Urologic Oncology: Seminars and Original Investigations
Original articleIs The Cancer Genome Atlas (TCGA) bladder cancer cohort representative of invasive bladder cancer?
Introduction
The comprehensive molecular characterization of urologic malignancies by The Cancer Genome Atlas (TCGA) and other groups is an important effort that has provided important insights into genomic and transcriptomic alterations of various tumor entities including invasive bladder cancer [1]. Moreover, these clinically annotated molecular datasets are publically available and represent critical reference datasets for molecular research and the validation of biomarkers [2].
The use of the molecular data for both purposes, however, is facilitated if the datasets represent the target patient population. The cohort can be also used for validation of biomarkers that have been explored in cohorts with special features (e.g., metastatic tumors or patients treated with radiotherapy). However, cohorts with strongly differing characteristics require a meticulous matching of important variables such as age and tumor stage. The TCGA bladder data is only relevant to analyses of genomic alterations or transcriptomic pathways in treatment-naïve invasive bladder cancer without distant metastasis if the TCGA patient cohort is representative of this patient population as reported in the literature. Similarly, many studies are now using the TCGA dataset to validate candidate biomarkers, but successful validation also depends on the clinicopathologic characteristics and outcomes of this validation cohort being similar to the wider bladder cancer population. The aim of this study was to analyze clinicopathologic characteristics and outcomes of the TCGA BCa cohort [1] in the context of previously published large single-center cystectomy series [3], [4], [5]. We hypothesize that these features of the TCGA BCa cohort are comparable to previous cystectomy cohorts and that the TCGA, therefore, represents a valuable resource for biomarker validation and the study of molecular pathways in bladder cancer.
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Patients and methods
We downloaded the complete dataset of the bladder TCGA (n = 413) from cbioportal.org on November 11, 2016 and ported the file directly in the statistical platform (R Software Package, version 3.1.0). For 1 patient, no clinical data were available and 1 patient was recorded twice in the database. Patients with cM1 disease (n = 11) and those with neoadjuvant treatment before tissue harvesting (n = 10) were excluded from further analysis.
Wilcoxon rank-sum test was used to compare continuous data
Baseline Patient Characteristics
Median age of the 390 TCGA patients at surgery was 69 years (Table 1). Although the median follow-up was 30 months, the number of patients at risk at 5 years is low (Fig. 1 A and B). Outcome data for OS and DFS were available for 388 (99%) and 306 (78%) patients, respectively. Eighty-eight out of 388 patients (22%) were alive after 3 years and a follow-up longer than 3 years was available.
Information on primary tumor and LN stage was available in 92% and 90% of patients, respectively. Complete
Discussion
We analyzed clinical characteristics of the TCGA BCa cohort and observed an enrichment of patient with more advanced primary tumor stages; however, similar outcomes were seen in important subgroups when compared with prior large standard cystectomy series [3], [4], [5]. Importantly, previously identified risk factors for poor outcome are confirmed in the TCGA BCa cohort and strengthen the applicability of this cohort as a discovery and validation set for prognostic biomarkers.
In the TCGA BCa
Conclusion
The TCGA provides an invaluable source for the assessment of molecular alterations and investigation of prognostic biomarkers in bladder cancer. The patients captured in the TCGA BCa cohort have higher risk disease than most reference cystectomy series, and therefore have lower rates of OS and disease-specific survival, but these outcomes are equivalent to prior series when adjusting for the risk of disease. Researchers can, therefore, be encouraged to use the TCGA BCa dataset for evaluation of
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