Diagnostic predictive value of Xpert Bladder Cancer Monitor in the follow-up of patients affected by non-muscle invasive bladder cancer

AimsCystoscopy and urine cytology represent the gold standard for monitoring superficial bladder cancer (BC). Xpert BC Monitor is a new urinary marker based on the evaluation of five target mRNAs overexpressed in patients with bladder cancer. The aim of our study was to evaluate the diagnostic accuracy of Xpert BC Monitor in follow-up of patients with non-muscle invasive bladder cancer (NMIBC).Methods230 patients were included in this prospective study. Xpert BC Monitor cut-off was set to 0.5. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of cytology, Xpert BC Monitor and their combination were calculated and compared with cystoscopy/histology.Results52/230 patients showed a NMIBC recurrence, 45 low grade (LG) and 7 high grade (HG). Overall sensitivity was 11.5% for cytology, 46.2% for Xpert BC Monitor and 48.1% for the two tests combined. Sensitivity of cytology increased from 4.4% in LG to 57.1% in HG tumours whereas for the Xpert BC Monitor it was 40% in LG and 85.7% in HG tumours. Combined cytology and Xpert BC Monitor yielded an overall sensitivity of 42% for LG and 85.7% for HG. Overall specificity was 97.2% for cytology, 77% for Xpert BC Monitor and 75.8% for the two tests.ConclusionsSensitivity for the Xpert BC Monitor Test was significantly higher than for cytology. The test performed very well in terms of specificity but could not reach the value of cytology, while PPV and NPV performed approximately the same for both tests.

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

Diagnostics ◽

10.3390/diagnostics10100745 ◽

2020 ◽

Vol 10 (10) ◽

pp. 745

Author(s):

Caroline A. Sieverink ◽

Rui P. M. Batista ◽

Hugo J. M. Prazeres ◽

João Vinagre ◽

Cristina Sampaio ◽

...

Keyword(s):

Bladder Cancer ◽

Predictive Value ◽

Disease Recurrence ◽

Urine Cytology ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

History Of ◽

Muscle Invasive ◽

Sensitivity Specificity

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.

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Reducing the frequency of follow up cystoscopies for recurrence through the utilization of the urinary biomarker test ADXBLADDER in patients with Low grade, Low stage non-muscle invasive bladder cancer

European Urology ◽

10.1016/s0302-2838(21)01101-5 ◽

2021 ◽

Vol 79 ◽

pp. S998-S999

Author(s):

P. Gontero ◽

M. Roupret ◽

J. Witjes ◽

E. Montanari ◽

F. Longo ◽

...

Keyword(s):

Bladder Cancer ◽

Invasive Bladder Cancer ◽

Low Grade ◽

Urinary Biomarker ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

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Prognostic significance of the level of serum osteoprotegerin in patients with bladder cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4581 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4581-4581

Author(s):

Y. Mizutani ◽

Y. N. Li ◽

T. Shiraishi ◽

T. Nakamura ◽

T. Nomoto ◽

...

Keyword(s):

Bladder Cancer ◽

Cytotoxic Activity ◽

Superficial Bladder Cancer ◽

Invasive Bladder Cancer ◽

Autologous Tumor ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive ◽

High Level ◽

Low Serum

4581 Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in cytotoxic T lymphocyte-mediated and natural killer cell-mediated apoptosis against cancer cells. Since Osteoprotegerin (OPG) is a soluble decoy receptor for TRAIL, circulating OPG has been implicated in protection from TRAIL-mediated apoptosis. This possibility was examined in patients with bladder cancer. Methods: Serum OPG levels of 185 patients with bladder cancer were determined by using an enzyme-linked immunosorbent assay. Anti-autologous tumor cytotoxic activity of peripheral blood lymphocytes was assessed by the 12-h Cr release assay. Results: The mean serum OPG level in patients with bladder cancer was approximately 3-fold higher than that in normal donors. The serum OPG level in patients with muscle-invasive bladder cancer was higher than that in superficial bladder cancer. Furthermore, serum level of OPG in patients with metastatic bladder cancer was higher than that in muscle-invasive bladder cancer. Serum OPG level in Grade 2 bladder cancer was higher than that in Grade 1 cancer. Moreover, serum OPG level in Grade 3 bladder cancer was higher than that in Grade 2 cancer. Patients with superficial bladder cancer with low serum OPG level had a longer postoperative tumor-free rate than those with high level in the 5-year follow-up. In addition, patients with muscle-invasive bladder cancer with low serum OPG level had a higher disease-specific survival rate when compared with patients with high level in the 5-year follow-up. There was an inverse correlation between serum OPG level and anti-autologous tumor cytotoxic activity. Conclusions: The present study is the first to demonstrate that the serum OPG level correlates with the stage/grade of bladder cancer, and that elevated level serum OPG predicted early recurrence in patient with bladder cancer. These findings suggest that serum OPG level may be used as a prognostic parameter in patients with bladder cancer, and that OPG may be a molecular therapeutic target in bladder cancer. No significant financial relationships to disclose.

