Validation of confocal laser endomicroscopy features of bladder cancer: The next step towards real-time histologic grading

Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for real-time in vivo microscopic imaging of bladder tissue. In this first validation of CLE features, we confirm that the proposed CLE features suffice for real-time tumour grading.Background: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy. Objective: To validate and adapt CLE criteria for bladder cancer diagnosis and grading. Design, setting, and participants: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison. Intervention: Cystoscopic CLE imaging. Outcome measurements and statistical analysis: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2 × 2 tables. Results and limitations: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%). Conclusions: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify. Patient summary: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management.Cure Brain Cancer FoundationCure for Cancer Foundatio

Prostate-specific markers to identify rare prostate cancer cells in liquid biopsies

WOS: 000455051200006PubMed ID: 30479377Despite improvements in early detection and advances in treatment, patients with prostate cancer continue to die from their disease. Minimal residual disease after primary definitive treatment can lead to relapse and distant metastases, and increasing evidence suggests that circulating tumour cells (CTCs) and bone marrow-derived disseminated tumour cells (BM-DTCs) can offer clinically relevant biological insights into prostate cancer dissemination and metastasis. Using epithelial markers to accurately detect CTCs and BM-DTCs is associated with difficulties, and prostate-specific markers are needed for the detection of these cells using rare cell assays. Putative prostate-specific markers have been identified, and an optimized strategy for staining rare cancer cells from liquid biopsies using these markers is required. The ideal prostate-specific marker will be expressed on every CTC or BM-DTC throughout disease progression (giving high sensitivity) and will not be expressed on non-prostate-cancer cells in the sample (giving high specificity). Some markers might not be specific enough to the prostate to be used as individual markers of prostate cancer cells, whereas others could be truly prostate-specific and would make ideal markers for use in rare cell assays. The goal of future studies is to use sensitive and specific prostate markers to consistently and reliably identify rare cancer cells.NCI [F32CA206394, U54CA143803, CA163124, CA093900, CA143055]; Prostate Cancer Foundation; Patrick C. Walsh Fund; Cure for Cancer FoundationThis work is supported by NCI grants U54CA143803, CA163124, CA093900, and CA143055 as well as the Prostate Cancer Foundation, the Patrick C. Walsh Fund and a gift from the Stutt family. E.E.v.d.T. is supported by the Cure for Cancer Foundation. K.C.V. is supported by NCI grant F32CA206394