Comprehensive Evaluation of the Ability of Comorbidity and Health Status Indices to Improve the Prediction of Perioperative Morbidity and Long-Term Survival Outcomes After Radical Cystectomy.

BACKGROUND: In the era of standardized outcome reporting, it remains unclear if widely used comorbidity and health status indices can enhance predictive accuracy for morbidity and long-term survival outcomes after radical cystectomy (RC). PATIENTS AND METHODS: In this monocentric study, we included 468 patients undergoing open RC with pelvic lymph node dissection for bladder cancer between January 2009 and December 2017. Postoperative complications were meticulously assessed according to the EAU guideline criteria for standardized outcome reporting. Multivariable regression models were fitted to evaluate the ability of ASA physical status (ASA PS), Charlson comorbidity index (± age-adjustment) and the combination of both to improve prediction of (A) 30-day morbidity key estimates (major complications, readmission, and cumulative morbidity as measured by the Comprehensive Complication index [CCI]) and (B) secondary mortality endpoints (overall [OM], cancer-specific [CSM], and other-cause mortality [OCM]). RESULTS: Overall, 465 (99%) and 52 (11%) patients experienced 30-day complications and major complications (Clavien-Dindo grade ≥IIIb), respectively. Thirty-seven (7.9%) were readmitted within 30 days after discharge. Comorbidity and health status indices did not improve the predictive accuracy for 30-day major complications and 30-day readmission of a reference model but were associated with 30-day CCI (all P < .05). When ASA PS and age-adjusted Charlson index were combined, ASA PS was no longer associated with 30-day CCI (P = .1). At a median follow-up of 56 months (IQR 37-86), OM, CSM, and 90-day mortality were 37%, 24%, and 2.9%, respectively. Both Charlson and age-adjusted Charlson index accurately predicted OCM (all P < .001) and OM (all P ≤ .002) but not CSM (all P ≥ .4) and 90-day mortality (all P > .05). ASA PS was not associated with oncologic outcomes (all P ≥ .05). CONCLUSION: While comorbidity and health status indices have a role in predicting OCM and OM after RC, their importance in predicting postoperative morbidity is limited. Especially ASA PS performed poorly. This highlights the need for procedure-specific comorbidity assessment rather than generic indices.

What do patients with Peyronie's disease expect from therapy? A prospective multi-center study.

BACKGROUND: Little is known about patients' pre-treatment expectations in Peyronie's disease (PD). OBJECTIVE: To evaluate in detail patients' expectations of conservative therapy and surgery. PATIENTS AND METHODS: This multi-center study prospectively enrolled 317 PD patients, who were scheduled to receive conservative therapy or surgery between 2019 and 2022 at the Department of Urology of the University Medical Center Hamburg-Eppendorf, and the Center of Reproductive Medicine and Andrology, University Medical Center Muenster, both Germany. The primary end-point was patients' pre-treatment expectations of conservative therapy and surgery, measured with the Stanford Expectations of Treatment Scale (SETS). Secondary end-points included patient-reported psychological and physical symptoms, penile pain, symptom bother and erectile function, measured with the Peyronie's disease questionnaire (PDQ) and International Index of Erectile Function Erectile Function Domain (IIEF-EF). RESULTS: In total, 239 (75%) and 78 (25%) patients were scheduled for the conservative therapy and surgery, respectively. Patients undergoing surgery had higher positive and negative mean SETS expectations scores (14 vs. 11, p < 0.001; 9.6 vs. 6.0, p < 0.001). In multivariable analysis, surgery was an independent predictor of positive and negative patients' pre-treatment expectations (all p ≤ 0.001). In thematic analysis, patients undergoing surgery emphasized distinct themes of pre-treatment expectations. Patients undergoing surgery had higher mean PDQ symptom bother as well as higher psychological and physical symptom scores (14 vs. 10, p < 0.001; 9.2 vs. 7.1, p = 0.001). There were significant positive correlations between SETS negative expectation score and PDQ symptom bother (|ρ| = 0.25; p < 0.001) as well as PDQ psychological and physical symptoms score, respectively (|ρ| = 0.21; p = 0.001). CONCLUSION: PD patients expect both more benefit and more harm from surgery. In addition, patients undergoing surgery have more psychological and physical symptoms and more symptom bother. To set realistic expectations, it is of pivotal importance to assess patients' expectations before starting treatment.

Rational peri-operative management of antithrombotic therapy in patients undergoing radical cystectomy: A 30-day morbidity analysis based on the updated European Association of Urology guidelines for standardized complication reporting.

