Side effects of drug-antibody conjugates enfortumab-vedotin and sacituzumab-govitecan in targeted therapy in cancer.

OBJECTIVE: Antibody-drug conjugates (ADC), enfortumab-vedotin (EV) and sacituzumab-govitecan are new drugs in the treatment of urologic tumors, whose safety profile has not been fully investigated. Therefore, the aim of our study was to evaluate adverse events related to both agents reported to VigiBase, the World Health Organization's global pharmacovigilance database. METHODS: We employed Bayesian disproportionality analysis based on the information component (IC) to explore the safety profile associated with both therapies. Additionally, we used the proportional reporting ratio approach to examine the safety profile further. RESULTS: We identified 41,752 reports connected to ADC therapy (EV: n=5359; SG: n=36,393). In the EV subgroup, most reports were associated with dermatologic (38.6%), neurologic adverse events (16.5%), or adverse laboratory assessments (19.4%). In contrast, reports in the SG subgroup were mainly associated with gastrointestinal adverse events (24.2%) and adverse laboratory assessments (39.0%). Adverse laboratory assessments in both cohorts were often based on haematotoxic adverse events. CONCLUSION: We could provide a comprehensive real-world safety profile of EV and SG using a global pharmacovigilance database. Based on the safety signals explored in this study, further research regarding the impact of these side effects on patient outcomes is justified.

Improvements in urinary symptoms, health-related quality of life, and psychosocial distress in the early recovery period after radical cystectomy and urinary diversion in 842 German bladder cancer patients: data from uro-oncological rehabilitation.

PURPOSE: This study aims to investigate urinary symptoms (continence and stoma care), health-related quality of life (HRQoL) and psychosocial distress (PD) in the early postoperative period after radical cystectomy (RC) and urinary diversion for ileal conduit (IC) and ileal neobladder (INB) to obtain a better basis for patient counseling. METHODS: Data for 842 bladder cancer patients, who underwent 3 weeks of inpatient rehabilitation (IR) after RC and urinary diversion (447 IC, 395 INB) between April 2018 and December 2019 were prospectively collected. HRQoL, PD, and urinary symptoms were evaluated by validated questionnaires at the beginning (T1) and the end of IR (T2). In addition, continence status and micturition volume were objectively evaluated in INB patients by 24-h pad test and uroflowmetry, respectively. RESULTS: Global HRQoL was severely impaired at T1, without significant difference between the two types of urinary diversion. All functioning and symptom scales of HRQoL improved significantly from T1 to T2. In INB patients, all continence parameters improved significantly during IR, while patients with an IC reported fewer problems concerning urostomy management. The proportion of patients suffering from high PD decreased significantly from 50.7 to 34.9%. Age ≤ 59 years was the only independent predictor of high PD. Female patients and patients ≤ 59 years were more likely to use individual psycho-oncological counseling. CONCLUSION: HRQoL, PD and urinary symptoms improved significantly in the early recovery period after RC. Patients with urinary continence reported higher HRQoL and less PD. Psychosocial support should be offered especially to younger patients.

An Empirical Survey on the Adaption of Neoadjuvant Chemotherapy in Bladder Cancer.

INTRODUCTION: The aim of the study was to determine the adaption of neoadjuvant chemotherapy (NAC) in patients with muscle-invasive bladder cancer (MIBC) in Germany, Austria, and Switzerland and especially underlying reasons for potential low adherence to guidelines. METHODS: We conducted a non-validated survey among 336 urologic departments in Germany, Austria, and Switzerland. RedCap questionnaires were electronically distributed and included 23 items concerning the general NAC administration standards and guideline compliance in patient counseling regarding the actual treatment. RESULTS: The return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as the standard of care, only 49% of eligible patients actually receive NAC. An advanced disease stage (≥cT3) and a high tumor volume were mentioned to support the application of NAC, whereas 35% of responders worry about deterioration of patients' preoperative status due to NAC. Furthermore, 26.7% of respondents are concerned about the low extent of survival benefit. CONCLUSION: Application of NAC in eligible MIBC patients in Germany, Austria, and Switzerland remains low. Although the majority of urologic departments discuss NAC and acknowledge the need for intensified treatment in advanced disease stages, not all eligible patients will actually receive NAC before radical cystectomy.

A prospective evaluation of quality of life, psychosocial distress, and functional outcomes two years after radical cystectomy and urinary diversion in 842 German bladder cancer patients.

