Background: There is still some limitations for the diagnosis of urinary cancers, such as the invasiveness of cystoscopy and ureteroscopy, the requirements of experienced experts in interpreting the images, the low sensitivity of urinary cytology and FISH, the great economic pressure for long-term monitoring, etc. Thus, there is an urgent need for an accurate, less-expensive, and non-invasive method for the diagnosis of urinary cancers. Previously, A Genetron Urinary Assay were developed, which showed good performances in the diagnosis of upper urinary urothelial cancer and bladder cancer. In the following, a prospective, multicenter study was conducted to evaluate the clinical performance of this assay on patients with urinary diseases.

Materials and Methods: From October 2018 to October 2019, 120 patients underwent hematuria were enrolled before any treatment. The clinical pathological diagnosis of all the patients were completed by experienced urologists from eight hospitals in China. The urine samples were collected before cystoscopy or ureteroscopy, and the DNA was extracted from the urine cell pellets. The Genetron Urinary Assay, including the multiplex PCR-based next generation sequencing of 17 genes and the detection of methylation levels of CpG-sites located in ONECUT2 gene, was used. For the statistical analysis, either the mutation of the detected gene (at least one gene mutated) or the lower ΔCt value of methylated ONECUT2 (≤7.6) was considered as positive.

Results: Data from 109 urine samples was available for analysis. Among them, 78 were males and 31 were females, and their average age was 61.5. Based on the clinical features and rigorous clinical diagnosis, 74 cases were bladder diseases, 32 were upper urinary tract diseases, and 3 were urinary tract multifocal diseases. According to the results of cystoscopy, ureteroscopy or pathology, 79 patients (72.5%) were confirmed with malignant tumors and 30 were benign. In samples that were pathologically diagnosed as malignant, our method detected 66 cases as positive and 13 cases as negative. And in the 30 benign samples, the numbers of positives and negatives detected by our method were 3 and 27. Based on these data, the overall sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of our assay were 83.5%, 90.0%, 67.5%, and 95.7%, respectively.

Conclusion: This prospective, multicenter study shows that our liquid biopsy assay has a good performance in the diagnosis of urinary cancers. It has advantages such as non-invasiveness, low-cost, high sensitivity and specificity, so that it is worth expecting to supplement or even replace some traditional clinical diagnostic techniques.

Citation Format: Hu Qu, Yu Zeng, Yan Li, Youyan Guan, Jianhe Liu, Kewen Zheng, Jia Lyu, Xiaoyan Zhang, Le Li, Jiao Feng, Yiming Liang, Tonghui Ma. A multicenter, prospective evaluation of urine-based ctDNA assay for urinary cancers diagnosis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2296.