Functional Outcomes After Localized Prostate Cancer Treatment.

Importance: Adverse outcomes associated with treatments for localized prostate cancer remain unclear. Objective: To compare rates of adverse functional outcomes between specific treatments for localized prostate cancer. Design, Setting, and Participants: An observational cohort study using data from 5 US Surveillance, Epidemiology, and End Results Program registries. Participants were treated for localized prostate cancer between 2011 and 2012. At baseline, 1877 had favorable-prognosis prostate cancer (defined as cT1-cT2bN0M0, prostate-specific antigen level <20 ng/mL, and grade group 1-2) and 568 had unfavorable-prognosis prostate cancer (defined as cT2cN0M0, prostate-specific antigen level of 20-50 ng/mL, or grade group 3-5). Follow-up data were collected by questionnaire through February 1, 2022. Exposures: Radical prostatectomy (n = 1043), external beam radiotherapy (n = 359), brachytherapy (n = 96), or active surveillance (n = 379) for favorable-prognosis disease and radical prostatectomy (n = 362) or external beam radiotherapy with androgen deprivation therapy (n = 206) for unfavorable-prognosis disease. Main Outcomes and Measures: Outcomes were patient-reported sexual, urinary, bowel, and hormone function measured using the 26-item Expanded Prostate Cancer Index Composite (range, 0-100; 100 = best). Associations of specific therapies with each outcome were estimated and compared at 10 years after treatment, adjusting for corresponding baseline scores, and patient and tumor characteristics. Minimum clinically important differences were 10 to 12 for sexual function, 6 to 9 for urinary incontinence, 5 to 7 for urinary irritation, and 4 to 6 for bowel and hormone function. Results: A total of 2445 patients with localized prostate cancer (median age, 64 years; 14% Black, 8% Hispanic) were included and followed up for a median of 9.5 years. Among 1877 patients with favorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -12.1 [95% CI, -16.2 to -8.0]), but not worse sexual function (adjusted mean difference, -7.2 [95% CI, -12.3 to -2.0]), compared with active surveillance. Among 568 patients with unfavorable prognosis, radical prostatectomy was associated with worse urinary incontinence (adjusted mean difference, -26.6 [95% CI, -35.0 to -18.2]), but not worse sexual function (adjusted mean difference, -1.4 [95% CI, -11.1 to 8.3), compared with external beam radiotherapy with androgen deprivation therapy. Among patients with unfavorable prognosis, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel (adjusted mean difference, -4.9 [95% CI, -9.2 to -0.7]) and hormone (adjusted mean difference, -4.9 [95% CI, -9.5 to -0.3]) function compared with radical prostatectomy. Conclusions and Relevance: Among patients treated for localized prostate cancer, radical prostatectomy was associated with worse urinary incontinence but not worse sexual function at 10-year follow-up compared with radiotherapy or surveillance among people with more favorable prognosis and compared with radiotherapy for those with unfavorable prognosis. Among men with unfavorable-prognosis disease, external beam radiotherapy with androgen deprivation therapy was associated with worse bowel and hormone function at 10-year follow-up compared with radical prostatectomy.

Novel Therapies for High-Risk Non-Muscle Invasive Bladder Cancer.

PURPOSE OF REVIEW: The treatment options for high-risk non-muscle invasive bladder cancer (NMIBC), particularly following BCG, remain limited. We highlight recent, promising therapies for high-risk NMIBC. RECENT FINDINGS: Several therapies utilizing different mechanisms of action have demonstrated favorable results in the BCG-naïve and BCG-unresponsive settings. These treatments include intravenous and intravesical immunotherapy, viral- and bacterial-based intravesical therapies, combination intravesical chemotherapy regimens, and novel intravesical chemotherapy administration. Overall, the efficacy and tolerability of emerging treatments for NMIBC appear promising and provide potential alternatives to radical cystectomy. As the landscape of managing BCG-unresponsive disease evolves, clinical trials will explore future options and determine effective alternatives.

Adoption, Safety, and Retreatment Rates of Prostatic Urethral Lift for Benign Prostatic Enlargement.