PURPOSE: This study aims to evaluate survival, health-related quality of life (HRQoL), psychosocial distress, and functional outcomes after radical cystectomy (RC) and urinary diversion for ileal neobladder (INB) or ileal conduit (IC) in a contemporary German cohort of bladder cancer patients. METHODS: Patients undergoing inpatient rehabilitation after RC between April 2018 and December 2019 in one high-volume rehabilitation center were surveyed regarding HRQoL, psychosocial distress, and functional outcomes until two years after RC. RESULTS: Eight-hundred forty-two patients (683 male, 159 female; 395 INB, 447 IC) were included. Patients with an IC suffered more often from locally advanced disease (≥ pT3; 41.4% vs. 24.1%, p < 0.001) and lymph node metastases (19.9% vs. 11.8%, p = 0.002), resulting in worse probability of survival (p < 0.001). Global HRQoL improved steadily during follow-up, but significant differences in subscales persisted between cohorts. Multivariable regression analysis identified IC, male sex, and patient age ≤ 59 years as independent predictors for persistent high psychosocial distress. Almost 42% of female patients reported severe urinary incontinence two years after RC. Most men reported severely diminished erectile function, even after nerve-sparing surgery. CONCLUSION: Global HRQoL two years after RC is comparable to the general German population. Female patients should be informed about worse continence rates. Conversely, men should be educated about erectile dysfunction. Aftercare should include psycho-oncologic counseling, especially for patients at risk. IMPLICATIONS FOR CANCER SURVIVORS: Patients should be counseled on long-term functional outcomes and persistent psychosocial distress after RC. Closer cooperation between urologists and psycho-oncologists is needed.

Prospective evaluation of return to work, health-related quality of life and psychosocial distress after radical cystectomy: 1-year follow-up in 230 employed German bladder cancer patients.

PURPOSE: To evaluate return to work (RTW), health-related quality of life (HRQoL) and psychosocial distress (PD) after radical cystectomy (RC) and creation of an ileal conduit (IC) or an orthotopic ileal neobladder (NB) for bladder cancer. METHODS: The study relied on prospectively collected data for 842 patients, who underwent 3 weeks of inpatient rehabilitation (IR) after surgery between April 2018 and December 2019. HRQoL (EORTC QLQ-C30) and PD (Questionnaire on Stress in Cancer Patients [QSC-R10]) were evaluated at the beginning (T1) and end (T2) of IR as well as both 6 (T3) and 12 months after surgery (T4). Regression analyses were performed to identify predictors of HRQoL and RTW, respectively. RESULTS: Two hundred thirty patients (IC n = 51, NB n = 179) were employed before surgery (27.3%). HRQoL improved steadily, while high PD was present in 51.0% of patients at T4. RTW rate was 86.8 and 80.6% at T3 and T4, respectively. Linear regression analysis identified RTW as the only predictor for better HRQoL at T4 (OR [odds ratio] 12.823, 95% CI [confidence interval] 2.927-22.720, p = 0.012). Multivariate regression analysis identified age ≤ 59 years (OR 7.842; 95% CI 2.495-24.645; p < 0.001) as an independent positive predictor and lymph node metastasis (OR 0.220; 95% CI 0.054-0.893; p = 0.034) as an independent negative predictor of RTW at T4. CONCLUSION: Global HRQoL improved steadily during the follow-up and RTW rates are high. However, patients often reported high PD, reflecting a need for additional psychosocial support within aftercare.

Prospective evaluation of functional outcomes in 395 patients with an ileal neobladder 1 year after radical cystectomy.

PURPOSE: This study aims to report on functional outcomes in a large cohort of patients who underwent inpatient rehabilitation (IR) in a highly specialized, high-volume German urologic rehabilitation center after radical cystectomy (RC) and creation of an ileal neobladder (INB). METHODS: Data for 842 patients, who underwent three weeks of IR after RC and urinary diversion between April 2018 and December 2019 were prospectively collected. INB patients were surveyed on continence and sexual function. Data were collected at 4 weeks (T1), 6 months (T2), and 12 months (T3) after RC. Multivariate logistic regressions were performed to identify predictors of better functional outcomes. RESULTS: INB was chosen as urinary diversion in 395 patients (357 male, 38 female). Social continence (maximum of one safety pad/24 h) was reported by 78.3% of men and 64.0% of women at T3. Severe incontinence was reported by 27.3% of men and 44.0% of women. Male sex was identified as an independent predictor for the use of no pads at T3 (OR 4.110; 95% CI 1.153-14.655; p = 0.029). Nerve-sparing surgery was identified as an independent predictor both for the use of only a safety pad (OR 1.918; 95% CI 1.031-3.569; p = 0.040) and good erectile function at T3 (OR 4.377; 95% CI 1.582-12.110; p = 0.004). CONCLUSION: Urologists should aspire for nerve-sparing surgery. When advising patients before RC, functional outcomes (continence, sexual function) should be given special attention. Women should be counseled on potentially prolonged urinary incontinence.

