Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers.

BACKGROUND: Bladder cancer (BC) is highly immunogenic. Bacillus Calmette-Guérin (BCG) immunotherapy offers the best results in non-muscle-invasive BC (NMIBC). Natural killer cells (NKcs) play decisive roles in BCG-mediated immune response and in general cancer immune-surveillance. OBJECTIVE: To analyze killer-cell immunoglobulin-like receptors (KIRs), their human leukocyte antigen class-I (HLA-I) ligands, and the expression of DNAX Accessory Molecule-1 (DNAM-1/CD226) on peripheral blood (PB) NKcs, to identify useful predictive biomarkers in BC. DESIGN, SETTING, AND PARTICIPANTS: KIR/HLA-ligand genotypes were compared between 132 BC, 201 other solid cancers, 164 plasma cell disorders, and 615 healthy Caucasoid controls. CD226 expression was evaluated by flow cytometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: KIR/HLA-I interactions and CD226 expression on NKcs (CD226high or CD226low) were compared across study groups, cancer stages, treatments, and progression-free and overall survival of patients, using chi-square, analysis of variance/post hoc, Kaplan-Meier/log-rank, and regression analyses. RESULTS AND LIMITATIONS: Three immunological risk groups were identified: low risk (KIR2DL1-L2+L3-/C1C1- and KIR2DL1+L2+L3+/C1C1+), intermediate risk (rest), and high risk (KIR2DL5+/HLA-C*16+ and KIR2DL1+L2+L3-), which displayed different 10-yr progression-free rates (83.3%, 48.6%, and 0%, respectively; p<0.001) and survival rates (83.3%, 54.3%, and 6.2%, respectively; p<0.001) for muscle-invasive T2/T4, and 10-yr progression-free rates (100%, 81.6%, and 50%, respectively; p<0.05) for NMIBC-T1 treated with BCG. Immunological risk stratification had an independent prognostic value to just histological staging for survival (hazard ratio=2.93, p<0.00001, Harrell C-statistic=0.779). CD226 expression on PB NKcs improved immunological stratification in intermediate-risk T1-T4 BC patients, with survival rates of 94.1% and 66.7% for CD226high and CD226low (p<0.05), respectively. CONCLUSIONS: Immunological risk stratification will complement BC histopathology to improve risk stratification and guide the selection of personalized treatments. Understanding of the molecular mechanisms of NKc tumor immune surveillance will enable the development of future NKc-based therapies. PATIENT SUMMARY: This work describes a peripheral blood test that aids in our understanding of the immune defense mechanisms against bladder cancer, is useful for classifying patient risk, and will guide personalized treatments.

Optimisation of sonourethrography: the clamp method.

PURPOSE: To describe the clamp method for performing retrograde sonourethrography (RSUG) and contrast-enhanced voiding sonourethrography (CE-VSUG) via the transperineal approach in male adults. MATERIALS AND METHODS: Prospective study of 113 males (14-86 years) with urethral strictures confirmed by urethrography who received sonourethrography via the clamp method between 2011 and 2015. The characteristic parameters of the quantitative variables were calculated and a comparative analysis of the qualitative variables was conducted using the McNemar test. RESULTS: RSUG was performed successfully in all the cases (n = 113) and detected 49 cases with anterior urethral strictures; the strictures in the proximal bulbar cone in five of them (10.2%) were not visualised on retrograde urethrography (RUG) (p < 0.05). CE-VSUG was performed successfully in 97 cases and observed posterior urethral strictures in 82; the bladder neck strictures in 6 of them (7.3%) were not observed on voiding cystourethrography (VCUG) (p < 0.05). Retrograde bladder filling was achieved in approximately 6 min. CONCLUSION: The clamp method enables RSUG and CE-VSUG to be performed simply, effectively and painlessly by a single operator. It also allows the evaluation of cases with urethromeatal alterations (stricture, hypospadias and meatotomy). KEY POINTS: • The clamp method enables RSUG to be performed simply and painlessly. • The clamp method requires only one operator and allows assessing urethromeatal alterations. • RSUG shows greater capacity for detecting anterior urethral strictures than RUG. • The clamp method achieves retrograde bladder filling in approximately 6 min. • CE-VSUG shows greater capacity for detecting strictures than VCUG.