Apalutamide efficacy, safety and wellbeing in older patients with advanced prostate cancer from Phase 3 randomised clinical studies TITAN and SPARTAN.

BACKGROUND: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in metastatic castration-sensitive prostate cancer (mCSPC) and non-metastatic castration-resistant PC (nmCRPC) in the Phase 3 randomised TITAN and SPARTAN studies, respectively, and maintained health-related quality of life (HRQoL). Apalutamide treatment effect by patient age requires assessment. METHODS: Post-hoc analysis assessed patients receiving 240 mg/day apalutamide (525 TITAN and 806 SPARTAN) or placebo (527 TITAN and 401 SPARTAN) with ongoing ADT, stratified by age groups. Prostate-specific antigen declines, radiographic progression-free survival, metastasis-free survival, overall survival (OS), HRQoL and safety were assessed using descriptive statistics, Kaplan-Meier method, Cox proportional-hazards model and mixed-effects model for repeated measures. RESULTS: Hazard ratios (95% confidence intervals) generally favoured apalutamide plus ADT versus ADT alone across all endpoints regardless of age; e.g., OS values were 0.57 (0.40-0.80), 0.70 (0.54-0.91) and 0.74 (0.40-1.39) (TITAN) and 0.39 (0.19-0.78), 0.89 (0.69-1.16) and 0.81 (0.58-1.15) (SPARTAN) in patients aged <65, 65-79 and ≥80 years. Regardless of age, apalutamide also maintained HRQoL and was tolerated well with a potential trend in rates of adverse events increasing with age. Limitations include post-hoc nature and variability in sample size of age groups. CONCLUSIONS: Apalutamide plus ADT was an effective and well-tolerated option maintaining HRQoL in patients with mCSPC and nmCRPC regardless of age. CLINICAL TRIAL REGISTRATION: TITAN (NCT02489318); SPARTAN (NCT01946204).

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

OBJECTIVES: To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). MATERIAL AND METHODS: Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. RESULTS: In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6-9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12-0.14) and the risk of death from all causes was 0.32 (95% CI 0.31-0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08-0.10) and the risk of death from all causes was 0.19 (95% CI 0.18-0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41-0.44) and 0.21 (95% CI 0.20-0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030-0.36) after RT and 0.27 (95% CI 0.24-0.30) after RP. CONCLUSION: Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy.

OBJECTIVE: To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC). PATIENTS AND METHODS: Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used. RESULTS: By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients. CONCLUSIONS: In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. PATIENT SUMMARY: Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.

Real-world performance of Uromonitor® in urothelial bladder cancer detection: a multicentric trial.

OBJECTIVES: To compare Uromonitor® (U-Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto-oncogenes (telomerase reverse transcriptase [TERT], fibroblast growth factor receptor 3 [FGFR-3], Kirsten rat sarcoma viral oncogene homologue [KRAS]), with urine cytology in the urine-based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real-world setting. PATIENTS AND METHODS: This multicentre, prospective, double-blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real-world setting. Sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV), and accuracy of the tests were measured, in addition to multivariate analyses to assess the ability of individual proto-oncogene mutations in detecting UCB. The biometric sample size was designed to achieve a 10% difference in sensitivity. RESULTS: Patients with UCB comprised 63.7% (339/532) of the study group. Uromonitor showed a sensitivity, specificity, PPV, NPV, accuracy, and an area-under-the-curve of 49.3%, 93.3%, 92.8%, 51.1%, 65.2%, and 0.713%, respectively. These metrics did not demonstrate statistical superiority over urine cytology in terms of sensitivity (44.6%; P = 0.316). Moreover, the comparison of additional test parameters, as well as the comparison within various sensitivity analyses, yielded no significant disparity between the two urinary tests. Multivariate logistic regression underscored the significant predictive value of a positive Uromonitor for detecting UCB (odds ratio [OR] 9.03; P < 0.001). Furthermore, mutations in TERT and FGFR-3 were independently associated with high odds of UCB detection (OR 13.30 and 7.04, respectively), while KRAS mutations did not exhibit predictive capability. CONCLUSION: Despite its innovative approach, Uromonitor fell short of confirming the superior results anticipated from previous studies in this real-world setting. The search for an optimal urine-based biomarker for detecting and monitoring UCB remains ongoing. Results from this study highlight the complexity of developing non-invasive diagnostic tools and emphasise the importance of continued research efforts to refine these technologies.

