medwireNews: Chinese researchers have developed a noninvasive test for urothelial cancer, based on low-coverage whole-genome sequencing, that has better sensitivity and comparable specificity to that of cytology.
The technique, called Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD), detects copy number variations in urine-exfoliated cell DNA samples.
Chuanliang Xu (Changhai Hospital, Shanghai, China) and co-investigators believe it could “be used as a noninvasive approach for diagnosis and recurrence surveillance in urothelial carcinomas prior to the use of cystoscopy, which would largely reduce the burden on patients.”
The UroCAD model was built by incorporating all autosomal chromosomal changes detected in morning urine samples from 126 patients with urothelial carcinomas and 64 patients with benign urinary disease.
In this training cohort, the area under the receiver operating characteristic curve (AUC) for the detection of urothelial cancer was 0.92 with the model and the optimal cutoff was a Z-score of 3.21.
At this cutoff, the model had a sensitivity of 82.5%, specificity of 96.9%, and accuracy of 89.0%, and the researchers note that the results were not affected by different timepoints of urine collection.
Xu and team also report in Clinical Cancer Research that test performance significantly correlated with tumor grade but not with tumor stage or size. Specifically, the sensitivity was 65.6% and 87.9% for histologically low-grade and high-grade urothelial carcinomas, respectively. The sensitivity among patients with low-grade, pTa tumors was 60.0%.
When compared with cytology, the UroCAD model detected urothelial cancer in 100% of 14 cytology-positive tumors and also in 78.9% of 38 cytology-negative tumors, meaning that it produced 214% more positive findings than cytology, the researchers remark.
Furthermore, the model outperformed cytology for the detection of upper tract urothelial carcinoma (UTUC; 100 vs 21.4%), bladder cancer (78.8 vs 28.9%), high- (87.9 vs 35.3%) and low- grade (65.6 vs 13.3%) tumors, and tumors less than 3 cm in diameter (78.2 vs 22.0%).
The researchers validated their findings in an independent cohort of 95 patients. In this group, the AUC was 0.91 and the sensitivity and specificity were 80.4% and 94.9%, respectively.
Sensitivity was 60.0% and 86.7% for low-grade and high-grade urothelial carcinomas, respectively, 71.4% in pTa tumors and 63.6% in UTUC. Unlike the development cohort, sensitivity also correlated with tumor size in this cohort, at 66.7% for tumors of 1 cm or smaller, 72.0% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.
Compared with cytology in this cohort, the UroCAD assay had better sensitivity (80.4 vs 33.9%) and similar specificity (94.9 vs. 100%) overall, and better sensitivity for pTa tumors (71.4 vs 0.0%) and UTUC (63.6 vs 18.2%).
Xu and team note that the US FDA has approved six non-invasive urinary methods for diagnosis and surveillance of bladder cancer but say that “the clinical application of these methods is still rare due to the low sensitivity, poor accuracy for low-stage and low-grade tumors, high-cost, and ambiguous clinical readout.”
They add: “The lack of standardized kits, controlling for patient demographics, and extensive multi-center validation is also an issue. Therefore, a noninvasive diagnostic method with high accuracy is warranted.”
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