BACKGROUND: Radical cystectomy (RC) in bladder cancer patients with cardiovascular comorbidity poses challenges due to the need for antithrombotic therapy and high perioperative risk. We aimed to assess 30-day complications after RC in patients receiving antithrombotic therapy. PATIENTS AND METHODS: Retrospective study of 416 bladder cancer patients (2009-2017) undergoing open RC with pelvic lymph node dissection, with or without antithrombotic therapy. Antithrombotic therapy and complication reporting followed European guidelines. Procedure-specific 30-day complications were cataloged, graded (Clavien-Dindo), and quantified using the 30-day Comprehensive Complication Index. Multivariable regressions evaluated antithrombotic therapy's independent effect on key morbidity outcomes. RESULTS: Median age was 70 years, 78% were male. Patients on antithrombotic therapy were mostly male, had higher comorbidity burden, worse kidney function, more frequent incontinent diversion, and shorter operative time (all p ≤ 0.027). Bleeding complications occurred in 135 patients (32%; 95%CI = 28-37%), more prevalent with antithrombotic therapy (46% vs. 29%; p = 0.004). Thromboembolic complications occurred in 18 patients (4.3%; 95%CI = 2.6-6.8%), no difference between patients with and without antithrombotic therapy (8.4% vs. 3.3%; p = 0.063). Prevalence of myocardial infarction, new-onset hypertension, acute congestive heart failure, and angina pectoris showed no difference (all p ≥ 0.3). Multivariable analyses indicated no association between antithrombotic therapy and cardiac complications, 30-day major complications, or cumulative morbidity (all p ≥ 0.2). Antithrombotic therapy was associated with bleeding complications (OR = 1.92; 95%CI = 1.07-3.45; p = 0.028), predominantly transfusion-related (75% of 152 bleeding complications). Limitations include retrospective data assessment with biases. CONCLUSIONS: RC in patients on antithrombotic therapy exhibits a higher incidence of adverse events due to underlying comorbidities. Adherence to thromboprophylaxis guidelines enables safe RC in patients with significant comorbidities, without substantial increase in major bleeding or severe thromboembolic events.

Outcomes and Complication Rates of Cuff Downsizing in the Treatment of Worsening or Persistent Incontinence After Artificial Urinary Sphincter Implantation.

PURPOSE: This study investigated the functional outcomes and complication rates of cuff downsizing for the treatment of recurrent or persistent stress urinary incontinence (SUI) in men after the implantation of an artificial urinary sphincter (AUS). METHODS: Data from our institutional AUS database spanning the period from 2009 to 2020 were retrospectively analyzed. The number of pads per day was determined, a standardized quality of life (QoL) questionnaire and the International Consultation on Incontinence Questionnaire (ICIQ) were administered, and postoperative complications according to the Clavien-Dindo classification were analyzed. RESULTS: Out of 477 patients who received AUS implantation during the study period, 25 (5.2%) underwent cuff downsizing (median age, 77 years; interquartile range [IQR], 74-81 years; median follow-up, 4.4 years; IQR, 3-6.9 years). Before downsizing, SUI was very severe (ICIQ score 19-21) or severe (ICQ score 13-18) in 80% of patients, moderate (ICIQ score 6-12) in 12%, and slight (ICIQ score 1-5) in 8%. After downsizing, 52% showed an improvement of >5 out of 21 points. However, 28% still had very severe or severe SUI, 48% had moderate SUI, and 20% had slight SUI. One patient no longer had SUI. In 52% of patients, the use of pads per day was reduced by ≥50%. QoL improved by >2 out of 6 points in 56% of patients. Complications (infections/urethral erosions) requiring device explantation occurred in 36% of patients, with a median time to event of 14.5 months. CONCLUSION: Although cuff downsizing carries a risk of AUS explantation, it can be a valuable treatment option for selected patients with persistent or recurrent SUI after AUS implantation. Over half of patients experienced improvements in symptoms, satisfaction, ICIQ scores, and pad use. It is important to inform patients about the potential risks and benefits of AUS to manage their expectations and assess individual risks.

Time-to-complication Patterns After Radical Cystectomy: A Secondary Analysis of a 30-day Morbidity Assessment Using the European Association of Urology Quality Criteria for Standardized Reporting.

Complications following radical cystectomy (RC) have been extensively investigated but evidence on the timing of their occurrence is scarce. We aimed to decipher timing patterns for 30-d complications after open RC for bladder cancer at our institution between 2009 and 2017. Complication data were extracted according to a predefined, procedure-specific catalog following the European Association of Urology criteria for standardized reporting. Timing was assessed for each complication and patterns were compared across urinary diversion types and Clavien-Dindo grades. Overall, 2485 complications occurred in 503/506 patients (99%) in three timing patterns: very early during the first week (bleeding, cardiac, neurological), early after 1 wk (gastrointestinal), and intermediate after approximately 2 wk (wound, infectious complications). Some 90% of complications occurred within the first 2 wk. Major complications (Clavien-Dindo grade ≥IIIa) occurred in 78 patients (15%) after a median of 10 days (interquartile range 4-15). Among patients with a continent diversion, the median time to infectious complications was longer (9 vs 7 d; p = 0.005) and major complications tended to occur later (median 13.5 vs 10 d; p = 0.4) over a wider time span in comparison to those with an incontinent diversion. Close clinical monitoring in both inpatient and outpatient settings after RC is mandatory to detect and adequately manage complications, particularly for more complex continent diversions. PATIENT SUMMARY: The time at which different complication types occur varies after surgical removal of the bladder. It is important to be aware of these times to improve patient-centered care and anticipate possible problems after surgery.

