Benjamin P. Saylor is associate editor of Urology Times, an Advanstar Communications publication.

Benjamin P. Saylor

A recent study has found an association between preoperative low bladder contractility and prolonged deterioration of voiding function in patients undergoing robot-assisted radical prostatectomy (RARP).

The findings were presented at the 2021 International Continence Society Annual Meeting in Melbourne, Australia. Discussing the background for the study, first author Junya Hata, PhD, of Fukushima Medical University in Fukushima, Japan, explained that a previous study had found that a lower bladder contractile index (BCI) level was predictive of postoperative detrusor underactivity (DU) at 1 month after RARP.

“This result suggested that the decrease in reserve capacity of bladder function preoperatively might contribute to the development of postoperative DU in relatively early phase after RARP… However, the long-term prognosis of lower urinary tract function and symptoms including voiding and storage in the patients with lower bladder contractility remained unclear,” the authors wrote in their abstract for the current study.

For the current study, the investigators sought to evaluate the time-dependent change of lower urinary tract function in patients undergoing RARP. A total of 115 patients undergoing RARP underwent urodynamics testing preoperatively. Patients were divided into 2 groups based on BCI level; these were referred to as the preserved group (BCI ≥ 100, 70 patients) and the impaired group (BCI < 100, 45 patients). Maximum flow rate (Qmax), voiding volume, postvoiding residual volume, International Prostate Symptom Score (IPSS), quality of life score, and Overactive Bladder Symptom Score were assessed at 1, 3, 6, 9, and 12 months post RARP. Univariate and multivariate logistic regression analyses were performed using patient parameters including age, body mass index, prostate weight, diabetes, and LDL cholesterol.

“No significant differences in patient characteristics were observed between the preserved and impaired groups,” Hata reported. IPSS voiding score was significantly higher in the preserved group vs the impaired group (6.1 ± 5.2 vs 2.9 ± 3.2, respectively; 

“Qmax at 1, 3, 6, 9, and 12 months and voiding volume at 3 months were significantly lower in the impaired group than in the preserved group. This suggests that preoperative lower bladder contractility was associated with prolonged deterioration of voiding function,” Hata said.

In addition, IPSS voiding score at 1, 3, 6, 9, and 12 months was significantly lower in the impaired group compared with the preserved group. “This suggests that preoperative lower bladder contractility was associated with prolonged deterioration of voiding symptoms,” Hata said.

Logistic regression analysis of patient parameters related to preoperative low bladder contractility before RARP identified LDL cholesterol as a predictive factor for low bladder contractility.

“In conclusion, preoperative lower bladder contractility was associated with prolonged deterioration of voiding function. It was suggested that dyslipidemia might be associated with decrease in bladder contractility,” Hata said.

1. Hata J, Hasegawa A, Harigane Y, et al. Long-term prognosis of lower urinary tract function after robot-assisted radical prostatectomy in patients with preoperative low bladder contractility. Paper presented at: 2021 International Continence Society Annual Meeting; October 14-October 17; Melbourne, Australia. Abstract 5

2. Hata J, Onagi A, Tanji R, et al. Prevalence and predictors of postoperative detrusor underactivity after robot-assisted radical prostatectomy: A prospective observational study. 

2021;28(7):734-740. doi:10.1111/iju.14549

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“Qmax at 1, 3, 6, 9, and 12 months and voiding volume at 3 months were significantly lower in the impaired group than in the preserved group. This suggests that preoperative lower bladder contractility was associated with prolonged deterioration of voiding function,” says Junya Hata, PhD.

Low bladder contractility linked with deterioration of voiding function post RARP

Worse urinary incontinence appears to be associated with worse sexual function in patients presenting with lower urinary tract symptoms (LUTS), according to a study presented at the 2021 American Urological Association Annual Meeting.

“Patients with low urinary tract symptoms (LUTS) frequently complain [of] sexual dysfunction and sometimes even urinary incontinence (UI),” the authors wrote in their abstract.

For the cross-sectional study, the investigators retrospectively retrieved data from 938 patients older than 18 years of age seeking treatment for self-reported LUTS. Patients had to have a minimum International Prostate Symptom Score (IPSS) of at least 1 to be included. The cohort was stratified into categories as follows: no urinary incontinence (UI): International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form (ICIQ-UI-SF) = 0; mild UI: ICIQ-UI-SF = 1-7; moderate UI: ICIQ-UI-SF = 8-13; and severe UI: ICIQ-UI-SF = 14-21. The Spearman correlation test was used to evaluate correlation between ICIQ-UI-SF and International Index of Erectile Function (IIEF) domain scores. Linear regression analysis tested putative risk factors associated with increased ICIQ-UI-SF scores.

Of the 938 patients studied, 589 (63%) had no UI, 247 (25%) had mild UI, 76 (8%) had moderate UI, and 36 (4%) had severe UI.

