Joerg Schmidbauer

Photodynamic Diagnosis of Non–muscle-invasive Bladder Cancer with Hexaminolevulinate Cystoscopy: A Meta-analysis of Detection and Recurrence Based on Raw Data

BACKGROUND Studies on hexaminolevulinate (HAL) cystoscopy report improved detection of bladder tumours. However, recent meta-analyses report conflicting effects on recurrence. OBJECTIVE To assess available clinical data for blue light (BL) HAL cystoscopy on the detection of Ta/T1 and carcinoma in situ (CIS) tumours, and on tumour recurrence. DESIGN, SETTING, AND PARTICIPANTS This meta-analysis reviewed raw data from prospective studies on 1345 patients with known or suspected non-muscle-invasive bladder cancer (NMIBC). INTERVENTION A single application of HAL cystoscopy was used as an adjunct to white light (WL) cystoscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS We studied the detection of NMIBC (intention to treat [ITT]: n=831; six studies) and recurrence (per protocol: n=634; three studies) up to 1 yr. DerSimonian and Lairds random-effects model was used to obtain pooled relative risks (RRs) and associated 95% confidence intervals (CIs) for outcomes for detection. RESULTS AND LIMITATIONS BL cystoscopy detected significantly more Ta tumours (14.7%; p<0.001; odds ratio [OR]: 4.898; 95% CI, 1.937-12.390) and CIS lesions (40.8%; p<0.001; OR: 12.372; 95% CI, 6.343-24.133) than WL. There were 24.9% patients with at least one additional Ta/T1 tumour seen with BL (p<0.001), significant also in patients with primary (20.7%; p<0.001) and recurrent cancer (27.7%; p<0.001), and in patients at high risk (27.0%; p<0.001) and intermediate risk (35.7%; p=0.004). In 26.7% of patients, CIS was detected only by BL (p<0.001) and was also significant in patients with primary (28.0%; p<0.001) and recurrent cancer (25.0%; p<0.001). Recurrence rates up to 12 mo were significantly lower overall with BL, 34.5% versus 45.4% (p=0.006; RR: 0.761 [0.627-0.924]), and lower in patients with T1 or CIS (p=0.052; RR: 0.696 [0.482-1.003]), Ta (p=0.040; RR: 0.804 [0.653-0.991]), and in high-risk (p=0.050) and low-risk (p=0.029) subgroups. Some subgroups had too few patients to allow statistically meaningful analysis. Heterogeneity was minimised by the statistical analysis method used. CONCLUSIONS This meta-analysis confirms that HAL BL cystoscopy significantly improves the detection of bladder tumours leading to a reduction of recurrence at 9-12 mo. The benefit is independent of the level of risk and is evident in patients with Ta, T1, CIS, primary, and recurrent cancer.

Hybrid renal cell carcinomas containing histopathologic features of chromophobe renal cell carcinomas and oncocytomas have excellent oncologic outcomes.

BACKGROUND Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe-oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear. OBJECTIVE To determine the clinical course of hybrid RCC. DESIGN, SETTING, AND PARTICIPANTS Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells). INTERVENTIONS Radical tumor nephrectomy or nephron-sparing surgery. MEASUREMENTS Recurrence-free and tumor-specific survival. RESULTS AND LIMITATIONS Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n=17), pT2 in 23.5% of tumors (n=8), and pT3a in 26.5% of tumors (n=9). Low-grade RCC was found in 76.5% of tumors (n=26), and vascular invasion was found in 11.8% of tumors (n=4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively. CONCLUSIONS Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses.

Fluorescence Cystoscopy with High-Resolution Optical Coherence Tomography Imaging as an Adjunct Reduces False-Positive Findings in the Diagnosis of Urothelial Carcinoma of the Bladder

BACKGROUND The advantage of photodynamic diagnosis in detecting urothelial cell carcinoma (UCC) of the bladder has been demonstrated clearly, but it comes at the price of a higher false-positive rate. Optical coherence tomography (OCT) is a noninvasive, real-time, microstructural imaging modality that uses near-infrared light for a point analysis of the bladder-wall microstructure. OBJECTIVE To evaluate whether adding targeted OCT analysis of lesions that are suspicious at white-light (WL) and hexaminolevulinate (HAL) fluorescence cystoscopy improves diagnostic accuracy in the detection of UCC. DESIGN, SETTING, AND PARTICIPANTS In this prospective single-center study with same-patient comparison, patients with suspected UCC first received an intravesical instillation of HAL. Cystoscopy was performed in WL, followed by blue-light inspection and OCT scanning. INTERVENTION Suspicious lesions identified by WL or HAL were evaluated by OCT and were subsequently resected or biopsied. MEASUREMENTS We measured changes in sensitivity and specificity in detecting UCC using WL, HAL, and targeted OCT. RESULTS AND LIMITATIONS In 66 patients studied, 232 lesions were detected, were scanned by OCT, and were subsequently resected or biopsied. Additionally, 132 areas of normal-appearing urothelium were investigated by all three methods and biopsied. On a per-lesion basis, sensitivity and specificity were respectively 69.3% and 83.7% for WL, 97.5% and 78.6% for HAL, and 97.5% and 97.9% for HAL combined with OCT. Overall, UCC was diagnosed in 58 patients (87.9%), with a per-patient sensitivity of 89.7% for WL and 100% for both HAL alone and HAL with targeted OCT. Per-patient specificity for HAL alone and targeted HAL was 62.5% and 87.5%, respectively. The limitation of OCT results from poor visualization of flat lesions in WL, making scanning a time-consuming procedure. CONCLUSIONS Combining fluorescence cystoscopy with targeted OCT increases the specificity of fluorescence cystoscopy significantly, with no added morbidity, and reduces the need for unnecessary (false-positive) biopsies.

Technical solutions to improve the management of non‐muscle‐invasive transitional cell carcinoma: summary of a European Association of Urology Section for Uro‐Technology (ESUT) and Section for Uro‐Oncology (ESOU) expert meeting and current and future perspectives

The aim of the present review was to compare state‐of‐the‐art care and future perspectives for the detection and treatment of non‐muscle‐invasive transitional cell carcinoma (TCC) of the bladder. We provide a summary of the third expert meeting on ‘Optimising the management of non‐muscle‐invasive bladder cancer, organized by the European Association of Urology Section for Uro‐Technology (ESUT) in collaboration with the Section for Uro‐Oncology (ESOU), including a systematic literature review. The article includes a detailed discussion on the current and future perspectives for TCC, including photodynamic diagnosis, optical coherence tomography, narrow band imaging, the Storz Professional Image Enhancement system, magnification and high definition techniques. We also provide a detailed discussion of future surgical treatment options, including en bloc resection and tumour enucleation. Intensive research has been conducted to improve tumour detection and there are promising future perspectives, that require proven clinical efficacy. En bloc resection of bladder tumours may be advantageous, but is currently considered to be experimental.

Gene expression test for the non-invasive diagnosis of bladder cancer: A prospective, blinded, international and multicenter validation study

OBJECTIVE This study aimed to validate, in a prospective, blinded, international and multicenter cohort, our previously reported four non-invasive tests for bladder cancer (BC) diagnosis based on the gene expression patterns of urine. METHODS Consecutive voided urine samples from BC patients and controls were prospectively collected in five European centres (n=789). Finally, 525 samples were successfully analysed. Gene expression values were quantified using TaqMan Arrays and previously reported diagnostic algorithms were applied to gene expression data. Results from the most accurate gene signature for BC diagnosis were associated with clinical parameters using analysis of variance test. RESULTS High diagnostic accuracy for the four gene signatures was found in the independent validation set (area under curve [AUC]=0.903-0.918), with the signature composed of two genes (GS_D2) having the best performance (sensitivity: 81.48%; specificity: 91.26%; AUC: 0.918). The diagnostic accuracy of GS_D2 was not affected by the number of tumours (p=0.58) but was statistically associated with tumour size (p=0.008). Also, GS_D2 diagnostic accuracy increases with increasing BC tumour risk. We found no differences in the performance of the GS_D2 test among the populations and centres in detecting tumours (p=0.7) and controls (p=0.2). CONCLUSIONS Our GS_D2 test is non-invasive, non-observer dependent and non-labour-intensive, and has demonstrated diagnostic accuracy in an independent, international and multicenter study, equal or superior to the current gold standard (cystoscopy combined with cytology). Additionally, it has higher sensitivity than cytology while maintaining its specificity. Consequently, it meets the requirements for consideration as a molecular test applicable to clinical practice in the management of BC.

