At the 2023 ASCO Genitourinary Cancers Symposium, Kyle Rose, MD, Moffitt Cancer Center & Research Institute, Tampa, FL, presented results on the use of cell-free urinary tumor DNA in measuring minimal residual disease at the time of repeat transurethral resection of bladder tumor (TURBT) for patients with non-muscle invasive bladder cancer (NMIBC).

From this study, Dr Rose and coauthors concluded, “Urinary tumor DNA shows promise as a surrogate for minimal residual disease and may predict TURBT pathology for NMIBC.”

Transcript:

Hi, good evening. I'm Dr. Kyle Rose. I'm a Moffitt Urologic Oncology Fellow here in Tampa, Florida. I'll be presenting some of our work that we presented recently in San Francisco at the 2023 ASCO Genitourinary Cancers Symposium. The work that I'll be presenting is on cell-free urinary tumor DNA to detect [minimal residual disease] MRD prior to repeat transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer. The purpose of our work was to determine if we can use a cell-free assay, which is similar to circulating tumor DNA, but utilizing nucleic acid shed directly into the urine in the form of urinary tumor DNA, to detect MRD in the bladder.

To best answer this question, we designed a prospective trial here at Moffitt Cancer Center in Tampa, Florida, where we took patients with high-risk, non-muscle invasive bladder cancer who were undergoing a standard-of-care repeat TURBT. These were patients with high-risk features that as standard of care, we would take them back to the operating room and scrape out again the portion of the bladder where we found tumor. That serves several purposes: one, it allowed us to compare the resected tissue from the primary tumor to the re-resected tumor tissue. Secondly, we collected urine prior to that repeat TURBT to determine if the urine results from the utDNA could predict the presence of disease on the repeat TURBT. We enrolled 11 patients prospectively in this study. Eight of those patients had residual tumor present at the time of repeat TURBT. In the urine, we had performed ultra-deep sequencing. We’re looking at the patients’ primary and repeat TUR specimen. We performed whole-exome sequencing, and we noticed that patients' index tumors had a higher rate of non-synonymous mutations as compared to the repeat TUR tumors. Some of the most commonly identified genomic alterations included TP53 and TERT mutations.

When analyzing the concordance between the index and the repeat TURBT we found, on average, there was an 83% concordance rate. This was highest in patients who had muscle invasion and lowest in patients with carcinoma in situ. When analyzing the urine, we were able to detect index tumor specific mutations in the urine in 10 of the 11 patients. When using the definition of ≥2 variants detected as positive utDNA, we had utDNA positivity in 9 of those 11 patients. The most frequently detected markers were TP53 and KMT2D. And importantly, the patients who had no evidence of disease, which were 3 of the 11 on repeat TURBT, we were only able to detect 2 or more mutations in 1 of those patients.

As an exploratory analysis, we also analyzed urinary tumor DNA tumor fraction and we noticed that patients who had a disease present on their repeat TURBT, they had  higher tumor fractions compared to patients with no evidence of disease. When using that tumor fraction to answer the question, can utDNA predict MRD? We noticed an area under the curve of 0.85 with a sensitivity of 75% and a specificity of 100%.

From the study, we can conclude that the index and repeat TUR tumors are highly concordant, and this will help drive intravesical or systemic therapy selection, and that urinary tumor DNA as a liquid biomarker shows tremendous promise. However, significant work is still left with larger cohorts and longer follow-up to determine if it can properly risk-stratify patients prior to repeat TURBT and predict their long-term recurrence.

As always, we owe a huge debt to our patients, the collaborators in this group for this exciting and promising work. I want to also thank Predicine, who has led the way in cell-free DNA assays. Thank you.

Source:

Rose K, Murthy P, Gould B, et al. Cell-free urinary tumor DNA to detect minimal residual disease prior to repeat-transurethral resection of bladder tumor in non–muscle-invasive bladder cancer: A prospective study. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract LBA445