Extrahepatic cholangiocarcinoma (perihilar and distal): lines of therapy

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7 standard-of-care settings across 4 lines and 2 biomarker subgroups. Rows come from the cancer page's standard of care; the grid places each on its line and subgroup.

Line	All comers	HER2
Screening, prevention and diagnosis	1	·
Early / localised	2	·
Advanced, first line	2	·
Second line	1	1

Screening, prevention and diagnosis

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Diagnosis and jaundice	MRI with cholangiography and CT for staging, endoscopic brushing or biopsy, and biliary drainage by stent or percutaneous route with antibiotics for cholangitis.	MRICT (computed tomography)Endoscopy (EGD, EUS, ERCP)Biliary stenting and drainageCA 19-9		66

Early / localised

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Resectable perihilar	Bile duct resection with hemihepatectomy and caudate lobectomy after portal vein embolisation and drainage where needed, then six months of capecitabine (BILCAP).	Hepatectomy (liver resection)Lymphadenectomy (lymph node dissection)BILCAPCapecitabine		82
All comers	Resectable distal	Pancreaticoduodenectomy (Whipple) with lymphadenectomy, then adjuvant capecitabine.	Whipple procedure (pancreaticoduodenectomy)Lymphadenectomy (lymph node dissection)BILCAPCapecitabine		82

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Unresectable perihilar, selected	Neoadjuvant chemoradiation followed by liver transplantation under the Mayo protocol in specialist centres.	Liver transplantation for cancer (Milan criteria and beyond)		40
All comers	Advanced, first line	Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).	TOPAZ-1KEYNOTE-966ABC-02Gemcitabine + cisplatinDurvalumabPembrolizumabGemcitabine-cisplatin + PD-(L)1 blockade in biliary cancer		98

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Second line without a target	FOLFOX (ABC-06); pembrolizumab for microsatellite-unstable tumours, dabrafenib-trametinib for BRAF V600E.	FOLFOX (5-FU, leucovorin, oxaliplatin)PembrolizumabMicrosatellite instability (MSI-H) / mismatch repair deficiency (dMMR)Dabrafenib + trametinib		98
HER2	Advanced, HER2-positive after chemotherapy	Zanidatamab (HERIZON-BTC-01) or trastuzumab deruxtecan; zanidatamab first line in HERIZON-BTC-302.	ZanidatamabTrastuzumab deruxtecanHER2HERIZON-BTC-302		97

Sequence and caution pairings

CautionApproved

Caution: DXd ADC + agents with pneumonitis risk

Enhertu and its DXd cousins can inflame the lungs; combining them with immunotherapy, radiation, or mTOR inhibitors stacks that risk.

Lines and subgroups are parsed from the setting text of each standard-of-care row and can misclassify an unusual phrasing; the row’s own setting is always shown. Guideline chips reflect the NCCN category and ESMO-MCBS grade recorded on the cancer page, checked on its stated date. Not medical advice.