Endovascular aneurysm sealing as an alternative for the treatment of failed endovascular aneurysm repair.

OBJECTIVE: The Nellix EndoVascular Aneurysm Sealing (EVAS) system has offered a novel approach in the treatment of abdominal aortic aneurysm (AAA). While it is currently indicated as a primary procedure in patients with infrarenal AAA with suitable anatomy according to the indications for use, a few studies aimed to address its potential interest in failed endovascular aneurysm repair (EVAR). The aim of this systematic review was to analyze the postoperative outcomes of patients with prior EVAR who underwent EVAS. DESIGN OF THE STUDY: A literature search was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines in May 2019 and included patients with prior EVAR who underwent EVAS. The publications had to report at least one of the basic postoperative outcomes (technical success rate, all-cause complications, mortality, length of in-hospital stay, length of stay in intensive care unit, the need of re-intervention). RESULTS: Eleven studies fulfilled the inclusion criteria, for a total of 46 patients. EVAS was used to treat endoleaks in 45 cases (97.8%): 29 type Ia endoleaks (63%), 6 type IIIa endoleaks (13%), and 10 type IIIb endoleaks (21.7%). Standard EVAS procedure was performed in 21 patients (45.7%), and 25 patients (54.3%) had chimney-EVAS. The technical success was achieved in all the studies. Two patients (4.9%) died during the 30-day postoperative period, but no aneurysm-related mortality was reported. The presence of endoleaks was reported in five patients (9.8%) during the follow-up. CONCLUSION: The results suggest the safety and the efficiency of EVAS in the treatment of complications following EVAR including type Ia, type IIIa, and type IIIb endoleaks. Further studies on larger cohorts and longer follow-up periods are required to confirm the interest of EVAS in the endovascular management of failed EVAR.

Role of survivin expression in predicting biochemical recurrence after radical prostatectomy: a multi-institutional study.

OBJECTIVE: To assess the association of survivin expression with clinicopathological features and biochemical recurrence (BCR) after radical prostatectomy (RP) in a large multi-institutional cohort. METHODS: Survivin expression was evaluated by immunohistochemistry on a tissue microarray of RP cores from 3 117 patients. Survivin expression was considered altered when at least 10% of the tumour cells stained positive. The association of altered survivin expression with BCR was evaluated using Cox proportional hazards regression models. RESULTS: Survivin expression was altered in 1 330 patients (42.6%). Altered expression was associated with higher Gleason score on RP (P = 0.001), extracapsular extension (P = 0.019), seminal vesicle invasion (P < 0.001) and lymph node metastases (P = 0.009). The median (interquartile range) follow-up was 38 (21-66) months. Patients with altered survivin expression had a shorter BCR-free survival time than those with normal expression (5-year BCR-free survival estimates: 74.7 vs 79.0%; P = 0.008). Altered survivin expression did not retain its prognostic value, however, after adjustment for the effect of established clinicopathological factors (P = 0.73). Subgroup analyses also showed no independent prognostic value of survivin. CONCLUSIONS: Survivin expression is commonly altered in patients undergoing RP. Altered survivin expression is associated with the clinicopathological features of biologically and clinically aggressive PCa. Survivin expression was associated with BCR only in univariable analysis, limiting its value in daily clinical decision-making.

Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare and heterogeneous disease. Several clinical and biological prognostic factors have been identified in multi-institutional collaborative works with the aim of helping decision-making in pursuit of tailored individual patient care. This review provides an overview of these existing prognostic factors and predictive tools for the management of patients with UTUC. METHODS: A systematic literature search was performed using PubMed/MEDLINE, Web of Science and Scopus databases regarding articles published in English between January 2000 and November 2015 according to PRISMA guidelines. Thresholds of 100 and 300 patients were applied for studies on biomarkers and clinical studies, respectively. All the studies on predictive tools were included for analysis. Outcomes of interest were features associated with advanced-stage UTUC, disease recurrence and survival. RESULTS: A total of 116 studies were included in this review. These large and/or multi-institutional studies have confirmed the prognostic value of standard pathological factors (i.e., tumor stage, grade and lymph node metastasis) and identified novel features such as lymphovascular invasion, tumor architecture, multifocality, concomitant CIS, variant histology and biomarker status among others. Based on these variables, several predictive tools have been developed; however, they often lack of validation. The value of these features and tools needs prospective testing. CONCLUSION: Efforts provided by international collaboration groups have permitted to validate established features and identify new features of biologically and clinically aggressive UTUC. Further investigation on prognostic factors and biomarkers is still needed to assess the benefit of these features and tools on clinical decision-making.

