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. Author manuscript; available in PMC: 2024 Oct 1.
Published in final edited form as: Eur Urol Oncol. 2023 Apr 20;6(5):516–524. doi: 10.1016/j.euo.2023.03.008

Fig. 4 –

Fig. 4 –

A proposed risk-stratification model to predict NAC response using circulating bladder DNA fraction and mR-score. (A) Circulating bladder DNA (%) in patients in different response groups. There was no statistically significant difference among the groups. (B) Correlation between mR-scores and circulating bladder DNA (%) obtained before chemotherapy. Spearman correlation coefficient R = 0.073 (p = 0.5). (C) Using mR-score and circulating bladder DNA fraction to risk-stratify patients before chemotherapy. Tentative cutoffs were selected at the Youden’s index for demonstration purpose only, and further biomarker development is needed before the final cutoffs are selected. Patients with high mR-scores or high circulating bladder DNA were given 1 point each. The high-risk group was defined as patients with a high pretreatment mR-score (>0.496) and high circulating bladder DNA fraction (>1.11%), the low-risk group was defined as patients with a low pretreatment mR-score and low circulating bladder DNA fraction, and the intermediate-risk group was defined as the patients not in the high- or low-risk groups. (D) Intermediate-risk group patients were further risk stratified into intermediate-high (Int-high) and intermediate-low (Int-low) groups using their on-treatment mR-scores. The Int-high risk group was defined as the intermediate-risk group patients with a high on-treatment mR-score (>0.433); the Int-low risk group was defined as the intermediate-risk group patients with a low on-treatment mR-score. (E) Proposed approach that may utilize cfDNA methylation for patient risk stratification. Out of 57 patients, 45 were correctly classified in our cohort using this approach; model performance will require further validation in independent cohorts.

cfDNA = cell-free DNA; CR = patients with pathologic T0 response; mR-score = methylation-based response score; NAC = neoadjuvant chemotherapy; NR = patients without pathologic response; PR = patients with downstaged partial response; R = responders including patients with pathologic T0 response and downstaged partial response.