History Of Non-muscle Invasive Bladder Cancer Research Articles

Oncologic Outcomes of Intravesical Therapy in the Management of Non-Muscle Invasive Bladder Cancer with Variant Histology

PurposeThere are limited data on oncologic outcomes in non-muscle invasive bladder cancer (NMIBC) with variant histology (VH) managed with intravesical therapy. We sought to evaluate oncologic outcomes for this cohort at a high volume center. Materials and MethodsA retrospective review of an IRB-approved bladder cancer database was performed. Patients with history of NMIBC with VH present on transurethral resection of bladder tumor (TURBT) treated with intravesical therapy (BCG or chemotherapy) were identified. Outcomes of interest included recurrence within the bladder, progression to muscle-invasive bladder cancer (MIBC), metastatic progression, cancer-specific and overall survival. Survival time was computed from date of initiation of intravesical therapy to date of event or censoring. For patients who underwent radical cystectomy, recurrence-free, cancer-specific, and overall survival were also computed. The Kaplan Meier method with log rank was utilized to compare survival time between VH sub-groups. ResultsNinety patients were included in the final cohort with a median follow-up of 38 months. The majority of patients had T1 disease (72%) and received intravesical BCG (83%) as their only form of intravesical therapy. The most commonly represented VH in this series were glandular and squamous differentiation (26%). Forty-eight patients (53%) experienced recurrence within the bladder with a median recurrence-free survival of 24 months (95% Confidence Interval (CI): 2-46 months). Five-year rates of progression to MIBC and distant metastasis were both 14% respectively. Twenty-six patients (28%) eventually required cystectomy. When stratifying by VH, patients with sarcomatoid, plasmacytoid, and micropapillary had significantly worse oncologic outcomes. ConclusionIn this series of highly-selected patients with NMIBC and VH, bladder-sparing treatment with intravesical therapy demonstrated acceptable oncologic outcomes for most VHs. This may be an acceptable treatment option for patients without plasmacytoid, sarcomatoid, or micropapillary features who are not suitable cystectomy candidates or who prioritize bladder-sparing treatment.

LBA02-02 A PROSPECTIVE STUDY COMPARING PENK METHYLATION, NMP22, AND CYTOLOGY FOR DETECTING BLADDER CANCER RECURRENCE AFTER TRANSURETHRAL RESECTION

