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.

Treating BCG-Induced Cystitis with Combined Chondroitin and Hyaluronic Acid Instillations in Bladder Cancer.

In non-muscle invasive bladder cancer, Bacillus Calmette-Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

OBJECTIVE: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. PATIENTS AND METHODS: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni- and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer-specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. RESULTS: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2-year OS estimates were 63% (95% confidence interval [CI] 0.53-0.74) and 63% (95% CI 0.58-0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni- or multivariable Cox regression analyses. CONCLUSION: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

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.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

An empirical survey on the adaption of neoadjuvant chemotherapy in bladder cancer.

OBJECTIVE: 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 amongst 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 counselling regarding actual treatment. RESULTS: Return rate of the questionnaire was 19.1% (63/336). Although 45 departments (71.4%) claim to perform NAC as 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 application of NAC, whereas 35% of responders worry a 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 discusses NAC and acknowledges 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.

Impact of the extent of lymph node dissection on survival outcomes in clinically lymph node-positive bladder cancer.

OBJECTIVE: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node-positive (cN+) bladder cancer (BCa). PATIENTS AND METHODS: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin-based peri-operative chemotherapy for cTany N1-3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence-free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity-score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. RESULTS: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4-16) months, and median (IQR) follow-up of alive patients was 30 (13-51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70-1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60-1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. CONCLUSION: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach.

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.

Functional outcome after radical prostatectomy in 1313 patients: A single-center study.

OBJECTIVES: To assess the impact of urinary continence and erectile function on the quality of life in men undergoing radical prostatectomy (RP) for prostate cancer (PC), we analyzed the preoperative and 1-year postoperative outcomes of five functional domains and their influencing factors. PATIENTS AND METHODS: In this prospective study, all patients undergoing open or robot-assisted RP between Febuary 2017 and March 2020 in a single academic center were included. Patient-reported outcomes were assessed pre- and 12 months postoperatively using the Expanded Prostate Index Composite (EPIC-26) survey, evaluating continence, irritative/obstructive micturition, gastrointestinal symptoms, sexuality, and overall vitality. We examined the impact of RP on sexual function and urinary continence using multivariable logistic regression models, accounting for patient and tumor characteristics. RESULTS: Overall, 1313 consecutive patients gave consent for study participation and completed both surveys. The median age was 66 years (IQR: 60-70). The majority of patients (n = 601, 46%) had an intermediate risk PC. Robotic RP was performed in 71.6% and nerve-sparing technique in 81% of the cases. The median pre- versus postoperative scores were the following: urinary continence 100 (IQR: 91.8-100) versus 85.5 (64.8-100), irritative micturition 87.5 (IQR: 75-100) versus 93.8 (IQR: 87.5-100), gastrointestinal symptoms the same with 100 (IQR: 95.8-100), vitality 95 (IQR: 80-100) versus 90 (IQR: 75-100), and erectile function 65.3 (IQR: 38.8-87.5) versus 22.2 (IQR: 12.5-48.7), respectively. Age (p < 0.001), risk classification (p = 0.002), and nerve-sparing surgery (p = 0.016) were associated with good sexual function (EPIC-26 score ≥60), while only age (p = 0.001) was statistically significantly associated with good urinary continence (EPIC-26 score ≥80). CONCLUSION: Non-modifiable factors such as age and PC risk classification impact urinary continence and sexual function after RP. Nevertheless, urologic surgeons should further focus on improving nerve-sparing techniques, the only modifiable variable, to reduce the surgery's negative impact on urinary continence and sexual function.

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).

Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis.

BACKGROUND: In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. METHODS: PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. RESULTS: In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. CONCLUSION: We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

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.

The Natural History of Renal-Cell Carcinoma with Sarcomatoid Differentiation, a Stage-by-Stage Analysis.

