Meanwhile, urine cytology, although specific, lacks sensitivity, especially in low-grade BCa. Urinary tumor DNA offers avenues for improvement in the diagnosis, recurrence monitoring, and prognosis of BCa cases, with its non-invasive nature, ability to be monitored serially, and high performance in detecting minimal residual disease (MRD).1
Urinary tumor DNA-based methods have been investigated for their potential in MRD testing, as effective and noninvasive methods are lacking, and effective MRD tests would yield improved recurrence monitoring and treatment planning. One study using the utDNA-based technique “utMeMA” found that it was more sensitive than urine cytology in detecting early-stage and minimal tumors. Another utDNA-based technique, UroAmp, identified muscle-invasive tumors with 100% sensitivity, NMIBC with a sensitivity of 94%, and low-grade disease with a sensitivity of 87%.
MRD detection using utDNA was also found to accurately predict pathological response, introducing the potential for clinicians to be able to forgo radical cystectomy, a complicated and often dangerous surgery, in MRD-negative patients. In contrast, MRD-positive patients are prioritized for targeted therapy or immunotherapy. utDNA-based techniques also hold the potential to decrease costs of treatment for patients, with the combination of a technique dubbed “UroSEEK” and gold-standard cytology being estimated to be one-third of the cost of cystoscopy alone while achieving a sensitivity of 95%.
In recurrence monitoring, utDNA was found to significantly predict future recurrence as well as to distinguish new tumors from recurrent tumors. Some utDNA techniques even outperform gold-standard techniques, with “uCAPP-Seq” outperforming the combination of cytology and cystoscopy and detecting 100% of BCa cases detected by cytology and 82% of those missed by cytology. In addition, high utDNA levels were found to correlate with the presence of high-grade, late-stage carcinoma in situ and increased Ki-67 proliferation index, indicating that utDNA yields information on the staging of tumors and may help identify patients with BCa who are at a high risk of recurrence and progression. utDNA also shows promise in improving prognosis, as the absence of utDNA has been associated with an improved survival rate following radical cystectomy and certain treatments.
In summary, utDNA has demonstrated potential in multiple studies to improve on most, if not all, stages of BCa detection, treatment, and monitoring. By offering advancements in MRD testing, noninvasiveness, and cost effectiveness, utDNA offers patients a more comfortable, repeatable, and accurate way of detecting BCa.1
Written by: Joanne Lee & Liang Cheng
- Department of Pathology and Laboratory Medicine, The Warren Albert Medical School of Brown University, Brown University Health, and the Legorreta Cancer Center at Brown University, Providence, RI, USA.
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