You have accessJournal of UrologyCME1 Apr 2023LBA02-02 A PROSPECTIVE STUDY COMPARING PENK METHYLATION, NMP22, AND CYTOLOGY FOR DETECTING BLADDER CANCER RECURRENCE AFTER TRANSURETHRAL RESECTION Hyunho Han, Youngheun Jo, Ji Eun Heo, Jong Soo Lee, Won Sik Jang, Seung Hwan Lee, Won Sik Ham, Young Deuk Choi, Tae Jeong Oh, and Sungwhan An Hyunho HanHyunho Han More articles by this author , Youngheun JoYoungheun Jo More articles by this author , Ji Eun HeoJi Eun Heo More articles by this author , Jong Soo LeeJong Soo Lee More articles by this author , Won Sik JangWon Sik Jang More articles by this author , Seung Hwan LeeSeung Hwan Lee More articles by this author , Won Sik HamWon Sik Ham More articles by this author , Young Deuk ChoiYoung Deuk Choi More articles by this author , Tae Jeong OhTae Jeong Oh More articles by this author , and Sungwhan AnSungwhan An More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective of this study is to evaluate the efficacy of a PENK methylation test in detecting recurrent non-muscle invasive bladder cancer (NMIBC) and to compare its performance to that of NMP22 and cytology in a prospective pilot study. METHODS: A total of 188 patients with a history of NMIBC and scheduled for cystoscopy surveillance after TURBT were enrolled in the study. Urine samples were collected and analyzed using the Linear Target Enrichment (LTE)-quantitative methylation-specific real-time PCR (qMSP) test (mePENK-LTE-qMSP) for measuring PENK methylation, as well as the NMP22 test. The reference standard for NMIBC was cystoscopy and pathology. The mePENK-LTE-qMSP test was conducted with a cut-off value determined by ROC analysis of 32.0, and results were classified as positive or negative. The cystoscopy results were classified as recurrence or non-recurrence, and recurrences were further subcategorized as progression or non-progression. The clinical performance of the mePENK-LTE-qMSP test was analyzed and compared to NMP22 and cytology. RESULTS: The mePENK-LTE-qMSP test had a sensitivity of 78.4% (40/51) and a specificity of 85.0% (108/127) in detecting NMIBC. It had higher sensitivity than NMP22 (p=0.0106) or cytology (p<0.001), while its specificity was not significantly different from NMP22 (p=0.6076) but inferior to cytology (p=0.0001). Subgroup analysis demonstrated that the mePENK-LTE-qMSP test had a sensitivity of 46.7% (7/15) and a specificity of 96.6% (28/29) in detecting NMIBC among low- and intermediate-risk patients. It also had a sensitivity of 91.2% (31/34) and a specificity of 81.0% (68/84) in detecting NMIBC among high-risk patients. Patients who were recurrence-free at the time of diagnosis had follow-up cystoscopy, at a median follow-up duration of 223 days (n=71). The mePENK test positive patients (n=14) had a significantly shorter recurrence-free survival than test-negative patients (n=57) (245 days vs 503 days, hazard ratio=9.4 (95% CI 2.4 to 35.9), p<0.0001). CONCLUSIONS: The mePENK-LTE-qMSP test demonstrated high sensitivity and specificity in detecting recurrent NMIBC and accurately excluded non-recurring or non-progressing NMIBC during surveillance. Additionally, it was able to predict NMIBC recurrence before recognition by cystoscopy. Source of Funding: Genomictree, Inc. of South Korea sponsored this study © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1186 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hyunho Han More articles by this author Youngheun Jo More articles by this author Ji Eun Heo More articles by this author Jong Soo Lee More articles by this author Won Sik Jang More articles by this author Seung Hwan Lee More articles by this author Won Sik Ham More articles by this author Young Deuk Choi More articles by this author Tae Jeong Oh More articles by this author Sungwhan An More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparative Analysis of the Efficacy of Transurethral Bipolar Plasma Needle Electrode and Ring Electrode in the Treatment of Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is the most prevalent tumor of the urinary tract, ranking seventh in males and seventeenth in women. The gold standard for the definitive diagnosis and initial treatment of non-muscle-invasive bladder cancer is transurethral resection (TUR) of the bladder tumor. The ability to accurately detect disease, typically in the presence of hematuria as well as to detect early recurrent tumors in patients with a history of NMIBC, is critical to the successful treatment of non-muscle-invasive bladder cancer (NMIBC). Unfortunately, the current biomarker landscape for NMIBC is still evolving. Cystoscopy remains the gold standard, but it can still miss 10% of tumors. As a result, physicians frequently employ additional diagnostic tools to aid in the diagnosis of bladder cancer. The efficacy of transurethral bipolar plasma needle electrodes and ring electrodes in the treatment of non-muscle-invasive bladder cancer was compared and analyzed in this study. During our study, 100 patients with non-muscle-invasive bladder cancer admitted to our hospital between June 2019 and June 2020 were randomly assigned to a control group and an observation group, with 50 cases in each group. The observation group was given a bipolar plasma needle electrode, while the control group was given a bipolar plasma ring. Patients continued to receive bladder irrigation chemotherapy as well as traditional Chinese medicine (TCM) treatment as part of our treatment plan, while the control group received only bladder irrigation chemotherapy. Clinical factors such as operational blood loss, catheter indention time, length of hospital stay, and others were compared between the two groups. When the risk grades in the two groups were compared, the observation group had fewer medium- and high-risk grades than the control group, but the control group had more low-risk grades, with statistical significance (P < 0.05).

Clinical Validation of a Urine Test (Uromonitor-V2®) for the Surveillance of Non-Muscle-Invasive Bladder Cancer Patients.

The costly and burdensome nature of the current follow-up methods in non-muscle-invasive bladder cancer (NMIBC) drives the development of new methods that may alternate with regular cystoscopy and urine cytology. The Uromonitor-V2® is a new urine-based assay in the detection of hotspot mutations in three genes (TERT, FGFR3, and KRAS) for evaluation of disease recurrence. The aim of this study was to investigate the Uromonitor-V2®’s performance in detecting NMIBC recurrence and compare it with urine cytology. From February 2018 to September 2019 patients were enrolled. All subjects underwent a standard-of-care (SOC) cystoscopy, either as part of their follow-up for NMIBC or for a nonmalignant urological pathology. Urine cytology was performed in NMIBC patients. Out of the 105 patients enrolled, 97 were eligible for the study. Twenty patients presented nonmalignant lesions, 29 had a history of NMIBC with disease recurrence, and 49 had a history of NMIBC without recurrence. In NMIBC, the Uromonitor-V2® displayed a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 93.1%, 85.4%, 79.4%, and 95.3%, respectively. Urine cytology was available for 52 patients, and the sensitivity, specificity, PPV, and NPV were 26.3%, 90.9%, 62.5%, and 68.2%, respectively. With its high NPV of 95.3%, the Uromonitor-V2® revealed promising properties for the follow-up of patients with NMIBC.

MCM5 urine expression (ADXBLADDER) is a reliable biomarker of high-risk non- muscle-invasive bladder cancer recurrence: A prospective matched case-control study.