PURPOSE: Novel minimally invasive therapies like the prostatic urethral lift are among the many endoscopic options for the treatment of benign prostatic enlargement and lower urinary tract symptoms (BPE/LUTS). To further understand the relative uptake, complications and retreatment rates of contemporary endoscopic procedures for BPE/LUTS across diverse practice types, we performed a retrospective study of inpatient and ambulatory surgery encounters in the Premier Healthcare database. MATERIALS AND METHODS: We included men who underwent endoscopic procedures for BPE/LUTS between 2000 and 2018. We determined the utilization of endoscopic therapies for BPE/LUTS, 30-day and 90-day readmission rates, and retreatment rate. Multivariable logistic regression was used to assess the association of procedure type with outcomes for the 3 most commonly performed procedures. RESULTS: We identified 175,150 men treated with endoscopic surgery for BPE/LUTS. The annual percent utilization of the prostatic urethral lift increased from <1% in 2014 to 10.4% in 2018. Compared to transurethral resection of the prostate and prostate photovaporization, prostatic urethral lift was associated with a lower odds of readmission at 30 (OR 0.58, p <0.01) and 90 (OR 0.55, p <0.01) days and a higher odds of retreatment within 2 years of followup (OR 1.78, p <0.01). CONCLUSIONS: Providers have rapidly adopted prostatic urethral lift which accounted for more than 1 in 10 endoscopic procedures captured for BPE/LUTS in 2018. Men treated with prostatic urethral lift are readmitted less within 30 and 90 days but are more likely to be retreated within 2 years of their index procedure as compared to men treated with transurethral resection of the prostate or prostate photovaporization.

Magnetic Resonance Imaging Radiomics-Based Machine Learning Prediction of Clinically Significant Prostate Cancer in Equivocal PI-RADS 3 Lesions.

BACKGROUND: While Prostate Imaging Reporting and Data System (PI-RADS) 4 and 5 lesions typically warrant prostate biopsy and PI-RADS 1 and 2 lesions may be safely observed, PI-RADS 3 lesions are equivocal. PURPOSE: To construct and cross-validate a machine learning model based on radiomics features from T2 -weighted imaging (T2 WI) of PI-RADS 3 lesions to identify clinically significant prostate cancer (csPCa), that is, pathological Grade Group ≥ 2. STUDY TYPE: Single-center retrospective study. POPULATION: A total of 240 patients were included (training cohort, n = 188, age range 43-82 years; test cohort, n = 52, age range 41-79 years). Eligibility criteria were 1) magnetic resonance imaging (MRI)-targeted biopsy between 2015 and 2020; 2) PI-RADS 3 index lesion identified on multiparametric MRI; (3) biopsy performed within 1 year of MRI. The percentages of csPCa lesions were 10.6% and 15.4% in the training and test cohorts, respectively. FIELD STRENGTH/SEQUENCE: A 3 T; T2 WI turbo-spin echo, diffusion-weighted spin-echo echo planar imaging, dynamic contrast-enhanced MRI with time-resolved T1-weighted imaging. ASSESSMENT: Multislice volumes-of-interest (VOIs) were drawn in the PI-RADS 3 index lesions on T2 WI. A total of 107 radiomics features (first-order histogram and second-order texture) were extracted from the segmented lesions. STATISTICAL TESTS: A random forest classifier using the radiomics features as input was trained and validated for prediction of csPCa. The performance of the machine learning classifier, prostate specific antigen (PSA) density, and prostate volume for csPCa prediction was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The trained random forest classifier constructed from the T2 WI radiomics features good and statistically significant area-under-the-curves (AUCs) of 0.76 (P = 0.022) for prediction of csPCa in the test set. Prostate volume and PSA density showed moderate and nonsignificant performance (AUC 0.62, P = 0.275 and 0.61, P = 0.348, respectively) for csPCa prediction in the test set. CONCLUSION: The machine learning classifier based on T2 WI radiomic features demonstrated good performance for prediction of csPCa in PI-RADS 3 lesions. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 2.

Practice patterns of vasal reconstruction in a large United States cohort.

