Novel Use of Circulating Tumor DNA to Identify Muscle-Invasive and Non-organ-confined Upper Tract Urothelial Carcinoma - Beyond the Abstract
Similarly, cross-sectional imaging does not accurately evaluate for ureteral muscle invasion except in cases of clearly locally advanced tumors. Identification of those patients with invasive UTUC likely to benefit from cisplatin-based NAC administration prior to extirpation of the kidney and ureter, however, is paramount, as a significant proportion of patients are rendered ineligible due to declines in renal function postoperatively.
Therefore, we set out to investigate whether the detection of plasma circulating tumor DNA (ctDNA) can predict muscle-invasive and non-organ-confined (MI/NOC) staging in UTUC. Patients with treatment-naïve, clinically localized, high-grade UTUC were prospectively enrolled and plasma was collected 1-2 hours prior to nephroureterectomy.
Detection of at least two plasma ctDNA variants achieved a specificity of 94% for MI/NOC staging at the time of nephroureterectomy using a panel-based assay. Over a median of 15 months of follow-up, six patients experienced disease progression and five died. All had MI/NOC UTUC at the time of surgery, and all but one were positive for ctDNA. Thus, detection of plasma ctDNA prior to nephroureterectomy was strongly prognostic for shorter progression-free and cancer-specific survival in UTUC.
The performance of ctDNA detection using this panel-based assay exceeds our currently available tools such as clinical nomograms in prediction of UTUC stage. This is a first step in using tumor genomic information to predict staging and stratify prognosis in UTUC patients. Though this data must be validated in a larger cohort, it highlights the importance of incorporating potentially predictive and prognostic biomarkers such as ctDNA into future clinical trial designs for patients being managed surgically and with perioperative systemic therapy for UTUC.
Written by Heather Huelster, MD, Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
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