflect differences between Asian ethnic groups. Second, research on preoperative MUL largely comprises single-center studies owing to the intense efforts required to perform two-reviewer ratings with a referee [7], which limits their generalizability. Furthermore, confirmatory studies and comparative racial studies of MUL are needed to elucidate disparities in outcomes [10]. Third, accurate measurement of MUL requires expertise; urologists who would like to incorporate preoperative MUL measurement in their practice would require education or standardized reporting by a skilled uroradiologist. Finally, we recognize that preservation of maximal urethral length, minimal urethral trauma, and individual pelvic-floor parameters is also important for postprostatectomy continence and cannot be objectively quantified.

In summary, we demonstrate that Asian men have significantly shorter MUL and worse post-RP incontinence. Confirmatory studies are needed to validate our findings.

: Spyridon P. Basourakos had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Hu.

Acquisition of data: Basourakos, Ramaswamy, Yu, Margolis, Hu.

Analysis and interpretation of data: Basourakos, Ramaswamy, Yu, Margolis, Hu.

Drafting of the manuscript: Basourakos, Ramaswamy, Margolis, Hu.

Critical revision of the manuscript for important intellectual content: Basourakos, Ramaswamy, Hu.

Statistical analysis: Ramaswamy, Yu, Basourakos.

Obtaining funding: Hu.

Administrative, technical, or material support: Hu.

Supervision: Hu.

Other: None.

Spyridon P. Basourakos certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Jim C. Hu receives research support from the Frederick J. and Theresa Dow Wallace Fund of the and salary support from grants NIH R01 CA241758, CER-2019C1-15682 and PCORI CER-2019C2-17372. The sponsors did not play a role in the design and conduct of the study, collection and management of the data, and preparation of the manuscript. Weill Cornell Medicine is the recipient of a research agreement with Siemens Healthineers.