Nephrometry and cumulative morbidity after partial nephrectomy: A standardized assessment of complications in the context of PADUA and R.E.N.A.L. scores.

BACKGROUND: Nephrometry scores aid in clinical decision-making, yet evidence is scarce regarding their impact on cumulative morbidity following partial nephrectomy (PN). PATIENTS AND METHODS: Retrospective, monocentric study of 122 patients with suspicious renal masses undergoing open or robot-assisted PN between January 2019 and August 2020. Morbidity assessment followed European Association of Urology guidelines on complication reporting. 30-d complications were extracted using a PN-specific catalog, were graded by the Clavien-Dindo classification (CDC), and Comprehensive Complication Index (CCI®) values were calculated. The impact of nephrometry on cumulative morbidity was evaluated by (1) comparing morbidity estimates between Preoperative Aspects and Dimensions Used for an Anatomical (PADUA)/R.E.N.A.L. complexity groups, (2) by Pearson's correlation between nephrometry scores and CCI®, and (3) by multivariable regression models using any 30-d complication and 30-d CCI® as endpoints. RESULTS: Of 122 patients, 101 (83%) underwent open and 21 (17%) robot-assisted PN. Median PADUA and R.E.N.A.L. scores were 9 (interquartile range, IQR 8-10) and 8 (IQR 6-9), respectively. Of 218 complications in 92 patients (75%), the majority was classified as minor (CDC grade ≤IIIa). Median 30-d CCI® was 8.7 (IQR 0.50-15). There was a small positive correlation between PADUA or R.E.N.A.L. score with CCI® (all P ≤ 0.026), explaining 4.7% and 4.1% of the variation in CCI®, respectively. After adjustment, nephrometry scores were associated with any 30-d complication and the CCI® (all P ≤ 0.011). PADUA and R.E.N.A.L. high complexity tumors were positively associated with both morbidity endpoints compared to low complexity tumors (all P ≤ 0.041). CONCLUSIONS: At a referral center, PN may be safely performed, even if morbidity assessment follows a strict protocol. Nephrometry risk classification does only marginally translate into clinical relevant differences regarding short-term complications. Thus, nephron-sparing surgery should not be withheld from patients with high complexity renal masses.

Which Men Do or Do Not Achieve Long-Term Symptom Relief After Holmium Laser Enucleation of the Prostate (HoLEP): 11 Years of HoLEP Experience.

Purpose: Apart from the existing level-one evidence, few centers have reported on long-term outcomes after Holmium Laser Enucleation of the Prostate (HoLEP). Against this backdrop we aimed to report on our treatment experience and identify predictors of persistent/recurrent lower urinary tract symptoms (LUTS) after the procedure. Materials and Methods: From 2006 to 2017, 2566 men underwent HoLEP at our institution. Only patients with available, cross-sectional follow-up (F/u) ≥6 months were included. Perioperative and F/u characteristics were compared by duration of F/u in months (quartiles). Multivariable logistic regression models (MVAs) were used to identify predictors of persistent/recurring symptoms, defined as International Prostate Symptom Score (IPSS) >7 at F/u. Results: A total of 774 patients with a median age of 70 years (interquartile range [IQR] = 66-75), prostate volume of 80 mL (IQR = 60-105), American Society of Anesthesiologists score 2 (IQR = 2-3), IPSS of 19 (IQR = 14-24), and quality of life (QoL) of 4 (3-5) at the time of operation were analyzed. Median F/u was 52 months (IQR = 32-77), overall current median prostate-specific antigen was 0.91 mg/dL (0.5-1.8), median IPSS and QoL were 3 (IQR = 1-7) and 1 (IQR 0-2), respectively. LUTS medication was present in 20 patients (2.6%), 15 (2%) patients required reoperation, and permanent urinary incontinence was present in 17 (2.2%) patients. On MVA age at operation (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.1; p = 0.013), prostate volume (OR = 0.99 [95% CI, 0.98-0.99;], p = 0.003), body mass index (OR = 1.06 [95% CI, 1.0-1.1], p = 0.043), presence of indwelling catheter (OR = 0.51 [95% CI, 0.32-0.81], p = 0.004), and anticholinergics before procedure (OR = 1.74 [95% CI, 1.01-3.0], p = 0.046) were predictors of persistent/recurring symptoms. Conclusions: Our HoLEP experience confirms durable and profound symptom relief in the vast majority men. A small fraction of patients complained about subjective persistent/recurring LUTS stressing the need for proper patient selection and timing of surgical intervention.