Promising role of preoperative neutrophil-to-lymphocyte ratio in patients treated with radical nephroureterectomy.

OBJECTIVE: Several retrospective studies with small cohorts reported neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU). We aimed at validating the predictive and prognostic role of NLR in a large multi-institutional cohort. METHODS: Preoperative NLR was assessed in a multi-institutional cohort of 2477 patients with UTUC treated with RNU. Altered NLR was defined by a ratio >2.7. Logistic regression analyses were performed to assess the association between NLR and lymph node metastasis, muscle-invasive and non-organ-confined disease. The association of altered NLR with recurrence-free survival (RFS) and cancer-specific survival (CSS) was evaluated using Cox proportional hazards regression models. RESULTS: Altered NLR was observed in 1428 (62.8 %) patients and associated with more advanced pathological tumor stage, lymph node metastasis, lymphovascular invasion, tumor necrosis and sessile tumor architecture. In a preoperative model that included age, gender, tumor location and architecture, NLR was an independent predictive factor for the presence of lymph node metastasis, muscle-invasive and non-organ-confined disease (p < 0.001). Within a median follow-up of 40 months (IQR 20-76 months), 548 (24.1 %) patients experienced disease recurrence and 453 patients (19.9 %) died from their cancer. Compared to patients with normal NLR, those with altered NLR had worse RFS (0.003) and CSS (p = 0.002). In multivariable analyses that adjusted for the effects of standard clinicopathologic features, altered NLR did not retain an independent value. In the subgroup of patients treated with lymphadenectomy in addition to RNU, NLR was independently associated with CSS (p = 0.03). CONCLUSION: In UTUC, preoperative NLR is associated with adverse clinicopathologic features and independently predicts features of biologically and clinically aggressive UTUC such as lymph node metastasis, muscle-invasive or non-organ-confined status. NLR may help better risk stratify patients with regard to lymphadenectomy and conservative therapy.

Dynamic Prognostication Using Conditional Recurrence and Progression Estimates for Patients with Nonmuscle Invasive Bladder Cancer.

PURPOSE: Conditional estimates provide a dynamic prediction of outcomes but to our knowledge there are no data on nonmuscle invasive bladder cancer. We assessed changes in conditional recurrence and progression rates after transurethral resection of the bladder and explored the prognostic impact of established factors and risk groups with time. MATERIALS AND METHODS: We retrospectively analyzed data on 1,292 consecutive patients with newly diagnosed Ta/T1 bladder cancer who underwent transurethral resection of the bladder. Study end points were time to first recurrence and time to progression. RESULTS: The 2-year recurrence rate at baseline was 36%, which improved as a function of the time that patients were free of disease recurrence. After 6, 12, 24, 36 and 48 months the 2-year conditional recurrence rate improved to 31% (14% improvement vs baseline), 22% (39% improvement), 16% (56% improvement), 13% (64% improvement) and 11% (69% improvement), respectively. Comparably, conditional progression rates improved with increasing followup, although relative differences were less distinct. The prognostic impact of established factors and nonmuscle invasive bladder cancer risk groups progressively decreased with time and finally disappeared. However, bacillus Calmette-Guérin had a protective effect on progression even after 3 years. We provide tables with dynamic prognostic information at all analyzed time points. CONCLUSIONS: In patients with primary Ta/T1 bladder cancer recurrence and progression rates improve with time. The prognostic impact of established factors and risk groups decreases and finally disappears. The effect of bacillus Calmette-Guérin on progression is long-lasting. Conditional outcome estimates may improve patient counseling and individualize surveillance planning.

Prognostic value of Caveolin-1 in patients treated with radical prostatectomy: a multicentric validation study.

