Correlation of circulating tumor DNA (ctDNA) dynamics with clinical response in muscle-invasive bladder cancer (MIBC) patients (pts) undergoing trimodality therapy (TMT).

4602 Background: TMT is a curative treatment option for pts with MIBC. Plasma circulating tumor DNA (ctDNA) is associated with treatment response and clinical outcomes following cystectomy for MIBC, but the association of plasma ctDNA with treatment response and clinical outcomes in pts treated with TMT is poorly understood. We hypothesize that ctDNA dynamics are correlated with clinical outcomes in pts with MIBC treated with TMT. Methods: Pts with MIBC who received TMT at Dana-Farber/Brigham and Women’s Cancer Center or Massachusetts General Hospital, consented to a research protocol, and underwent ctDNA evaluation with the commercially available Signatera assay were included in the analysis. Individual chart review was performed to collect demographic and clinical data. Results: A total of 67 pts had at least one ctDNA evaluation and were included in this analysis. Cohort characteristics are summarized in Table 1. Forty-eight pts had at least one ctDNA evaluation prior to TMT, and 17 (35%) were ctDNA(+). Of the pts who were ctDNA(+) prior to TMT, 12 had at least one post-TMT ctDNA evaluation and 7 of 12 (58%) converted to ctDNA(-). Thirty-one pts were ctDNA(-) prior to TMT: 24 (77%) have had ≥1 post-TMT ctDNA evaluation and all 24 remained ctDNA(-) at the first post-TMT evaluation (median 8 weeks after TMT completion). Of the 55 pts with ≥1 post-TMT ctDNA result, 46 (84%) have remained ctDNA(-) during subsequent follow-up and do not have clinical evidence of recurrence (median number of ctDNA evaluation, 2; median follow up, 44 weeks). Nine pts had a ctDNA(+) result in the post-TMT setting: 5 were also ctDNA(+) prior to TMT, 2 did not have a pre-TMT ctDNA assessment but were ctDNA(+) at first-post TMT assessment, and 2 were ctDNA(-) before and initially after TMT but subsequently converted to ctDNA(+). Of these 9 ctDNA(+) cases, 6 pts (67%) have developed clinical evidence of metastatic disease to date with a median lead time of 5.3 weeks (range, 0-27 weeks) between first ctDNA(+) assessment and clinical evidence of metastatic disease. Overall, the sensitivity of plasma ctDNA testing in the post-TMT setting was 100% and the specificity was 94%. Conclusions: Most pts with MIBC treated with TMT in this cohort were ctDNA(-) following TMT and did not develop evidence of recurrent invasive or metastatic disease. Pts with ctDNA(+) status in the post-TMT setting frequently developed clinical evidence of metastatic disease. Larger cohorts with longer follow-up will be required to determine whether ctDNA status may be useful in guiding clinical decisions in MIBC pts undergoing TMT. No. of Pts 67 Median Age (Yrs) 75 M:F 59:8 T3-4 (%) 16 (24%) ≥N1 (%) 3 (4%) Presence of variant histology (%) 13 (19%) Received neoadjuvant chemotherapy (%) 12 (18%) Received concurrent chemotherapy (%) 61 (91%) Median RT dose (Gy) 55 Median length of follow up (weeks) 39