Anesthetic Technique (Spinal vs. General Anesthesia) in Holmium Laser Enucleation of the Prostate: Retrospective Analysis of Procedural and Functional Outcomes among 1,159 Patients.

OBJECTIVE: The aim of the study was to compare procedural efficacy, early and late functional outcomes in holmium laser enucleation of the prostate (HoLEP) under spinal anesthesia (SA) versus general anesthesia (GA). METHODS: We retrospectively reviewed patients undergoing HoLEP at our institution between 2012 and 2017. Standard pre-, peri-, and postoperative characteristics were compared according to anesthetic technique. Multivariable logistic regression analyses (MVAs) were employed to study the impact of SA on procedural efficacy and postoperative complications. RESULTS: Our study cohort consisted of 1,159 patients, of whom 374 (32%) underwent HoLEP under SA. While a medical history of any anticoagulation/antiplatelet therapy except low-dose acetylsalicylic acid was significantly more common among patients undergoing GA (16% vs. 10%, p = 0.001), no other significant differences in preoperative characteristics were noted including age, body mass index, American Society of Anesthesiologists Classification (ASA), prostate size, or International Prostate Symptom Score (IPSS), and quality of life scores. Patients under SA exhibited shorter times of enucleation 42 min (interquartile range [IQR]:27-59 vs. 45 min [IQR: 31-68], p = 0.002), and combined time of enucleation/morcellation/coagulation (57 min [IQR: 38-85] vs. 64 min [IQR: 43-93], p = 0.002), as well as fewer complications (Clavien-Dindo ≥3) (12 [3.2%] vs. 55 [7%], p = 0.013). These associations were confirmed in MVA. Patients did not differ significantly with regard to early micturition including post-void residual volume and maximum flow-rate improvement. At a median follow-up of 33 months (IQR: 32-44), patients with SA had a lower IPSS score (median 3 [IQR: 1-6] vs. 4 [IQR: 2-7], p = 0.039). However, no significant differences were observed with respect to any urinary incontinence, urge symptoms, and postoperative pain. CONCLUSION: In this large retrospective series, HoLEP under SA was a safe and efficacious procedure with comparable early and long-term functional outcomes.

Oncological validation and discriminative ability of pentafecta criteria after open radical cystectomy.

OBJECTIVES: To validate the pentafecta criteria (PC) proposed by the PROMETRICS group for outcome reporting after radical cystectomy in an open radical cystectomy (ORC) cohort with long-term follow-up and to assess the discriminative ability of PC attainment for oncological endpoints. PATIENTS AND METHODS: Between January 2009 and December 2017, 420 patients underwent ORC with pelvic lymph node dissection and urinary diversion for non-metastatic bladder cancer. The PC were defined as reported by the PROMETRICS group. The primary endpoint was PC attainment, and oncological outcomes comprised further endpoints. We used uni- and multivariable logistic regression analysis to assess predictors of PC attainment. The discriminative ability of PC for overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM) was compared using Kaplan-Meier curves and cumulative incidence functions. After stratification by the number of PC attained, the association between PC attainment and the survival endpoints was tested on multivariable Cox regression and competing-risks models. RESULTS: A total of 108 patients (26%) fulfilled all PC, while 195 (46%), 77 (18%), 35 (8.3%) and five (1.2%) attained 4/5, 3/5, 2/5 and ≤1/5 PC, respectively. Increasing age-adjusted Charlson comorbidity index (odds ratio [OR] 0.80, P = 0.015) and incontinent diversion (OR 0.38, P = 0.005) were independent predictors of PC non-attainment. The median follow-up was 73 months. PC attainment (≥4/5 vs 3/5 vs ≤2/5 PC attained) was used to stratify patients into groups at significantly different risk of death (P < 0.001). A decreasing number of PC attained (<4/5) was associated with unfavourable survival estimates for both OM and CSM (all P ≤ 0.005) but not for OCM (all P ≥ 0.2). CONCLUSIONS: The PC proposed by the PROMETRICS group represent accurate quality indicators for oncological outcome reporting after ORC for non-metastatic bladder cancer and have a distinct discriminative ability to predict long-term OM and CSM.

Salvage Chemotherapy with Cisplatin, Ifosfamide, and Paclitaxel in Aggressive Variant of Metastatic Castration-Resistant Prostate Cancer.