Psychosocial distress and quality of life in patients after radical cystectomy - one year follow-up in 842 German patients.

PURPOSE: This study aims to report on psychosocial distress and QoL in bladder cancer patients after radical cystectomy (RC) and urinary diversion to obtain a better basis for patient counseling and postoperative care. METHODS: The study relied on prospectively collected data for 842 patients, who underwent three weeks of inpatient rehabilitation after RC and creation of an ileal conduit (IC) or ileal neobladder (INB). Data on QoL and psychosocial distress were collected by validated questionnaires. Multivariate logistic regression was performed to identify predictors for high psychosocial distress. RESULTS: Four-hundred and forty-seven patients (326 male, 121 female) received an IC, while 395 patients (357 male, 38 female) received an INB. Health-related QoL improved steadily in the whole cohort during follow-up. Patients with an INB reported better physical function but suffered more from diarrhea and financial worries. Patients with an IC reported reduced satisfaction with their body image, increased worries about the future, and suffered more from constipation. Psychosocial distress increased significantly during follow-up. One year after surgery, 43.1% of patients suffered from high psychosocial distress. Multivariate regression analysis identified age ≤ 59 years (OR 1.731; CI 1.056-2.838; p = 0.030) and lymph node metastases (OR 2.073; CI 1.133-3.793; p = 0.018) as independent predictors for high psychosocial distress. CONCLUSION: QoL improves significantly in all patients one year after RC. However, psychosocial distress remains high in a substantial number of patients. IMPLICATIONS FOR CANCER SURVIVORS: To prevent chronic psychological disorders, easily accessible opportunities for psycho-oncological counseling are needed for patients following RC.

Return to work improves quality of life and reduces psychosocial distress after radical cystectomy: data from a contemporary series of 230 German patients.

PURPOSE: This study aims to evaluate health-related quality of life (HRQoL), psychosocial distress, and return to work (RTW) 2 years after radical cystectomy (RC) and inpatient rehabilitation (IR). MATERIAL AND METHODS: The study relied on prospectively collected data for 842 patients, who underwent 3 weeks of IR after RC and creation of an ileal conduit (IC) or ileal neobladder (INB). Validated questionnaires surveyed patients on HRQoL and psychosocial distress (EORTC QLQ-C30, QSC-R10). Furthermore, employment status was evaluated. Regression was performed to identify predictors for HRQol, psychosocial distress, and RTW. RESULTS: Two-hundred and thirty patients were employed pre-surgery (77.8% INB, 22.2% IC). Patients with an IC suffered significantly more often from locally advanced disease (≥ pT3: 43.1% vs 22.9%; p = 0.004). Two years after surgery, 16.1% of patients had died (median days of survival 302 (IQR 204-482). Global HRQoL improved steadily, while high psychosocial distress was present in 46.5% of patients 2 years after surgery. Employment was reported by 68.2% of patients, of which 90.3% worked full-time. Retirement was reported by 18.5%. Multivariate logistic regression analysis identified age ≤ 59 years as the only positive predictor for RTW 2 years after surgery (OR 7.730; 95% CI 3.369-17.736; p < 0.001). Gender, surgical technique, tumor stage, and socioeconomic status did not influence RTW in this model. In multivariate linear regression analysis, RTW was identified as an independent predictor of better global HRQoL (p = 0.018) and lower psychosocial distress (p < 0.001), whereas younger patient age was identified as an independent predictor for higher psychosocial distress (p = 0.002). CONCLUSION: Global HRQoL and RTW are high among patients two years after RC. However, role and emotional, cognitive, and social functioning were significantly impaired, while high psychosocial distress persists in a material number of patients. IMPLICATIONS FOR CANCER SURVIVORS: Our study highlights how a successful RTW decreases psychosocial distress and increases QoL in patients after RC for urothelial cancer. Nonetheless, additional efforts by employers and healthcare providers are needed in aftercare after creation of an INB or IC.

