Figure 3
Presence of mutDNA at the 2nd cycle of NAC predicts early recurrence in MIBC. (A) Kaplan-Meier curve depicting time to recurrence from initial TUR. We compared the rate of recurrence of patients with detectable mutDNA (red line) and undetectable mutDNA (blue line) in peripheral samples taken immediately prior to the 2nd cycle of NAC (i.e. 2–3 weeks after the initiation of NAC). MutDNA was detected in 5/6 patients who recurred and in 0/6 recurrence free patients. Median time to recurrence in patients with detected mutDNA was 293 days while in patients with undetected mutDNA the recurrence rate was low. (B) Sensitivity and specificity for recurrence prediction. Overall sensitivity and specificity were 83.3% and 100% with positive predict value and negative predictive values of 100% and 85.7% respectively. One “other” patient was excluded from recurrence analysis due to post-operative death. (C) Heatmap comparing SNV maximum AF for each patient across all sample types and recurrence states at this time-point. Mutant allele fractions (mAFs) are represented by coloured cells ranging from white to scarlet as mAF increases (raw data in Supplementary Table 4). Patients are grouped by recurrence status. Generally, SNV mAFs are noticeably higher in USN and UCP as compared to PLS. There is a clear correlation between SNV mAF in peripheral samples and patient recurrence status.