Significant progress has been achieved in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, results in patients with aggressive variant prostate cancer (AVPC) have been disappointing. Here, we report retrospectively collected data from intensively pretreated AVPC patients (n = 17; 88.2% visceral metastases; 82% elevation of neuroendocrine markers) treated with salvage chemotherapy consisting of cisplatin, ifosfamide, and paclitaxel (TIP). At the interim analysis, 60% of patients showed radiographic response or stable disease (PFS = 2.5 months; OS = 6 months). In men who responded to chemotherapy, an OS > 15 months was observed. Preclinical analyses confirmed the high activity of the TIP regimen, especially in docetaxel-resistant prostate cancer cells. This effect was primarily mediated by increased cisplatin sensitivity in the emergence of taxane resistance. Proteomic and functional analyses identified a lower DNA repair capacity and cell cycle machinery deficiency to be causative. In contrast, paclitaxel showed inconsistent effects, partially antagonizing cisplatin and ifosfamide in some AVPC models. Consequently, paclitaxel has been excluded from the TIP combination for future patients. In summary, we report for the first time the promising efficacy of TIP as salvage therapy in AVPC. Our preclinical data indicate a pivotal role for cisplatin in overcoming docetaxel resistance.

Penile Flap Inversion Vaginoplasty in Transgender Women: Contemporary Morbidity and Learning-Curve Analysis From a High-Volume Reconstructive Center.

Objectives: Numbers of PIV are rising. The aim of this study is to analyze the surgical learning-curve (LC) on the grounds of perioperative complications. Patients and Methods: 108 PIVs, performed by a single surgeon between 2015 and 2018 have been analyzed. Learning-curve analysis was based on three factors: operating time, vaginal depth and complications. Results: The median FU was 6.3 months. Median age at surgery was 36 years, median time of hormone treatment was 36 months. The median CI was 0.3 and the median BMI was 25 kg/cm3. Median CCI® was 8.08. 40.7% of the patients developed short-term complications, more than half of which were Clavien I. Overall only 1.9% had Clavien IIIb complications. There were no Clavien IV or V complications. 17.6% of patients had wound infections, 13% wound dehiscence, 9.3% introitus strictures, 13.9% suffered from atrophy of the neovagina, i.e. loss of depth or width, and 8.3% from meatus urethrae strictures. Duration of hormonal therapy, BMI and CI had no impact on surgical outcome. Age had a significant impact on CCI®, as younger patients had a higher risk for complications. Use of scrotal skin and surgeries performed had a significant influence. LC analysis via CUSUM analysis showed that after 32 surgeries, the PIV is performed safely. Conclusion: The PIV is a safe GAS-technique, associated with minor complications leading to low rates of revision surgery. Younger age, the use of scrotal skin and surgeon's experience has significant impact on complications. Duration of hormonal therapy, circumcision and BMI has no impact on complications.

Urinary Diversion With or Without Concomitant Cystectomy for Benign Conditions: A Comparative Morbidity Assessment According to the Updated European Association of Urology Guidelines on Reporting and Grading of Complications.

BACKGROUND: Evidence is scarce on morbidity after urinary diversion ± cystectomy as treatment for benign bladder indications. OBJECTIVE: To conduct a morbidity assessment and to evaluate the impact of concomitant subtrigonal cystectomy (SC) versus urinary diversion (UD) alone. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective study of 97 patients with benign bladder conditions between 2009 and 2017. INTERVENTION: Open UD and/or concomitant SC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Data for 30-d complications were extracted using a procedure-specific catalog and were graded according to the Clavien-Dindo classification (CDC), and Comprehensive Complication Index (CCI) values were calculated. Traditional morbidity endpoints focused on the comparative morbidity of UD + SC versus UD alone. Multivariable regressions were computed to evaluate the impact of SC versus UD alone on cumulative morbidity. Subgroup analyses were repeated for patients with previous irradiation. RESULTS AND LIMITATIONS: Of 97 patients, 46 (47%) underwent UD + SC and 51 (53%) underwent UD alone. Forty-nine patients (51%) had a history of abdominopelvic radiotherapy. Overall, 69 (71%) patients underwent continent UD and 26 (27%) underwent a Mitrofanoff procedure. We registered 390 complications in 97 (100%) patients, the majority of which were classified as minor (CDC grade ≤IIIa; 93%). Overall, three patients (3.1%) were readmitted and no patient died within 30 d. On multivariable analyses, neither concomitant SC nor previous radiotherapy was associated with higher cumulative morbidity (all p = 0.2). Similarly, concomitant SC was not predictive of a higher complication burden in the irradiation subgroup (all p ≥ 0.05). Limitations include heterogeneity for indications and a lack of information on the radiation dose and field. CONCLUSIONS: In a high-volume referral center, neither SC nor abdominopelvic radiotherapy increased perioperative cumulative morbidity for patients with benign bladder conditions undergoing UD. This is particularly relevant for patients who would benefit from concomitant SC to avert adverse sequelae related to the retained bladder. PATIENT SUMMARY: Urinary diversion (UD) is a surgical procedure to create a new way for urine to exit the body. We found that among patients undergoing UD for benign bladder conditions, those who also have their bladder removed and patients who have received previous radiotherapy do not experience more complications.

