Outcome of sentinel lymph node biopsy in patients with clinically non-metastatic renal cell carcinoma.

OBJECTIVE: To investigate the rate of occult SN metastases, oncological outcome, and association of recurrence with the pattern of lymphatic tumour drainage in RCC. MATERIALS AND METHODS: A pooled RCC sub-group analysis was conducted of secondary endpoints from a published feasibility and a phase II prospective single-arm SN study to investigate oncological outcome. Patients with cT1-3 (<10 cm) cN0M0 RCC of any sub-type were enrolled. After intratumoural injection of Tc99m nanocolloid, pre-operative imaging of SNs with SPECT/CT was followed by (partial) nephrectomy with SN and regional lymph node dissection using a γ-probe. The patients were followed with a risk-adapted surveillance programme. Endpoints of the studies were analysed using Cox proportional hazard models. RESULTS: Sixty-six RCC patients were included. Two patients (3%, 95% CI =0.5-11%) had occult SN metastases and remained free of disease at 57 and 72 months. Ten patients (15%, 95% CI =7-26%) developed recurrences, and four (6%, 95% CI =2.3-14.5%) had died of disease at a median follow-up of 57 months (IQR =18-72 months). Occurrence of distant metachronous metastases were associated with tumour size (HR =1.39, p = 0.02), pT stage (HR =6.83, p < 0.01 for comparison T1 vs T3/4), Grade 3/4 (HR =8.38, p = 0.05 for comparison 1/2 vs 3/4) and interaortocaval sentinel lymph node location (HR =10.52, p = 0.03 for comparison yes vs no). CONCLUSIONS: The rate of occult metastatic SN is low, but long disease-free survival (DFS) was observed in two patients with occult SN metastases. We hypothesize an interaortocaval lymphatic route in thoracic recurrences. Evaluation of the prognostic and therapeutic role of sentinel lymph node biopsy (SLNB) requires a clinical trial in high-risk RCC.

The diagnostic accuracy of methylation markers in urine for the detection of bladder cancer: a systematic review.

AIM: Several urinary hypermethylation-markers (hmDNA) have been described for bladder cancer (BC) detection, but none have been able to replace cystoscopy yet. We systematically reviewed and evaluated current literature on urinary hmDNA markers for BC diagnostics. PATIENTS & METHODS: A systematic search of PubMed, EMBASE.com and The Cochrane Library up to February 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was conducted. RESULTS: A total of 30/42 studies included compared gene panels, with varying sensitivities (52-100%) and specificities (0-100%). Considerable heterogeneity across studies was observed and most was case-control studies. CONCLUSION: Reported diagnostic accuracy of urinary hmDNA for BC detection is highly variable and there is a lack of validation studies. Recent studies indicate that complementary markers are needed to allow for clinical implementation.

Infiltrative lamina propria invasion pattern as an independent predictor for cancer-specific and overall survival of instillation treatment-naïve stage T1 high-grade urothelial bladder cancer.

OBJECTIVES: To investigate established prognostic factors and relatively new histopathological tumor characteristics including metric substage and lamina propria invasion patterns in a large series of T1 high-grade non-muscle-invasive bladder cancer. METHODS: Between 1989 and 2012, 322 patients with initial stage T1 high-grade bladder cancer underwent transurethral resection, followed by re-transurethral resection and a conservative approach with follow-up regime alone or instillation treatment. Transurethral resection specimens were reassessed by two experienced urological pathologists for tumor grade according to the World Health Organization 1973 classification, metric T1 substage, lamina propria invasion pattern and associated carcinoma in situ. The median follow-up period was 42 months (interquartile range 25-72 months). In addition to Kaplan-Meier analyses, uni- and multivariable Cox regression analyses were used to compare progression-free survival, cancer-specific survival and overall survival for the studied parameters comparing two subcohorts. RESULTS: While in patients after instillation treatment no examined feature was shown as an independent predictor for prognosis, there were predictive histopathological features in multivariable Cox regression analyses in instillation treatment-naïve patients: associated carcinoma in situ (hazard ratio 2.278, 95% confidence interval 1.119-4.634, P = 0.023) and World Health Organization 1973 grade 3 (hazard ratio 2.950, 95% confidence interval 1.021-8.536, P = 0.046) for worse progression-free survival, infiltrative lamina propria tumor pattern for worse cancer-specific survival (hazard ratio 2.369, 95% confidence interval 1.034-5.429, P = 0.042) and overall survival (hazard ratio 1.049, 95% confidence interval 1.024-1.075, P = 0.001). CONCLUSIONS: The results of the present T1 high-grade bladder cancer series suggest that lamina propria invasion pattern is a promising parameter to predict the prognosis of T1 high-grade bladder cancer in an instillation treatment-naïve subcohort. Prospective multicenter evaluations are warranted. The need for instillation treatment in T1 high-grade bladder cancer is clearly demanded.

Detecting primary bladder cancer using delayed (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography imaging after forced diuresis.

OBJECTIVE: The aim of this study was to evaluate the use of delayed pelvic (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography combined with the computed tomography (FDG-PET/CT) imaging, according to a standardized protocol including, pre-hydration and forced diuresis, for the detection of primary bladder cancer. MATERIALS AND METHODS: We evaluated 38 consecutive patients with primary cT1-4 bladder cancer. They underwent standard FDG-PET/CT followed by delayed pelvic imaging after administration of 20 mg furosemide intravenously and extra oral water intake of 0.5 L. Two observers, blinded for patient data, scored both image sets for tumor visibility using a 3-point ordinal scale: (1) negative; (2) indeterminate; (3) positive. FDG-PET/CT findings were compared with histopathology and/or follow-up imaging. RESULTS: The procedure was completed successfully in 37/38 patients and the reference standard revealed a bladder tumor in 26/37 patients. Delayed PET/CT images showed reduction of urinary bladder activity to (near) background levels in 17 of 37 cases (45.9%). Standard PET/CT detected hyper-metabolic bladder lesions in 15/37 patients (40.5%) of which 8 were indeterminate. Delayed FDG-PET/CT showed hyper-metabolic bladder lesions in 30/37 (81.1%) patients, of which 5 were indeterminate. When indeterminate lesions were considered positive, the sensitivity of standard and delayed PET/CT was 46% versus 88%, respectively. The specificity was 72% versus 36%. When indeterminate lesions were considered negative, the sensitivity of standard and delayed PET/CT was 23% and 85%. The specificity was 93% versus 73%. CONCLUSIONS: Our data suggest that delayed pelvic FDG-PET/CT imaging after forced detects more primary bladder tumors than standard FDG-PET/CT protocols. However, indeterminate bladder lesions on delayed PET/CT remain a problem and should be interpreted cautiously in order to avoid false positive results.