Diagnosis Of Carcinoma In Situ Research Articles

Phase 1b/2 dose expansion, open-label study to evaluate safety and anti-tumor activity of intravesical instillation of TARA-002 in adults with high-grade non-muscle invasive bladder cancer.

TPS4618 Background: Bladder cancer is the most common malignancy involving the urinary system, with over 700,000 individuals living with bladder cancer in the US in 2019. In the US, approximately 80,000 new cases and 18,000 deaths occur each year due to bladder cancer. Approximately 70% of new urothelial bladder cancer cases are classified as non-muscle invasive bladder cancer (NMIBC). With the current Bacillus Calmette-Guerin (BCG) shortage and limited effective alternate therapies, there continues to be a significant unmet need for treatment options for patients with NMIBC. TARA-002 is being developed for intravesical instillation for the treatment of high-grade (HG) NMIBC. TARA-002 is a lyophilized biological preparation for instillation containing cells of Streptococcus pyogenes (Group A, type 3) Su strain treated with benzylpenicillin. The chemical characteristics of TARA-002 are intended to be comparable to OK-432. Therefore, nonclinical and clinical evidence with OK-432 and TARA-002 support the ADVANCED-1 study (dose escalation Phase 1a [NCT05085977] and dose expansion Phase 1b/2 [NCT05085990]). The dose for the planned Phase 1b/2 study (ADVANCED-1-Ph1b/2) will be based on the recommended Phase 2 dose (RP2D) established in the Phase 1a study. Methods: ADVANCED-1-Ph1b/2 is a Phase 1b/2, dose expansion, open-label study of intravesical instillation of TARA-002 in adults with HG carcinoma in situ (CIS) NMIBC. The purpose of this study is to evaluate the safety and anti-tumor activity of TARA-002 administered intravesically for the treatment of subjects with CIS NMIBC (± Ta/T1) with active disease. The study includes approximately 102 eligible male and female subjects ≥ 18 years of age enrolled in 2 cohorts based on their prior BCG experience. Cohort A includes subjects unable to obtain BCG or subjects who have not received BCG in the last 24 months prior to CIS diagnosis, and Cohort B includes subjects with CIS who are BCG unresponsive after completion of adequate BCG therapy (at least 5 of 6 doses of an initial induction course plus either at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course). Those with current or a history of penicillin allergy or current evidence of any condition, therapy, or laboratory abnormality that might confound the results are excluded. The overall study duration is 6 months/24 weeks per subject for Ph1b/2-Cohort A (includes induction, reinduction [if applicable]), and 24 months/96 weeks per subject for Ph1b/2-Cohort B (includes induction, reinduction [if applicable], maintenance until 18 months). The ADVANCED-1 study started in March 2022. Phase 1a is open for enrollment. Phase 1b/2 is expected to begin enrollment in May 2023. Clinical trial information: NCT05085977 ; NCT05085990 .