Multiparametric MRI may Help to Identify Patients With Prostate Cancer in a Contemporary Cohort of Patients With Clinical Bladder Outlet Obstruction Scheduled for Holmium Laser Enucleation of the Prostate (HoLEP).

Objective: To investigate the value of standard [digital rectal examination (DRE), PSA] and advanced (mpMRI, prostate biopsy) clinical evaluation for prostate cancer (PCa) detection in contemporary patients with clinical bladder outlet obstruction (BOO) scheduled for Holmium laser enucleation of the prostate (HoLEP). Material and Methods: We retrospectively analyzed 397 patients, who were referred to our tertiary care laser center for HoLEP due to BOO between 11/2017 and 07/2020. Of those, 83 (20.7%) underwent further advanced clinical PCa evaluation with mpMRI and/or prostate biopsy due to elevated PSA and/or lowered PSA ratio and/or suspicious DRE. Logistic regression and binary regression tree models were applied to identify PCa in BOO patients. Results: An mpMRI was conducted in 56 (66%) of 83 patients and revealed PIRADS 4/5 lesions in 14 (25%) patients. Subsequently, a combined systematic randomized and MRI-fusion biopsy was performed in 19 (23%) patients and revealed in PCa detection in four patients (5%). A randomized prostate biopsy was performed in 31 (37%) patients and revealed in PCa detection in three patients (4%). All seven patients (9%) with PCa detection underwent radical prostatectomy with 29% exhibiting non-organ confined disease. Incidental PCa after HoLEP (n = 76) was found in nine patients (12%) with advanced clinical PCa evaluation preoperatively. In univariable logistic regression analyses, PSA, fPSA ratio, and PSA density failed to identify patients with PCa detection. Conversely, patients with a lower International Prostate Symptom Score (IPSS) and PIRADs 4/5 lesion in mpMRI were at higher risk for PCa detection. In multivariable adjusted analyses, PIRADS 4/5 lesions were confirmed as an independent risk factor (OR 9.91, p = 0.04), while IPSS did not reach significance (p = 0.052). Conclusion: In advanced clinical PCa evaluation mpMRI should be considered in patients with elevated total PSA or low fPSA ratio scheduled for BOO treatment with HoLEP. Patients with low IPSS or PIRADS 4/5 lesions in mpMRI are at highest risk for PCa detection. In patients with a history of two or more sets of negative prostate biopsies, advanced clinical PCa evaluation might be omitted.

Exploring the intersection of functional recurrence, patient-reported sexual function, and treatment satisfaction after anterior buccal mucosal graft urethroplasty.

PURPOSE: To evaluate the interplay of stricture recurrence, sexual function, and treatment satisfaction after substitution urethroplasty. METHODS: Observational study of men undergoing 1-stage buccal mucosal graft urethroplasty for anterior urethral stricture between 2009 and 2016. Patients were dichotomized by self-reported treatment satisfaction. Sexual function was assessed by validated and non-validated patient-reported outcome measures. Functional recurrence was defined as symptomatic need of re-intervention. Bivariate analyses, Kaplan-Meier estimates, qualitative and quantitative analyses by uni- and multivariable regression were employed to evaluate the interplay of sexual function, functional recurrence, and treatment satisfaction. RESULTS: Of 534 men with bulbar (82%), penobulbar (11%), and penile strictures (7.3%), 451 (84%) were satisfied with the surgery. There were no differences in stricture location, previous treatment, graft length, or surgical technique between satisfied and unsatisfied patients (all p ≥ 0.2). Recurrence-free survival was 85% at a median follow-up of 33 mo and decreased significantly with each Likert item towards increasing dissatisfaction (p < 0.001). Dissatisfied patients more often reported postoperative loss of rigidity, tumescence, reduced ejaculatory volume, ejaculatory pain, and reduced penile length (all p ≤ 0.042). In 83 dissatisfied men, functional recurrence (28%) and oral morbidity (20%) were the main drivers of dissatisfaction in qualitative analysis. Multivariable analyses revealed functional recurrence and impaired postoperative ejaculatory function as independent predictors of treatment dissatisfaction (all p ≤ 0.029) after adjusting for confounders. CONCLUSION: We found an association of both functional success and sexual function with patient-reported treatment satisfaction after substitution urethroplasty. Such findings validate the clinical significance of defining the symptomatic need for re-intervention as an endpoint and underline the importance of further research evaluating sexual function before and after open urethral reconstruction.

Regression Discontinuity Analysis of Salvage Radiotherapy in Prostate Cancer.