We aimed to characterise diverse practice patterns for vasal reconstruction and to determine whether surgeon volume is associated with vasoepididymostomy performance at the time of reconstruction. We identified adult men who underwent vasal reconstruction from 2000 to 2020 in Premier Healthcare Database and determined patient, surgeon, cost and hospital characteristics for each procedure. We identified 3,494 men who underwent either vasovasostomy-alone (N = 2,595, 74.3%) or any-vasoepididymostomy (N = 899, 25.7%). The majority of providers (N = 487, 88.1%) performed only-vasovasostomy, 10 (1.8%) providers performed only-vasoepididymostomy and 56 (10.1%) providers performed both. Median total hospital charge of vasoepididymostomy was significantly higher than vasovasostomy ($39,163, interquartile range [IQR]$11,854-53,614 and $17,201, IQR$10,904-29,986, respectively). On multivariable regression, men who underwent procedures at nonacademic centres (OR 2.71, 95% CI 2.12-3.49) with higher volume surgeons (OR 11.60, 95% CI 8.65-16.00) were more likely to undergo vasoepididymostomy. Furthermore, men who underwent vasoepididymostomy were more likely to self-pay (OR 2.35, 95% CI 1.83-3.04, p < .001) and more likely had procedures in the Midwest or West region (OR 2.22, 95% CI 1.66-2.96 and OR 2.11, 95% CI 1.61-2.76, respectively; p < .001). High-volume providers have increased odds of performing vasoepididymostomy at the time of reconstruction but at a significantly higher cost. These data suggest possibly centralising reconstructive procedures among high-volume providers.

Association of Smoking and Death from Genitourinary Malignancies: Analysis of the National Longitudinal Mortality Study.

PURPOSE: We explored the association between tobacco use and genitourinary cancer specific survival in a contemporary, nationally representative sample of the United States civilian population. MATERIALS AND METHODS: A total of 493,282 participants in the National Longitudinal Mortality Study who provided detailed tobacco information from 1993 to 2005 were included in study. Our primary outcome was death from bladder, kidney or prostate cancer. Cause of death was determined from death certificates. Analyzed smoking parameters included smoking status at the time of the survey, age at the start of smoking and home smoking rules. Multivariable Cox regression models were used to assess associations of different smoking parameters with bladder, kidney and prostate cancer specific mortality. RESULTS: During a 5-year followup 5.6% of participants who had ever smoked died compared to 3.1% of those who had never smoked (p <0.0001). Of those who died of bladder, kidney and prostate cancer 62%, 58% and 62%, respectively, were ever smokers. On multivariable analysis ever smoking was associated with bladder and kidney cancer mortality (HR 1.92, 95% CI 1.25-2.97, and HR 1.54, 95% CI 1.01-2.34, respectively). Additionally, starting to smoke during teenage years and smoking at home were associated with bladder cancer specific mortality (HR 2.14, 95% CI 1.28-3.56 and HR 2.99, 95% CI 1.34-6.65) and kidney cancer specific mortality (HR 1.65, 95% CI 1.03-2.66 and HR 2.84, 95% CI 1.54-5.23, respectively). However, only everyday smoking was associated with an increased risk of prostate cancer mortality (HR 1.81, 95% CI 1.30-2.53). CONCLUSIONS: In a nationally representative study we confirmed the association between smoking intensity and mortality from genitourinary malignancies. Starting to smoke at a younger age and smoking at home conferred a significantly higher risk of death from bladder and kidney cancers.

Urinary pH and the risk of recurrence in patients with non-muscle invasive bladder cancer.