Avoiding Prostate Biopsies in Patients at Low Risk for Prostate Cancer: A Prospective Evaluation of a PSA-Density-Based Safety Net.

INTRODUCTION AND OBJECTIVES: Decision-making to perform prostate biopsy should include individual risk assessment. Patients classified as low risk by the Rotterdam Prostate Cancer Risk Calculator are advised to forego biopsy (PBx). There is concern about missing clinically significant prostate cancer (csPCa). A clear pathway for follow-up is needed. MATERIAL AND METHODS: Data for 111 consecutive patients were collected. Patients were encouraged to adhere to a PSA-density-based safety net after PBx was omitted. Cut off values indicating a re-evaluation were PSA density >0.15 ng/mL/ccm in PBx-naïve patients and >0.2 ng/mL/ccm in men with past-PBx. Primary endpoint was whether men had their PSA taken regularly. Secondary endpoint was whether a new multiparametric MRI was performed when PSA-density increased. Tertiary endpoint was whether biopsy was performed when risk stratification revealed an increased risk. RESULTS: Median follow-up was 12 months (IQR 9-15 months). The primary endpoint was reached by 97.2% (n = 106). The secondary endpoint was reached by 30% (n = 3). The tertiary endpoint was reached by 50% (n = 2). Histopathologic analyses revealed csPCa in none of these cases. Risk stratification did not change (p = 0.187) with the majority of patients (89.2%, n = 99). CONCLUSION: The concern of missing csPCa when omitting PBx in the risk-stratified pathway may be negated. Changes in risk stratification during follow-up should lead to subsequent PBx. We suggest implementing a safety net based on PSA density and digital rectal examination (DRE).

Assessment of complications after transperineal and transrectal prostate biopsy using a risk-stratified pathway identifying patients at risk for post-biopsy infections.

INTRODUCTION: Evidence of transperineal (TP) superiority over transrectal (TR) biopsy is growing due to lower infectious complication rates. However, TR biopsy is the most common procedure, and it seems that a cross-over to TP is delayed by logistical challenges such as costs, complexity, and lack of experience. We investigate whether well-selected patients without any risk factors may further undergo TR biopsy if all precautions to avoid infections are warranted. MATERIALS AND METHODS: Data were collected in our academic institution between August 2021 and March 2022 and after clinical implementation of the currently updated European Association of Urology guideline recommendations on the performance of prostate biopsy. Patients underwent either TP or TR biopsy according to a riskstratification based on risk factors of infectious complications. Follow-up asked for post-biopsy complications. Inverse Probability of Treatment Weighting (IPTW) propensity score was used to balance baseline characteristics. Complications were subdivided into infectious and non-infectious complications. RESULTS: In total, 294 patients were included with 161 patients undergoing TR vs. 133 patients undergoing TP biopsy. Complication rates were 2.2% for TP vs. 5.5% for TR biopsy concerning all complications. Infectious complication rates only were 0.7% for TP vs. 1.8% for TR biopsy. After IPTW adjustment, differences were statistically significant different (p = 0.01). CONCLUSION: Our study revealed that even in a well-selected patient cohort with presumably lower risk of infectious complications, TR biopsy leads to more post-biopsy complications than TP biopsy. This conclusion should motivate the urological community to switch to TP biopsy.

Complications in the Early Recovery Period After Radical Cystectomy-Real Data From Impartial Inpatient Rehabilitation.

PURPOSE: To examine postoperative complications after radical cystectomy (RC) and creation of an ileum conduit (IC) or a neobladder (NB), and to identify preoperative risk factors in a contemporary series of bladder cancer patients. PATIENTS AND METHODS: The study relied on prospectively collected data for 842 patients, who underwent inpatient rehabilitation (IR) after RC and urinary diversion (IC n = 447, NB n = 395) between April 2018 and December 2019. Postoperative complications until the end of IR were assessed according to the Clavien-Dindo classification. Uni- and multivariate analyses were performed to identify predictors for complications. RESULTS: A total of 2689 complications occurred in 813 patients (96.6%). High-grade complications occurred more frequently before IR onset (25.5% vs. 5.7%; P < .001), whereas a higher percentage of low-grade complications occurred during IR (89.0% vs. 77.8%; P < .001). The most common complication categories were genitourinary (60.9%), infectious (54.0%) and gastrointestinal (49.2%). Rates of high-grade complications do not differ between IC and NB patients (26.8% vs. 31.6%, P = .126). Independent predictors for overall complications were NB (odds ratio [OR] 21.520; P < .001), age ≥70 years (OR 2.522; P = .027) and higher body mass index (OR 1.153, P = .008). Risk factors for high-grade complications were NB (OR 1.448; P = .039) and Charlson Comorbidity Index ≥2 (OR 1.999; P = .001). Hospital readmission rate was 9.4%. CONCLUSION: Our study revealed significantly higher overall and high-grade complication rates after RC with IC or NB creation than previously published. A high percentage of low-grade complications occur after hospital discharge. The hospital readmission rate was lower compared to historical data.