BACKGROUND: Sarcomatoid differentiation in patients diagnosed with renal cell carcinoma (sRCC) imply aggressive behavior and often metastatic disease at the time of diagnosis. We aim to examine the overall survival (OS) in patients with sRCC using the National Cancer Database (NCDB). MATERIALS AND METHODS: We identified patients diagnosed with sRCC between 2010-2015. We employed Kaplan-Meier curves and multivariable Cox proportional hazards regression models to examine the impact of several potential risk factors on OS in patients diagnosed with sRCC. RESULTS: In total, 8582 patients with renal cancer were found to have sarcomatoid differentiation, with 4105 patients (47.8%) being diagnosed with AJCC stage IV disease. The median OS was 17.2 months (IQR 5.4, 68.7 months). Compared to patients who did not undergo surgery, OS was significantly longer in patients undergoing partial or total nephrectomy across all stages. This result remained consistent on multivariable Cox proportional hazards regression adjusting for patient and tumor characteristics (Surgery: Hazard ratio 0.54, 95%Confidence interval 0.43 - 0.68, P < .001). CONCLUSION: In our cohort sRCC was found to have an unfavorable median OS, which was mainly caused by the high number of cases diagnosed with late-stage disease. Additionally, surgery was associated with favorable OS across all stages. This study supports the notion that surgical therapy, even in the setting of cytoreductive surgery, provides a survival benefit in patients with sRCC.

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.

C-reactive protein flare predicts response to anti-PD-(L)1 immune checkpoint blockade in metastatic urothelial carcinoma.

PURPOSE: Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response. METHODS: We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS). RESULTS: Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P < 0.001). CRP flare response was associated with prolonged PFS and OS (P < 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P < 0.001). CONCLUSION: CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.

A Multivariable Approach Using Magnetic Resonance Imaging to Avoid a Protocol-based Prostate Biopsy in Men on Active Surveillance for Prostate Cancer-Data from the International Multicenter Prospective PRIAS Study.

BACKGROUND: There is ongoing discussion whether a multivariable approach including magnetic resonance imaging (MRI) can safely prevent unnecessary protocol-advised repeat biopsy during active surveillance (AS). OBJECTIVE: To determine predictors for grade group (GG) reclassification in patients undergoing an MRI-informed prostate biopsy (MRI-Bx) during AS and to evaluate whether a confirmatory biopsy can be omitted in patients diagnosed with upfront MRI. DESIGN, SETTING, AND PARTICIPANTS: The Prostate cancer Research International: Active Surveillance (PRIAS) study is a multicenter prospective study of patients on AS (www.prias-project.org). We selected all patients undergoing MRI-Bx (targeted ± systematic biopsy) during AS. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A time-dependent Cox regression analysis was used to determine the predictors of GG progression/reclassification in patients undergoing MRI-Bx. A sensitivity analysis and a multivariable logistic regression analysis were also performed. RESULTS AND LIMITATIONS: A total of 1185 patients underwent 1488 MRI-Bx sessions. The time-dependent Cox regression analysis showed that age (per 10 yr, hazard ratio [HR] 0.84 [95% confidence interval {CI} 0.71-0.99]), MRI outcome (Prostate Imaging Reporting and Data System [PIRADS] 3 vs negative HR 2.46 [95% CI 1.56-3.88], PIRADS 4 vs negative HR 3.39 [95% CI 2.28-5.05], and PIRADS 5 vs negative HR 4.95 [95% CI 3.25-7.56]), prostate-specific antigen (PSA) density (per 0.1 ng/ml cm3, HR 1.20 [95% CI 1.12-1.30]), and percentage positive cores on the last systematic biopsy (per 10%, HR 1.16 [95% CI 1.10-1.23]) were significant predictors of GG reclassification. Of the patients with negative MRI and a PSA density of <0.15 ng/ml cm3 (n = 315), 3% were reclassified to GG ≥2 and 0.6% to GG ≥3. At the confirmatory biopsy, reclassification to GG ≥2 and ≥3 was observed in 23% and 7% of the patients diagnosed without upfront MRI and in 19% and 6% of the patients diagnosed with upfront MRI, respectively. The multivariable analysis showed no significant difference in upgrading at the confirmatory biopsy between patients diagnosed with or without upfront MRI. CONCLUSIONS: Age, MRI outcome, PSA density, and percentage positive cores are significant predictors of reclassification at an MRI-informed biopsy. Patients with negative MRI and a PSA density of <0.15 ng/ml cm3 can safely omit a protocol-based prostate biopsy, whereas in other patients, a multivariable approach is advised. Being diagnosed with upfront MRI appears not to significantly affect reclassification risk; hence, a confirmatory MRI-Bx cannot totally be omitted yet. PATIENT SUMMARY: A protocol-based prostate biopsy while on active surveillance can be omitted in patients with negative magnetic resonance imaging (MRI) and prostate-specific antigen density <0.15 ng/ml cm3. A confirmatory biopsy cannot simply be omitted in all patients diagnosed with upfront MRI.