ImmunoCyt/uCyt+™ improves the sensitivity of urine cytology in patients followed for urothelial carcinoma

Abstract

ImmunoCyt/uCytt is a fluorescent test combining three monoclonal antibodies. In this study, it has been tested as a complement to cytology in the detection of urothelial carcinoma in urine. It has been performed simultaneously with standard cytology and cystoscopy on 870 urine analyses from one hospital. In 136 cases, one or more bladder tumors were found. Overall sensitivity of cytology, ImmunoCyt/uCytt and combined analyses reached 29, 74 and 84%, respectively, and overall specificity was 98, 62 and 61%. The negative predictive value of cytology, ImmunoCyt/uCytt and both analyses was 88, 93 and 95%, respectively, and the positive predictive value was 70, 26 and 29%. The sensitivity of cytology for low malignant potential neoplasms, low-and high-grade papillary carcinomas was 6, 18 and 53%, while it reached 71, 79 and 93% when combined with ImmunoCyt/uCytt. The sensitivity of cytology for stages Ta, T1, T2 and over and Tis tumors was12, 67, 47 and 50%, while it reached 78, 83, 79 and 100% when combined with ImmunoCyt/uCytt. In the absence of tumor on cystoscopy but with positive ImmunoCyt/uCytt, 18% of patients developed a tumor, 2-6 months later. Of the 109 cases diagnosed as suspicious for malignancy by cytology, a tumor was present in 30 cases and ImmunoCyt/uCytt was positive in 22 (73%) of them. In conclusion, ImmunoCyt/uCytt may be used to postpone cystoscopies in patients followed for bladder cancer and may help to save cytologist and pathologist screening Keywords: urothelial carcinoma; cytology; ImmunoCyt/uCytt; immunofluorescence; urinary bladder; recurrence Superficial bladder cancers are defined as tumors limited to the mucosa (Tis, Ta) or invading into the lamina propria (T1), without muscle invasion. 1 They represent more than 80% of urothelial carcinomas and more than 50% will recur. 1-3 Patients with bladder cancer are followed with regular cytologies and cystoscopies. Cytology is very specific but this test is limited by its low sensitivity ranging from 16 to 60%. 4 Cytology is most useful at detecting highgrade (HG) cancer, whereas its sensitivity for lowgrade (LG) urothelial tumors is low and merely reaches 17%. 4 Furthermore, criteria used in urinary cytology to detect tumor cells are largely subjective and the ability to detect cancer cells is dependent on the experience of cytologists or pathologists. For instance, atypical cells and papillary aggregates may be found in either reactive or neoplastic conditions. 5 Furthermore, LG urothelial carcinomas do not always exfoliate in aggregates and the cell characteristics are often so subtle that they might not be recognizable even by an experienced cytologist. 5 Standard practice in the follow-up of patients with bladder cancer requires cystoscopies at regular intervals, but this technique is invasive, costly and causes discomfort to the patient. It is thus estimated that by improving the sensitivity of cytology, fewer follow-up cystoscopies would be needed. Furthermore, improved sensitivity would help cytologists and pathologists to save time c...

Value of the Innovated Technique Agarose Cell Block in Improving the Sensitivity of Urine Cytology in Cases of Bladder Carcinoma

“…The previous reports about the diagnostic sensitivity of urine cytology for low-grade neoplastic bladder lesions show a range between 40 and 60% [5,7,[13][14][15]. In the present work, application of agarose cell block technique in the processing of urine samples proved to be effective in increasing the sensitivity of urine cytology.…”

“…Cystoscopy and biopsy are reliable but invasive [3]. Urine cytology has the advantage of being noninvasive, fast, and inexpensive, but is of limited value because of its low sensitivity in low-grade UCC [4,5]. Finding new techniques that may improve urine sample processing becomes an important task.…”

Biomarkers for detection and surveillance of bladder cancer

“…31 In general, studies suggest that ImmunoCyt/uCyt+ has superior sensitivity over cytology for pathological stage Ta-T2 and grade 1-2 tumours and similar or better sensitivity for grade 3 tumours and carcinoma in situ. 31,32,38 Unlike the molecular-based tests, ImmunoCyt/uCyt+ is relatively unaffected by benign conditions and instillation therapy. 57 Still, this test, like cytology, remains subjective and depends in part on the technician.…”

“…Specificity of the combined assay reaches 61.0%-77.7%, which is less than that offered by cytology alone. 27,[31][32][33]38,39 The ImmunoCyt/uCyt+ assay requires technical expertise, extensive sample handling and preparation and specialized equipment. However, a person with minimal cytology training and experience can perform the test.…”

Molecular Markers for Bladder Cancer Screening, Early Diagnosis, and Surveillance: The WHO/ICUD Consensus

“…After removal of reviews, meta-analyses, and redundant trials, 20 studies assessable for criteria concerning assay performance and comprising more than 5,000 individuals were identified, forming the basis for this assessment of assay performance [13,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114]. …”