Barrett’s esophagus: Review of natural history and comparative efficacy of endoscopic and surgical therapies

Table 1 Efficacy of surgery for Barrett’s esophagus with intramucosal adenocarcinoma

Ref.	Type	n1	LNMrate	5-yr DFS or DSS	5-yr OS
Rice et al[97]	Retrospective	53	2%	-	77%
Liu et al[61]	Retrospective	53	-	100%	91%
Prasad et al[75]	Retrospective	46	8.6%	97%	95%
Pennathur et al[59]	Retrospective	29	7%	82%	73%
Wang et al[109]	Retrospective	60; T1a 32%; HGD 68%	-	-	88%
Sepesi et al[72]	Retrospective	25	0%	-	85%
Zehetner et al[96]	Retrospective	48	-	88%	94% (3 yr)
Hölscher et al[56]	Retrospective	70; SCC 29%	0%	-	87%
Leers et al[55]	Retrospective	75	1.3%	98%	82%
Pech et al[95]	Retrospective	38	-	100% (3.7 yr)	93%
Ngamruengphong et al[120]	Retrospective	671	-	-	76%
Lorenz et al[57]	Retrospective	42	8.7%	93.4%	91%
Newton et al[54]	Retrospective	303	3.6%	-	80%
Marino et al[121]	Retrospective	1317	-	-	79%
Semenkovich et al[74]	Retrospective	428; SCC 16%	8.7%	-	80%

¹Pure T1a cohort unless otherwise stated.

DFS: Disease free survival; DSS: Disease specific survival; HGD: High grade dysplasia; LNM: Lymph node metastasis; OS: overall survival; SCC: Squamous cell carcinoma.

Table 2 Efficacy of surgery for Barrett’s esophagus with submucosal adenocarcinoma

Ref.	Type	n	LNM rate	5-yr DFS	5-yr OS
Rice et al[97]	Retrospective	31	5%	-	60%
Liu et al[61]	Retrospective	37	-	60%	58%
Pennathur et al[59]	Retrospective	71	27%	62%	60%
Sepesi et al[72]	Retrospective	29	31%	-	60%
Hölscher et al[56]	Retrospective	101; SCC 35%	34%	-	66%
Leers et al[55]	Retrospective	51	22%	79%DSS	71%
Ngamruengphong et al[120]	Retrospective	523	-	-	64%
Lorenz et al[57]	Retrospective	168	20.6%	85%	74%
Schölvinck et al[78]	Retrospective	26	17% (n = 69 including EET group)	-	Median survival: 51 mo
Schwameis et al[76]	Retrospective	32	22%	-	84%
Newton et al[54]	Retrospective (NCDB)	512	23.4%	-	64.4%
Semenkovich et al[74]	Retrospective (NCDB)	1146; SCC 16%	14%	-	60%
Otaki et al[77]	Retrospective	68	14.7%	92%	89%

DSS: Disease specific survival; EET: Endoscopic eradication therapy; NCDB: National cancer database; DFS: Disease free survival; OS: Overall survival; SCC: Squamous cell carcinoma.

Table 3 Efficacy of endoscopic eradication therapy for Barrett’s esophagus with low-grade dysplasia

Ref.	Type	n	CE-IM	CE-D	NNT to prevent disease progression	Annual disease progression, treatment vs placebo (P value)
Wani et al[22]	Meta-analysis	1512	-	-	65.5 (EAC)	0.16% vs 1.7% (P = 0.99) (EAC)
Shaheen et al[42]	RCT	64	81%	90.5%	11.3 (HGD)	5% vs 14% (HGD) (P = 0.33)
Shaheen et al[91]	Retrospective	52	98%	98%	NA	NA
Bulsiewicz et al[92]	Retrospective	41	93%	100%	NA	NA
Phoa et al[45]	RCT	136	88.2%	92.6%	13.6 (EAC)	1.5% vs 8.8% at 3 yr (EAC) (P = 0.03)
Qumseya et al[100]	Meta-analysis	2746	-	-	16 (EAC)	NA
Pouw et al[101]	Retrospective	83	90%	90%	11.4 (EAC)	NA
Barret et al[46]	RCT	82	37.5%	52.5%	-	5% vs 2.4% at 3 yr: (EAC) (P = 0.52)

n: Patient number; CE-D/IM: Complete eradication of dysplasia/intestinal metaplasia; EAC: Esophageal adenocarcinoma; HGD: High grade dysplasia; NNT: Number needed to treat; NA: Not application.

