{"entity":{"id":"idea-gbc-ctdna-residual-disease-guided-adjuvant-trial","kind":"idea","name":"A ctDNA residual disease-guided adjuvant trial after gallbladder cancer resection","aka":[],"tldr":"After surgery for bile duct or gallbladder cancer, a blood test for leftover tumour DNA picks out the people whose cancer will return with hazard ratios of 16 to 26 in two recent cohorts. Nobody has yet tested giving those people more than the standard capecitabine.","summary":"Tumour-informed ctDNA in the 2 to 12 week window after biliary resection was positive in 23 percent of 167 patients and carried a relapse-free survival hazard ratio of 15.86 (Malla 2026); in a 56-patient cohort the hazard ratio was 26 (Yu 2025). Gallbladder cancer recurs early and distantly after re-resection (Varshney 2025), which is the setting where a residual disease test could pick who gets escalation. The template exists in colon and bladder cancer (DYNAMIC, IMvigor011). A biliary trial would randomise ctDNA-positive patients after resection to capecitabine or gemcitabine-cisplatin with durvalumab, and could de-escalate ctDNA-negative T1b or T2a patients to observation.","asOf":"2026-09-24","links":[{"label":"Malla et al.: real-world ctDNA after resection of stage I to III biliary tract cancer (ESMO GI Oncol 2026)","url":"https://europepmc.org/article/MED/42583118"},{"label":"Yu et al.: ctDNA and early recurrence after biliary resection (JCO Precis Oncol 2025)","url":"https://europepmc.org/article/MED/39772829"}],"tags":["gallbladder-evidence"],"related":["ctdna-tests","idea-btc-ctdna-fgfr-resistance"],"cancers":["gallbladder","biliary-tract-cancer"],"sections":[],"technologies":["liquid-biopsy","mrd-testing"],"targets":[],"drugs":["signatera","capecitabine","gemcitabine-cisplatin","durvalumab"],"companies":[],"institutions":[],"pathways":[],"terms":["ctdna","mrd","neoadjuvant-adjuvant","de-escalation"],"trials":["bilcap","acticca-1"],"people":[],"bottlenecks":["b-dormancy-mrd","b-trial-design"],"keyPapers":["paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026","paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In resected gallbladder cancer with detectable ctDNA at 4 to 8 weeks, adjuvant gemcitabine-cisplatin plus durvalumab improves two-year recurrence-free survival over capecitabine by at least 15 percentage points; in ctDNA-negative early-stage disease, observation is non-inferior to capecitabine.","rationale":"Residual disease positivity is the strongest prognostic factor yet measured after biliary resection, and stronger than CA 19-9; adjuvant capecitabine's benefit is unproven in gallbladder cancer specifically.","test":"Two-cohort randomised trial (escalation in ctDNA-positive, de-escalation in ctDNA-negative) nested in a national incidental cancer pathway, with tumour-informed assay from the resection specimen; about 400 patients over four years across a hepatobiliary network.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":6},"route":"/ideas/idea-gbc-ctdna-residual-disease-guided-adjuvant-trial/","neighbours":{"roadmap":[{"id":"ctdna-tests","kind":"roadmap","name":"ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment","route":"/roadmaps/ctdna-tests/"},{"id":"gallbladder-cancer-roadmap","kind":"roadmap","name":"Gallbladder cancer roadmap: from a chance finding at gallstone surgery to a disease with its own trials","route":"/roadmaps/gallbladder-cancer-roadmap/"}],"idea":[{"id":"idea-btc-ctdna-fgfr-resistance","kind":"idea","name":"ctDNA-guided switching among FGFR inhibitors","route":"/ideas/idea-btc-ctdna-fgfr-resistance/"}],"cancer":[{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"gallbladder","kind":"cancer","name":"Gallbladder cancer","route":"/cancers/gallbladder/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"},{"id":"mrd-testing","kind":"technology","name":"MRD / molecular residual disease testing","route":"/technologies/mrd-testing/"}],"drug":[{"id":"capecitabine","kind":"drug","name":"Capecitabine","route":"/drugs/capecitabine/"},{"id":"durvalumab","kind":"drug","name":"Durvalumab","route":"/drugs/durvalumab/"},{"id":"gemcitabine-cisplatin","kind":"drug","name":"Gemcitabine + cisplatin","route":"/drugs/gemcitabine-cisplatin/"},{"id":"signatera","kind":"drug","name":"Signatera","route":"/drugs/signatera/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"de-escalation","kind":"term","name":"De-escalation, escalation and response-adapted therapy","route":"/terms/de-escalation/"},{"id":"mrd","kind":"term","name":"Minimal / molecular residual disease (MRD)","route":"/terms/mrd/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"}],"trial":[{"id":"acticca-1","kind":"trial","name":"ACTICCA-1","route":"/trials/acticca-1/"},{"id":"bilcap","kind":"trial","name":"BILCAP","route":"/trials/bilcap/"}],"bottleneck":[{"id":"b-dormancy-mrd","kind":"bottleneck","name":"Dormant cells and minimal residual disease","route":"/bottlenecks/b-dormancy-mrd/"},{"id":"b-trial-design","kind":"bottleneck","name":"Trial design, endpoints and cost","route":"/bottlenecks/b-trial-design/"}],"paper":[{"id":"paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025","kind":"paper","name":"Detecting Early Recurrence With Circulating Tumor DNA in Stage I-III Biliary Tract Cancer After Curative Resection","route":"/key-papers/paper-yu-ctdna-early-recurrence-biliary-tract-cancer-jco-po-2025/"},{"id":"paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026","kind":"paper","name":"Real-world analysis of ctDNA and other biomarkers in patients with curatively resected stage I-III biliary tract cancer","route":"/key-papers/paper-malla-ctdna-resected-biliary-tract-cancer-esmo-gi-onc-2026/"}]}}