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Circulating Tumor DNA Can Predict Muscle-Invasive UTUC – Renal and Urology News

Preoperative circulating tumor DNA predicts whether upper tract urothelial carcinoma (UTUC) has invaded the muscle layer of the urinary tract and may help identify patients who could benefit from neoadjuvant chemotherapy (NAC) prior to nephroureterectomy, according to investigators.

In a prospective study, plasma cell-free DNA was collected from 30 patients with high-risk UTUC prior to surgery and sequenced using a 152-gene panel and low-pass whole-genome sequencing. Surgical pathology revealed that 16 patients had nonmuscle-invasive disease and 14 patients had muscle-invasive and non-organ-confined UTUC. The median number of variants detected within plasma was significantly higher for invasive and non-organ-confined disease than for noninvasive disease (3 vs 0). At least 1 circulating tumor DNA variant was detected in plasma from 21 patients (70%), but it had only 52% concordance with DNA from matching tumor samples.

The presence of presurgical circulating tumor DNA — defined as at least 2 panel-based plasma molecular alterations (MAs) — strongly predicted muscle-invasive and non-organ-confined UTUC at the time of surgery, achieving a sensitivity of 71% and specificity of 94%, Roger Li, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues reported in European Urology. Adding a plasma copy number burden score of more than 6.5 increased sensitivity to 79%.

“Although needing validation, this represents a clear improvement over the 42-48% sensitivity achieved using available clinical nomograms,” Dr Li’s team wrote.

The presence of  at least 2 MAs in circulating tumor DNA, compared with its absence, predicted significantly lower 1-year rates of progression-free survival (69% vs 100%) and cancer-specific survival (56% vs 100%), the investigators reported.

Surgical resection of the kidney renders some patients ineligible for adjuvant cisplatin-based chemotherapy.

“A preoperative ctDNA analysis is feasible and may be used to select high-risk UTUC patients benefiting from NAC,” Dr Li’s team concluded.

Disclosure: This research was partly supported by Predicine. Please see the original reference for a full list of disclosures.

References:

Huelster HL, Gould B, Schiftan EA, et al. Novel use of circulating tumor DNA to identify muscle-invasive and non-organ-confined upper tract urothelial carcinoma. Eur Urol. 2023 Oct 4:S0302-2838(23)03144-5. doi:10.1016/j.eururo.2023.09.017