MP63-17 PHOTODYNAMIC DIAGNOSIS (PDD) DIRECTED BIOPSIES VS WHITE LIGHT BLADDER MAPPING IN PATIENTS WITH POSITIVE CYTOLOGY AND NEGATIVE PREOPERATIVE WORKUP: AN INTERNATIONAL MULTICENTER RETROSPECTIVE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP63-17 PHOTODYNAMIC DIAGNOSIS (PDD) DIRECTED BIOPSIES VS WHITE LIGHT BLADDER MAPPING IN PATIENTS WITH POSITIVE CYTOLOGY AND NEGATIVE PREOPERATIVE WORKUP: AN INTERNATIONAL MULTICENTER RETROSPECTIVE STUDY Luciano Ola, Francesco Soria, Beatrice Lillaz, Francesca Pisano, Rosazza Matteo, Dutto Daniele, Simone Livoti, Matteo Debellis, Simone Mazzoli, Gautier Marcq, Edouard Jarry, and Paolo Gontero Luciano OlaLuciano Ola More articles by this author , Francesco SoriaFrancesco Soria More articles by this author , Beatrice LillazBeatrice Lillaz More articles by this author , Francesca PisanoFrancesca Pisano More articles by this author , Rosazza MatteoRosazza Matteo More articles by this author , Dutto DanieleDutto Daniele More articles by this author , Simone LivotiSimone Livoti More articles by this author , Matteo DebellisMatteo Debellis More articles by this author , Simone MazzoliSimone Mazzoli More articles by this author , Gautier MarcqGautier Marcq More articles by this author , Edouard JarryEdouard Jarry More articles by this author , and Paolo GonteroPaolo Gontero More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003321.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Bladder Carcinoma in situ (CIS) is a flat, non-vegetating, high-grade tumor and is associated with a high risk of progression to muscle invasive cancer (MIBC), especially if not timely diagnosed and treated. Since it may be often not visible with white light cystoscopy (WL), international guidelines therefore recommend the use of bladder mapping in case of suspected CIS (positive urine cytology and negative preoperative workup). Photodynamic diagnosis (PDD) has been shown to increase the sensitivity in diagnosing CIS compared to WL cystoscopy. However, a direct comparison between PDD-guided biopsies (PDD-GB) and WL bladder mapping (WL-M) is lacking. The aim of our study is therefore to compare the diagnostic capability of PDD-GB versus that of WL-M. METHODS: A retrospective analysis was conducted from March 2018 to May 2022 at two European referral Centers. Overall, 73 patients were enrolled according to the following inclusion criteria: positive urinary cytology or gross hematuria and negative flexible cystoscopy and / or negative CT scan. Patients underwent either PDD-GB or WL-M, as per international guidelines. The main endpoint of the study was the diagnostic accuracy in the diagnosis of bladder cancer (BCa) and, particularly, of CIS. Recurrence-free and progression-free survival were investigated as secondary endpoint. RESULTS: Overall, 50 patients (68%) underwent (PDD-GB) and 23 (32%) WL-M. No differences in baseline characteristics were observed among the two groups.BCa was found in 16 patients (32%) among the PDD-GB group and in 8 patients (34.78%) among the WL-M group (p=0.8); CIS was found in 11 (22%) patients undergoing PDD-GB and in 6 patients (26.09%) in the WL-M group (p=0.7). On univariable logistic regression the type of intervention (PDD-GB vs WL-M) was not associated with either BCa or CIS diagnosis (all p>0.05). Disease recurrence was found in 18 patients, but no statistically significant differences were observed among the two groups (p=0.3); disease progression was found in 7 patients and, again, no differences were observed (p=0.3). CONCLUSIONS: We did not observe statistically significant differences between the PDD-GB group and the WL-M group in the diagnosis of BCa and CIS. WL-M remains a valid alternative to PDD-GB in patients with suspected CIS. The main limitations of this study are inherent its retrospective nature and the small sample size. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e878 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luciano Ola More articles by this author Francesco Soria More articles by this author Beatrice Lillaz More articles by this author Francesca Pisano More articles by this author Rosazza Matteo More articles by this author Dutto Daniele More articles by this author Simone Livoti More articles by this author Matteo Debellis More articles by this author Simone Mazzoli More articles by this author Gautier Marcq More articles by this author Edouard Jarry More articles by this author Paolo Gontero More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract P6-02-10: Prevalence of breast cancer predisposing variants in patients with breast carcinoma in situ