INTRODUCTION: To evaluate the effect of urine pH on tumor recurrence rates in patients undergoing surveillance after initial diagnosis of non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: All patients diagnosed with NMIBC at a tertiary referral center from January 2004 to March 2015 were reviewed. Our primary outcome was time to first recurrence after transurethral resection of bladder tumor (TURBT). Patients were analyzed according to the average urine pH of all urinalysis data over the surveillance period from TURBT to first recurrence. Kaplan-Meier survival analysis was used to determine differences in median time to recurrence. Cox proportional hazards regression was used to assess independent predictors of cancer recurrence. RESULTS: A total of 252 patients were included, of which 155 patients had average pH ≤ 6 (median pH 5.5) and 97 patients had average pH > 6 (median pH 6.8), p < 0.001. There was no significant difference in median time to recurrence between low/acidic pH (≤ 6) and high/basic pH (> 6) groups (28 months versus 17 months, respectively, p = 0.3444). Similarly, urine pH did not affect the risk of recurrence in a subgroup analysis stratified by smoking status. On multivariable Cox regression analysis, there was no association between average pH and recurrence among high grade tumors (HR = 1.33, 95% CI = 0.76 to 2.34, p = 0.3186), or low grade tumors (HR = 1.013, 95% CI = 1.01 to 1.58, p = 0.96). CONCLUSIONS: There was no association between urine pH and risk of tumor recurrence, regardless of smoking status. These findings suggest that modification of urine pH is unlikely to decrease the frequency of tumor recurrence in patients with NMIBC.

Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study.

PURPOSE: To our knowledge it is unknown whether urinary biomarkers for prostate cancer have added utility to clinical risk calculators in different racial groups. We examined the utility of urinary biomarkers added to clinical risk calculators for predicting prostate cancer in African American and nonAfrican American men. MATERIALS AND METHODS: Demographics, PCPT (Prostate Cancer Prevention Trial) risk scores, data on the biomarkers data PCA3 (prostate cancer antigen 3) and T2ERG (transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog gene fusion), and biopsy pathology features were prospectively collected on 718 men as part of EDRN (Early Detection Research Network). Utility was determined by generating ROC curves and comparing AUC values for the baseline multivariable PCPT model and for models containing biomarker scores. RESULTS: PCA3 and T2ERG added utility for the prediction of prostate cancer and clinically significant prostate cancer when combined with the PCPT Risk Calculator. This utility was seen in nonAfrican American men only for PCA3 (AUC 0.64 increased to 0.75 for prostate cancer and to 0.69-0.77 for clinically significant prostate cancer, both p <0.001) and for T2ERG (AUC 0.64-0.74 for prostate cancer, p <0.001, and 0.69-0.73 for clinically significant prostate cancer, p = 0.029). African American men did not have an added benefit with the addition of biomarkers, including PCA3 (AUC 0.75-0.77, p = 0.64, and 0.65-0.66, p = 0.74) and T2ERG (AUC 0.75-0.74, p = 0.74, and 0.65-0.64, p = 0.88), for prostate cancer and clinically significant prostate cancer, respectively. Limitations include the small number of African American men (72). The post hoc subgroup analysis nature of the study limited findings to being hypothesis generating. CONCLUSIONS: As novel biomarkers are discovered, clinical utility should be established across demographically diverse cohorts.

The impact of socioeconomic status on perioperative complications and oncologic outcomes in patients undergoing radical cystectomy.

PURPOSE: To examine if patients of lower socioeconomic status (SES) are at higher risk of perioperative complications and experience different oncologic outcomes after radical cystectomy (RC). METHODS: Retrospective review was performed on 383 consecutive non-metastatic patients who underwent definitive RC at a tertiary referral center. Along with clinical and pathologic parameters traditionally utilized for risk stratification, potential social determinants of health were estimated using US Census data. Zip code-derived proxies of SES included median annual household income and percentage of residents completing high school education. Patients were grouped based on SES parameters, and potential differences were assessed. Multivariable logistic regression was then performed to identify predictors of complication within 90 days of RC. Survival outcomes were plotted using Kaplan-Meier survival curves. RESULTS: Overall, 167 (46.2%) patients suffered any complication within 90 days of RC. On multivariable analysis, length of stay (p ≤ 0.001), lower income grouping (p = 0.03), and lowest education tertile (p = 0.007) were significant predictors of any complication. Income (p = 0.04) and education (p = 0.008) groupings remained significant predictors in a subset analysis looking specifically at post-discharge complications. No significant differences in recurrence-free or overall survival estimates were observed among education (log-rank test: p > 0.9 and p = 0.6, respectively) or income (log-rank test: p = 0.2 and p = 0.09, respectively) groupings. CONCLUSION: Patients of lower socioeconomic status who undergo RC for bladder cancer are at increased risk of perioperative complications. Further studies are needed to clarify this relationship, and to explore interventions aimed to improve outcomes.

