Prognostic Value of TERT Alterations, Mutational and Copy Number Alterations Burden in Urothelial Carcinoma.

Point mutations in the TERT gene promoter occur at high frequency in multiple cancers, including urothelial carcinoma (UC). However, the relationship between TERT promoter mutations and UC patient outcomes is unclear due to conflicting reports in the literature. In this study, we examined the association of TERT alterations, tumor mutational burden per megabase (Mb), and copy number alteration (CNA) burden with clinical parameters and their prognostic value in a cohort of 398 urothelial tumors. The majority of TERT mutations were located at two promoter region hotspots (chromosome 5, 1 295 228 C>T and 1 295 250 C>T). TERT alterations were more frequently present in bladder tumors than in upper tract tumors (73% vs 53%; p=0.001). ARID1A, PIK3CA, RB1, ERCC2, ERBB2, TSC1, CDKN1A, CDKN2A, CDKN2B, and PTPRD alterations showed significant co-occurrence with TERT alterations (all p<0.0025). TERT alterations and the mutational burden/Mb were independently associated with overall survival (hazard ratio[HR] 2.31, 95% confidence interval [CI] 1.46-3.65; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), disease-specific survival (HR 2.23, 95% CI 1.41-3.53; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), and metastasis-free survival (HR 1.63, 95% CI 1.05-2.53; p=0.029; and HR 0.98, 95% CI 0.96-1.00; p=0.063) in multivariate models. PATIENT SUMMARY: The majority of TERT gene mutations that we detected in urothelial carcinoma are located at two promoter hotspots. Urothelial tumors with TERT alterations had worse prognosis compared to tumors without TERT alterations, whereas tumors with a higher mutational burden had more favorable outcome compared to tumors with low mutational burden.

Development and validation of surgical training tool: cystectomy assessment and surgical evaluation (CASE) for robot-assisted radical cystectomy for men.

BACKGROUND: We aimed to develop a structured scoring tool: cystectomy assessment and surgical evaluation (CASE) that objectively measures and quantifies performance during robot-assisted radical cystectomy (RARC) for men. METHODS: A multinational 10-surgeon expert panel collaborated towards development and validation of CASE. The critical steps of RARC in men were deconstructed into nine key domains, each assessed by five anchors. Content validation was done utilizing the Delphi methodology. Each anchor was assessed in terms of context, score concordance, and clarity. The content validity index (CVI) was calculated for each aspect. A CVI ≥ 0.75 represented consensus, and this statement was removed from the next round. This process was repeated until consensus was achieved for all statements. CASE was used to assess de-identified videos of RARC to determine reliability and construct validity. Linearly weighted percent agreement was used to assess inter-rater reliability (IRR). A logit model for odds ratio (OR) was used to assess construct validation. RESULTS: The expert panel reached consensus on CASE after four rounds. The final eight domains of the CASE included: pelvic lymph node dissection, development of the peri-ureteral space, lateral pelvic space, anterior rectal space, control of the vascular pedicle, anterior vesical space, control of the dorsal venous complex, and apical dissection. IRR > 0.6 was achieved for all eight domains. Experts outperformed trainees across all domains. CONCLUSION: We developed and validated a reliable structured, procedure-specific tool for objective evaluation of surgical performance during RARC. CASE may help differentiate novice from expert performances.

Idiographic quality of life assessment before radical cystectomy.

BACKGROUND: We sought to determine if idiographic, or self-defined, measures added to our understanding of patients with bladder cancer's quality of life (QOL) prior to radical cystectomy (RC). We tested whether idiographic measures increased prediction of global QOL beyond standard (nomothetic) measures of QOL components. METHODS: We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (QLQ)-C30 and QLQ-BLM30, and our own idiographic Quality of Life Appraisal Profile prior to RC. Idiographic measures included number of goal statements, distance from goal attainment, and ability to complete goal attainment activities. Multivariate linear regression was used to predict measures of global QOL and related constructs of life satisfaction and mental health. RESULTS: Two hundred fiftheen patients reported a median of 8 (interquartile range [IQR] 6, 11) goals and half had an average goal attainment rating above 6.9 out of 10 (IQR 5.5, 8.2). On multivariable analysis, QLQ-C30 role functioning and QLQ-BLM30 future perspective explained 15.7% of the variability in preoperative global QOL. Including goal attainment and activity difficulty explained an additional 12% of global QOL variance. Smaller gains were seen on measures of global health, life satisfaction, mental health, and activity, suggesting that idiographic measures capture aspects of QOL distinct from health and functional status defined by nomothetic scales. CONCLUSIONS: Idiographic assessment of QOL added to prediction of global QOL above and beyond health-related components measured using nomothetic instruments. This self-defined information may be valuable in communicating with cancer patients about their QOL. Copyright © 2015 John Wiley & Sons, Ltd.

Cost comparison of open and robotic partial nephrectomy using a short postoperative pathway.

