Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

OBJECTIVES: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). PATIENTS AND METHODS: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. RESULTS: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. CONCLUSIONS: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

Cyclin A2 Expression as Predictive Biomarker in Muscle-Invasive Upper Tract Urothelial Carcinoma.

INTRODUCTION: The aim was to evaluate the prognostic value of altered Cyclin A2 (CCNA2) gene expression in upper tract urothelial carcinoma (UTUC) and to assess its predictive potential as a prognostic factor for overall survival (OS) and disease-free survival. METHODS: 62 patients who underwent surgical treatment for UTUC were included. Gene expression of CCNA2, MKI67, and p53 was analyzed by quantitative reverse transcriptase polymerase chain reaction. Survival analyses were performed using the Kaplan-Meier method and the log-rank test. For Cox regression analyses, uni- and multivariable hazard ratios were calculated. Spearman correlation was used to analyze correlation of CCNA2 expression with MKI67 and p53. RESULTS: The median age of the cohort was 73 years, and it consisted of 48 males (77.4%) and 14 females (22.6%). Patients with high CCNA2 expression levels showed longer OS (HR 0.33; 95% CI: 0.15-0.74; p = 0.0073). Multivariable Cox regression analyses identified CCNA2 overexpression (HR 0.37; 95% CI: 0.16-0.85; p = 0.0189) and grading G2 (vs. G3) (HR 0.39; 95% CI: 0.17-0.87; p = 0.0168) to be independent predictors for longer OS. CCNA2 expression correlated positively with MKI67 expression (Rho = 0.4376, p = 0.0005). CONCLUSION: Low CCNA2 expression is significantly associated with worse OS. Thus, CCNA2 might serve as a potential biomarker in muscle-invasive UTUC and may be used to characterize a subset of patients having an unfavorable outcome and for future risk assessment scores.

[Incidence, therapy, and prognosis of prostate cancer in Baden-Württemberg: analysis based on cancer registry data]. / Inzidenz, Behandlung und Prognose des Prostatakarzinoms in Baden-Württemberg: Analyse anhand von Krebsregisterdaten.

BACKGROUND: Prostate cancer (PCa) is the most common solid tumor in men in Germany. Collection of epidemiological and clinical data has been centralized for several years due to legal requirements via the state cancer registries. Thus, the reporting of diagnosis, therapy, and progression of cancer is obligatory in Germany. These data needs to be processed based on the questions of the treating physicians. OBJECTIVES: Intention of this work was to present the development of new cases, disease stages, treatment procedures and prognosis of PCa in Baden-Württemberg (BW). METHODS: For this purpose, data of the cancer registry BW regarding patients with PCa first diagnosed between 2013 and 2021 were evaluated. The evaluation was performed using descriptive statistics, Χ2 test and Kaplan-Meier analysis. RESULTS: A total of 84,347 new diagnoses of PCa were reported. Clinical stage was present in 55.3% of patients. Assignment by International Society of Urological Pathology (ISUP) groups was present in 75.7%. A steady increase in primary diagnosis was evident through 2019. The proportion of primary metastatic disease decreased (2013: 19.6% vs. 2021: 12.0%), and the proportion of localized tumors increased (2013: 65.5% vs. 2021: 77.1%). Radical prostatectomy (RP) dominated the treatment of localized tumors with a mean of 60.1%. The proportion of robot-assisted surgery increased from 23.7% (2013) to 60.8% (2021) with a decrease in the R1 rate from 34.8 to 26.2%. Progression-free survival correlated closely with tumor stage and ISUP group. CONCLUSION: An increase in PCa cases and a decrease of advanced tumors were observed. Treatment was mostly surgical in localized stages, with increasing proportion of robotic-assisted RP. Early diagnosis and treatment are critical for long-term prognosis.

Prognostic significance of EGFR, AREG and EREG amplification and gene expression in muscle invasive bladder cancer.

Introduction: Muscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor (EGFR) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma. Materials and methods: We investigated the prognostic significance of EGFR, AREG, and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range [IQR] 64-78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60-77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models. Results: Significant gene expression differences in EGFR, AREG, and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 - 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR, AREG, and EREG expression correlated with shorter OS (AREG: HR = 1.57, CI 1.12 - 2.20, p = 0.0090) and DFS (EGFR: HR = 1.91, CI 1.31 - 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS. Discussion: High EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study.

Comorbidity Scores and Machine Learning Methods Can Improve Risk Assessment in Radical Cystectomy for Bladder Cancer.

BACKGROUND: Pre-operative risk assessment in radical cystectomy (RC) is an ongoing challenge especially in elderly patients. OBJECTIVE: To evaluate the ability of comorbidity indices and their combination with clinical parameters in machine learning models to predict mortality and morbidity after RC. METHODS: In 392 patients who underwent open RC, complication and mortality rates were reported. The predictive values of the age-adjusted Charlson Comorbidity index (aCCI), the Elixhauser Index (EI), the Physical Status Classification System (ASA) and Gagne's combined comorbidity Index (GCI) were evaluated using regression analyses. Various machine learning models (Gaussian naïve bayes, logistic regression, neural net, decision tree, random forest) were additionally investigated. RESULTS: The aCCI, ASA and GCI showed significant results for the prediction of complications (χ2 = 8.8, p < 0.01, χ2 = 15.7, p < 0.01 and χ2 = 4.6, p = 0.03) and mortality (χ2 = 21.1, p < 0.01, χ2 = 25.8, p < 0.01 and χ2 = 2.4, p = 0.04) after RC while the EI showed no significant prediction. However, areas under receiver characteristic curves (AUROCs) revealed good performance only for the prediction of mortality by the aCCI and ASA (0.81 and 0.78, CGI 0.63) while the prediction of complications was poor (aCCI 0.6, ASA 0.63, CGI 0.58). The combination of ASA, age, body mass index and sex in machine learning models showed a better prediction. Gaussian naïve bayes (0.79) and logistic regression (0.76) showed the best performance using a hold-out test set. CONCLUSIONS: The ASA and aCCI show good prediction of mortality after RC but fail predicting complications accurately. Here, the combination of comorbidity indices and clinical parameters in machine learning models seems promising.