Metabolic syndrome and voiding dysfunction.

PURPOSE OF REVIEW: The metabolic syndrome (MetS) is an ever growing pandemic consisting of a constellation of abnormalities. Many hypotheses have been put forth to establish a link between this syndrome and voiding dysfunction. We created a layout of the possible, probable, and proven relationships connecting the MetS with voiding dysfunction in men. RECENT FINDINGS: There has been growing interest in the relationship linking MetS and voiding dysfunction, with or without benign prostatic hyperplasia, during the past several years. Different mechanisms have been proposed to establish the connection. SUMMARY: A clear-cut association between MetS and voiding dysfunction is not clearly defined; rather, voiding dysfunction occurring in men with MetS has been shown to be related to numerous pathologies. MetS is a complex disease that includes numerous pathophysiological aspects that may contribute to the causation and advancement of voiding dysfunction. In light of this association, future research is needed to better define this relationship to enable therapy targeted against MetS in patients with voiding dysfunction.

Factors Impacting the Occurrence of Local, Distant and Atypical Recurrences after Robot-Assisted Radical Cystectomy: A Detailed Analysis of 310 Patients.

PURPOSE: Peritoneal carcinomatosis and extrapelvic lymph node metastases can be seen following robot-assisted radical cystectomy. In an attempt to identify predictors of these atypical metastases we report a detailed analysis of patients treated with robot-assisted radical cystectomy in whom recurrences developed. MATERIALS AND METHODS: A total of 310 patients underwent robot-assisted radical cystectomy for bladder cancer from 2001 to 2015. Descriptive statistics were used to compare baseline variables between patients without recurrence and those with local, distant or atypical recurrence. Univariate and multivariable regression models were used to assess the effect of variables on oncologic outcomes including recurrence location. RESULTS: At a median followup of 24 months (IQR 14-51) 81 patients had recurrence. On multivariable analysis tumor classification, lymphovascular invasion, estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion were significantly associated with any recurrence. Specific analyses showed that tumor and nodal classification, lymphovascular invasion and positive surgical margins were associated with all 3 recurrence locations (all p <0.05). Previous abdominal surgery was protective against atypical recurrences (HR 0.36, 95% CI 0.13-0.95, p = 0.04). Estimated glomerular filtration rate less than 60 ml/minute/1.73 m2 and perioperative blood transfusion conferred a higher risk of distant or atypical recurrence but not of local recurrence (all p <0.05). Operative time and previous pelvic radiotherapy were not associated with any recurrence locations. CONCLUSIONS: Predictors of distant recurrences, peritoneal carcinomatosis and extrapelvic lymph node metastases after robot-assisted radical cystectomy did not significantly differ and were mainly dictated by pathological tumor characteristics. Results suggest that the risk of atypical recurrence is chiefly influenced by tumor biology rather than surgical aspects.

The safety of robot-assisted cystectomy in patients with previous history of pelvic irradiation.

OBJECTIVE: To determine the safety of robot-assisted cystectomy (RAC) in patients with an irradiated pelvis, by comparing perioperative complication outcomes after RAC in patients with and without a history of pelvic irradiation. PATIENTS AND METHODS: In all, 252 consecutive patients underwent RAC at a tertiary referral centre from 2002 to 2013. Of all patients, 46 (18%) had a history of pelvic irradiation. Complications occurring at ≤30 days and ≤90 days of RAC were graded using the modified Clavien-Dindo classification system and additionally categorised by organ system. Baseline variables and outcomes of irradiated and non-irradiated patients were compared using descriptive statistics. Multivariable logistic regression models were generated to test the effect of previous pelvic irradiation on complications. RESULTS: The indications for RAC in patients with a history of pelvic irradiation were: bladder cancer (30 patients, 65%), prostate cancer (two, 4%), fistulae (five, 11%), and intractable symptoms from radiation cystitis (nine, 20%). In all, 25 (54%) irradiated and 112 (54%) non-irradiated patients had complications at ≤90 days (P > 0.9), of which 11 (24%) and 43 (21%) respectively had major complications (P = 0.7). One (2%) patient with and two (1%) patients without a history of irradiation died from surgical complications (P = 0.5). Infectious, bleeding, and gastrointestinal complications were the most common events in both groups. In multivariable analyses, a history of pelvic irradiation was not associated with a higher risk of complications. CONCLUSION: RAC performed by an experienced surgeon is a reasonable option in selected patients with a history of pelvic irradiation, as complication rates do not significantly differ compared with non-irradiated patients.