OBJECTIVE: To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). PATIENTS AND METHODS: Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. RESULTS: Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum (P = 0.002) and lymph node metastases (P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). CONCLUSIONS: We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice.

Impact of smoking status on survival after cytoreductive nephrectomy for metastatic renal cell carcinoma.

OBJECTIVE: To assess the association of smoking status with standard clinicopathological features and overall survival (OS) in a large multi-institutional cohort of patients with metastatic renal cell carcinoma (mRCC) treated with cytoreductive nephrectomy (CNT). METHODS: A total of 613 patients with mRCC treated with CNT in US and Europe institutions between 1990 and 2013 were included. Smoking history comprised smoking status, smoking duration in years, number of cigarettes per day and years since smoking cessation. Cumulative smoking exposure was categorized as light short term, heavy long term and moderate. Association between smoking history and OS was assessed by Cox regression logistic analysis. RESULTS: One hundred and seventy-one patients (27.9 %) never smoked, 193 (31.5 %) were former smokers and 249 (40.6 %) were current smokers. Smoking status was associated with a higher number of metastases (p < 0.001) and an abnormal preoperative corrected calcium level (p = 0.01). Median follow-up was 16 (IQR 7-24) months. Current smokers had a shorter OS than never and former smokers (log rank, p = 0.004). Smoking status was significantly associated with OS in univariable analysis (HR 1.45; 95 % CI 1.16-1.82; p < 0.001), and in multivariable analysis that adjusted for established prognostic factors (HR 1.46; 95 % CI 1.16-1.84; p = 0.002). Daily consumption of more than 20 cigarettes, more than 20 years of smoking exposure and heavy long exposure were all independent prognosticators of worse OS. CONCLUSIONS: Current smoking and a higher cumulative smoking exposure are associated with a higher risk of death in patients with mRCC treated with CNT. Even at this stage, smoking negatively affects kidney cancer outcomes.

Prognostic role of ERCC1 protein expression in upper tract urothelial carcinoma following radical nephroureterectomy with curative intent.

BACKGROUND: Excision repair cross-complementing 1 (ERCC1) has been associated with outcomes of urothelial carcinoma of the bladder, but was not yet studied in upper tract urothelial carcinoma (UTUC). The aim of this study was to assess the prognostic role of ERCC1 expression in a large international cohort of UTUC patients. METHODS: Immunohistochemical ERCC1 expression was evaluated in 716 UTUC patients who underwent radical nephroureterectomy with curative intent. ERCC1 was considered positive when the H-score was >1.0. Associations with overall survival and cancer-specific survival were assessed using univariable and multivariable Cox models. RESULTS: ERCC1 was expressed in 303 tumors (42.3 %) and linked with the presence of tumor necrosis (16.2 vs. 10.4 %, p = 0.023), but not with any other clinical or pathological variable. ERCC1 status did not predict cancer-specific survival and overall survival on both univariable (p = 0.70 and 0.32, respectively) and multivariable analyses (p = 0.48 and 0.33, respectively). CONCLUSIONS: ERCC1 is expressed in a significant proportion of UTUC and is linked with tumor necrosis, but its expression appears not to be associated with prognosis following radical nephroureterectomy.

A rare case of histopathological bladder necrosis associated with Actinobaculum schaalii: the incremental value of an accurate microbiological diagnosis using 16S rDNA sequencing.

We describe here a rare case of bladder wall necrosis associated with Actinobaculum schaalii in a 72-year-old patient with non-muscle-invasive bladder cancer (NMIBC). A. schaalii microbiological diagnosis requires high index of suspicion and accurate identification methods such as 16S rDNA sequencing or MALDI-TOF Mass spectrometry.

Salvage prostate re-irradiation using high-dose-rate brachytherapy or focal stereotactic body radiotherapy for local recurrence after definitive radiation therapy.