Although no substantial differences were found in total prostate-specific antigen levels and uroflowmetry levels among the groups, prostate volume, IPSS, and overactive bladder-questionnaire score were all higher as UI increased (

The investigators also found a negative correlation between IIEF-Total (rho = –0.12; 

< .001), IIEF-Erectile Function (rho = –0.15; 

< .001), IIEF-Intercourse Satisfaction (rho = –0.1; 

= .004), and IIEF-Overall Satisfaction scores (rho = –0.12; 

< .001) and ICIQ-UI-SF scores. In addition, they reported that higher body mass index (Coeff 0.12; 95% CCI: .03-0.32, 

= .011), diabetes (Coeff 1.76; 95% CI: .035-3.18, 

= .015), and presence of comorbidities (Coeff 0.9; 95% CI: 0.06-0.174; 

= .035) were all associated with higher ICIQ-UI-SF scores.

“In conclusion, we found that in patients presenting with LUTS, there is an association between urinary incontinence and [worse] sexual function,” said study author Giuseppe Fallara, MD, urology resident at San Raffaele Scientific Institute, Milan Italy, who worked on the study with Andrea Salonia, MD, and colleagues.

1. Fallara G, Boeri L, Candela L, et al. Impact of urinary incontinence on sexual function in patients presenting for lower urinary tract symptoms. Paper presented at 2021 American Urological Association Annual Meeting; September 10-13; virtual. Abstract PD04-07.

“We found that in patients presenting with LUTS, there is an association between urinary incontinence and [worse] sexual function,” said study author Giuseppe Fallara, MD.

Urinary incontinence linked to worse sexual function in patients with LUTS

A real-world assessment of treatment patterns and clinical outcomes in patients with metastatic urothelial carcinoma found that more than 50% of patients had not received first-line systemic treatment. Among those who did, unadjusted real-world overall survival (OS) was longer in patients receiving frontline cisplatin versus other upfront options.

“Real-world data related to treatment patterns and OS in patients with [metastatic urothelial carcinoma] are limited since [immune-oncology therapy] introduction, and this descriptive study fills that gap,” the investigators wrote in their poster, which was shared during the 2021 European Society for Medical Oncology Annual Congress.

The investigators used deidentified Centers for Medicare & Medicaid Services data from fee-for-service Parts A, B, and D claims. Patients 18 years or older with 1 or more inpatient or 2 or more outpatient visits with ICD-9/10 code for urothelial carcinoma were identified between January 1, 2015, and June 30, 2019. Patients had to have continuous enrollment for 6 months or longer pre-diagnosis index date and were followed from first-line treatment through the end of the study period, disenrollment, or death. Patient cohorts were divided into types of first-line treatment as follows: cisplatin, carboplatin-containing chemotherapy, immuno-oncology monotherapy, and non–platinum-containing chemotherapy.

A total of 18,888 patients met the study’s selection criteria, of whom 8630 (45.7%) had an identified first-line systemic treatment, and 10,258 had no identified first-line treatment. In the cohort who received first-line treatment, 37.6% received cisplatin, 30.2% received carboplatin-containing chemotherapy, 20.0% received immuno-oncology monotherapy, and 12.2% received non–platinum-containing chemotherapy. The majority of the patients who received first-line treatment were men (70%) and White (90%).

Patients who received cisplatin had a median Charlson Comorbidity Index Score of 3; all other treatment cohorts had a score of 4. Renal disease was present in 33.8% of patients who received immuno-oncology monotherapy, 28.3% of those receiving carboplatin, 26.0% of those receiving non–platinum-containing chemotherapy, and 11.9% of those receiving cisplatin.

Median survival was 20 months for patients receiving cisplatin, 14 months for those receiving non–platinum-containing chemotherapy, 11 months for those receiving carboplatin, and 8 months for those receiving immuno-oncology monotherapy.

Limitations outlined in the study’s poster include potential limited generalizability of the data due to being from a Medicare fee-for-service population; potential for miscoding of clinical conditions; the fact that algorithms were used to identify lines of therapy based on administrative claims; the fact that it was a descriptive study; and that no information was available regarding possible reasons why patients did not receive first-line treatment.

“Future research should assess outcomes with the newer standard of care and evaluate unmet needs in untreated populations,” the investigators concluded.

1. Bilen MA, Xi AD, Wong A, et al. Real-world (RW) treatment (Tx) patterns and clinical outcomes in patients (pts) with metastatic urothelial carcinoma (mUC) receiving first-line (1L) Tx: Results from IMPACT UC. Paper presented during the 2021 European Society for Medical Oncology Annual Congress; September 16-21, 2021; virtual. Abstract 701P.

Unadjusted real-world overall survival was longer in patients receiving first-line cisplatin compared with patients receiving other first-line treatments.

First-line urothelial carcinoma analysis offers new insight into treatment selection and outcomes

Survival benefits were observed in patients considered hard to treat who received the antibody-drug conjugate enfortumab vedotin-ejfv (Padcev) for advanced urothelial carcinoma, according to results presented at the 2021 European Society for Medical Oncology Annual Congress.