Is continent cutaneous urinary diversion a suitable alternative to orthotopic bladder substitute and ileal conduit after cystectomy?

OBJECTIVE: To evaluate functional outcomes of continent cutaneous urinary diversion (CCUD) after radical cystectomy (RC) and to compare diversion-related complications and long-term renal function in a contemporary cohort of patients undergoing urinary diversion with CCUD, orthotopic bladder substitute (OBS) and ileal conduit (IC). PATIENTS AND METHODS: In all, 322 patients underwent RC and CCUD, OBS or IC from January 2002 to June 2013. CCUD was performed using either a modified Indiana pouch or an appendiceal stoma. For patients with CCUD, continence status and time intervals between clean intermittent catheterisations at last follow-up were recorded. For all three diversion types, diversion-related complications and renal function outcome, as determined by the estimated glomerular filtration rate (eGFR) at baseline and at different time intervals after surgery, were evaluated. Multivariate regression analysis was used to evaluate the association of diversion type, baseline variables and diversion-related complications with renal function over time. RESULTS: Of all 322 patients, 73 (23%) received a CCUD, 79 (25%) received an OBS, and 170 (53%) received an IC. After a median follow-up of 36 months, the continence rate for patients with a CCUD was 89%. In all, 64 (88%) patients with a CCUD were able to catheterise every 4-8 h and five (7%) were able to catheterise every 8-10 h. After a median follow-up of 35 months, rates of diversion-related complications were similar among patients who underwent a CCUD, an OBS or an IC. Patients who received an IC had poorer renal function preoperatively than those who received a CCUD or an OBS. However, at 1 year after surgery and thereafter, the three groups had comparable renal function. On multivariate analysis, the type of urinary diversion was not associated with decline in renal function. However, patient age at surgery, diabetes mellitus, baseline eGFR, postoperative non-obstructive hydronephrosis and uretero-enteric stricture were associated with decline in renal function. CONCLUSIONS: A CCUD is associated with excellent functional outcomes. The rates of diversion-related complications and renal function outcomes are comparable with those from an OBS and an IC. A CCUD should be considered a valid alternative for patients who undergo cystectomy and require urinary diversion.

Trends in the Utilization of Penile Prostheses in the Treatment of Erectile Dysfunction in the United States.

BACKGROUND: The utilization of penile prosthesis (PP) insertion in the general population for medically refractory erectile dysfunction (ED) has not been well-characterized. This study assessed the national temporal trends in the surgical management of ED utilizing PP. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files from 2001 to 2010 was performed to assess the use of PP. Regression analysis was performed to identify factors associated with PP placement, type of PP utilized, and factors associated with revisions. RESULTS: A total of 1,763,260 men were diagnosed with ED, 3% (53,180) of whom underwent PP insertion. The utilization of PP for ED decreased from 4.6% in 2002 to 2.3% in 2010 (P < 0.01). This temporal decline in utilization was significant across all demographic factors including age, ethnicity, and geographic location. Men aged 65-74, from the U.S. South and West, and those with Charlson comorbidity scores >1 were more likely to have a PP inserted for ED (P < 0.01). African American men were more likely to have a semirigid PP placed compared with a multicomponent inflatable PP, and were more likely to undergo a revision or removal of the PP compared with Caucasian men (P < 0.01). CONCLUSIONS: The surgical management of ED with PP changed significantly between 2001 and 2010. The overall utilization of PP decreased, but its use in patients with significant medical comorbidities increased. Age >65, ethnicity, and geography influenced the likelihood of PP placement, prosthesis type, as well as the likelihood of prosthesis removal or revision.