Abstract Background. Carcinoma in situ (CIS) of the breast is a non-obligatory pre-malignant breast lesion and a highly suspected precursor of invasive cancer. Although the selection criteria for referral to genetic testing are well established for patients diagnosed with invasive breast cancer, these are not clear for patients diagnosed with CIS. Our goal is to assess the prevalence of predisposing pathogenic variants in key genes, as well as to describe factors in patients with CIS that might be associated with genetic predisposition. Methods. A total of 267 patients solely diagnosed with CIS (mean age 43.65 years, range 18-74) through years 2010-2022, were referred for genetic testing and were analyzed, following their informed consent, implementing a 42-gene panel. Of these, 81.5%, 12.4% and 5.8% were ductal, lobular and mixed CIS, respectively. Patients having a synchronous invasive breast cancer diagnosis were not included in the study. Of patients with known grade, 52.28%, 28.9% and 18.8% were grade 3, 2 and 1, respectively. Strong family history for breast cancer (>2 close family relatives) was positive in 28% (75/267) of patients, while 67.8% of CIS were hormone receptor positive. Results. A total of 12.7% (34/267) of patients carried pathogenic variants in seven clinically actionable genes, i.e. CHEK2 (10), BRCA2 (9), BRCA1 (5), ATM (5), PALB2 (2), MSH6 (2) and TP53 (1). Mean age at diagnosis of carriers was 42.1 years (range 29-61 years, p=0.26), 60% of patients had a grade 3 CIS diagnosis (OR 1.1, 95% 0.589-2.1, p=0.73), 96% had a hormone positive diagnosis (OR 1.4, 95% 0.78-2.50, p=0.24), while 73.5% (25/34) reported as having at least two close family relatives with breast cancer (OR 2.9, 95% 1.6-5.1, p=0.0001). The vast majority of carriers had a ductal CIS (DCIS) diagnosis, i.e. 91.2% (31/34) although this did not reach statistical significance (OR 1.087, 95% 0.64-1.82, p=0.72), probably due to small numbers. Notably, carriers were more likely to have a diagnosis with comedo characteristics, although this parameter has not been monitored closely for the whole cohort. Conclusion. Herein, an important fraction of patients with breast CIS carried pathogenic variants in clinically actionable genes, with the most frequent being CHEK2, BRCA2, BRCA1 and ATM. Notably, the prevalence is comparable to that of patients with invasive breast cancer. Strong family history for breast cancer was strongly associated with the identification of predisposing variants. Other factors, such as high grade, hormone positivity, age at diagnosis and others might also be associated with predisposition to CIS, but larger, prospective, studies are needed to confirm these. This is one of the few studies evaluating the inherited predisposition associated with both high and moderate penetrant breast cancer genes, highlighting that individuals with CIS diagnosis and strong family history for breast cancer should be offered the option to genetic testing via multigene panel. Citation Format: Florentia Fostira, Dimitrios Nasikas, Paraskevi Apostolou, Vassiliki Dellatola, Anna Fokianou, Panagiota Kontogianni, Romina Alevizou, Sofia Filippidou, Dimitrios Maniatis, Lazaros Papadopoulos, Emmanouil Pavlakis, Panagiota Ntasiou, Sofia Karageorgopoulou, Grigorios Xepapadakis. Prevalence of breast cancer predisposing variants in patients with breast carcinoma in situ [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-02-10.

A systematic review and meta-analysis of CK20, CD44, Ki67 and p53 as immunohistochemical markers in bladder carcinoma in situ

BackgroundUrothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis. Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS. ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively. ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.

Revisión sistemática y metaanálisis sobre CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en el carcinoma in situ vesical

IntroductionUrothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis. Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS. ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively. ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.

Focal parenchymal atrophy of pancreas: An important sign of underlying high-grade pancreatic intraepithelial neoplasia without invasive carcinoma, i.e., carcinoma in situ

ObjectivesDiagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS. MethodsForty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses. ResultsTwo clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy. ConclusionsFPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

Urothelial Carcinoma In Situ of the Bladder: Correlation of CK20 Expression With Adaptive Immune Resistance, Response to BCG Therapy, and Clinical Outcome.

Immunohistochemical stains have been suggested to aid in diagnostically challenging cases of urothelial carcinoma in-situ (CIS). Although full thickness immunostaining for CK20 is supportive of CIS, a subset of CIS cases is CK20(-), the clinical significance of which was unknown. This study included 43 patients with primary diagnosis of bladder CIS including 32 with only CIS, 5 with CIS and separate noninvasive high-grade papillary urothelial carcinoma, and 6 with CIS and separate high-grade urothelial carcinoma with lamina propria invasion. Digital morphometric image analysis showed that the average nuclear areas of enlarged nuclei were similar in CK20(+) and CK20(-) CIS (26.9 vs. 24.5 µM2; P=0.31). Average Ki67 index for CK20(+) CIS was higher than CK20(-) CIS (31.1% vs. 18.3%; P=0.03). Patients with CK20(+) CIS [28 (65%)] and patients with CK20(-) CIS [15 (35%)] had the same rates of Bacillus Calmete-Guerin (BCG) failure but patients with CK20(-) CIS had higher stage progression [3 CK20(+) (11%) vs. 6 CK20(-) (40%); P=0.02]. Given recent approval of immune checkpoint inhibitors in patients with CIS refractory to BCG, programmed death ligand-1 expression and colocalization with CD8(+) lymphocytes was investigated as signature of adaptive immune response and was seen in 8 patients regardless of CK20 status and exclusively among patients who failed BCG. Our results confirm that negative CK20 IHC does not exclude CIS and that those patients have similar clinical outcomes as patients with CK20(+) CIS. Programmed death ligand-1 and CD8 colocalization seen among patients who failed BCG therapy is an easy assay to perform to identify patients who could potentially benefit from combined BCG therapy and immune checkpoint inhibition.

Does the addition of AMACR to CK20 help to diagnose challenging cases of urothelial carcinoma in situ?