How does artificial intelligence master urological board examinations? A comparative analysis of different Large Language Models' accuracy and reliability in the 2022 In-Service Assessment of the European Board of Urology.

PURPOSE: This study is a comparative analysis of three Large Language Models (LLMs) evaluating their rate of correct answers (RoCA) and the reliability of generated answers on a set of urological knowledge-based questions spanning different levels of complexity. METHODS: ChatGPT-3.5, ChatGPT-4, and Bing AI underwent two testing rounds, with a 48-h gap in between, using the 100 multiple-choice questions from the 2022 European Board of Urology (EBU) In-Service Assessment (ISA). For conflicting responses, an additional consensus round was conducted to establish conclusive answers. RoCA was compared across various question complexities. Ten weeks after the consensus round, a subsequent testing round was conducted to assess potential knowledge gain and improvement in RoCA, respectively. RESULTS: Over three testing rounds, ChatGPT-3.5 achieved RoCa scores of 58%, 62%, and 59%. In contrast, ChatGPT-4 achieved RoCA scores of 63%, 77%, and 77%, while Bing AI yielded scores of 81%, 73%, and 77%, respectively. Agreement rates between rounds 1 and 2 were 84% (κ = 0.67, p < 0.001) for ChatGPT-3.5, 74% (κ = 0.40, p < 0.001) for ChatGPT-4, and 76% (κ = 0.33, p < 0.001) for BING AI. In the consensus round, ChatGPT-4 and Bing AI significantly outperformed ChatGPT-3.5 (77% and 77% vs. 59%, both p = 0.010). All LLMs demonstrated decreasing RoCA scores with increasing question complexity (p < 0.001). In the fourth round, no significant improvement in RoCA was observed across all three LLMs. CONCLUSIONS: The performance of the tested LLMs in addressing urological specialist inquiries warrants further refinement. Moreover, the deficiency in response reliability contributes to existing challenges related to their current utility for educational purposes.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Evaluating the Efficacy of AI Chatbots as Tutors in Urology: A Comparative Analysis of Responses to the 2022 In-Service Assessment of the European Board of Urology.

INTRODUCTION: This study assessed the potential of Large Language Models (LLMs) as educational tools by evaluating their accuracy in answering questions across urological subtopics. METHODS: Three LLMs (ChatGPT-3.5, ChatGPT-4, and Bing AI) were examined in two testing rounds, separated by 48-hours, using 100 Multiple-Choice Questions (MCQs) from the 2022 European Board of Urology (EBU) In-Service Assessment (ISA), covering five different subtopics. The correct answer was defined as "formal accuracy" (FA) representing the designated single best answer (SBA) among four options. Alternative answers selected from LLMs, which may not necessarily be the SBA but are still deemed correct, were labeled as "extended accuracy" (EA). Their capacity to enhance the overall accuracy rate when combined with FA was examined. RESULTS: In two rounds of testing, the FAs scores were achieved as follows: ChatGPT-3.5: 58% and 62%, ChatGPT-4: 63% and 77%, and BING AI: 81% and 73%. The incorporation of EA did not yield a significant enhancement in overall performance. The achieved gains for ChatGPT-3.5, ChatGPT-4, and BING AI were as a result 7% and 5%, 5% and 2%, and 3% and 1%, respectively (p>0.3). Within urological subtopics, LLMs showcased best performance in Pediatrics/Congenital and comparatively less effectiveness in Functional/BPS/Incontinence. CONCLUSION: LLMs exhibit suboptimal urology knowledge and unsatisfactory proficiency for educational purposes. The overall accuracy did not significantly improve when combining EA to FA. The error rates remained high ranging from 16 to 35%. Proficiency levels vary substantially across subtopics. Further development of medicine specific LLMs is required before integration into urological training programs.

A US real-world study of treatment patterns and outcomes in localized or locally advanced prostate cancer patients.