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Urinary Metabolic Signatures Detect Recurrences in Non-Muscle Invasive Bladder Cancer

Cancers ◽

10.3390/cancers11070914 ◽

2019 ◽

Vol 11 (7) ◽

pp. 914 ◽

Cited By ~ 1

Author(s):

Alba Loras ◽

M. Carmen Martínez-Bisbal ◽

Guillermo Quintás ◽

Salvador Gil ◽

Ramón Martínez-Máñez ◽

...

Keyword(s):

Bladder Cancer ◽

1H Nmr ◽

Partial Least Square ◽

Proton Nuclear Magnetic Resonance ◽

Invasive Bladder Cancer ◽

Low Grade ◽

Muscle Invasive Bladder Cancer ◽

Invasive Approach ◽

Muscle Invasive

Patients with non-muscle invasive bladder cancer (NMIBC) undergo lifelong monitoring based on repeated cystoscopy and urinary cytology due to the high recurrence rate of this tumor. Nevertheless, these techniques have some drawbacks, namely, low accuracy in detection of low-grade tumors, omission of pre-neoplastic lesions and carcinomas in situ (CIS), invasiveness, and high costs. This work aims to identify a urinary metabolomic signature of recurrence by proton Nuclear Magnetic Resonance (1H NMR) spectroscopy for the follow-up of NMIBC patients. To do this, changes in the urinary metabolome before and after transurethral resection (TUR) of tumors are analyzed and a Partial Least Square Discriminant Analysis (PLS-DA) model is developed. The usefulness of this discriminant model for the detection of tumor recurrences is assessed using a cohort of patients undergoing monitoring. The trajectories of the metabolomic profile in the follow-up period provide a negative predictive value of 92.7% in the sample classification. Pathway analyses show taurine, alanine, aspartate, glutamate, and phenylalanine perturbed metabolism associated with NMIBC. These results highlight the potential of 1H NMR metabolomics to detect bladder cancer (BC) recurrences through a non-invasive approach.

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733 Long-Term Outcomes of Outpatient Laser Ablation for Recurrent Non-Muscle Invasive Bladder Cancer: A Retrospective Cohort Study

British Journal of Surgery ◽

10.1093/bjs/znab259.1092 ◽

2021 ◽

Vol 108 (Supplement_6) ◽

Author(s):

S Grover ◽

S Raj ◽

B Russell ◽

K Thomas ◽

R Nair ◽

...

Keyword(s):

Bladder Cancer ◽

Laser Ablation ◽

Bladder Tumour ◽

Invasive Disease ◽

Invasive Bladder Cancer ◽

Low Grade ◽

Muscle Invasive Bladder Cancer ◽

Muscle Invasive

Abstract Aim Non-muscle-invasive bladder cancer (NMIBC) is the most prevalent form of bladder cancer, predominantly affecting the elderly population. The most common treatment for recurrent NMIBC is transurethral resection of the bladder tumour (TURBT), which carries a risk of perioperative morbidity and mortality in this often-co-morbid population. Outpatient laser ablation of low-grade NMIBC recurrences is a minimally invasive treatment option, but long-term efficacy is poorly reported. Method We retrospectively reviewed the case notes of all patients treated with Holmium:YAG laser ablation from 2008-2016. Data regarding patient demographics, original histology, dates of procedures, follow-up time, recurrence, progression, and complications were recorded. Results A total of 199 procedures were performed on 97 patients (mean age of 83.56), 73 (75.3%) of which originally had low-grade (G1 or G2) tumours. Overall, 55 (56.7%) patients developed tumour recurrence at long-term follow-up (mean 5.36 years), and only 9 (9.3%) patients had tumour progression to a higher stage or grade, but there was no progression to muscle-invasive disease. The median recurrence-free, progression-free and overall survival times were 1.69 years (95% CI 1.20-2.25), 5.70 years (95% CI 4.10-7.60) and 7.60 years (95% CI 4.90-8.70), respectively. No patients required emergency inpatient admission after laser ablation for any associated complications. Conclusions Office-based Holmium: YAG laser ablation is an oncologically-safe method of managing recurrent low-grade non-muscle-invasive bladder cancer in the long-term, with no patients progressing to muscle-invasive disease. Furthermore, the procedure is safe, and no significant complications were seen in this elderly and co-morbid population.

