REAL-WORLD PATTERNS OF CTDNA TESTING, MOLECULAR RESIDUAL DISEASE, AND TREATMENT AFTER RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER
Author(s)
Jennifer J. Stuart, ScD1, Tyler F. Stewart, MD2, Xinyue Liu, PhD1, Patrick J. Squires, PharmD, PhD1, Ching-Yu Wang, PhD1, Vasily N. Aushev, PhD3, Haojie Li, MD, PhD1, Chethan Ramamurthy, MD1, Blanca Homet Moreno, MD1, Ronac Mamtani, MD4, Mehmet Burcu, PhD1;
1Merck & Co., Inc., Rahway, NJ, USA, 2University of California San Diego, Department of Medicine, La Jolla, CA, USA, 3Natera, Inc., Austin, TX, USA, 4University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA
1Merck & Co., Inc., Rahway, NJ, USA, 2University of California San Diego, Department of Medicine, La Jolla, CA, USA, 3Natera, Inc., Austin, TX, USA, 4University of Pennsylvania, Abramson Cancer Center, Philadelphia, PA, USA
OBJECTIVES: Patients with muscle-invasive bladder cancer (MIBC) remain at substantial risk for recurrence after radical cystectomy (RC). Circulating tumor DNA (ctDNA) testing is increasingly used for early detection of molecular residual disease. However, real-world testing patterns and the extent to which MRD informs treatment are unknown.
METHODS: Adult US patients diagnosed with MIBC after 01Jan2021 with EHR linkage who underwent RC (≤1y post-diagnosis) and received ≥1 tumor-informed ctDNA test (Signatera Exome; Natera) by 31Mar2025 were eligible. Patients were considered high-risk for recurrence if they: a) received cisplatin-based neoadjuvant therapy (NAT) and had ypT2-T4 or pN+; or b) did not receive cisplatin-based NAT and had pT3-4 or pN+.
RESULTS: Among 500 randomly selected RC-treated MIBC patients who received ≥1 ctDNA test, 3468 plasma samples were analyzed (90% post-RC, n=3129), with a median 6 tests/patient (IQR:4-9). Patients were predominantly male (74%), White (87%), current/former smokers (61%) in an academic setting (64%) with Stage II disease (60%), pure urothelial histology (70%), and average age of 68.1±9.5yrs. Overall, 65% (n=326) received NAT, 49% (n=246) received adjuvant therapy (AT), and 31% (n=155) received both. Among those tested ≤3-months post-RC (n=362,72%), ctDNA positivity was 22% overall (n=80/362) and 21% in NAT recipients (n=49/229). Seventeen percent of NAT recipients achieved pCR (ypT0N0). ctDNA positivity was higher among patients without pCR (25%[n=48/191] vs. 3%[n=1/38]) and those at high-risk (27%[n=64/233] vs. 12%[n=16/129]). Among high-risk patients, the proportion receiving AT was similar for ctDNA-positive (70%,n=45/64) and ctDNA-negative patients (67%,n=113/169;p=0.62).
CONCLUSIONS: Patients with RC-treated MIBC who received ctDNA testing were more likely to be seen in an academic facility, be at high risk for recurrence, and receive AT than the general RC-treated MIBC patient population. Descriptively, ctDNA positivity was more common among patients without pCR, and those at high risk. Among high-risk patients, AT use did not appear to vary by post-RC ctDNA status.
METHODS: Adult US patients diagnosed with MIBC after 01Jan2021 with EHR linkage who underwent RC (≤1y post-diagnosis) and received ≥1 tumor-informed ctDNA test (Signatera Exome; Natera) by 31Mar2025 were eligible. Patients were considered high-risk for recurrence if they: a) received cisplatin-based neoadjuvant therapy (NAT) and had ypT2-T4 or pN+; or b) did not receive cisplatin-based NAT and had pT3-4 or pN+.
RESULTS: Among 500 randomly selected RC-treated MIBC patients who received ≥1 ctDNA test, 3468 plasma samples were analyzed (90% post-RC, n=3129), with a median 6 tests/patient (IQR:4-9). Patients were predominantly male (74%), White (87%), current/former smokers (61%) in an academic setting (64%) with Stage II disease (60%), pure urothelial histology (70%), and average age of 68.1±9.5yrs. Overall, 65% (n=326) received NAT, 49% (n=246) received adjuvant therapy (AT), and 31% (n=155) received both. Among those tested ≤3-months post-RC (n=362,72%), ctDNA positivity was 22% overall (n=80/362) and 21% in NAT recipients (n=49/229). Seventeen percent of NAT recipients achieved pCR (ypT0N0). ctDNA positivity was higher among patients without pCR (25%[n=48/191] vs. 3%[n=1/38]) and those at high-risk (27%[n=64/233] vs. 12%[n=16/129]). Among high-risk patients, the proportion receiving AT was similar for ctDNA-positive (70%,n=45/64) and ctDNA-negative patients (67%,n=113/169;p=0.62).
CONCLUSIONS: Patients with RC-treated MIBC who received ctDNA testing were more likely to be seen in an academic facility, be at high risk for recurrence, and receive AT than the general RC-treated MIBC patient population. Descriptively, ctDNA positivity was more common among patients without pCR, and those at high risk. Among high-risk patients, AT use did not appear to vary by post-RC ctDNA status.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH111
Topic
Epidemiology & Public Health
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology