(UroToday.com) Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy, comprising a small subset of urothelial disease. Compared to bladder cancer, endoscopic management of UTUC and intraluminal therapy is substantially more difficult. As a result, organ-preserving treatments are technically difficult. Thus, these approaches are often reserved for easily accessible, small, low-grade tumors. In part due to these nuances of treatment and in part due to underlying disease biology, UTUC has a relatively high recurrence and progression risk. Unfortunately, currently utilized methods of surveillance including cytology and imaging have low sensitivity and repeated ureteroscopy is invasive and costly. However, circulating tumor DNA (ctDNA) analysis using digital polymerase chain reaction (dPCR) has demonstrated promising results for monitoring of several types of cancers. This approach is noninvasive, highly-sensitive, and low-cost.
In a podium presentation at the American Urologic Association Annual Meeting, Dr. Daichi Tamura and colleagues presented the results of their study evaluating the validity of plasma and urinary ctDNA as a tumor biomarker in UTUC.
The authors examined 11 Japanese patients with UTUC who underwent radical nephroureterectomy (RNU) as the curative therapy at Iwate Medical University Hospital from January 2019 to September 2019, including patients who underwent neoadjuvant chemotherapy (NAC). Whole exome sequencing (WES) of tumor DNA and corresponding peripheral blood mononuclear cell (PBMC) DNA were performed by next-generation sequencer. Tumor-unique mutations were identified by comparing the single nucleotide variants from tumors and PBMCs. To investigate ctDNA by dPCR analysis, we designed primers and probes for each mutation. We obtained pre- and post-operational plasma and urine supernatant. Longitudinal variant allele frequency (VAF) of ctDNA was plot on a time course along with the imaging diagnosis.
Among the 11 included patients, the median number of point mutations was 340 per case (range 0-958). WES showed no mutations in 1 case who underwent NAC because of the absence of tumor. Three tumor-unique mutations were selected, and tumor burden monitoring with plasma and urinary DNA by dPCR was performed in 4 cases. Tumor-unique mutations were detected in ctDNA of preoperative plasma or urine for each case. Moreover, VAFs of plasma and urinary ctDNA decreased after RNU for each case.
The authors, therefore, concluded that, in UTUC, VAFs of plasma and urinary ctDNA were related to tumor burden and, thus, ctDNA could be a useful biomarker of UTUC. However, this work requires further validation.
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.