In the randomized phase 3 EV-301 trial (NCT03474107), enfortumab vedotin demonstrated superior overall survival (OS) compared with standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma.

 In July of this year, the FDA approved enfortumab vedotin for the treatment of patients with locally advanced or metastatic urothelial cancer who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy; or patients who are ineligible for cisplatin-containing chemotherapy and have previously received 1 or more prior lines of therapy.

“Effective therapies are still needed for advanced urothelial cancer, particularly pretreated patients with poor prognostic factors, such as liver metastases, and those who did not respond to prior immune checkpoint inhibitor treatment,” explained study author Jonathan Rosenberg, MD, chief of the Genitourinary Medical Oncology Service at Memorial Sloan Kettering Cancer Center in New York.

For the current study, investigators sought to evaluate the efficacy and safety of enfortumab vedotin in patients from EV-301 who were considered hard to treat. Hard-to-treat subgroups consisted of age 65 years or older, presence of liver metastasis, primary upper tract disease, and nonresponse to prior PD-1/L1 inhibitor treatment. The primary end point was OS and secondary end points were progression-free survival (PFS), and overall response rate (ORR) per RECIST v1.1, as well as safety.

The investigators found that OS was maintained across the majority of subgroups. Specifically, median OS in patients receiving enfortumab vedotin vs those receiving standard chemotherapy was as follows:

• Age 65 years or older: 14.32 vs 9.46 months (HR, 0.745; 95% CI, 0.558-0.995)

• Presence of liver metastasis: 9.63 vs 5.95 months (HR, 0.660; 95% CI, 0.456-0.957)

• Primary upper tract disease: 12.62 vs 10.91 months (HR, 0.848; 95% CI, 0.567-1.269)

• Nonresponse to prior PD-1/L1 inhibitor: 11.63 vs 9.17 months (HR, 0.757; 95% CI, 0.580-0.988).

Similar benefits were seen with median PFS in patients receiving enfortumab vedotin vs those receiving standard chemotherapy:

• Age 65 years or older: 5.65 vs 3.78 months (HR, 0.616; 95% CI, 0.485-0.781)

• Presence of liver metastasis: 4.14 vs 2.63 months (HR, 0.597; 95% CI, 0.428-0.833)

• Primary upper tract disease: 5.62 vs 3.78 months (HR, 0.716; 95% CI, 0.511-1.003)

• Nonresponse to prior PD-1/L1 inhibitor: 5.42 vs 3.65 months (HR, 0.697; 95% CI, 0.556-0.873).

ORR across the subgroups was also higher in patients receiving enfortumab vedotin compared with standard chemotherapy:

• Age 65 years or older: 40.8% vs 19.9%

• Presence of liver metastasis: 35.5% vs 10.8%

• Primary upper tract disease: 43.9% vs 19.0%

• Nonresponse to prior PD-1/L1 inhibitor: 39.7% vs 17.4%.

Regarding adverse events (AEs), overall rates were similar across the subgroups in both the enfortumab vedotin and standard chemotherapy cohorts. Treatment-related AEs were also comparable. When adjusted for treatment exposure, grade 3 or higher AEs occurred less frequently with patients receiving enfortumab vedotin vs those receiving standard chemotherapy across all subgroups.

“Based on these data, enfortumab vedotin shows consistent efficacy and safety in its use in this broad population of patients with previously treated advanced urothelial cancer, including those who might have hard-to-treat poor prognostic factors,” Rosenberg said.

1. Rosenberg JE, Powles T, Sonpavde GP, et al. Analysis of hard-to-treat subgroups from EV-301: A phase III trial of enfortumab vedotin (EV) vs chemotherapy for previously treated advanced urothelial carcinoma. Paper presented at 2021 European Society for Medical Oncology Annual Congress; September 16-21, 2021; virtual. Abstract 698P.

2. Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab vedotin in previously treated advanced urothelial carcinoma. 

2021;384(2):1125-1135. doi:10.1056/NEJMoa2035807

3. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. March 9, 2021. News release. FDA. Accessed March 9, 2021. https://bit.ly/3jZoA4D

4. U.S. FDA grants regular approval and expands indication for PADCEV (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer. News release. Seagen Inc. March 9, 2021. Accessed March 9, 2021. https://bwnews.pr/3xxmsF9

The hard-to-treat subgroups consisted of age 65 years or older, presence of liver metastasis, primary upper tract disease, and nonresponse to prior PD-1/L1 inhibitor treatment. 

Benjamin P. Saylor

Articles

Low bladder contractility linked with deterioration of voiding function post RARP

Urinary incontinence linked to worse sexual function in patients with LUTS

First-line urothelial carcinoma analysis offers new insight into treatment selection and outcomes

Enfortumab vedotin effective in hard-to-treat urothelial carcinoma subgroups