The diagnostic accuracy of urine-based tests for bladder cancer varies greatly by patient

BACKGROUND: Spectrum effects refer to the phenomenon that test performance varies across subgroups of a population. When spectrum effects occur during diagnostic testing for cancer, difficult patient misdiagnoses can occur. Our objective was to evaluate the effect of test indication, age, gender, race, and smoking status on the performance characteristics of two commonly used diagnostic tests for bladder cancer, urine cytology and fluorescence in situ hybridization (FISH). METHODS: We assessed all subjects who underwent cystoscopy, cytology, and FISH at our institution from 2003 to 2012. The standard diagnostic test performance metrics were calculated using marginal models to account for clustered/repeated measures within subjects. We calculated test performance for the overall cohort by test indication as well as by key patient variables: age, gender, race, and smoking status. RESULTS: A total of 4023 cystoscopy-cytology pairs and 1696 FISH-cystoscopy pairs were included in the analysis. In both FISH and cytology, increasing age, male gender, and history of smoking were associated with increased sensitivity and decreased specificity. FISH performance was most impacted by age, with an increase in sensitivity from 17 % at age 40 to 49 % at age 80. The same was true of cytology, with an increase in sensitivity from 50 % at age 40 to 67 % at age 80. Sensitivity of FISH was higher for a previous diagnosis of bladder cancer (46 %) than for hematuria (26 %). Test indication had no impact on the performance of cytology and race had no significant impact on the performance of either test. CONCLUSIONS: The diagnostic performance of urine cytology and FISH vary significantly according to the patient demographic in which they were tested. Hence, the reporting of spectrum effects in diagnostic tests should become part of standard practice. Patient-related factors must contextualize the clinicians’ interpretation of test results and their decision-making

Your opinion counts: How do you treat atypical/suspicious cytology?

463 Background: Urine cytology has often been reported as a highly specific but poorly sensitive test. Cytology is reported as positive, negative, atypical, or suspicious. Atypical/suspicious cytologies account for roughly a quarter of the results and present a clinical dilemma. Physicians’ risk aversion means they are typically treated as positive and result in clinical action. We test the effects of this assumption on sensitivity and specificity. Methods: After IRB approval, we queried clinical and pathology databases to identify all subjects at Duke University Medical Center who had undergone both a urine cytology and a cystoscopy from 1/2003 to 1/2012. Diagnostic test performance metrics were calculated using logistic models: (a) a generalized estimating equation (GEE) and (b) a generalized linear mixed model (GLMM). These take into account clustered/correlated test results that occur due to repeated testing within subjects. Results: A total of 990 unique subjects were identified that provided 4,733 pairs of cytology and cystoscopy for analysis. Our cohort was 61% male, 75% Caucasian, and had 54% current or former smokers. Of cytologies, 1898 (40%) were negative, 423 (9%) positive, and 2408 (51%) suspicious or atypical. When suspicious/atypical cytology results using the GLMM model were classified as positive, the specificity was 62% [95%CI: 58-66%] and the sensitivity was 41% [95% CI: 38-44%]. When these results were re-classified as negative, this had the effect of a large increase in specificity 100% [95%CI: 100-100%] with a consequent decrease in sensitivity 0% [95%CI: 0-2%]. Conclusions: In our study, the performance of urine cytology depended heavily on how the equivocal (atypical/suspicious) results were classified and dealt with. Our sensitivity was maximized when equivocal cytologies were considered positive, but at significant detriment of the specificity. Contrarily, our specificity improved greatly when the equivocal results were considered negative, but at the expense of a poor sensitivity. Furthermore, the diagnosis of an atypical/suspicious cytology was higher at our medical center than reported in the literature, and therefore significantly overestimated the performance of the urine cytology test. </jats:p

Effect of diet on bladder cancer survivors.