PURPOSE: Men with localized or locally advanced prostate cancer (LPC/LAPC) are at risk of progression after radiotherapy (RT) or radical prostatectomy (RP). Using real-world data, we evaluated patient characteristics, treatment patterns, and outcomes in LPC/LAPC. METHODS: Optum claims and electronic health records (EHR) data from January 2010 to December 2021 were queried for men with LPC/LAPC who received primary RT, RP, or androgen deprivation therapy alone within 180 days after diagnosis. Survival outcomes were analyzed using descriptive statistics and Kaplan-Meier curves. Real-world overall survival (rwOS) was compared in patients with and without evidence of disease (i.e., disease recurrence, metastasis, diagnosis of castration-resistant PC) at defined time points. RESULTS: 61,772 and 62,361 men in claims and EHR cohorts met the inclusion criteria. Median follow-up was 719 and 901 days, respectively. Most men received primary RT (51.0% claims, 35.0% EHR) or RP (39.4% claims, 53.8% EHR). Survival was greatest among men treated with RP, followed by RT. Adjusted for age and comorbidity, rwOS was shorter among men with evidence of disease within 1, 3, 4, and 5 years after primary treatment than those without at the same time points. CONCLUSION: Real-world claims and EHR data show that survival among men with LPC/LAPC differs by primary treatment and time point of disease recurrence thereafter. Poor outcomes in men with LPC/LAPC who progress early indicate an unmet medical need for more effective primary treatment. If validated for surrogacy, no evidence of disease at specific time points could represent an intermediate efficacy endpoint in future trials.

A Rejected Hypothesis: Phenomenon of High Treatment Adherence in Direct-to-Consumer Teledermatology Despite Lack of Direct Physician-Patient Interaction.

Background: Adherence to dermatological treatment is described as poor. Empathy and open communication in the physician-patient relationship has been proven to improve adherence. As direct-to-consumer teledermatology enables patients to access dermatological consultations without in-person interactions, we hypothesized treatment adherence in teledermatology to be low. Methods: The objective of the study was to examine treatment adherence in teledermatology. This retrospective cross-sectional study used data from patients treated through a German direct-to-consumer teledermatology platform between July 2021 and April 2022. Additional information was collected through voluntary follow-up questionnaires provided to patients to assess individual treatment success, treatment-related adverse events, and treatment adherence. Results: Data collection included 771 patients; 61.6% (475/771) were women (mean age 35 years). In 46% (355/771), skin disease had been present for <3 months before teleconsultation. Of all patients who answered the follow-up questionnaire (n = 228), 28.5% (65/228) reported treatment-related adverse events, with skin dryness being the most common (56.9%, 37/65). Adverse events resulting in treatment discontinuation were reported in 1.3% (3/228) of all cases. Improvement in skin condition on therapy was described by 75.4% (172/228). In 85.5% (195/228), full treatment adherence was reported. Conclusion: This is the first study worldwide to examine data on treatment adherence in direct-to-consumer-teledermatology. Despite the lack of doctor-patient interaction, the results of our study demonstrate that most patients show high treatment adherence. Possible drivers contributing to high compliance rates could be the high proportion of new-onset skin diseases, the high treatment success of the prescribed therapies, and the low rate of serious adverse events.

Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study.

BACKGROUND: The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC. METHODS: ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone-prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone-prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov, number NCT02257736. FINDINGS: 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone-prednisone; 490 to abiraterone-prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0-28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4-27·4) in the apalutamide plus abiraterone-prednisone group versus 16·6 months (13·9-19·3) in the abiraterone-prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58-0·83; p<0·0001). At the updated analysis (final analysis for overall survival; median follow-up 54·8 months [IQR 51·5-58·4]), median radiographic progression-free survival was 24·0 months (95% CI 19·7-27·5) versus 16·6 months (13·9-19·3; HR 0·70, 95% CI 0·60-0·83; p<0·0001). The most common grade 3-4 treatment-emergent adverse event was hypertension (82 [17%] of 490 patients receiving apalutamide plus abiraterone-prednisone and 49 [10%] of 489 receiving abiraterone-prednisone). Serious treatment-emergent adverse events occurred in 195 (40%) patients receiving apalutamide plus abiraterone-prednisone and 181 (37%) patients receiving abiraterone-prednisone. Drug-related treatment-emergent adverse events with fatal outcomes occurred in three (1%) patients in the apalutamide plus abiraterone-prednisone group (2 pulmonary embolism, 1 cardiac failure) and five (1%) patients in the abiraterone-prednisone group (1 cardiac failure and 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death). INTERPRETATION: Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone-prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC. FUNDING: Janssen Research & Development.