Mini Chromosome Maintenance 5 (MCM5) is considered as a urinary biomarker of bladder cancer. ADXBLADDER is a commercially available test to detect MCM5 antibodies. External validation of ADXBLADDER test as a urinary biomarker of histopathologically confirmed non-muscle invasive bladder cancer (NMIBC) recurrence. The study enrolled 119 consecutive patients with a history of NMIBC and 37 healthy volunteers matched as controls. Single, full-void urine samples were collected from patients before cystoscopy ± TUR. To measure MCM5 expression, Arquer Diagnostics ADXBLADDER test was used. The study protocol was registered within the clinical trials database (NCT03796299). Among patients with NMIBC history, recurrence was diagnosed in 83 patients (69.7%). ADXBLADDER demonstrated sensitivity of 73.5% (95% confidence interval (CI) 62.7%-82.6%), specificity of 33.3% (95% CI 18.6% to 51%), overall negative predictive value (NPV) of 35.3% (95% CI 23.3% to 49.5%) and overall positive predictive value of 71.8% (95% CI 66.1% to 76.8%) for detecting recurrence. In a control group, false positive ADXBLADDER results were noticed in 18 patients (48.6%). The sensitivity and NPV were the highest in invasive tumors (100% and 100%, respectively) and in high-grade recurrences (81.8% and 94.1%, respectively). ADXBLADDER has a moderate sensitivity and poor specificity in detecting NMIBC recurrence. However, it properly diagnoses patients with T1+ stage recurrence or high-grade tumors.

The value of intravesical instillation of Nocardiarubra cell wall skeleton in preventing recurrent after transurethral resection for the treatment of non-muscle invasive bladder cancer

Objective To investigate the efficacy and safety of Nocardiarubra cell wall skeleton (N-CWS)bladder irrigation in prevention of recurrence after transurethral resection for the treatment of non-muscle invasive bladder cancer (NMIBC). Methods The clinical data of patients with NMIBC treated by N-CWS and epirubicin collected between October 2013 and November 2018 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. All patients underwent TURBT. Among the 118 NMIBC patients, the average age was (65.1±11.9)years, and the sex ratio (male/female) was 1.9∶1 (77/41). Patients were divided into two group: N-CWS group (n=55) and epirubicin group (n=63) according to different instillation regimens. N-CWS was given as an instillation of 800 μg in 50 ml of saline and maintained in the bladder for 2 h in the N-CWS group. Epirubicin was given as an instillation of 50 mg in 50 ml of saline and maintained in the bladder for 1 h in the epirubicin group. In the N-CWS group, mean age was (64.9±12.1) years and 37 (67.3%) were male. Multiple tumors were present in 17(69.1%) patients. Tumor size was ≤3 cm in 49(89.1%) and 7(12.7%) had a history of NMIBC. Stage was Ta and T1 in 36(65.5%) and 19(34.5%), respectively. Grade 1, Grade 2 and Grade 3 were the primary grades in 38(69.1%), 13(23.6%) and 4(7.3%), respectively. Low risk, intermediate risk and high risk were present in 14 patients(25.5%), 16(29.1%)and 25(45.5%), respectively. In the epirubicin group, mean age was (65.3±11.2) years and 40(63.5%)were male. Multiple tumors were present in 19(30.2%) patients. Tumor size was ≤3 cm in 56(88.9%) and 11(17.5%) had a history of NMIBC. Stage was Ta and T1 in 37(58.7%) and 26(41.3%), respectively. Grade 1, Grade 2 and Grade 3 were the primary grades in 44(69.8%), 12(19.0%)and 7(11.1%), respectively. Low risk, intermediate risk and high risk were present in 13(20.6%), 19(30.2%)and 31(49.2%), respectively. The tumor recurrence, progression and adverse reactions after Intravesical Instillation in both groups were followed up and recorded. No significant differences were found between the two groups. Results A total of 118 patients were followed up.Mean follow-up time was (33.7±5.4) months. 25.5%(14/55) in the N-CWS group vs. 42.8%(27/63) in the epirubicin group had recurrence after 5 years (χ2=3.922, P=0.048). The five-year RFS was higher in the N-CWS group than in the epirubicin group (74.2% vs. 56.5%, P=0.044). No significant difference was found in the progression rate between the two groups(5.5% vs. 7.9%, P=0.867). The incidences of adverse events in the two groups were 16.4%(9/55) and 19.0% (12/63), respectively. The N-CWS group had significantly fewer cases with urinary frequency and dysuria than the epirubicin group. No significant differences were found in other side effects. Conclusions Intravesical instillation of N-CWS after NMIBC TURBT was found to be a promising procedure to prevent recurrence and prolong the recurrence-free survival with less side effects. Key words: Non-muscle invasive bladder cancer; Nocardiarubra cell wall skeleton; Intravesical Instillation

Prognostic significance of history of nonmuscle invasive bladder cancer in patients with muscle invasive bladder cancer treated with neoadjuvant chemotherapy followed by surgery.

375 Background: Efficacy of cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) for T2-4aN1M0 muscle-invasive bladder cancer (MIBC) was proved by randomize controlled trials. Recent retrospective studies suggested that MIBC patients who had a history of non-muscle invasive bladder cancer (NMIBC) had lower pathologic complete response and worse overall survival rate to NAC and RC. This study aimed to compare clinical outcomes between MIBC that progressed from NMIBC (secondary MIBC) and primary MIBC. Methods: A retrospective analysis of patients with urothelial carcinoma (cT2-4aN0-1M0) who received neoadjuvant chemotherapy from January 2011 and December 2017 in Asan Medical Center was conducted. Clinicopathologic outcomes were compared between 187 patients with primary MIBC and 38 patients with secondary MIBC. Results: Baseline characteristics are well balanced between the groups. Downstaging rate ( &lt; ypT2 and no N upstaging) are 46.7% for secondary MIBC group, 55.6% for primary MIBC group (p = 0.390), and positive pathologic metastatic nodes (ypN1+) are observed in 23.3% for secondary MIBC group, 18.3% for primary MIBC group (p = 0.523). There were no differences in overall survival (OS) (3 year OS 69.3% for secondary MIBC, 70.3% for primary MIBC, p = 0.420), disease-free survival (DFS) (3 year DFS 57.7% vs 56.6%, p = 0.880) between the groups. History of NMIBC is not independent prognostic factor for OS on multivariable analysis. Conclusions: Patients with secondary MIBC treated with NAC showed no differences in NAC response, pathologic downstaging rate, OS, DFS compared to patients with primary MIBC. Prospective or larger cohort study are required in the future. Genomic analysis is ongoing to identify genetic differences between two groups.

The significance of calprotectin, CD147, APOA4 and DJ-1 in non-invasive detection of urinary bladder carcinoma.

Aim of the study is to define the diagnostic accuracy of selected urinary protein biomarkers in the non-invasive detection of primary and recurrent urothelial carcinoma of the urinary bladder. The urinary levels of calprotectin, CD147, APOA4 and protein deglycase DJ-1 were examined in 255 individuals, including 60 controls with non-malignant urological disease, 61 patients with a history of urinary bladder cancer with negative cytology and negative cystoscopy and 134 patients with urinary bladder cancer. Urinary concentrations of biomarkers were determined by Enzyme-Linked Immunosorbent Assay (ELISA). During the follow-up of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared to the group of 61 patients with a history of NMIBC but with no evidence of disease. Urinary concentrations of the evaluated markers did not reveal any significant difference between these groups. During the primary diagnosis, a group of 90 patients with primary bladder cancer and 60 subjects with benign disease were compared. Urinary levels of CD147 were not significantly higher in patients with tumors. The greatest diagnostic accuracy was observed in APOA4 (sensitivity 55.6, specificity 83.3, AUC 0.75), and lesser in calprotectin (sensitivity 39.4, specificity 87.7, AUC 0.66) and in DJ-1 (sensitivity 61.1, specificity 66.7, AUC 0.64), respectively. Apolipoprotein A4 may be used potentially as a supplemental urinary marker in the diagnosis of primary bladder cancer.

Diagnostic biomarkers in non-muscle invasive bladder cancer

Successful treatment of non-muscle invasive bladder cancer (NMIBC) relies heavily on our ability to accurately detect disease typically in the presence of hematuria as well as to detect the early recurrent tumors in patients with a history of NMIBC. Unfortunately, the current biomarker landscape for NMIBC is a work in progress. Cystoscopy continues to be the gold standard, but can still miss 10% of tumors. Therefore, physicians frequently use additional tools to aid in the diagnosis of bladder cancer, such as urinary cytology. The urinary cytology is a good option for high-grade disease; however, it is limited by low sensitivity in detecting low-grade disease, as well as variable interpretation among cytopathologists. Thus, the limitations of cystoscopy and urinary cytology have brought to light the need for more robust diagnostic assays. In this non-systematic review, we discuss the performance, potential advantages or disadvantages of these tests, and the future direction of biomarkers in NMIBC.

History of Non-Muscle-Invasive Bladder Cancer May Have a Worse Prognostic Impact in cT2-4aN0M0 Bladder Cancer Patients Treated With Radical Cystectomy.

To investigate whether a history of non-muscle-invasive bladder cancer (NMIBC) plays a prognostic role in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy in the era when neoadjuvant chemotherapy was established as standard therapy for MIBC. A total of 282 patients who were diagnosed with cT2-T4aN0M0 bladder cancer treated with open radical cystectomy at our institutions were included. Initially diagnosed MIBC without a history of NMIBC was defined as primary MIBC group (n= 231), and MIBC that progressed from NMIBC was defined as progressive MIBC (n= 51). The rate of cT3/4a tumors was significantly higher in the primary MIBC group than in the progressive MIBC group (P= .004). Five-year recurrence-free survival and cancer-specific survival (CSS) rates for the primary MIBC group versus progressive MIBC group were 68.2% versus 55.9% (P= .039) and 76.1% versus 61.6% (P= .005), respectively. Progressive MIBC (hazard ratio, 2.170; P= .008) was independently associated with cancer death. In the primary MIBC group, the 5-year CSS rate in patients treated with neoadjuvant chemotherapy was 85.4%, which was significantly higher than that in patients without (71.5%, P= .023). In the progressive MIBC group, no significant differences were observed in CSS between patients treated with and without neoadjuvant chemotherapy. MIBC that progressed from NMIBC had a significantly worse clinical outcome than MIBC without a history of NMIBC and may not respond as well to neoadjuvant chemotherapy. These results are informative, even for NMIBC patients treated with conservative intravesical therapy.

MP08-07 THE IMPACT OF BLUE-LIGHT CYSTOSCOPY ON RESPONSE TO INDUCTION BCG IN PATIENTS WITH HIGH-GRADE NON-MUSCLE- INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2018MP08-07 THE IMPACT OF BLUE-LIGHT CYSTOSCOPY ON RESPONSE TO INDUCTION BCG IN PATIENTS WITH HIGH-GRADE NON-MUSCLE- INVASIVE BLADDER CANCER Nina Mikkilineni, Samuel Antoine, Ashley Alford, Gen Li, Sven Wenske, G. Joel Decastro, James McKiernan, and Christopher Anderson Nina MikkilineniNina Mikkilineni More articles by this author , Samuel AntoineSamuel Antoine More articles by this author , Ashley AlfordAshley Alford More articles by this author , Gen LiGen Li More articles by this author , Sven WenskeSven Wenske More articles by this author , G. Joel DecastroG. Joel Decastro More articles by this author , James McKiernanJames McKiernan More articles by this author , and Christopher AndersonChristopher Anderson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.312AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The use of blue light cystoscopy (BLC) during transurethral resection of bladder tumor (TURBT) is known to improve the detection of bladder cancer and reduce long-term recurrence rates. Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard of care for the treatment of high-grade non-muscle-invasive bladder cancer (NMIBC), and is associated with complete response rates of approximately 70%. We performed a retrospective study to investigate if response to induction BCG is affected by the use of BLC during pre-treatment TURBT in patients found with high-grade NMIBC. METHODS We retrospectively reviewed the charts of 148 patients with high-grade NMIBC at our institution who received induction BCG from 2014 to 2016. The primary exposure was white light cystoscopy (WLC) or BLC during the TURBT prior to induction BCG. Of the 148 patients, 103 patients had 3-month follow up with a cystoscopy with or without biopsy following completion of induction BCG. Disease recurrence was defined as visible or biopsy-proven tumor or positive urine cytology at 3 months. We used multivariate logistic regression to examine the association between type of cystoscopy and 3 month recurrence rate. Model covariates included stage, history of NMIBC, and prior intravesical therapy. RESULTS We identified 33 patients who had a BLC TURBT and 70 patients who had a WLC TURBT prior to induction BCG. Patients in the BLC group were more likely to have carcinoma in situ (67% vs. 47%, p=0.10), prior NMIBC (42% vs. 30%, p=0.31), and prior intravesical therapy (36% vs. 11%, p=0.007). At first cystoscopy after BCG induction, 13 patients (39%) in the BLC group and 24 (34%) in the WLC group had recurrent disease (p=0.78). On multivariate logistic regression, BLC did not have a lower recurrence rate compared to WLC (OR = 1.11, [95% CI 0.42, 2.93]; p=0.83). CONCLUSIONS There was no significant difference in 3 month recurrence rates after BCG induction for patients with BLC or WLC. The selection criteria for BLC differed from WLC, although our conclusion was unchanged after adjusting for confounding factors. BLC has been shown to improve detection of certain high risk tumors, but it is unclear if there is a therapeutic benefit to BLC for patients with known or suspected high risk disease. Further study is required to determine the value of BLC in improving response rates to intravesical BCG in patients with high grade NMIBC. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e98 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Nina Mikkilineni More articles by this author Samuel Antoine More articles by this author Ashley Alford More articles by this author Gen Li More articles by this author Sven Wenske More articles by this author G. Joel Decastro More articles by this author James McKiernan More articles by this author Christopher Anderson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Effects of Previous or Synchronous Non-Muscle Invasive Bladder Cancer on Clinical Results after Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Multi-Institutional Study.

To evaluate the effects of the presence of previous or synchronous non-muscle invasive bladder cancer (NMIBC) on the oncologic outcomes of radical nephroureterectomy in patients with upper tract urothelial carci­noma (UTUC). In total, 505 patients with UTUC were enrolled from four different institutions. The clinicopathologic parameters of patients with and without previous or synchronous NMIBC were compared, and Kaplan-Meier estimates and multivariate Cox regression analyses were performed. The median follow-up period was 38.4 months. In all, 408 patients had primary UTUC, 45 (8.9%) had a history of NMIBC, 59 (11.7%) had concomitant bladder cancer, and seven (1.4%) had experienced both. Tumors in patients with associated NMIBC were more commonly multifocal (P = .001) and associ­ated with surgical margin positivity (P = .001). Kaplan-Meier estimates revealed that previous or synchro­nous NMIBC was significantly associated with bladder recurrence (P < .001) and locoregional recurrence/distant metastasis (P = .008). A multivariate Cox regression model identified previous or synchronous NMIBC as an independent predictor of bladder recurrence (P < .001). However, the presence of previ­ous or synchronous NMIBC was not a prognostic indicator of locoregional recurrence/distant metastasis. In patients with UTUC, previous or synchronous NMIBC was significantly associated with an increased risk of cancer recurrences in the bladder after radical nephroureterectomy. The present find­ings suggest that a close monitoring should be required for the patients with previous or concomitant NMIBC.

Panel of Urinary Diagnostic Markers for Non-Invasive Detection of Primary and Recurrent Urothelial Urinary Bladder Carcinoma

Objectives: To determine the combination of urinary protein markers for noninvasive detection of primary and recurrent urothelial bladder carcinomas. Methods: Urinary concentrations of 27 biomarkers (NSE, ATT, AFABP, Resistin, Midkine, Clusterin, Uromodulin, ZAG2, HSP27, HSP 60, NCAM1/CD56, Angiogenin, Calreticulin, Chromogranin A, CEACAM1, CXCL1, IL13Ra2, Progranulin, VEGFA, CarbAnhydIX, Annexin-V, TIM4, Galectin1, Cystatin B, Synuclein G, ApoA1 and ApoA2) were assessed by enzyme-linked immunosorbent assay or by electrochemiluminiscence immunoassay. Results: During the primary diagnostics, a group of 70 patients with primary occurrence of bladder cancer and 49 healthy control subjects were compared. For this clinical situation, the most accurate combination proved to be the combination of cytology with markers Midkine and Synuclein G (sensitivity 91.8%, specificity 97.5%). During the monitoring of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared with the group of 61 patients with a history of NMIBC without current disease. For this clinical situation, the most accurate combination proved to be the combination of cytology and erythrocytes count in urine sediment with markers Midkine, ZAG2, CEACAM1, and Synuclein G (sensitivity 92.68%, specificity 90.16%). A lower accuracy of the diagnostic panel and the necessity to use more markers in the case of recurrence was connected with a different structure of patients. Conclusions: Multi-marker test can significantly improve the bladder cancer detection both during the primary diagnostics and monitoring of patients with NMIBC. This outcome should result in other, larger studies.

MP22-19 HIGH NEGATIVE PREDICTIVE VALUE OF A CYTOGENETICALLY NORMAL BARBOTAGE (CNB) FISH IN PREDICTING BLADDER CANCER NON-RECURRENCE

