Oesophageal cancer: lines of therapy

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12 standard-of-care settings across 6 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	·
Locally advanced	2	·
Advanced, first line	3	·
Second line	1	1
Other settings	2	·

Screening, prevention and diagnosis

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Prevention and screening	Tobacco and alcohol control; endoscopic screening of high-risk populations in China and Japan (Lugol chromoendoscopy); surveillance of Barrett's oesophagus with ablation or resection of dysplasia; non-endoscopic capsule-sponge screening in trials (BEST4).	Endoscopic resection (EMR / ESD)Barrett's oesophagusNon-endoscopic screening for Barrett's oesophagus and early adenocarcinoma		40

Early / localised

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Localised	Neoadjuvant chemoradiation (CROSS) or perioperative FLOT → surgery → nivolumab if residual disease.	NivolumabIMRT / IGRT (modern external beam)	NCCN Guidelines: Esophageal and Esophagogastric Junction Cancers	91
All comers	Early (T1a, high-grade dysplasia)	Endoscopic resection (EMR/ESD) with radiofrequency ablation of residual Barrett's; oesophagectomy for T1b with high-risk features.	Endoscopic resection (EMR / ESD)	NCCN · Category 1 (endoscopic therapy for Tis/T1a)	40

Locally advanced

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Resectable locally advanced (cT2-4a or N+)	CROSS chemoradiation (carboplatin/paclitaxel + 41.4 Gy) then oesophagectomy for squamous and adenocarcinoma; perioperative FLOT for adenocarcinoma/GEJ (ESOPEC). Adjuvant nivolumab for residual disease after chemoradiation (CheckMate 577).	CROSSCheckMate 577FLOT (5-FU, leucovorin, oxaliplatin, docetaxel)NivolumabCROSS chemoradiation → surgery → adjuvant nivolumab if residual disease	NCCN · Category 1 (preoperative chemoradiation; ad…	93
All comers	Unresectable locally advanced or cervical	Definitive chemoradiation (50-50.4 Gy with cisplatin/5-FU or carboplatin/paclitaxel); PD-1 blockade added in trials.	IMRT / IGRT (modern external beam)Platinum agents	NCCN · Category 1 (definitive chemoradiation)	91

Advanced, first line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Advanced	Chemotherapy + pembrolizumab/nivolumab; iza-bren in trials.	PembrolizumabIzalontamab brengitecan	NCCN Guidelines: Esophageal and Esophagogastric Junction Cancers	98
All comers	Advanced squamous cell carcinoma, first line	Chemotherapy + pembrolizumab (KEYNOTE-590), nivolumab (CheckMate 648), or tislelizumab (RATIONALE-306, PD-L1 ≥1%); nivolumab + ipilimumab chemotherapy-free option; camrelizumab/sintilimab/toripalimab in China.	KEYNOTE-590CheckMate 648RATIONALE-306ESCORT-1stPembrolizumabNivolumabIpilimumabTislelizumabCamrelizumab	NCCN · Category 1 (PD-L1-positive)	98
All comers	Advanced adenocarcinoma, first line	As for gastric cancer: chemotherapy + pembrolizumab or nivolumab (PD-L1 CPS ≥5 or ≥1); trastuzumab-based therapy if HER2-positive; zolbetuximab if CLDN18.2-positive (GEJ eligible in SPOTLIGHT/GLOW).	KEYNOTE-590CheckMate 649TrastuzumabZanidatamabZolbetuximab		96

Second line

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Second line, squamous cell carcinoma	Izalontamab brengitecan after PD-(L)1 + platinum (PANKU-Esophagus01, OS and PFS benefit, 2026; approval pending); otherwise taxane or irinotecan; nivolumab/pembrolizumab if IO-naive.	PANKU-Esophagus01 (BL-B01D1-305)Izalontamab brengitecan		68
HER2	Second line, adenocarcinoma	T-DXd if HER2-positive (DESTINY-Gastric04); ramucirumab + paclitaxel; CLDN18.2 ADC after CLARITY-Gastric 01.	DESTINY-Gastric04Trastuzumab deruxtecanRamucirumabCLARITY-Gastric 01		97

Other settings

Subgroup	Setting	Approach	Products and trials	Guideline	Evidence
All comers	Clinical complete response after chemoradiation	Active surveillance with surgery on regrowth is a non-inferior option (SANO); requires intensive endoscopic and PET surveillance.	SANOActive surveillanceClinical complete response (cCR)		87
All comers	Palliation of dysphagia	Self-expanding metal stent, brachytherapy, or external beam radiation; nutritional support; early palliative care.	BrachytherapyIMRT / IGRT (modern external beam)		91

Sequence and caution pairings

SequencePositive

CROSS chemoradiation → surgery → adjuvant nivolumab if residual disease

Chemotherapy and radiation, then surgery, then a year of immunotherapy if the operation shows cancer was still there. This is the current curative-intent pathway.

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.

Regimens in the library

mFOLFOX6 CAPOX FLOT CROSS chemoradiation Nivolumab + FOLFOX or CAPOX Pembrolizumab + cisplatin + fluorouracil

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.