Clinical Implementation of a Noninvasive, Multi-Analyte Droplet Digital PCR Test to Screen for Androgen Receptor Alterations.

Alterations of the androgen receptor (AR) are associated with resistance to AR-directed therapy in prostate cancer. Thus, it is crucial to develop robust detection methods for AR alterations as predictive biomarkers to enable applicability in clinical practice. We designed and validated five multiplex droplet digital PCR assays for reliable detection of 12 AR targets including AR amplification, AR splice variant 7, and 10 AR hotspot mutations, as well as AR and KLK3 gene expression from plasma-derived cell-free DNA and cell-free RNA. The assays demonstrated excellent analytical sensitivity and specificity ranging from 95% to 100% (95% CI, 75% to 100%). Intrarun and interrun variation analyses revealed a high level of repeatability and reproducibility. The developed assays were applied further in peripheral blood samples from 77 patients with advanced prostate cancer to assess their feasibility in a real-world scenario. Optimizing the reverse transcription of RNA increased the yield of plasma-derived cell-free RNA by 30-fold. Among 23 patients with castration-resistant prostate cancer, 6 patients (26.1%) had one or a combination of several AR alterations, whereas only 2 of 54 patients (3.7%) in the hormone-sensitive stage showed AR alterations. These findings were consistent with other studies and suggest that implementation of comprehensive AR status detection in clinical practice is feasible and can support the treatment decision-making process.

The Impact of Gender on Tumour Stage in In-House Complications and Choice of Urinary Diversion: Results of the Austrian Cystectomy Registry.

INTRODUCTION AND OBJECTIVES: Bladder cancer is characterized by gender-dependent disparities. To further address this issue, we analysed a prospective, multicentre cystectomy registry. METHODS: An online database was developed that included patient demographics, intra/perioperative data, surgical data and in-house complications. RESULTS: Four hundred fifty-eight patients (112 [24.5%] women and 346 [75.5%] men) were analysed. Men and women were comparable regarding age (mean 68 years), body mass index (mean 26.5) and the mean Charlson score (4.8). Women had more advanced tumour-stages (pT3/pT4; women: 57.1%; men: 48.1%). The rate of incontinent urinary diversion was higher in women (83.1%) than in men (60.2%) and in a multivariate analysis, the strongest predictors were M+ status (OR 11.2), female gender (OR 6.9) and age (OR 6.5). Women had a higher intraoperative blood transfusion rate. The overall rate of in-house complications was similar in both genders (men: 32.0%, women: 32.6%). Severe (Clavien-Dindo grade >2) medical (women: 6.3%; men: 5.2%) and surgical (women: 21.5%; men: 14.4%) in-house complications, however, were more frequent in women. CONCLUSIONS: This multicentre registry demonstrates several gender-related differences in patients undergoing radical cystectomy. The higher transfusion rate, the rare use of orthotopic bladder substitutes and the higher in-house complication rate underline the higher complexity of this procedure in women.

Impact of the use of bowel for urinary diversion on perioperative complications and 90-day mortality in patients aged 75 years or older.

OBJECTIVE: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥ 75 years. PATIENTS AND METHODS: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥ 75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.

Perioperative complications and 90-day mortality of radical cystectomy in the elderly (75+): a retrospective, multicentre study.

OBJECTIVE: To assess perioperative complications and 90-day mortality of radical cystectomy (RC) in elderly patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This is a retrospective, multicentre (n = 11) study of a consecutive series of patients ≥75 years who underwent RC for MIBC between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients with a mean age of 79.6 years (range 75.0-86.6) were analysed. Urinary diversion with the use of bowel was performed in 79.5% and ureterocutaneostomy in 20.5%, with a higher proportion in the ≥80 cohort (32.2 vs. 14%; p = 0.001). 41.4% of patients had an uneventful postoperative course (Clavien grade 0) and 26.6% developed severe complications (Clavien grade III-V). In a multivariable regression analysis, the Charlson comorbidity index (odds ratio 1.5 per unit increase; p < 0.001) and the body mass index (odds ratio 1.13 per kg/m(2) increase; p = 0.015) were predictors for the development of complications. The 90-day mortality rate was 9% and the independent correlates thereof were the development of severe medical complications (p = 0.004), the American Society of Anesthesiologists (ASA) score (p = 0.03) and age (p = 0.005). CONCLUSIONS: Morbidity and 90-day mortality of RC in the elderly remain substantial. The interrelation between comorbidity, complication rate and 90-day mortality underlines the need for a comprehensive geriatric assessment of elderly patients with MIBC in whom RC is indicated.

Results and outcomes after endoscopic treatment of upper urinary tract carcinoma: the Austrian experience.

INTRODUCTION: Through evolution in technology, endoscopic treatment has gained popularity for the treatment of upper tract urothelial carcinoma (ENDO-UTUC). METHODS: A total of 20 patients with ENDO-UTUC were compared to 178 treated by radical nephroureterectomy (RNU) for a pTa-1 UTUC, and a systematic review was performed. RESULTS: Mean age for ENDO-UTUC was 71.9 ± 16.0 years, and tumor features were favorable (90 % papillary, 14 low grade, 11 pTa). All ENDO-UTUC were performed ureteroscopically. Mean follow-up was 20.4 ± 30 months. The 5-year overall survival (OS) rate was 45 %. Local (LR) and bladder recurrence (BR) was 25 and 15 %. Time to definitive treatment was longer, ASA higher, LR rates higher, OS lower for ENDO-UTUC (all p < 0.001), but no difference was recorded for BR (p = 0.056) and cancer-specific survival (CSS) (p = 0.364). Postoperative kidney function (KF) was better in the ENDO-UTUC (p = 0.048), though preoperative KF showed no difference. The maximal level of evidence was 3b, patients were highly selected, numbers of patients were low, and ASA scores high. OS was rather low and CSS high. LR rate was high (61 %) and BR rate moderate (39 %) for ureteroscopic and 36 and 28 %, respectively, for percutaneous approach. CONCLUSIONS: LR for ENDO-UTUC is high. In high-grade UTUC, oncological outcome is worse. RNU is associated with a significant loss of KF, but LR is rare. ENDO-UTUC is reserved for selected cases if elective. In imperative cases, it has to be balanced between KF, morbidity of the procedure, risk of operation and tumor control. ENDO-UTUC is not necessarily underused in Austria, because of lack in evidence, but 41 % of all RNU were performed in pTa/pTis/pT1 lesions.

Evolution of endoscopic extraperitoneal radical prostatectomy (EERPE)--technical improvements and development of a nerve-sparing, potency-preserving approach.

During the last decade, laparoscopy has become a standard technique in the armoury of the urologist due to constant technological advances and refinements. Laparoscopic radical prostatectomy (LRPE), although technically demanding and associated with a considerable learning curve, has become the surgical procedure of choice in selected and specialized urological centers around the globe for patients with clinically localized prostate cancer. However, a major drawback of LRPE is the transperitoneal route of access to the extraperitoneal prostate. The principal disadvantages of LRPE are potential intraperitoneal complications, such as bowel injury, ileus, intraperitoneal bleeding, intraperitoneal urinary leakage, intraperitoneal adhesion formation and concomitant small bowel obstruction. Endoscopic extraperitoneal radical prostatectomy (EERPE) is a further advancement of minimal invasive surgery as it overcomes the limitations of LRPE by the strictly extraperitoneal route of access combining the advantages of minimal invasive surgery with those of an extraperitoneal procedure. Based on our growing experience with this procedure, we have introduced several technical modifications, improvements and refinements including a nerve-sparing, potency-preserving approach (nEERPE) in an effort to further improve this minimally invasive procedure.