BACKGROUND: Optimal management of locally recurrent prostate cancer after definitive radiation therapy is still challenging. With the development of highly accurate radiotherapy devices, prostate salvage re-irradiation might generate lower toxicity rates than classical salvage therapies. We retrospectively evaluated the toxicity and the feasibility of a prostate re-irradiation after definitive radiation therapy failure. Two modalities were investigated: high-dose-rate brachytherapy (HDRB) on whole prostate gland and focal stereotactic radiotherapy (SBRT) using CyberKnife® linac. METHODS: Between 2011 and 2015, 28 patients with imaged and/or biopsy-proven intra-prostatic recurrence of cancer after definitive radiation therapy underwent a salvage re-irradiation using HDRB (n = 10) or focal SBRT (n = 18). The schedule of re-irradiation was 35 Gy in 5 fractions. Biological response (defined as post-salvage radiation PSA variation) and biochemical no-evidence of disease (bNED) were evaluated in the whole cohort. For patients who had a positive biological response after salvage radiation, biochemical recurrence (BCR) and survival after salvage radiotherapy were evaluated. Post-salvage toxicities were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and were compared to baseline status. RESULTS: Within a median follow-up of 22.5 months (IQR = 8-42), 9 (90%) patients experienced a positive biological response after salvage HDRB and 5 (50%) remained bNED at the end of the follow-up. Among patients who initially responded to salvage HDRB, the BCR rate was 44.4% after a median interval of 19.5 months (IQR = 11.5-26). Only one patient experienced a transient grade 3 urinary complication. In the SBRT group, the median follow-up was 14.5 months (IQR = 7-23) and 10 (55.6%) out of the 18 patients remained bNED. Among the 15 patients who initially responded to salvage SBRT, 5 (33.3%) experienced a BCR. One patient experienced a transient grade 4 urinary complication. At the end of the follow-up, all evaluated patients had a urinary status grade variation ≤ +1 grade. No grade 3-4 digestive toxicity was observed. CONCLUSIONS: Salvage prostate re-irradiation for locally recurrent cancer is feasible and generate low toxicities rates when using with HDRB or focal SBRT. However, further investigations are necessary to confirm these findings and to determine predictive features for patients who might benefit from such an approach.

Current Status of Urinary Biomarkers for Detection and Surveillance of Bladder Cancer.

The standard of care for detection and surveillance of bladder cancer consists of cytology and cystoscopy, but both examinations suffer from many limitations, including issues related to accuracy, invasiveness, and cost. Several noninvasive methods for detection and surveillance of bladder cancer have been developed and urine-based biomarkers seem the most promising. This nonsystematic review critically analyzes the commercially available biomarkers and highlights some upcoming investigational biomarkers. To date, none of these biomarkers has sufficient validation to serve as a reliable alternative to cystoscopy.

Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature.

In the context of customized patient care for upper tract urothelial carcinoma (UTUC), decision-making could be facilitated by risk assessment and prediction tools. The aim of this study was to provide a critical overview of existing predictive models and to review emerging promising prognostic factors for UTUC. A literature search of articles published in English from January 2000 to June 2016 was performed using PubMed. Studies on risk group stratification models and predictive tools in UTUC were selected, together with studies on predictive factors and biomarkers associated with advanced-stage UTUC and oncological outcomes after surgery. Various predictive tools have been described for advanced-stage UTUC assessment, disease recurrence and cancer-specific survival (CSS). Most of these models are based on well-established prognostic factors such as tumor stage, grade and lymph node (LN) metastasis, but some also integrate newly described prognostic factors and biomarkers. These new prediction tools seem to reach a high level of accuracy, but they lack external validation and decision-making analysis. The combinations of patient-, pathology- and surgery-related factors together with novel biomarkers have led to promising predictive tools for oncological outcomes in UTUC. However, external validation of these predictive models is a prerequisite before their introduction into daily practice. New models predicting response to therapy are urgently needed to allow accurate and safe individualized management in this heterogeneous disease.

Urothelial cancer of the upper urinary tract: emerging biomarkers and integrative models for risk stratification.