Does Ureteral Stenting Increase the Risk of Metachronous Upper Tract Urothelial Carcinoma in Patients with Bladder Tumors? A Systematic Review and Meta-analysis.

PURPOSE: Ureteral stenting in patients with bladder cancer may become necessary in order to protect the ureteral orifice during transurethral resection of the tumor or for relief of upper urinary tract obstruction. However, it is believed to increase metachronous upper tract urothelial carcinoma risk. MATERIALS AND METHODS: We performed a systematic review and meta-analysis of studies comparing ureteral stenting versus nephrostomy or no drainage with regard to the risk of metachronous upper tract urothelial carcinoma. Records were identified through database searches and sources of grey literature up to October 2020 (PROSPERO: CRD42020178298). RESULTS: Five studies (3,309 individuals) were included. Overall, 278 ureteral stents were placed and 20 (7.2%) patients developed metachronous upper tract urothelial carcinoma, while 131 patients were treated with nephrostomy and 3 (2.3%) cases of metachronous upper tract urothelial carcinoma occurred. Patients treated with ureteral stents had a higher likelihood of metachronous upper tract urothelial carcinoma compared to no stents (OR: 3.49, 95% CI: 1.43-8.48, I2=52%) and no upper urinary tract drainage (OR: 3.37, 95% CI: 1.49-7.63, I2=45%). No difference with regard to metachronous upper tract urothelial carcinoma was observed between stent and nephrostomy (OR: 3.07, 95% CI: 0.41-22.98, I2=54%). For the same outcomes, no difference was noted for patients with hydronephrosis. The level of evidence for all measures was evaluated as low. CONCLUSIONS: Stenting as a preventive measure after resection of tumors involving the orifice should be avoided, when possible, as it increases the risk of metachronous upper tract urothelial carcinoma. In cases of hydronephrosis, drainage with either nephrostomy or stent is recommended depending on individual patient cases as both interventions do not differ regarding metachronous upper tract urothelial carcinoma risk.

Impact of Resection Technique on Perioperative Outcomes and Surgical Margins after Partial Nephrectomy for Localized Renal Masses: A Prospective Multicenter Study.

PURPOSE: The impact of resection technique on partial nephrectomy outcomes is controversial. The aim of this study was to evaluate the pattern of resection techniques during partial nephrectomy and the impact on perioperative outcomes, acute kidney injury, positive surgical margins and the achievement of the Trifecta (negative surgical margins, no perioperative Clavien-Dindo grade 2 or greater surgical complications and no postoperative acute kidney injury). MATERIALS AND METHODS: We prospectively collected data on consecutive patients with cT1-2N0M0 renal masses treated with partial nephrectomy at a total of 16 referral centers from September 2014 to March 2015. After partial nephrectomy the resection technique was classified by the surgeon as enucleation, enucleoresection or resection according to the SIB (Surface-Intermediate-Base) margin scores 0 to 2, 3 or 4 and 5, respectively. Multivariable logistic regression analysis was done to evaluate the potential impact of the resection technique on postoperative surgical complications, positive surgical margins, acute kidney injury and Trifecta achievement. RESULTS: Overall 507 patients were included in analysis. The resection technique was classified as enucleation in 266 patients (52%), enucleoresection in 150 (30%) and resection in 91 (18%). The resection technique (enucleoresection vs enucleation and resection) was the only significant predictor of positive surgical margins. Tumor complexity, surgical approach (open and laparoscopic vs robotic) and resection technique (enucleoresection vs enucleation) were significant predictors of Clavien-Dindo grade 2 or greater surgical complications. The surgical approach (open and laparoscopic vs robotic), the resection technique (enucleoresection vs enucleation) and warm ischemia time were significantly associated with postoperative acute kidney injury and Trifecta achievement. CONCLUSIONS: Resection techniques significantly impact surgical complications, early functional outcomes and positive surgical margins after partial nephrectomy of localized renal masses.