BackgroundUrothelial carcinoma in situ (CIS) in the bladder can be difficult to diagnose due to factors including procedural artifact, minimal tissue sampled, therapy-related changes, and various CIS growth patterns. Prior data has demonstrated an increase in alpha-methylacyl-CoA-racemase (AMACR) in urothelial CIS, but there is no information on its utility for diagnosing difficult cases. The aim of this investigation was to assess the expression of AMACR that was ordered on equivocal bladder cases during clinical practice.MethodsTransurethral resections of the bladder in which AMACR and CK20 were performed during diagnostic workup were identified and cases with a final diagnosis of CIS (n = 22) or non-neoplastic urothelium (n = 30) were selected. Additionally, cases in which a diagnosis of CIS was rendered without IHC (n = 20) were selected and tested for AMACR expression.ResultsSensitivity of AMACR for CIS diagnosed with IHC during clinical practice was 73% and specificity was 97%, while CK20 was 95% sensitive and 80% specific. Sensitivity of AMACR in CIS diagnosed without IHC was 100%. In all groups, AMACR had inconsistent intensity, compared to CK20 which had consistent, strong intensity.ConclusionsAMACR was usually positive in urothelial CIS and negative in non-neoplastic urothelium. However, it is important to note that AMACR was less sensitive in difficult cases, while CK20 was more sensitive with more consistent, strong staining compared to AMACR.

CK20 and p53 Immunohistochemical Staining Patterns in Urinary Bladder Specimens With Equivocal Atypia.

- Urinary bladder flat carcinoma in situ (CIS) is a worrisome lesion, requiring aggressive surveillance and treatment. Cytokeratin 20 (CK20) and p53 are common immunohistochemical antibodies used to supplement CIS diagnosis in biopsy samples. However, existing data come primarily from unequivocally benign and malignant specimens. - To correlate these markers in specimens with borderline histology with outcomes. - CK20 and p53 immunohistochemistry was analyzed for staining pattern, classified as CIS pattern (both stains yielding strong labeling of the area of concern), discordant (only 1 stain yielding CIS pattern), indeterminate (1 or both stains yielding partial or equivocal labeling), or benign (both stains yielding a benign pattern). - Specimens with equivocal atypia (n = 69) from 65 patients were studied. There were 9 specimens (13%) that had a CIS staining pattern, 18 (26%) were discordant, 31 (45%) were indeterminate, and 11 (16%) were benign. Of the discordant specimens, 13 labeled for CK20 but not p53, whereas 5 showed the opposite. Most specimens (n = 47; 68%) were obtained from patients with a known history of bladder cancer, of which recurrence developed in 27, with an average interval of 37 months (range, 2-216 months). A subset (n = 22; 34%) had no prior history of bladder cancer, from which only 1 patient with CK20-positive/p53-equivocal staining later developed diagnostic carcinoma. - In our cohort of specimens with equivocal urothelial atypia, very few patients without a prior diagnosis of bladder cancer progressed to diagnostic cancer (1 of 22), suggesting that staining results should be interpreted with caution in de novo atypia. Patients with a known history of bladder cancer had a substantial rate of recurrence, independent of staining pattern.

Outpatient photodynamic-guided diagnosis of carcinoma in situ with flexible cystoscopy: an alternative to conventional inpatient photodynamic-guided bladder biopsies in the operating theatre?

Objective: The aim of this prospective open comparative study was to establish whether conventional photodynamic-guided bladder biopsies using general anaesthesia and rigid resectoscopes (inpatient) can be replaced with less traumatic flexible cystoscopy in non-sedated patients (outpatient), without compromising the diagnosis of carcinoma in situ (CIS).Materials and methods: Thirty-one patients were included. After BCG instillation for CIS, bladder biopsies were obtained using photodynamic-guided flexible cystoscopy. Two weeks later, patients underwent the conventional inpatient procedure. An external pathologist reviewed the biopsy samples. Pain and quality of life (QoL) symptom score were recorded.Results: Post-BCG biopsies showed only CIS in 10 patients; high-grade Ta or T1 tumour in three patients, who were referred for cystectomy; and normal or low-grade tumour tissue in 18 patients. There was a high agreement of identification of high-grade disease in biopsies and cytology using the two methods (κ = 0.93, 95% confidence interval 0.8–1.0). The outpatient procedure identified four high-grade patients diagnosed as ‘normal/low-grade’ in the inpatient procedure. The opposite was observed in two patients. Quality of biopsies did not differ between the two procedures. Pain scores for outpatients were low, and median QoL symptom score was significantly lower than for inpatients (24 vs 33, p = 0.02). Hospital length of stay was significantly longer for inpatients.Conclusions: Outpatient photodynamic-guided flexible cystoscopy is less traumatic than the conventional inpatient procedure in the diagnosis of CIS. It is safe and cost-effective, and may be an alternative to conventional inpatient biopsy procedures in patients with malignant urine cytology and normal white-light cystoscopy.