INTRODUCTION: The aim of this review was to provide an overview of current biomarkers and risk stratification models in urothelial cancer of the upper urinary tract (UTUC). EVIDENCE ACQUISITION: A non-systematic Medline/PubMed literature search was performed using the terms "biomarkers", "preoperative models", "postoperative models", "risk stratification", together with "upper tract urothelial carcinoma". Original articles published between January 2003 and August 2015 were included based on their clinical relevance. Additional references were collected by cross referencing the bibliography of the selected articles. EVIDENCE SYNTHESIS: Various promising predictive and prognostic biomarkers have been identified in UTUC thanks to the increasing knowledge of the different biological pathways involved in UTUC tumorigenesis. These biomarkers may help identify tumors with aggressive biology and worse outcomes. Current tools aim at predicting muscle invasive or non-organ confined disease, renal failure after radical nephroureterectomy and survival outcomes. These models are still mainly based on imaging and clinicopathological feature and none has integrated biomarkers. Risk stratification in UTUC is still suboptimal, especially in the preoperative setting due to current limitations in staging and grading. Identification of novel biomarkers and external validation of current prognostic models may help improve risk stratification to allow evidence-based counselling for kidney-sparing approaches, perioperative chemotherapy and/or risk-based surveillance. CONCLUSIONS: Despite growing understanding of the biology underlying UTUC, management of this disease remains difficult due to the lack of validated biomarkers and the limitations of current predictive and prognostic tools. Further efforts and collaborations are necessaryry to allow their integration in daily practice.

Prognostic significance of markers of systemic inflammatory response in patients with non-muscle-invasive bladder cancer.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein (CRP) are markers of systemic inflammatory response, which have been associated with the prognosis of multiple malignancies, but their relationships with oncologic outcomes of non-muscle-invasive bladder cancer (NMIBC) have not been well studied yet. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 1,117 patients with NMIBC who underwent a transurethral resection of the bladder. Univariable and multivariable competing risk regression models were used to assess the association of preoperative NLR and CRP with disease recurrence and progression to muscle-invasive disease. The median follow-up was 64 months. RESULTS: In total, 360 patients (32.2%) had a high NLR (≥2.5) and 145 (13.0%) had a high CRP (≥5mg/l). On multivariable analyses, a high NLR was associated with both disease recurrence (subhazard ratio [SHR] = 1.27, P = 0.013) and progression (SHR = 1.72, P = 0.007), and high CRP was associated with disease progression (SHR = 1.72, P = 0.031). Adding NLR and CRP to the multivariable model predicting disease progression lead to a relevant change in discrimination (+2.0%). In a subgroup analysis of 300 patients treated with bacillus Calmette-Guerin, both high NLR and high CRP were associated with disease progression (SHR = 2.80, P = 0.026 and SHR = 3.51, P = 0.021, respectively), and NLR was associated with disease recurrence (SHR = 1.46, P = 0.046). There was also an increase in the discrimination of the model predicting progression after bacillus Calmette-Guerin following the inclusion of both markers (+2.4%). CONCLUSION: In patients with NMIBC, markers of systemic inflammation response are associated with disease recurrence and progression. The inclusion of such markers in prognostic models does enhance their accuracy.

The Neutrophil-to-lymphocyte Ratio as a Prognostic Factor for Patients with Urothelial Carcinoma of the Bladder Following Radical Cystectomy: Validation and Meta-analysis.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) as a marker of systemic inflammatory response has been proposed as a prognostic factor for patients with urothelial carcinoma of the bladder (UCB) following radical cystectomy (RC). OBJECTIVE: To validate NLR as a prognostic biomarker and to perform a pooled meta-analysis. DESIGN, SETTING, AND PARTICIPANTS: The NLR was assessed in 4061 patients within 30 days before RC. A systematic review of the literature was undertaken using electronic databases. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Associations with overall survival (OS) and cancer-specific survival (CSS) were evaluated using Cox models. Hazard ratios (HRs) were pooled in a meta-analysis using random-effects modeling. RESULTS AND LIMITATIONS: A high NLR (≥2.7) was associated with advanced pathological tumor stages (p<0.001), lymph node involvement (p<0.001), lymphovascular invasion (p=0.008), and positive soft0tissue surgical margins (p=0.001). In multivariate analyses, a high NLR was independently associated with both OS (HR 1.11, 95% confidence interval [CI] 1.01-1.22; p=0.029) and cancer-specific survival (CSS) (HR 1.21, 95% CI 1.07-1.37, p=0.003). The discrimination of the multivariate models increased by 0.2% on inclusion of NLR. Five studies were included in the meta-analysis. The HR for NLR greater than the cutoff was 1.46 (95% CI 1.01-1.92) for OS and 1.51 (95% CI 1.17-1.85) for CSS. Limitations include the retrospective study design and the lack of standardized follow-up. CONCLUSION: In patients with UCB treated with RC, a high preoperative NLR is associated with more advanced tumor stage, lymph node metastasis, and worse prognosis. The NLR may be a readily available and useful biomarker for preoperative prognostic stratification. PATIENT SUMMARY: We investigated the neutrophil-to-lymphocyte ratio (NLR) as a prognostic marker in patients with bladder cancer treated with radical cystectomy. We found that a high NLR is associated with worse oncologic outcomes, suggesting it could play a role in risk stratification.