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Accuracy of Inchworm Sign on Diffusion-Weighted MRI in Differentiating Muscle-Invasive Bladder Cancer

Bladder Cancer ◽

10.3233/blc-211535 ◽

2021 ◽

pp. 1-10

Author(s):

Huseyin Ozgur Kazan ◽

Meftun Culpan ◽

Nesrin Gunduz ◽

Ferhat Keser ◽

Ayberk Iplikci ◽

...

Keyword(s):

Bladder Cancer ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Predictive Values ◽

Diffusion Weighted ◽

Primary Bladder ◽

Muscle Invasive ◽

Sensitivity Specificity ◽

Primary Bladder Cancer

BACKGROUND: Inchworm sign is a finding on diffusion-weighted magnetic resonance imaging (DWI-MRI) and is used to better stratify T-staging in muscle invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC). An uninterrupted low submucosal signal on DWI, defined as inchworm sign (IS), indicates NMIBC. OBJECTIVE: We aimed to define the diagnostic accuracy of IS in primary bladder cancer, as well as find agreement between the urologists and the radiologist. METHODS: Between December 2018 and December 2020, we retrospectively analyzed 95 primary bladder cancer patients who had undergone multiparametric-MRI before transurethral resection. Patients with former bladder cancer history, tumors smaller than 10 mm, and MRI without proper protocol, as well as patients who did not attend follow-up, were excluded. In total, 71 patients’ images were evaluated by a genitourinary specialist radiologist and two urologists. Sensitivity, specificity, positive and negative predictive values of IS and VI-RADS in differentiating MIBC and NMIBC, and interreader agreement between the radiologist and urologists were analyzed. RESULTS: During follow-up, 38 patients (53.5%) were IS-positive, while 33 patients (46.5%) were negative. Among the 33 patients with negative IS, 14 patients (42.4%) had MIBC. Meanwhile, two out of the 38 IS-positive patients (5.3%) had MIBC (p = 0.00). Sensitivity, specificity, and positive and negative predictive values of IS in predicting MIBC were 87.5%, 63.6%, 41.2%and 94.6%, respectively. The interobserver agreement between the urologists and radiologist was almost perfect ( K = 0.802 and K = 0.745) CONCLUSION: The absence of IS on DWI is useful in differentiating MIBC from NMIBC. It is a simple finding that can be interpreted by urologists.

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The significance of protocol biopsy after intravesical BCG treatment in patients with non-muscle–invasive bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.356 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 356-356

Author(s):

Satoru Maruyama ◽

Nobuo Shinohara ◽

Norihiro Murahashi ◽

Hidetaka Suzuki ◽

Ryuji Matsumoto ◽

...

Keyword(s):

Bladder Cancer ◽

Survival Rate ◽

High Risk ◽

Adverse Events ◽

Predictive Value ◽

Invasive Bladder Cancer ◽

Muscle Invasive Bladder Cancer ◽

Protocol Biopsy ◽

Muscle Invasive

356 Background: Currently, there are few well-validated data of the optimal schedule of follow-up after BCG intravesical instillation. The objective of the study were to elucidate the ability of conventional exams (cystoscopy, urine cytology) to diagnose presence of carcinoma and the significance of protocol biopsy after BCG intravesical treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Methods: The study included patients treated with BCG intravesical treatment. From January 2002 to October 2012, we retrospectively reviewed a total of 72 patients (61 men and 11 women). The median age was 72 years (range 47-84). The pathological stages were Tis in 4 patients (6%), Ta in 29 (40%) and T1 in 39 (54%) (T1 with CIS in 30 [42%]). Tumors were multifocal in 56 (78%) and second TUR had been performed in 53 (74%) patients. We investigated the prognosis and accuracy of tumor existence by conventional exams referring with the protocol biopsy. A protocol biopsy was performed within 5 to 9 months after the final TUR. CTCAE v4.0 was used to grade adverse events. Results: Of 72 patients, we performed protocol biopsy in 62 patients and 9 (15%) had cancer. The conventional methods had a sensitivity of 78%, specificity of 81%, positive predictive value of 41% and negative predictive value of 96% in diagnosing cancer. Although three (5%) had grade2 adverse events, there were no grade 3 or greater adverse events. Of 53 patients with no cancer in protocol biopsy, 8 (8%) patients experienced a recurrence but 51patients (96%) were alive with no evidence of disease. Of 9 patients pointed out cancer in protocol biopsy, 7patients (78%) had no evidence of disease recurrence at last follow-up. The 5-year recurrence-free survival rate and overall survival rate were 77% and 95%, respectively. Conclusions: To the best of our knowledge, this is the first report of the ability of conventional exams for follow-up after BCG treatment. Our findings revealed that conventional exams were limited for meticulous follow-up, so that the protocol biopsy will be recommended to obtain the better survival in high-risk NMIBC patients.

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