not been well-described to date. For ctDNA, it is unclear whether a personalized targeted assay (as has been previously described) is necessary or whether a gene panel may suffice. Here, we compared the performance of these biologically distinct assays in a cohort of metastatic patients.METHODS: CTCs were defined as cytokeratin (CK) or EpCAM positive with the RareCyte selection-free immunofluorescent staining platform. ctDNA was assayed with the PlasmaSelect64 assay, a probe capture NGS panel with 1000x coverage. Matched tissue specimens were sequenced with elio Tissue Complete.RESULTS: Matched CTC and ctDNA samples were collected for N[16 patients. For 5 patients, 3 replicate time points were collected. Median (range) CTC count was 2.5 (0-170/7.5mL peripheral blood) and number of detected somatic mutations was 2 (0-7). 75% (12/16) patients had detectable CTCs, and 73% (11/15) patients had detectable somatic mutations, similar to the published parameter of 24/37 (67%) ctDNA detection in metastatic UC with a custom designed panel (Wyatt et al Vancouver). Median cell free DNA (cfDNA) yield was 9.03 ng/mL consistent with prior reports of a lower frequency of ctDNA in advanced bladder cancer as opposed to other malignancies. Multiple comparisons of CTC count to ct/cfDNA failed to produce any relationship. We discovered a similar genomic landscape to that which has been published in the past, with frequent mutations in TP53, TERT, and ERBB2.CONCLUSIONS: CTC and ctDNA assays provided distinct and complimentary results. Both liquid biopsies show promise in urothelial cancer and deserve further investigation. A ctDNA assay using a gene panel had similar detection sensitivity in a metastatic UC cohort when compared to a previously described custom patient mutation assay.
INTRODUCTION AND OBJECTIVE: Risk models predicting prognosis in non-muscle invasive bladder cancer including European Organization for Research and Treatment of Cancer (EORTC) risk tables, and Spanish Urological Club for Oncological Treatment (CUETO) scoring model. Both were based on cohorts 20 to 40 years ago, which has different adjuvant treatment patterns from today and may be out of date. Thus, we developed a nomogram predicting disease progression with our contemporary, single institution, real-world practice cohort in Taiwan.METHODS: Among 2007 and 2015, 939 patients diagnosed with Ta or T1 bladder urothelial carcinoma (UC) after transurethral resection of bladder tumors in our institution were enrolled. Patients with short-term (<6 months) follow up, pure CIS or upper tract UC were excluded. The definition of progression was muscle invasion, metastasis or death caused by UC. After multivariable analyses, we use significant covariates for nomogram development.RESULTS: Four hundred twenty-four (44.3%) recurrence and 132 (13.9%) progression were documented with a 55-month mean follow-up. The mean age was 73 (AE12.7) years old and there were 785 (81.9%) male patients, 103 (10.1%) concurrent CIS, 659 (64.6%) primary occurrence and 274 (26.9%) patients received adjuvant intravesical BCG instillation. Significant covariates including primary or not (HR[2.38, p<0.001), focality (HR[2.24, p<0.001), tumor stage (HR [2.01, p[0.001) and grade (HR[1.68, p[0.04), concurrent CIS (HR [1.62, p[0.033), high grade prostate urethral involvement (HR[2.21, p[0.044). Bootstrap refitting was done 200 times for internal validation and concordance index is 0.731, indicating good predicting performance. Total points of our nomogram also showed good correlation with AUA risk stratification (Figure).CONCLUSIONS: We developed a new, convenient nomogram to predict disease progression in non-muscle invasive bladder urothelial carcinoma patients with contemporary cohort. For better utility, change in practice over time and 2004/2016 WHO histology classification migration were both take into consideration. Further external validation is required to solidify this contemporary model.
p[0.037), tumor diameter !3cm (HR 2.8, 95%CI 1.01-7.9; p[0.049), previous history of UC 1 yr (HR 1.96, p[0.043) and combined EORTC risk group (HR 3.15,; p[0.017) were significant predictors of recurrence. Absence of detrusor muscle at pathologic report (HR 1.45,; p[0.4. Figure 1b) and adjuvant intravesical treatments (HR 0.95, 95%CI 0.5-1.78; p[0.87) had negligible impacts on RFS probabilities (Table 2).CONCLUSIONS: EORTC risk group is a strong predictive tool to assess the risk of recurrences in patients with Ta-LG UC of the bladder. Absence of detrusor muscle in the TURBt specimen has negligible role on recurrence of patients with Ta-LG tumors, therefore it should no longer be considered as a mandatory data to assess prognosis or treatment schedule.
chromosomal mutations occurring in high risk patients. The cohort was risk-stratified according to the presence of known histopathologic predictors of poor prognosis including Fuhrman grade 3-4, tumor size >7cm, tumor extension, sarcomatoid changes and tumor necrosis. 60 patients with resected clear cell RCC tumors were followed for disease recurrence or progression. Mean follow up is 36 months. 30 patients were low risk (0 or 1) and 30 patients were high risk (2 or more features). 42 patients have no evidence of disease, 8 are alive with disease, and 10 have died of disease progression. Chi-squared test was used to determine the relationship of specific chromosomal abnormalities and histopathologic risk with disease status.RESULTS: A number of novel chromosomal aberrations [deletions of 1p, 4, 10, 13q, 21q, 22q and gain of 1q] were associated with disease recurrence or progression (p<.05). Previously reported deletions of 14q and 9p were also associated with worse prognosis in this cohort (p<.05). Fig. 1 shows the relative distribution of chromosomal aberrations and associated histopathologic risk classification.CONCLUSIONS: SNP microarray detection of chromosome aberrations in clear cell RCC is a potential adjunct to histopathology to stratify risk and aid in determination of prognosis for individual patients.
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