OBJECTIVE: To compare immediate perioperative direct costs of open partial nephrectomy (OPN) and robotic partial nephrectomy (RPN), managed under a common care pathway. METHODS: Retrospective review of detailed institutional cost data for patients treated with OPN and RPN during 2011 was conducted. Cost and clinical data of OPN and RPN were compared for all patients and for patients stratified by length of stay (LOS), American Society of Anesthesiologists (ASA), and RENAL nephrometry scores. RESULTS: The study cohort included 190 OPN and 63 RPN cases. OPN was associated with higher ASA scores (P <.001), shorter operative times (P = .014), and higher estimated blood loss (P <.001). Median (interquartile range) LOS was 2 days (2-3 days) for OPN compared with 1 day (1-2 days) for RPN (P <.001). Median perioperative cost of OPN was lower than that of RPN with a difference of $3091 (P <.001). Although hospitalization costs were higher in OPN, surgical costs were higher in RPN ($854 and $3695 difference in median costs, respectively; P <.001 for both). The total cost of OPN for patients with an above-average LOS remained lower than that of RPN ($2680 difference in median costs; P = .001). RPN costs remained significantly higher when stratifying patients by their ASA and RENAL nephrometry scores. CONCLUSION: Despite the shorter hospital LOS associated with RPN, the immediate perioperative cost of OPN was lower than that of RPN for patients managed under a common care pathway, mainly due to high robotic purchase and maintenance costs. In light of the current health care debate, such financial disincentives may compromise the sustainability of advances in medical technology.

Adherence to surveillance guidelines after radical cystectomy: a population-based analysis.

OBJECTIVES: Surveillance after radical cystectomy is recommended to detect tumor recurrence and treatment complications. We evaluated adherence to National Comprehensive Cancer Network (NCCN) guidelines using a large population-based database. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify patients aged ≥66 years diagnosed with nonmetastatic bladder cancer who had undergone radical cystectomy between 2000 and 2007. Medicare claims information identified recommended surveillance tests for 2 years after cystectomy as outlined in the NCCN guidelines. Adherence was defined as receipt of urine cytology and imaging of the chest, abdomen, and pelvis in each year. We evaluated the effect of patient and provider characteristics on adherence, controlling for demographic and disease characteristics. RESULTS: Of 3,757 patients who had undergone radical cystectomy, 2,990 (80%) were alive after 2 years. Adherence to all recommended investigations was 17% for the first and the second years following surgery. Among patients surviving 2 years, only 9% had complete surveillance in both years. In either year, adherence was less likely in patients with advanced pathologic stage (III/IV) (adjusted odds ratio [AOR] = 0.74, 95% CI: 0.60-0.91) and unmarried patients (AOR = 0.82, 95% CI: 0.68-0.99). Adherence was more likely in patients treated by high-volume surgeons (AOR = 2.00, 95% CI: 1.70-2.36) and those who saw a medical oncologist (AOR = 1.52, 95% CI: 1.27-1.82). We also observed significant geographic variability in adherence. CONCLUSION: Patterns of surveillance after radical cystectomy deviate considerably from NCCN recommendations. Despite increased utilization of radiographic imaging investigations, the omission of urine cytology significantly contributed to the low rate of overall adherence to surveillance guidelines. Uniform adherence to surveillance guidelines was observed in patients treated by high-volume surgeons. This suggests an important opportunity for quality improvement in bladder cancer care.

Clinical benefits of a multivariate prediction model for bladder cancer: a decision analytic approach.

BACKGROUND: It has been demonstrated that multivariate prediction models predict cancer outcomes more accurately than cancer stage; however, the effects of these models on clinical management are unclear. The objective of the current study was to determine whether a previously published multivariate prediction model for bladder cancer ("bladder nomogram") improved medical decision making when referral for adjuvant chemotherapy was used as a model. METHODS: Data were analyzed from an international cohort study of 4462 patients who underwent cystectomy without chemotherapy from 1969 to 2004. The number of patients eligible for chemotherapy was determined using pathologic stage criteria (lymph node-positive disease or pathologic T3 [pT3] or pT4 tumor classification) and for 3 cutoff levels on the bladder nomogram (10%, 25%, and 70% risk of recurrence with surgery alone). The number of recurrences was calculated by applying a relative risk reduction to the baseline risk among eligible patients. Clinical net benefit was then calculated by combining recurrences and treatments and weighting the latter by a factor related to drug tolerability. RESULTS: A nomogram cutoff outperformed pathologic stage for chemotherapy in every scenario of drug effectiveness and tolerability. For a drug with a relative risk of 0.80, with which clinicians would treat

Risk assessment of prostatic pathology in patients undergoing radical cystoprostatectomy.

OBJECTIVES: To determine the incidence and location of prostate adenocarcinoma (PCa) and prostatic urothelial carcinoma (PUC) for patients undergoing radical cystoprostatectomy (RCP) for bladder cancer and to ascertain what preoperative information may be useful in predicting PUC or PCa in patients who may be candidates for prostate-sparing cystectomy. METHODS: Between 2001 and 2004, 235 consecutive patients underwent RCP and had whole-mount sections of the prostate. We reviewed our prospective radical cystectomy database for preoperative clinicopathological information associated with each patient. The bladder and whole-mount prostate sections were re-reviewed to determine the location and depth of the bladder tumor as well as the presence of any associated PCa and PUC. RESULTS: We identified 113 of 235 (48%) and 77 of 235 (33%) men with PCa and PUC, respectively. Among patients with PCa, 33 (29%) had Gleason score of > or = 7, 25 (22%) had PCa tumor volume > 0.5 cc, and 15 (13%) had extracapsular extension. On multivariable analysis, only increasing age was significantly associated with PCa (odds ratio=1.3, p=0.046). Of the 77 with PUC, 28 (36%) had in situ disease only, while 49 (64%) had prostatic stromal invasion. Bladder tumor location in the trigone/bladder neck (p<0.001) and bladder carcinoma in situ (p<0.001) was strongly associated with PUC in the final specimen. Overall, 158 (67%) had either PCa or PUC in the prostate. CONCLUSIONS: PCa and/or PUC is present in a majority of RCP specimens. Current preoperative staging and tumor characteristics are not adequate for determining who can safely be selected for prostate-sparing cystectomy.