MP15-08 HIGH GRADE NON-INVASIVE RECURRENCE FOLLOWING INDUCTION BCG FOR PT1/CIS UROTHELIAL CARCINOMA OF BLADDER, IS IT AN INDICATION FOR CYSTECTOMY?

You have accessJournal of UrologyBladder Cancer: Non-invasive I1 Apr 2017MP15-08 HIGH GRADE NON-INVASIVE RECURRENCE FOLLOWING INDUCTION BCG FOR PT1/CIS UROTHELIAL CARCINOMA OF BLADDER, IS IT AN INDICATION FOR CYSTECTOMY? Manmeet Saluja, Daljit Kaur, Jonathan Masters, Andrew Williams, Michael Rice, and Kamran Zargar-Shoshtari Manmeet SalujaManmeet Saluja More articles by this author , Daljit KaurDaljit Kaur More articles by this author , Jonathan MastersJonathan Masters More articles by this author , Andrew WilliamsAndrew Williams More articles by this author , Michael RiceMichael Rice More articles by this author , and Kamran Zargar-ShoshtariKamran Zargar-Shoshtari More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.493AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES For most patients with pT1 and Carcinoma in situ (CIS) urothelial carcinoma of the bladder (UCB), intravesical induction Bacillus Calmette Guérin (IND-BCG) is considered the gold standard treatment. However the criteria to abandon BCG therapy (i.e. BCG failure) in cases of recurrent but non-progressive UC can be vague. In this study we aim to assess a large cohort of CIS and pT1 UCB patients treated with intravesical IND-BCG and report on the outcomes according to the grade and stage of recurrences following IND-BCG. METHODS The data is from a single academic institution which is the only referral site for all BCG therapies for a large metropolitan area. Patients with initial diagnosis of pT1 and CIS received induction course of intravesical BCG. Post induction cystoscopy was carried out for all patients, and follow up was three monthly for the first two years, and at least biannually thereafter. RESULTS From 2001 to 2014, 261 patients received IND-BCG for pT1/CIS. Post BCG status were as follows: 132 (51%) pT0, 48 (18%) CIS, 31 (12%) pT1, 32 (12%) pTaHG and 10 (4%) pTaLG. Of the patients who were pT0 post-BCG, 74% remained disease free at a median of 8 mo. 19% developed high-grade recurrences including 4% with muscle invasive UC (MIUC) at a median of 16 mo (12-27) from diagnosis. Of patients with residual CIS, 60% responded to further BCG, with progression to invasive disease in 13%. Of residual pTaHG patients, 53% became pT0 and 9% eventually had cystectomy at 32.4 mo for disease progression to CIS or =pT1. 10 patients had pTa-LG recurrence and one required cystectomy. Only 36% of residual pT1 patients became pT0 with 29% developing invasive disease. 39% of pT1 compared to 17% of the CIS required cystectomy at a median of 17.5 mo (p=0.036). pT0 rates were significantly higher for CIS patients compared to pT1 (60% vs. 36%, 0.047), but similar between CIS and pTaHG. CONCLUSIONS Non-invasive recurrence of high grade UC following BCG may respond to further intravesical therapy however response is less likely in recurrent pT1 UC. Following BCG recurrent non-invasive high © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e173-e174 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Manmeet Saluja More articles by this author Daljit Kaur More articles by this author Jonathan Masters More articles by this author Andrew Williams More articles by this author Michael Rice More articles by this author Kamran Zargar-Shoshtari More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A meta-analysis of narrow band imaging for the diagnosis and therapeutic outcome of non-muscle invasive bladder cancer.