There is a lack of randomized evidence comparing early (eSRT) to late (lSRT) salvage radiotherapy (SRT) after radical prostatectomy (RP) for prostate cancer (PCa). Moreover, the existing evidence is often affected by lead-time bias. We sought to address this gap in a cohort of 1458 PCa patients undergoing SRT for biochemical recurrence (BCR) after RP in two tertiary care centers between 1992 and 2013. Using a quasi-randomized study design known as regression discontinuity (RD) and adjusting for lead-time bias, we compared metastasis-free survival (MFS) at 5 and 10 years after surgery between eSRT (prostate-specific antigen [PSA] <0.5 ng/ml) and lSRT (PSA ≥ 0.5 ng/ml). Overall, 1049 patients (71.9%) underwent eSRT and 409 (28.1%) lSRT at a mean follow-up of 84 mo (interquartile range (IQR) 52-120.4). The MFS rate decreased nonsignificantly at the proposed cutoff by 0.04 (95% confidence interval [CI]: -0.06 to 0.19) at 5 years and by 0.07 (95% CI: - 0.12 to 0.32) at 10 years. Cox regression analysis revealed a hazard ratio for the cutoff examined of 1.3 (95% CI: 0.8-2.4; p = 0.2). In conclusion, in a quasirandomized study design accounting for lead-time bias, eSRT (PSA < 0.5 ng/ml) did not improve MFS. Our results underline the need for level-one evidence to compare eSRT and lSRT. PATIENT SUMMARY: We compared early versus late salvage radiotherapy (SRT) for biochemical recurrence after radical prostatectomy by simulating a randomized trial. We found that early SRT (initiated at prostate-specific antigen <0.5 ng/ml) compared to late SRT did not improve metastasis-free survival.

Longitudinal Evaluation of Perineogenital Pain and Postoperative Complications After One-stage Buccal Mucosal Graft Urethroplasty: A Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Little is known about patient-reported intensity and quality of pain at the receiver site as well as postoperative complications following one-stage buccal mucosal graft urethroplasty (BMGU). OBJECTIVE: To evaluate perineogenital pain intensity and quality as well as short-term complications after BMGU, and to describe the impact of pain and complications on stricture recurrence. DESIGN, SETTING, AND PARTICIPANTS: A secondary analysis of a randomized controlled trial including 135 patients, who underwent BMGU from 2014 to 2015, was performed. INTERVENTION: One-stage BMGU. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient-reported perineogenital pain was assessed by the Numeric Pain Rating Scale and the Short-form McGill Pain Questionnaire preoperatively and at 1, 5, and 21 d, and 3, 6, and 12 mo postoperatively. Complications were assessed by the Clavien-Dindo classification and the Comprehensive Complication Index. Pain and complications were compared according to stricture recurrence. RESULTS AND LIMITATIONS: At a mean follow-up of 21±15 mo, 29 patients (21%) had stricture recurrence. Pain intensity as well as sensory and affective pain quality decreased over time, reaching a minimum at 6 mo. Postoperative complications at days 5 (95% of patients) and 21 (27% of patients) were predominantly "minor" (Clavien-Dindo classification grade≤IIIa). Neither patient-reported perineogenital pain nor cumulative morbidity burden was different between patients with and those without stricture recurrence (all p ≥ 0.05). CONCLUSIONS: Perineogenital pain is frequent after BMGU, but pain intensity and quality decrease over time. The same holds true for postoperative complications, which are frequent but mostly present as minor events. Current findings allow for thorough preoperative patient counseling regarding the expected perineogenital pain intensity and quality over time as well as complications following BMGU. PATIENT SUMMARY: In this study, we looked at pain intensity and pain quality as well as complications following buccal mucosal graft urethroplasty. We found that pain in the perineogenital region is frequent, but pain intensity and quality decrease over time. Similarly, postoperative complications are frequent, but mainly present as minor events.

Assessing the Outcome of Holmium Laser Enucleation of the Prostate by Age, Prostate Volume, and a History of Blood Thinning Agents: Report from a Single-Center Series of >1800 Consecutive Cases.

Purpose: To assess perioperative outcomes of holmium laser enucleation of the prostate (HoLEP) in a real-world scenario and with a focus on demanding patient factors, such as large prostate size, advanced patient age, and anticoagulation therapy (AT). Materials and Methods: We retrospectively analyzed HoLEP procedures at our institution between 2010 and 2016. After stratification by prostate volume, age, and AT, perioperative and early voiding characteristics were compared. A multivariable regression model was employed to identify predictors of prolonged time of catheterization (defined as being above group's median). Results: The study cohort consisted of 1816 men with a median age of 71 years (interquartile range [IQR]: 66-76), a median prostate volume of 80 mL (IQR: 58-105), and American Society of Anesthesiologists score ≥3 in 618 men (34%). Median time of enucleation and morcellation was 43 minutes (IQR: 31-60) and 10 minutes (IQR: 6-18), respectively. Perioperative blood transfusions were administered in 44 (2.4%) cases, severe postoperative complications (Clavien-Dindo grade ≥3b) occurred in 61 (3.3%) cases. The median time of catheterization was 2 days (IQR: 2-2), with prolonged catheterization occurring in 277 (15%) cases. After adjustment, large prostates (fourth volume quartile [106-280 mL]) (odds ratio [OR]: 1.8, 95% confidence interval [CI]: 1.3-2.6, p = 0.001), therapeutic low-molecular-weight heparin bridging regimen (OR: 2.2, 95% CI: 1.4-3.6, p = 0.037), low-dose acetylsalicylic acid (OR: 1.5, 95% CI: 1.0-2.2, p = 0.015), and a history of direct oral anticoagulation (OR: 2.3, 95% CI: 1.2-4.0, p = 0.022), but not patient age, were independently associated with prolonged catheterization. Conclusions: We confirm HoLEP as safe and efficient; however, patients with large prostates and patients with a history of AT are at risk of prolonged catheterization.

