Circulating Tumor DNA Predicts Muscle-Invasive, Non-Organ-Confined UTUC

Preoperative detection of plasma circulating tumor DNA (ctDNA) predicts muscle-invasive and non-organ-confined upper-tract urothelial carcinoma (UTUC) and may allow use of neoadjuvant chemotherapy for upstaged patients, new study findings suggest.

In a prospective study, investigators obtained presurgical plasma cell-free DNA samples (along with germline DNA and tumor tissue DNA) from 30 patients with clinically localized high-risk UTUC who were undergoing upfront surgery. The ctDNA samples underwent a 152-gene panel test.

Surgical pathology revealed muscle-invasive or non-organ confined UTUC in 14 patients. Detection of at least 2 panel-based molecular alterations in ctDNA yielded 71% sensitivity and 94% specificity to predict invasive disease with an area under the curve of 0.92, Roger Li, MD, of H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, and colleagues reported in European Urology.

The presence of at least 2 panel-based molecular alterations in ctDNA significantly predicted an 18.5-fold increased risk for cancer progression and a 9.3-fold increased risk for cancer death. At 1 year, progression-free survival (69% vs 100%) and cancer-specific survival (56% vs 100%) was lower at this ctDNA threshold compared with no ctDNA.

“Although needing validation, this represents a clear improvement over the 42-48% sensitivity achieved using available clinical nomograms,” Dr Li’s team wrote. They also noted that at least 1 ctDNA variant was detected on gene panel testing in 21 patients (70%), but it was concordant with tumor samples in only 52% of cases. This highlights that molecular alterations in cancers are not limited to the original tumor.

Genome-wide copy number alterations of more than 6.5 also distinguished invasive from noninvasive disease and increased the sensitivity of the prognostic model from 71% to 79%, but this finding may overfit the model and requires further validation, the investigators noted.

Understaged UTUC often denies the opportunity for systemic chemotherapy, such as when surgery renders patients ineligible for cisplatin due to deteriorating kidney function, according to Dr Li’s team. If preoperative ctDNA positivity identifies invasive UTUC, more patients may be eligible for neoadjuvant chemotherapy.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

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. Published online October 4, 2023. doi:10.1016/j.eururo.2023.09.017

This article originally appeared on Renal and Urology News