ObjectivesTo assess the additional detection rate (ADR) of within-patient comparisons of Narrow band imaging (NBI) and white light cystoscopy (WLC) for non-muscle invasive bladder cancer (NMIBC) detection and compare the impact of NBI and WLC on bladder cancer recurrence risk.MethodsWe searched relevant studies from PubMed, Embase, Medline, Web of Science and the Cochrane Library database for all articles in English published beforeJuly26th, 2016. Pooled ADR, diagnostic accuracy, relative risk (RR) and their 95% confidence intervals (CIs) were calculated.ResultsTwenty-five studies including 17 full texts and eight meeting abstracts were included for analysis. Compared to WLC, pooled ADR of NBI for NMIBC diagnosis was 9.9% (95% CI: 0.05–0.14) and 18.6% (95% CI: 0.15–0.25) in per-patient and per-lesion analysis, respectively. Pooled ADR of NBI for carcinoma in situ (CIS) diagnosis was 25.1% (95% CI: 0.09–0.42) and 31.1% (95% CI: 0.24–0.39) for per-patient and per-lesion analyses, respectively. The pooled sensitivity of NBI was significantly higher than WLC both at the per-patient (95.8% vs. 81.6%) and per-lesion levels (94.8% vs. 72.4%). In addition, NBI significantly reduced the recurrence rate of bladder cancer with a pooled RR value of 0.43 (95% CI: 0.23–0.79) and0.81 (95% CI: 0.69–0.95) at month three and twelve, respectively.ConclusionsNBI is a valid technique that improves the diagnosis of NMIBC and CIS compared to standard WLC either at per-patient or per-lesion level. It can reduce the recurrence rate of bladder cancer accordingly.

PD25-02 DIAGNOSTIC ACCURACY OF PROBE BASED CONFOCAL LASER ENDOMICROSCOPY IN BLADDER CANCER

INTRODUCTION AND OBJECTIVES: Probe based confocal laser endomicroscopy (pCLE) is a novel optical technology designed for real-time, in vivo histological assessment without taking biopsy. We evaluate the diagnostic accuracy of pCLE in prospective examination of bladder neoplastic lesions. METHODS: Patients were prospectively recruited to undergo transurethral resection of bladder (TURBT) based on abnormal cystoscopy. After white-light cystoscopy (WLC), CLE was performed to obtain diagnostic images. Confocal images were compared to histologic result using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In total 51 patients with 104 lesions were evaluated comprising 19 benign lesions (2 papilloma, 16 inflammation, 1 low malignant potential) and 85 malignant lesions (12 low grade, 55 high grade, 18 carcinoma in situ). The pCLE was found to have a cancer detection rate of 96.47%, and a false positive rate of 8.9%. The overall sensitivity for diagnosis of high grade papillary tumor versus low grade papillary tumor was 89.09% (95% confidence interval [CI], 80.85-97.33), specificity was 75.00% (95% CI, 50.5-99.5), PPV was 94.23% (95% CI, 87.89-100.57), and the NPV was 60.00% (95% CI, 35.21-84.79). The overall sensitivity for diagnosis of CIS versus inflammation was 83.33% (95% CI, 66.12-100.55), specificity was 62.50% (95% CI, 38.78-86.22), PPV was 71.43% (95% CI, 52.11-90.75), and the NPV was 76.92% (95% CI, 54.02-99.83). CONCLUSIONS: The pCLE is promissing method for detection of malignant lesion, high grade papillary tumor and carcinoma in situ (CIS). Therefore, use of pCLE may minimize the recurrence and positive resection margins associated with conventional white-light cystoscopic biopsy, ensure complete TURBT. Source of Funding: none

PD17-04 MOST PATIENTS WITH CARCINOMA IN SITU OF THE BLADDER ARE NOT RECEIVING INTRAVESICAL BACILLE CALMETTE-GUERIN (BCG)