You have accessJournal of UrologyBladder Cancer: Detection & Screening1 Apr 2014MP22-19 HIGH NEGATIVE PREDICTIVE VALUE OF A CYTOGENETICALLY NORMAL BARBOTAGE (CNB) FISH IN PREDICTING BLADDER CANCER NON-RECURRENCE Eric Andresen, Daniel Lee, and Michael O'Donnell Eric AndresenEric Andresen More articles by this author , Daniel LeeDaniel Lee More articles by this author , and Michael O'DonnellMichael O'Donnell More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.867AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Urovysion’s FISH analysis is used to monitor bladder cancer recurrence in patients with a history of non-muscle invasive bladder cancer (NMIBC). However, the efficiency and use of a cytogenetically normal FISH obtained by saline barbotage wash has not been previously studied. The purpose of the study is to investigate whether a CNB FISH can be used to predict continued tumor free follow-up for patients with a history of NMIBC. METHODS A retrospective chart review identified a cohort of 241 consecutive patients who were diagnosed with NMIBC from 2002 to 2008. We reviewed all of the FISH samples obtained from these patients during their follow-up visits. 344 total FISH analyses were identified in the cohort that had 3-month post-analysis cystoscopy and cytology. Of those, 165 were cytogenetically normal. We also identified 177 CNB FISH analyses that were followed at 6 months by a cystoscopy/cytology. Only FISH samples that were reported as completely cytogenetically normal (0/50 abnormal cells per sample) were included. Tumor recurrence was defined as either high-grade cytology and/or presence of tumor found during cystoscopy. If tumor was present, the pathology was noted whenever possible. RESULTS Of the 165 CNB FISH analyses with a corresponding 3-month follow-up, 96.36% remained recurrence free (159/165). All recurrences at 3 months were identified by cystoscopy. Pathology from these patients were Ta high-grade (HG) - (2/6), indeterminate (2/6), Ta low-grade (LG) - (1/6) and bladder adenocarcinoma (1/6). Of the 177 FISH analyses with a corresponding 6-month follow-up, 93.79% of the patients were recurrence free (166/177). Recurrences were identified by cystoscopy (8/11) and cytology (3/11). Pathology for these cystoscopic recurrences included TaHG (1/8), TaLG (6/8), and indeterminate (1/8). All visible tumors were described as “small papillary lesions”. The three high-grade cytologies were eventually found to be bladder CIS. CONCLUSIONS Our data supports that a CNB FISH is highly predictive of tumor free status at both 3 and 6 months, missing primarily small, low-stage papillary recurrences. A CNB FISH analysis may have value as an adjunct to cystoscopy and cytology for monitoring bladder cancer. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e242 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Eric Andresen More articles by this author Daniel Lee More articles by this author Michael O'Donnell More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer.

Background. The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC. Patients and Methods. 483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis. Results. 128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4–74.3 and 82.3–88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5–89.8 and 89.5–91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively. Conclusions. Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.

Utility of quantitative fluorescent in situ hybridization (FISH) to predict non-muscle-invasive bladder cancer (NMIBC) recurrence.

286 Background: Urovysion's (Abbot Laboratories, Downers Grove, IL) FISH analysis is used to monitor bladder cancer recurrence in patients with a history of NMIBC and is often reported as a binary variable (normal/abnormal). We investigated whether the percentage of abnormal cells as determined by FISH analysis in patients with a history of NMIBC correlated with risk of recurrence. Methods: At our institution, barbotage FISH analysis is routinely done along with cystoscopy and cytology on both high risk (Ta/T1 high grade or CIS) and low or intermediate risk patients (all others) at every 3-month follow-up for the first year post-resection. We retrospectively reviewed 241 consecutive NMIBC patients and identified 399 FISH analyses for which we had one year follow-up. Normal FISH analyses were defined as 2 or fewer abnormal cells per sample. We calculated the percentage of abnormal cells and correlated that to the number of patients who had a recurrence of NMIBC as defined by positive high grade cytology or tumor on cystoscopy during the first year of follow-up. Results: The sensitivity, specificity, and positive and negative predictive values of FISH analysis if reported as a binary variable was 55, 43, 16 and 89%, respectively. Considering only those patients with abnormal FISH, the average percentage of abnormal cells for patients who were found to have NMIBC recurrence at 1 year was 38% (range 6–100) compared to 21% (range 6–100) for patients who were recurrence-free at 1 year (p&lt;0.0001). High risk patients who recurred within 1 year had a statistically higher percentage of abnormal cells as compared to those who did not recur within 1 year (50% [range 6–100] vs. 25% [range 6– 100], respectively p=0.001). There was no difference in the percentage of abnormal cells for those patients with low or intermediate risk disease based on recurrence within 1 year (22% [range 6–100] vs. 20% [range 6–100], respectively p=0.25). Conclusions: The percentage of abnormal cells in FISH analysis correlates with risk of recurrence for patients with high risk disease and can be used to guide surveillance interval decisions in patients with no other evidence of recurrence. [Table: see text]

Risk-specific intensity of surveillance practices in non-muscle-invasive bladder cancer: Results from the BCAN/SUO/AUA/LUGPA electronic survey.