External validation of a postoperative nomogram for the prediction of disease-specific survival in patients with papillary renal cell carcinoma using a large multicenter database.

PURPOSE: Based on data retrieved from a comprehensive multicenter database, we externally validated a published postoperative nomogram for the prediction of disease-specific survival (DSS) in patients with papillary renal cell carcinoma (papRCC). METHODS: A multicenter database containing data of 2325 patients with surgically treated papRCC was used as validation cohort. After exclusion of patients with missing data and patients included in the development cohort, 1372 patients were included in the final analysis. DSS-probabilities according to the nomogram were calculated and compared to actual DSS-probabilities. Subsequently, calibration plots and decision curve analyses were applied. RESULTS: The median follow-up was 38 months (IQR 11.8-80.7). Median DSS was not reached. The c-index of the nomogram was 0.71 (95% CI 0.60-0.83). A sensitivity analysis including only patients operated after 1998 delivered a c-index of 0.84 (95% CI 0.77-0.92). Calibration plots showed slight underestimation of nomogram-predicted DSS in probability ranges below 90%: median nomogram-predicted 5-year DSS in the range below 90% was 55% (IQR 20-80), but the median actual 5-year DSS in the same group was 58% (95% CI 52-65). Decision-curve analysis showed a positive net-benefit for probability ranges between a DSS probability of 5% and 85%. CONCLUSIONS: The nomogram performance was satisfactory for almost all DSS probabilities; hence it can be recommended for application in clinical routine and for counseling of patients with papRCC.

Outcomes for Patients after Resection of Pulmonary Metastases from Clear Cell Renal Cell Carcinoma: 18 Years of Experience.

INTRODUCTION: Clear cell renal cell carcinoma (ccRCC) is the most common kidney tumor. If feasible, metastasectomy is preferably indicated in metastatic disease. OBJECTIVE: The aim of this study was to determine the outcome of patients after pulmonary metastasectomy (PM). METHODS: PM for ccRCC was performed in 35 patients in the period of January 2001-2019. Clinical characteristics, type of surgery, histopathology results, and follow-up data were recorded. Progression-free survival (PFS) after PM and overall survival (OS) were defined as outcome endpoints. RESULTS: A total of 77 PMs were performed in 35 patients after nephrectomy for ccRCC. The mean size of pulmonary metastasis was 19.0 mm (4-90). With a median follow-up after PM of 79.2 months, the 3- and 5-year OS rates were 63.5 and 44.9%, respectively. The only statistically significant prognostic factor affecting both PFS (p = 0.019) and OS (p = 0.015) was the dimension of pulmonary metastases. CONCLUSIONS: The prognosis of metastatic ccRCC is generally poor, particularly in cases of larger size of metastasis. PM might improve the individual prognosis of patients with lung metastasis even in cases with higher number of metastases, bilaterality, synchronous metastasis, or a short progression-free interval after nephrectomy.

Cystic Appearance on Imaging Methods (Bosniak III-IV) in Histologically Confirmed Papillary Renal Cell Carcinoma is Mainly Characteristic of Papillary Renal Cell Carcinoma Type 1 and Might Predict a Relatively Indolent Behavior of Papillary Renal Cell Carcinoma.

AIM: The aim of this study was to determine the proportion of cystic tumors according to preoperative CT (Bosniak III, IV) among surgically treated patients with histologically confirmed papillary renal cell carcinoma (pRCC) and to assess progression rates among patients with and without cystic appearance on imaging. METHODS: A total of 138 patients with pRCC histology surgically treated in the period of January 2007-March 2017 were included. Clinical and radiological characteristics, type of surgery, histopathology results, and follow-up data were recorded and statistically evaluated. RESULTS: Forty-one cases (29.7%) of cystic lesions (10× BIIF, 14× BIII, 17× BIV) were detected by CT. Patients with pRCC1 significantly more frequently presented with cystic appearance on CT (33/78; 42.3%) in comparison to other papillary types (8/60; 13.3%; p = 0.0002). During a median follow-up time of 49.4 months, only 2 patients with cystic lesions progressed after surgery. CONCLUSIONS: Cystic appearance on imaging methods is mainly a characteristic of pRCC1 (42.3%). Cystic morphology on imaging might predict a relatively indolent behavior of all pRCC types. Preoperative scoring systems including tumor growth patterns (cystic vs. solid) are needed for further classification.

