Organ preservation in esophageal cancer treatment, is it time now?

Table 1 Comparison of major clinical trials in esophageal cancer

Ref.	Study	Sample size	Histology composition	Neoadjuvant therapy	pCR rate	Key findings
Allum et al[40], 2009	OEO2	802	72% ESCC, 28% EAC	2 cycles (cisplatin + 5-FU)	NR	Improved OS (HR = 0.82) with chemo vs surgery alone
van Hagen et al[41], 2012	CROSS	368	75% ESCC, 25% EAC	5 cycles (carboplatin + paclitaxel) + RT (41.4 Gy)	23% (EAC); 49% (ESCC)	CRT improved OS (HR = 0.657) vs surgery
Yang et al[42], 2018	NEOCRTEC5010	451	100% ESCC	2 cycles (vinorelbine/cisplatin) + RT (40 Gy)	43.2%	nCRT significantly improved pCR
Bedenne et al[43], 2007	FFCD9102	259	88.8% ESCC, 11.2% EAC	2 cycles (cisplatin/5-FU) + CRT (46 Gy)	NR	CRT alone (non-surgical) had similar OS as CRT vs surgery
Qian et al[47], 2022		256	100% ESCC	4 cycles (docetaxel + cisplatin) + RT (40 Gy)	48.1%	dCRT vs nCRT → surgery for cCR patients; similar OS, supporting organ preservation in responders
van der Wilk et al[48], 2025	SANO	309	22.7% ESCC, 74.8% EAC	5 cycles (carboplatin + paclitaxel) + RT (41.4 Gy)	NR	Active surveillance feasible for cCR patients with low relapse risk
Yang et al[50], 2025	preSINO	309	100% ESCC	5 cycles (carboplatin + paclitaxel) + RT (41.4 Gy)	NR	Combining EUS-FNA and ctDNA improved residual disease detection sensitivity

NR: Not reported; pCR: Pathological complete response; ESCC: Esophageal squamous cell carcinoma; EAC: Esophageal adenocarcinoma; OS: Overall survival; HR: Hazard ratio; CRT: Chemotherapy, chemoradiotherapy; cCR: Clinical complete response; EUS-FNA: Endoscopic ultrasound-guided fine-needle aspiration; dCRT: Definitive chemoradiotherapy; nCRT: Neoadjuvant chemoradiotherapy; RT: Radiotherapy.

Table 2 Neoadjuvant immunotherapy trials in esophageal squamous cell carcinoma

Ref.	Study name/NCT No.	Type of EC	Sample size	Immunotherapy regimen	pCR rate	Other key findings
Zhang et al[64], 2021	ESONICT-1, ChiCTR2100045659	ESCC	30	2 cycles (sintilimab + nab-paclitaxel + cisplatin)	21.7%	MPR: 52.2%
Yang et al[66], 2022	NICE, ChiCTR2000028900	ESCC	23	2 cycles (camrelizumab + nab-paclitaxel + carboplatin)	25.0%	MPR: 50.0%
Liu et al[67], 2022	ChiCTR1900026240	Locally advanced resectable ESCC	60	2 cycles (camrelizumab + nab-paclitaxel + carboplatin)	39.2%	R0 resection: 98%
Yin et al[72], 2023	NATION-1907, NCT04215471	T2-4aN0-2M0 resectable ESCC	30	2 cycles, adebrelimab (1200 mg IV q3w)	8%	MPR: 24%
Zhang et al[65], 2023	ChiCTR1900027160	ESCC	60	2 cycles (toripalimab + nab-paclitaxel + oral S-1)	29.1%	MPR: 49%
Yan et al[68], 2022	TD-NICE, ChiCTR2000037488	ESCC	45	3 cycles (tislelizumab + nab-paclitaxel + carboplatin)	50.0%	MPR: 72%
Liu et al[69], 2022	NIC-ESCC2019, NCT04225364	ESCC	56	2 cycles (camrelizumab + nab-paclitaxel + cisplatin)	35.3%	ORR: 66.7%
Chen et al[70], 2023	KEEP-G 03, NCT03946969	RSCC	30	2 cycles [sintilimab + triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1)]	20.0%	MPR: 50.0%
Zhang et al[71], 2024	ChiCTR2200056728	Border-line resectable ESCC	32	2-4 cycles (camrelizumab + nab-paclitaxel + cisplatin)	40.9%	MPR: 63.6%
Yang et al[73], 2024	NICE Study, ChiCTR1900026240	Stage N2-3 ESCC	60	2 cycles (camrelizumab + nab-paclitaxel + carboplatin)	39.2%	MPR: 68.6%; RFS: 67.9%; OS: 78.1%
Qin et al[74], 2024	ESCORT-NEO/NCCES01, ChiCTR2000040034	Resectable ESCC (II-IVA)	432	2 cycles (camrelizumab + nab-paclitaxel/paclitaxel + cisplatin)	28.0% vs 15.4%	MPR: 59.1% vs 36.2%; 18-month PFS 69.1% vs 54.7%

EC: Esophageal cancer; pCR: Pathological complete response; ESCC: Esophageal squamous cell carcinoma; PFS: Progression-free survival; OS: Overall survival; ORR: Objective response rate; MPR: Major pathological response.