437 Background: Diet has been shown to affect cancer recurrence, progression, and overall survival. A reduction in overall mortality is associated with high intake of vegetables and whole grains, but little is known about the role of other macronutrients. Further, the role of macronutrients in bladder cancer survivors as they move beyond the treatment period is unknown. Methods: After IRB approval, an institutional database was used to identify a large cohort of bladder cancer patients. They were mailed a survey that included the Diet History Questionnaire II (DHQ II). This validated instrument is recommended by the American Cancer Society and National Cancer Institute. It involves 151 questions covering portion size over 134 food items and 8 supplements, and takes a patient roughly an hour to complete. Our cross-sectional survey used the results from the DHQ II to assess compliance with the US Dietary Guidelines for Americans. Results: Out of 962 subjects, 461 completed the survey (48%). Mean age was 73, 80% were male, and 87% were white. The recommended protein intake was met or exceeded 98% of respondents and 66.8% were able to meet the fruit and vegetable recommendations. Similarly, 62.9% met carbohydrate recommendations. Unfortunately, only 44.5% met fat recommendations, and 0.9% met the whole grain recommendations. Recommended sodium intake was exceeded by 62% of subjects. Conclusions: Bladder cancer survivors exhibit poor adherence to standard dietary recommendations, but they represent a unique metabolic state. It is unknown what constitutes a healthy diet in a bladder cancer survivor, but a healthy diet has potential to be a component of survivorship intervention and not merely sustenance. Cancer survivors are an important target population for health promotion efforts and we plan further investigation of diet and its impact on quality of life amongst other lifestyle factors. </jats:p

Associations between health-related quality of life and physical activity in bladder cancer survivors: A cross-sectional study.

432 Background: Physical activity has been shown to significantly improve health-related quality of life (HRQOL) and survivorship in a variety of cancer patients. However, little is known about the physical activity patterns of bladder cancer survivors and how these are related to HRQOL in the United States. Our objective was to describe HRQOL and self-reported physical activity patterns and examine the association between these measures in a large cohort of bladder cancer survivors. Methods: Bladder cancer survivors identified through an institutional database were mailed a survey that included the Functional Assessment of Cancer Therapy Bladder Cancer (FACT-Bl) and the International Physical Activity Questionnaire (IPAQ-L). Results: A total of 466 subjects (49% response rate) completed the survey. The mean age was 73 years, 80% were male, and 88% were White. Linear regression indicated a positive correlation between physical activity and physical well being (PWB, P &lt; 0.001), emotional well being (EWB, P &lt; 0.001), and functional well being (FWB, P &lt; 0.001) subscales, as well as the FACT-Bl (P &lt; 0.001), FACT general (P &lt; 0.001), and trial outcome index (TOI, P &lt; 0.001) composite scores. Conversely, total daily sitting time was negatively correlated with all of the aforementioned indices. Adjusting for demographic factors did not alter the findings. Conclusions: Physical activity is positively associated with HRQOL in bladder cancer survivors. Further studies investigating the causal relationship between physical activity and HRQOL in the post-treatment setting in bladder cancer survivors are warranted. </jats:p

Reporting Bias Leading to Discordant Venous Thromboembolism Rates in the United States Versus Non-US Countries Following Radical Cystectomy: A Systematic Review and Meta-analysis

CONTEXT: Postcystectomy bladder cancer (BCa) patients are at high risk for developing venous thromboembolism (VTE). The literature varies widely in the reporting of VTE in this population. OBJECTIVE: To determine the VTE rate in subjects undergoing radical cystectomy (RC) and highlight specific factors affecting this rate. EVIDENCE ACQUISITION: This meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database, registration number: CRD42015016776. We queried MEDLINE, the Cochrane Library, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Search terms captured BCa, RC, and VTE. Per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, abstracts were reviewed for inclusion/exclusion criteria by two reviewers, and disagreements were resolved by a third reviewer. A search of the gray literature and references of pertinent articles was also performed. The date of our last search was December 15, 2014. For unreported data, authors were contacted. Data were abstracted in duplicate and pooled using a random effects (RE) model. Subgroup analyses and meta-regression were performed to determine risk factors for VTE. EVIDENCE SYNTHESIS: We identified 2927 publications, of which 223 met inclusion criteria for this review. A total of 1 115 634 surgeries were performed on patient population (80% men) with a total of 51 908 VTEs. The VTE rate estimated by the RE model was 3.7%. Due to significant heterogeneity, subgroup and meta-regression analyses were undertaken. These revealed a higher rate of VTE in US studies at 4.49% compared with “westernized” non-US studies at 3.43% and “nonwesternized” non-US based studies at 2.50%. Other important modifiers included minimally invasive surgery at 5.54% versus open surgery at 3.55%, and age. The case-fatality rate of pulmonary emboli was 44%. CONCLUSIONS: VTE is common in patients undergoing RC. Reporting of VTE is heterogeneous and the rate varies according to study-level factors, including surgery type and country of origin. Limitations of this study include the preponderance of observational studies in the final analysis and lack of complete reporting of all variables of interest within each study. PATIENT SUMMARY: In this review, we determined the venous thromboembolism (VTE) rate in postsurgical bladder cancer patients. VTE events did vary significantly among certain subgroups