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma in the era of targeted therapy: a bibliographic review.

PURPOSE: To evaluate the role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC), against a background of lack of evidence following the introduction of targeted therapy. METHODS: A literature review was performed in January 2017 using the MEDLINE/PubMed and EMBASE databases. The PRISMA guidelines were followed for conduct of the study. Two authors independently screened the 270 papers retrieved from the search, and the finally selected publications were identified by consensus between the two reviewers. A total of 55 studies were included in the present review. RESULTS: Globally, the indications for CN have decreased over recent years. Although current guidelines consider CN an adequate option in selected patients based on prospective studies in the cytokine era, evidence for CN in the era of targeted therapy is based on retrospective studies only. CONCLUSIONS: The results of ongoing prospective studies are still awaited. Retrospective data suggest that young male patients with oligometastatic disease and a good performance status can be considered suitable surgical candidates who may benefit from CN.

Impact of photodynamic diagnosis-assisted transurethral resection of bladder tumors on the prognostic outcome after radical cystectomy: results from PROMETRICS 2011.

PURPOSE: Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. METHODS: To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25 months; IQR: 19-30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. RESULTS: In 88 (16.0 %) and 100 (18.2 %) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0 %) patients, a single TURBT was performed prior to RC; in 194 patients (35.3 %), TURBT had been performed in a different center. CSM and OM rates at 3 years were 32 and 40 %, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. CONCLUSIONS: PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

[Do General Surgeons Feel Adequately Prepared for the Complex Questions Associated with the Handling of Multi-Resistant Pathogens? - Results of the MR2 Survey]. / Fühlen sich Chirurgen gerüstet für die komplexen Fragestellungen im Umgang mit multiresistenten Erregern? ­ Ergebnisse der Fragebogenstudie MR2.

Background At the present time, there is no evidence available as to the knowledge of general surgeons regarding multi-resistant pathogens (MRP) and the rational use of antibiotic medication (antibiotic stewardship/ABS) compared with physicians from other disciplines. Methods As part of the MR2 survey (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria - a survey focussing on German hospitals), a questionnaire comprising 4 + 35 items was distributed to urologists, internists, gynaecologists and general surgeons in 18 hospitals. Multivariate regression models were applied to assess the impact of each discipline affiliation on predefined endpoints. Results 456 evaluable surveys were analysed. The response rate of surgeons (156/330; 47%) and physicians from other disciplines (300/731; 41%) did not differ significantly. Based on their self-assessment, surgeons indicated a significantly lower certainty regarding the correct choice of dose, frequency and duration of antibiotic treatment (p = 0.005), the decision between intravenous or oral application (p = 0.005), as well as the accurate interpretation of microbiological reports (p = 0.023). Both surgeons and doctors from other disciplines rated their knowledge of ABS as limited. An insignificant difference was found between surgeons and non-surgeons regarding the knowledge of E. coli resistance against Ciprofloxacin in their own hospital (27.6 vs. 35.3% estimated the correct category; p = 0.114), with 64% of surgeons underestimating the local resistance rates. Both physician groups assumed that the frequent use of broad-spectrum antibiotics is substantially responsible for the increase in MRP. However, in the given case study of a highly symptomatic female patient with uncomplicated urinary tract infection, both physician groups were almost equally likely to propose treatment with a broad-spectrum antibiotic (34.0 vs. 29.3%; p = 0.331). Based on the results of the multivariate models, there were no significant differences between surgeons and non-surgeons with regard to both the attendance of training courses related to MRP/ABS over the past 12 months and the quality of discharge summaries in their hospitals regarding the correct listing of MRP. Conclusion In due consideration of the results of the MR2 survey, mandatory ABS programs should be implemented in hospitals, including regular training of physicians regardless of their discipline.