How Many Cores Should Be Sampled during Systematic Prostate Biopsy in Case of Negative Multiparametric Magnetic Resonance Imaging? Analysis of 274 Men with Clinical Suspicion of Prostate Cancer.

INTRODUCTION: This study aimed to investigate the number of cores needed in a systematic biopsy (SB) in men with clinical suspicion of prostate cancer (PCa) but negative prebiopsy multiparametric magnetic resonance imaging and to test prostate-specific antigen (PSA) density as an indicator for reduced SB. METHODS: Two hundred and seventy-four patients were analyzed, extracted from an institutional database. Detection rates of any PCa and clinically significant (CS) PCa for different reduced biopsy protocols were compared by using Fisher's exact test. RESULTS: In total, 12-core SB revealed PCa in 103 (37.6%) men. Detection rates of reduced biopsy protocols were 74 (27%, 6-core) and 82 (29.9%, 8-core). Regarding CSPCa, 12-core SB revealed a detection rate of 26 (9.5%). Reduced biopsy protocols detected less CSPCa: 15 (5.5%) and 18 (6.6%), respectively. All differences were statistically significant, p < 0.05. PSA density ≥0.15 did not help to filter out men in whom a reduced biopsy may be sufficient. CONCLUSIONS: Twelve-core SB still has the highest detection rate of any PCa and CSPCa compared to reduced biopsy protocols. If the investigator and patient agree - based on individual risk calculation - to perform a biopsy, this SB should contain at least 12 cores regardless of PSA density.

Changing the Prostate Cancer Detection Paradigm: Clinical Application of European Association of Urology Guideline-recommended Magnetic Resonance Imaging-based Risk Stratification in Men with Suspected Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging using the Prostate Imaging Reporting and Data System version 2.1 allows for a personalized, risk-stratified approach to indicating prostate biopsies (PBx) in order to reduce PBx and concomitant complications in men with suspected prostate cancer (PCa). One way to achieve this goal is to implement the risk-stratified pathway (RSP) using the Rotterdam Prostate Cancer Risk Calculator. OBJECTIVE: To describe the clinical implementation of the RSP and to examine its impact on the number of PBx and the resulting changes in the PCa detection pattern compared with men undergoing PBx in a detection-focused pathway (DFP) without prior risk assessment. DESIGN, SETTING, AND PARTICIPANTS: An institutional dataset of 505 consecutive patients with suspected PCa between July 2019 and February 2020 was used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Chi-square test and Mann-Whitney U test were employed to examine differences in the number of PBx and the PCa detection pattern between the DFP (n = 195, 38.6%) and the RSP (n = 310, 61.4%). To minimize differences in risk stratification, inverse probability of treatment weighting was used. RESULTS AND LIMITATIONS: After implementing the RSP, the overall biopsy rate could be reduced by 11.2% (100% vs 88.8%, p < 0.001. Additionally, compared with the DFP, the number of biopsy cores per patient was reduced in the RSP (14 [interquartile range {IQR} 14-15] vs 14 [IQR 6-14], p < 0.001) and the detection of clinically significant PCa was increased (44.3% vs 57.7%, p = 0.038). Overdiagnosis of clinically insignificant disease was decreased in the RSP (22.8% vs 12.6%, p = 0.039). CONCLUSIONS: Implementation of the RSP in clinical practice reduced the number of PBx and brought forth a shift in the PCa detection pattern toward clinically significant disease, while reducing overdiagnosis of clinically insignificant disease. PATIENT SUMMARY: In this study, we examined the impact of risk stratification on the number of prostate biopsies (PBx) and the consecutive detection pattern in men with suspected prostate cancer (PCa). We found that the risk-stratified pathway reduced the number of PBx while simultaneously shifting the PCa detection pattern toward clinically significant PCa.