Follow-up of nonmuscle invasive transitional cell carcinoma of the bladder: how and how often?

Purpose of review Nonmuscle invasive bladder cancer represents a heterogeneous disease due to different natural history of its various appearances. The purpose of this article is to review recent literature regarding follow-up strategies. Recent findings Management of nonmuscle invasive bladder cancer has become more complex in respect to diagnosis, treatment and follow-up. Follow-up should therefore be based on individual patient-risk assessment. In addition to improved diagnosis by fluorescence-guided cystoscopy and other new diagnostic tools like optical-coherence tomography management has concentrated on optimizing different concepts of intravesical therapy. Summary The intent of nonmuscle invasive bladder cancer management is to control recurrence and progression and to identify invasive tumours at the earliest possible stage. To obtain exact staging, besides a proper transurethral resection of bladder, a restaging transurethral resection of bladder should be performed in T1 patients. Data from the literature supports the immediate postoperative intravesical instillation of different chemotherapeutic agents in low-risk patients. Multifocal papillary lesions might necessitate a more intensive adjuvant regimen, whereas intravesical immunotherapy using bacillus Calmette-Guerin is recommended in patients who are at a high-risk of progression. Early cystectomy should be considered in patients with recurrent T1 tumours or refractory carcinoma in situ to avoid unfavourable tumour progression.

Intraoperative imprint cytology for real-time assessment of surgical margins during partial nephrectomy: A comparison with frozen section

INTRODUCTION Partial nephrectomy (PN) is the standard therapy for small renal masses. Resection margin assessment continues to be a key issue during PN. Biopsy of the residual kidney and intraoperative gross pathological consultations are the most common methods today. Intraoperative imprint cytology (IC) examinations have been successfully used in other tumor entities to assess surgical margins. We aim to evaluate the diagnostic value of intraoperative IC for surgical margin assessment during PN. MATERIALS AND METHODS In addition to routinely performed frozen-section (FS) analysis, intraoperative IC examinations were performed on 114 tumors, which were resected with PN in our department between 2005 and 2010. These 2 were then matched with final histopathological examination findings. Before FS, roll-off IC slides were obtained, air dried, and stained by Hemacolor quick staining. Both the pathologist and the cytologist were blinded to the findings. RESULTS Our study included 29 women and 76 men. Of 331 IC slides, 317 (96%) contained sufficient diagnostic cells. IC revealed 21 tumors with positive resection margins. Of the 21 positive resection margins, 2 were false positives. IC showed a specificity of 98%, sensitivity of 100%, a positive predictive value of 90%, and negative predictive value of 100%. FS examinations revealed positive resection margins in 20 tumors. One of these 20 margins was false positive. Furthermore FS examination failed to diagnose a positive resection margin in 1 tumor. FS examination showed a specificity of 99% and sensitivity of 98% in assessing surgical margins with a positive predictive value of 95% and negative predictive value 98%. CONCLUSION IC examinations exhibit equivalent diagnostic value compared with FS analysis. IC is an inexpensive method with an ability to give rapid and highly accurate information. Like any cytological examination, there is interobserver variability. IC could be considered as an alternative to FS especially when the nature of resection margins is suspected but further investigations are necessary.