You have accessJournal of UrologyBladder Cancer: Non-invasive II1 Apr 2015PD17-04 MOST PATIENTS WITH CARCINOMA IN SITU OF THE BLADDER ARE NOT RECEIVING INTRAVESICAL BACILLE CALMETTE-GUERIN (BCG) Phillipe Nabbout, Sean Elliott, Oluwakayode Adejoro, and Joel Slaton Phillipe NabboutPhillipe Nabbout More articles by this author , Sean ElliottSean Elliott More articles by this author , Oluwakayode AdejoroOluwakayode Adejoro More articles by this author , and Joel SlatonJoel Slaton More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.661AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The current standard of care for treatment of isolated carcinoma in situ (CIS) of the bladder recommends an induction course of BCG as well as maintenance therapy in the setting of a good response. Given the current shortage of BCG and reports of its underuse by urologists, investigation of the factors associated with use of BCG in this population may be useful in identifying patients who are at risk of not receiving BCG METHODS We interrogated the SEER-Medicare database to identify all patients with an initial diagnosis of CIS of the bladder. Patients with mixed pathology (Ta or T1) or nonurothelial histology were excluded. Treatment after initial biopsy was identified(intravesical BCG or chemotherapy, cystectomy, or none). Patients receiving maintenance BCG were identified. Patients were characterized for age, race, gender, education, and income. Time to cystectomy, cancer-specific survival and overall survival were determined. RESULTS 3782 patients presented with CIS with an increasing rate from 3% in the first fiver years of study and-9% in the last five years. 75% were men and most were older than 75 yrs. Overall 9.5% of patient initially received BCG, 5.4% received mitomycin, and 85.1% reeceived no adjuvant therapy. From 1992-96, the BCG rate was 9.1%; from 2005-9, it was 10.1% The factors most closely associated with not receiving BCG were region of country (-22%, west - 10%, south 6%, northeast -4%) and wealth (12% for wealthiest vs 8% for the poorest). Among patients receiving BCG, 32% underwent either additional induction course or maintenance courses. The time to cystectomy was longer among those who received BCG compared to those who did not (24 months vs 14 month) Use of BCG was associated with superior overall survival compared to those who did not (p=0.004). CONCLUSIONS Despite being the standard of care, the number of patients with CIS of the bladder undergoing intravesical BCG is surprisingly low with few going on to receive maintenance therapy. Use of BCG is associated with lower rates of eventual cystectomy and improved overall survival. Efforts need to be made to educate our colleagues of the importance of BCG in the CIS population and given the current shortage of BCG, to explore use of alternative strategies such as use of intravesical therapy with multiple chemotherapeutic agents. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e382 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Phillipe Nabbout More articles by this author Sean Elliott More articles by this author Oluwakayode Adejoro More articles by this author Joel Slaton More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Photodynamic diagnosis - current tool in diagnosis of carcinoma in situ of the urinary bladder.

Photodynamic diagnosis - current tool in diagnosis of carcinoma in situ of the urinary bladder.

Contralateral biopsy in the management of testicular cancer: what we have learned and what we need to improve

Contralateral biopsy in the management of testicular cancer: what we have learned and what we need to improve

Carcinoma in-situ of the oral mucosa: Its pathological diagnostic concept based on the recognition of histological varieties proposed in the JSOP Oral CIS Catalog

ObjectiveThis article documents the process that led to the publication of the “Oral CIS (JSOP) Catalog” by the Working Committee on New Histopathological Criteria for Borderline Malignancies of the Oral Mucosa, a group which was organized within the Japanese Society of Oral Pathology between 2004 and 2007. MethodsThe committee collected 160 cases histologically diagnosed as oral carcinoma in-situ (CIS) at 20 hospitals to which the committee members belonged, and five sets of hematoxylin and eosin stained sections of those cases were circulated in five routes among 25 committee members for reviewing for their own diagnoses. Their diagnoses were collected, and cases diagnosed as CIS by more than 70% of the members were selected for further discussion. ResultsCommittee members wanted to emphasize that oral CIS contained greater histological variety than had previously been defined, and they came to the eventual conclusion that two major histological variations of oral CIS, basaloid and differentiated, were distinguishable. In particular, they emphasized that oral CIS had a definite tendency toward keratinization or that it was well differentiated. They also recommended the use of immunohistochemistry for Ki-67 and keratin subtypes as an essential aid tool for oral CIS diagnosis. ConclusionBy referring to the Catalog, which explains histopathological variations, pathologists can more easily make a diagnosis of oral CIS, and oral surgeons can carry out appropriate clinical interventions for treating oral borderline malignancies.

Utility of a Triple Antibody Cocktail Intraurothelial Neoplasm-3 (IUN-3-CK20/CD44s/p53) and α-Methylacyl-CoA Racemase (AMACR) in the Distinction of Urothelial Carcinoma In Situ (CIS) and Reactive Urothelial Atypia