Upper urinary tract disease: what we know today and unmet needs.

PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare and poorly investigated disease. Intense collaborative efforts have increased our knowledge and improved the management of the disease. The objective of this review was to discuss recent advances and unmet needs in UTUC. METHODS: A non-systematic Medline/PubMed literature search was performed on UTUC using the terms "upper tract urothelial carcinoma" with different combinations of keywords. Original articles, reviews and editorials in English language were selected based on their clinical relevance. RESULTS: UTUC is a disease with specific epidemiologic and risk factors different to urothelial carcinoma of the bladder (UCB). Similarly to UCB, smoking increases the risk of UTUC and worsens its prognosis, whereas aristolochic acid (AA) exposure and mismatch repair genes abnormality are UTUC specific risk factors. A growing understanding of biological pathways involved in the tumorigenesis of UTUC has led to the identification of promising prognostic/predictive biomarkers. Risk stratification of UTUC is difficult due to limitations in staging and grading. Modern imaging and endoscopy have improved clinical decision-making, and allowed kidney-sparing management and surveillance in favorable-risk tumors. In high-risk tumors, radical nephroureterectomy (RNU) remains the standard. Complete removal of the intramural ureter is necessary with inferiority of endoscopic management. Post-RNU intravesical instillation has been shown to decrease bladder cancer recurrence rates. While the role of neoadjuvant cisplatin based combination chemotherapy and lymphadenectomy are not clearly established, the body of evidence suggests a survival benefit to these. There is currently no evidence for adjuvant chemotherapy (AC) in UTUC. CONCLUSIONS: Despite growing interest and understanding of UTUC, its management remains challenging, requiring further high quality multicenter collaborations. Accurate risk estimation is necessary to avoid unnecessary RNUs while advances in technology are still required for optimal kidney-sparing approaches.

Carbonic anhydrase IX as a diagnostic urinary marker for urothelial bladder cancer.

UNLABELLED: Urinary biomarkers are needed to improve the management and reduce the cost of urothelial bladder cancer (UBC); however, none have been recommended yet for clinical practice. This study evaluated carbonic anhydrase IX (CAIX) as a diagnostic urinary biomarker for UBC. CAIX was analyzed by quantitative polymerase chain reaction in urine samples of 196 patients with UBC and 123 controls with hematuria. Paired samples from urine and tumor tissue were evaluated in 16 cases. Data were validated in 155 independent samples. The sensitivity and specificity of CAIX for UBC detection were 86.2% and 95.1%, respectively (area under the curve [AUC]: 90.5%). There was a significant association of CAIX expression between the paired urine and tumor specimens (p=0.002). CAIX showed a significantly higher predictive accuracy than urinary cytology (90.5% vs 71.7%), specifically in low-grade tumors (90.0% vs 61.8%). CAIX expression decreased with increasing tumor stage and grade. Analyses in an independent validation cohort confirmed the high accuracy of CAIX for diagnosing UBC (AUC: 88.3%). PATIENT SUMMARY: We evaluated carbonic anhydrase IX (CAIX) as a urinary marker for bladder cancer (BCa) using a large series of patients from a single hospital. We found that urinary CAIX has a high sensitivity and specificity for diagnosing BCa.