Copy number variations in primary tumor, serum and lymph node metastasis of bladder cancer patients treated with radical cystectomy.

The aim of the present study was to analyze copy number variations (CNV) of multiple oncogenes and tumor suppressor genes in genomic DNA from primary tumor tissue, lymph node metastasis and cell-free DNA (cfDNA) from serum of 72 urothelial carcinoma of bladder (UCB) patients treated with radical cystectomy (RC), using multiplex ligation-dependent probe amplification (MLPA). We hypothesized that primary tumor and lymph node metastasis show similar CNV profiles, and CNV are more present in lymph node metastasis compared to primary tumor tissue. Samples from 43 (59.7%) patients could be analyzed. In total, 35 (83%), 26 (68%) and 8 (42%) patients had CNV in primary tumor, serum and lymph node metastasis, respectively. MYC, CCND1, ERBB2 and CCNE1 displayed the most frequent amplifications. In particular, CNV in ERBB2 was associated with aggressive tumor characteristics. CNV in both ERBB2 and TOP2A were risk factors for disease recurrence. The current findings show that CNV are present in various oncogenes and tumor suppressor genes in genomic DNA from primary tumor, lymph node metastasis and cfDNA from serum. CNV were more present in genomic DNA from primary tumor tissue compared to cfDNA from serum and genomic DNA from lymph node metastasis. Patients with CNV in ERBB2 and TOP2A are at increased risk for disease recurrence following RC. Further studies are necessary to validate, whether these genes may represent promising candidates for targeted-therapy.

The association of cigarette smoking and pathological response to neoadjuvant platinum-based chemotherapy in patients undergoing treatment for urinary bladder cancer - A prospective European multicenter observational study of the EAU Young Academic Urologists (YAU) urothelial carcinoma working group.

OBJECTIVE: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS & METHODS: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival. RESULTS AND LIMITATIONS: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival. CONCLUSIONS: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers.

Retrograde ejaculation after holmium laser enucleation of the prostate (HoLEP)-Impact on sexual function and evaluation of patient bother using validated questionnaires.

BACKGROUND: A vast body of literature has focused on erectile function after Holmium Laser Enucleation of the Prostate (HoLEP). Interestingly, retrograde ejaculation (RE), despite its frequency has sparsely been investigated. OBJECTIVES: To study patient perception and impact of RE on sexuality following HoLEP. MATERIALS AND METHODS: We retrospectively analyzed 2,131 patients undergoing HoLEP 2006-2015 at our institution. Patients were followed via standardized questionnaires namely International Index of Erectile Function (IIEF) as well as Male Sexual Health Questionnaire Ejaculatory Short Form (MSHQ-EjD-SF). Exclusion criteria were missing/follow-up <6 months, missing data on MSHQ-EjD-SF and IIEF score, resulting in 535 assessable patients. Multivariable logistic regression was employed to identify independent predictors of satisfaction with overall sex life (IIEF question 13). RESULTS: Median follow-up was 50 months (IQR: 30-78). Overall, 495 (92.5%) patients reported RE. Patients differed significantly with respect to age (P = .036), IPSS at follow-up (P = .01), and erectile function (P < .001), whereas no other statistically significant differences were observed. In multivariable logistic regression analyses, presence of RE was not independently associated with satisfaction with overall sex life (OR: 2.7, 95% CI: 0.70-10.5, P = .1). However, in the cohort of patients exhibiting RE, patients who stated "feeling bothered by RE" had lower satisfaction with overall sex life (OR: 0.23, 95% CI: 0.13-0.38, P < .001). Bother by RE varied according to erectile function and did not impact overall satisfaction in men with superior erectile function. CONCLUSIONS: RE is a very common event after HoLEP but in this retrospective analysis was not associated with overall satisfaction with sex life. Contrary, satisfaction with sex life is impaired in patients who feel bothered by RE. Proper patient selection will pose key to identify patients in which RE bother will offset the benefits of LUTS relief.