Urothelial carcinoma in situ (CIS) is a prognostically and therapeutically significant lesion with considerable morphologic overlap with reactive conditions especially in the setting of prior therapy. Various markers including CK20, CD44s, and p53 have been used as an adjunct in making this distinction; however, the utility of these markers in the posttreatment scenario is not fully established. α-Methylacyl-CoA racemase (AMACR) is a tumor-associated marker that is expressed in a subset of high-grade urothelial carcinomas but has not been studied in CIS. This study was undertaken to evaluate the immunoreactivity of CK20, CD44s, and p53 as a triple antibody cocktail intraurothelial neoplasm-3 (IUN-3) in distinguishing CIS from its mimics and to compare its utility with AMACR in the diagnosis of CIS. A total of 135 specimens (7 benign ureters and 128 bladder biopsies-28 reactive, 33 posttherapy reactive, 43 CIS, 24 CIS posttherapy) were included in this study. Immunostaining for p53 (brown, nuclear), CD44s (brown, membranous), and CK20 (red, cytoplasmic and membranous) was performed as a cocktail, and the staining pattern was further classified as: malignant (full-thickness CK20 and/or full-thickness p53 with CD44s negativity), reactive/benign (CK20 limited to the umbrella cell layer, p53 negative, and CD44s positivity ranging from basal to full thickness), and indeterminate (CK20 and p53 positive but not full thickness and/or CD44s positive). AMACR staining was performed in 50 cases. Cytoplasmic staining for AMACR was graded as negative (absent to weak focal staining [<5% cells]) and positive (≥5%). The "IUN-3 malignant" pattern was observed in 84% of cases of CIS without a history of prior therapy and in 71% of the cases of CIS with a history of prior therapy. Cases with posttherapy reactive atypia showed an "IUN-3 reactive" pattern in 84% cases and "IUN-3 indeterminate" pattern in 16% of the cases; the IUN-3 malignant pattern was not identified in any of the cases. Benign and reactive urothelium (with and without a history of therapy) showed an IUN-3 reactive pattern and negative AMACR staining in all the cases (100%). AMACR positivity was observed in 78% of nontreated CIS cases and 50% of CIS posttherapy cases. In these cases, the IUN-3 cocktail showed an IUN-3 malignant pattern in 83% of untreated CIS cases and 88% of CIS posttherapy cases. AMACR positivity is a potentially useful marker of CIS. However, the IUN-3 malignant pattern is a more reliable indicator of CIS compared with AMACR, especially in the posttreatment setting. The simultaneous evaluation of all 3 markers (p53, CD44s, and CK20) in a single slide in the form of a cocktail is advantageous, especially in small biopsy specimens.

The role of immunohistochemistry in the diagnosis of flat urothelial lesions: a study using CK20, CK5/6, P53, Cd138, and Her2/Neu

Although differentiating reactive urothelial atypia from urothelial carcinoma in situ (CIS) relies primarily on histologic evaluation, confirming the morphologic impression using immunohistochemistry (IHC) has been increasingly used in routine clinical practice. The aims of this study are to confirm the utility of commonly used markers (CK20, P53) and to test the performance of CK5/6, CD138, and Her2/Neu in the diagnosis of CIS. Using a tissue microarray comprising 52 cases of normal/reactive urothelium and 45 cases of CIS, the IHC evaluation of 5 markers was undertaken. Although the individual specificity of CK20, P53, and Her2/Neu was high (94%, 90%, and 93%, respectively), their sensitivity for CIS detection was lower, with the most sensitive marker being HER2/Neu (63%). Whereas 78% of CIS shows positivity of at least 2 of those 3 markers, only 1 case of reactive urothelium shows positivity for 2 of those 3 markers. The discriminatory performance of CK5/6 and CD138 was poor. In conclusion, HER2/Neu can be added to a panel of CK20 and P53 to help differentiate reactive atypia from CIS in difficult cases. Positive staining for at least 2 of the 3 antibodies (CK20, P53, and HER2/Neu) is strongly associated with CIS. However, the histologic findings should be a primary determinant in the diagnosis of flat urothelial lesions, with IHC playing a supportive confirmatory role.

CIS of the bladder: a review of literature

Carcinoma in situ (CIS) of the bladder poses a clinical challenge to urologists worldwide. The clinical course of CIS ranges from benign, indolent tumor growth to highly progressive tumor proliferation with deleterious effects on patient outcome and increased disease-specific mortality. The aim of our review was to outline the natural history of bladder CIS in a single concise source for young urologists. We performed a PubMed review of the literature on CIS of the bladder. We used CIS, BCG and superficial bladder cancer as the keywords for our search. Following a group discussion, the authors selected 77 important publications to be included in our review article. The presence of bladder CIS increases the risk of panurothelial disease involving the prostate, urethra or upper urinary tracts. Urine cytology is the primary approach for the diagnosis of CIS. Intravesical BCG remains the gold standard for the initial treatment of CIS. Early radical cystectomy for cases that present BCG failure showed a higher rate of success with long-term cure. Frozen section biopsy of the distal ureter should be performed when CIS of the bladder has been preoperatively diagnosed. Whether frozen section biopsy was performed and regardless of the condition of the distal ureter at the time of cystectomy, postoperative follow-up with cytology, endoscopy of the new pouch and ureteroscopy of the ureters is recommended for early detection of possible recurrence.