251 Background: The ideal surveillance regimen for patients with non-muscle-invasive bladder cancer (NMIBC) is uncertain. Given different grade- and stage-specific risks of recurrence and progression, there is some question whether it might be acceptable to pursue less intensive surveillance practices for patients with lower risk disease, and there is a paucity of data on current patterns of care in this area of practice. Methods: An electronic survey was developed by the Bladder Cancer Advocacy Network (BCAN) to elicit self-reported practices of cystoscopy, cytology, and radiographic testing in the setting of surveillance for patients with a history of NMIBC. The survey was circulated to urologists via the AUA, SUO and LUGPA distribution lists. 512 respondents completed the survey. Results: Among respondents, 66% report performing cystoscopy every 3 months on all patients for at least the first two years following diagnosis of NMIBC. The remaining 33% report performing surveillance cystoscopy less frequently, 95% of whom report doing so in the setting of low grade pathology. Similarly, 51% report using cytology with every cystoscopy, 23% do so for all high grade cases, and 30% report not using cytology with every cystoscopy. In the absence of recurrence for patients with an initial high grade diagnosis, upper tract reimaging is performed annually in 48%, biannually in 37% and never in 3%. The corresponding figures for patients with an index diagnosis of low grade disease are 14%, 37% and 28%, respectively. In the event of a recurrence in the bladder, 80% of respondents report reimaging the upper tracts for patients with high grade disease, versus 45% in the event of a low grade recurrence. Conclusions: A substantial number of urologists responding to a survey report using relatively less intensive surveillance practices in patients with lower risk NMIBC. These results suggest a lack of consensus on the ideal intensity of evaluation in this setting, and provide a basis for prospective studies to validate the safest and most cost-effective strategies for surveillance. No significant financial relationships to disclose.

Assessing the clinical benefit of nuclear matrix protein 22 in the surveillance of patients with nonmuscle‐invasive bladder cancer and negative cytology

AbstractBACKGROUND:Several studies have demonstrated that abnormal levels of nuclear matrix protein 22 (NMP22) are associated with bladder cancer and have led to the approval of NMP22 as a urinary biomarker by the US Food and Drug Administration. Nonetheless, the clinical significance of NMP22 remains unclear. The objective of this study was to use decision analysis to determine whether NMP22 improves medical decision‐making.METHODS:The current study included 2222 patients who had a history of nonmuscle‐invasive bladder cancer and current negative cytology. The authors developed models to predict cancer recurrence or progression to muscle‐invasive disease using voided NMP22 levels, cystoscopy, age, and sex. Clinical net benefit was calculated by summing the benefits (true‐positives), subtracting the harms (false‐positives), and weighting these values by the threshold probability at which a patient or clinician would opt for cytoscopy.RESULTS:After cystoscopy, 581 patients (26%) had cancer identified. The NMP22 level was associated significantly with bladder cancer recurrence and progression (P &lt; .001 for both). The use of NMP22 in a model with age and sex was associated with better patient outcomes than performing cystoscopy on everyone and produced threshold probabilities &gt; 8% for recurrence and &gt; 3% for progression. Only offering cystoscopy to those who had a risk &gt; 15% reduced the number of cystoscopies by 229 while missing only 25 cancer recurrences per 1000 men with negative cytology. The current study was limited by its multicenter design.CONCLUSIONS:For clinicians who would perform a cystoscopy at a threshold of 5% for recurrence or 1% for progression, NMP22 did not aid clinical decision‐making. For less risk‐averse clinicians who would only perform a cystoscopy at a threshold probability &gt;thinsp;8% for recurrence or &gt; 3% for progression, NMP22 helped to indicate which patients required cystoscopy and which could be spared this procedure. Cancer 2011. © 2011 American Cancer Society.

Hexylaminolevulinate Photodynamic Diagnosis for Multifocal Recurrent Nonmuscle Invasive Bladder Cancer

To determine the potential for hexylaminolevulinate (HAL) photodynamic diagnosis (PDD) to improve the management of multifocal recurrent nonmuscle-invasive bladder cancer (NMIBC). Patients with a history of NMIBC and with at least two suspected papillary recurrences were enrolled in this prospective study between April 2005 and October 2006. The photosensitizer was hexylaminolevulinate (HAL) (PhotoCure, Norway), and the Storz D-light system was used to detect fluorescence. The bladder was mapped initially under white light and then using HAL-photodynamic diagnosis (PDD). The number and types of additional lesions detected by HAL-PDD over white light cystoscopy were measured. Eighteen patients (11 men), median age 74 years (range 35-84 yrs), underwent HAL-PDD. The median HAL instillation time was 109 minutes (range 60-250 min). Recurrent bladder cancer was confirmed histologically in 14/18 (78%) patients. Additional pathology was detected in 8/14 (57%) patients with confirmed recurrence and confirmed histologically in 6 of these. Additional pathology was papillary in 5/6 (83%) patients, and flat pathology was found in all six patients with additional foci. Carcinoma in situ (CIS) was detected in 4/6 (67%) patients with additional foci, three of whom were subsequently treated with intravesical bacille Calmette-Guérin (BCG). The sensitivity of HAL-PDD for the detection of tumor was 97.8%, compared with 69.6% for white light cystoscopy. The false-positive fluorescence-guided biopsy rate was 18/63 (29%). HAL-PDD allows more complete management of bladder tumor in patients with multifocal recurrence. The high frequency of additional lesions detected and the rate of detection of CIS suggest that HAL-PDD should be the standard of care.