Table 4 Efficacy of endoscopic eradication therapy for Barrett’s esophagus with high-grade dysplasia

Ref.	Type1	n	CE-IM	CE-D	NNT to prevent disease progression	Annual disease progression, treatment vs placebo (P value)
Overholt et al[52]	RCT (PDT)	208	52%	77% (including HGD)	22	3.6% vs 8.14% (P = 0.006)
Ganz et al[102]	Retrospective	92	54%	80%	NA	1.4%
Wani et al[22]	Meta-analysis	236	-	-	20.4	1.7% vs 6.6% (P = 0.02)
Shaheen et al[42]	RCT	63	73.8%	81%	6	2.4% vs 19% (P = 0.04)
Shaheen et al[91]	Retrospective	54	89%	93%	NA	0.6%
Moss et al[85]	Prospective (SRER)	35	94%	94%	NA	Nil
Zehetner et al[96]	Retrospective	22	89%	89.5%	NA	Nil
Okoro et al[103]	Retrospective	35	51.2%	79%	NA	2.3% (2 yr)
Bulsiewicz et al[92]	Retrospective	118	90%	97%	NA	NA
Haidry et al[104]	Retrospective	122	85%	92%	NA	2.5% (3 yr)
Li et al[105]	Retrospective	832	83.4%	92.1%	NA	3% (2.8 yr)

¹Studies used endoscopic mucosal resection and radiofrequency ablation unless otherwise stated.

CE-D/IM: Complete eradication of dysplasia/intestinal metaplasia; EAC: Esophageal adenocarcinoma; NNT: Number needed to treat; PDT: Photodynamic therapy; SRER: Stepwise radical endoscopic resection; NA: Not application.

Table 5 Efficacy of endoscopic eradication therapy for Barrett’s esophagus with intramucosal adenocarcinoma

Ref.	Type1	n2	Eradication of T1a	5-yr OS
Ell et al[111]	Prospective	100	99%	98%
Pech et al[112]	Prospective (EMR +/- PDT)	349; HGD 17.5%	97.4% (including HGD)	NA
Pouw et al[113]	Prospective (RFA +/- EMR)	44; HGD up to 27%	100%	NA
Prasad et al[75]	Retrospective (PDT)	132	94%	83%
Pouw et al[114]	Prospective (EMR + RFA)	24; HGD 25%; T1b 8%	100%	NA
Pech et al[95]	Retrospective (EMR +/- APC)	79	98.7%	96%
Van Vilsteren et al[115]	RCT	47; HGD up to 40%	97.9%	NA
Zehetner et al[96]	Retrospective	18	82% (14/17); 3/17 subsequently successfully treated under surveillance	NA
Bulsiewicz et al[92]	Retrospective	29	93%	NA
Ngamruengphong et al[120]	Retrospective	229; HGD 24%	-	60%
Saligram et al[116]	Retrospective	54	96%	89% (over 2 yr)
Pech et al[117]	Prospective	1000	96.3% (including HGD)	91.5%
Haidry et al[104]	Retrospective	63	97.5% (combined with HGD cohort)	NA
Agoston et al[118]	Retrospective	79	86%	NA
Li et al[105]	Retrospective	162	97.5%	NA
Phoa et al[119]	Prospective	132; ND/LGD 8.4%; HGD 30%; T1b 1.7%	92%	NA
Marino et al[121]	Retrospective	856	-	71.8%
Semenkovich et al[74]	Retrospective	1123	-	70%

¹Studies use endoscopic mucosal resection/radiofrequency ablation unless otherwise stated.

²Pure T1a cohort unless otherwise stated.

n: Patient number; APC: Argon plasma coagulation; OS: Overall survival; PDT: Photodynamic therapy; NA: Not application.

Table 6 Efficacy of endoscopic eradication therapy for Barrett’s esophagus with submucosal adenocarcinoma

Ref.	Type	n	Eradication of cancer	Survival
Manner et al[81]	Retrospective	61	87% (including HGD)	5-yr OS 84%
Ngamruengphong et al[120]	Retrospective	39	-	5-yr OS 66%
Schölvinck et al[78]	Retrospective	43	-	Median survival: 46 mo
Künzli et al[122]	Retrospective (RFA or APC)	35	100%	-
Semenkovich et al[74]	Retrospective	588	-	5-yr OS 50%
Otaki et al[77]	Retrospective (RFA/APC/Cryo)	73	63% (including HGD)	5-yr OS 59%

APC: Argon plasma coagulation; Cryo: Cryotherapy; HGD: High grade dysplasia; OS: Overall survival; RFA: Radiofrequency ablation.

Table 7 Recommendations for non-invasive Barrett’s esophagus

Stage	Annualized risk of cancer	Recommended management	Risks of intervention	Post-intervention cancer risk
NDBE	0.5%	Surveillance	Negligible	NA
LGD1	1%–3%	Surveillance or EET	Stricture 6%; Chest pain 5%; Bleeding 1%; Perforation 1%	1% per year
HGD	5%–10%	EET	Stricture 6%; Chest pain 5%; Bleeding 1%; Perforation 1%	2% per year

¹Low grade dysplasia diagnosed by an expert gastrointestinal pathologist.

HGD: High grade dysplasia; EET: Endoscopic eradication therapy; LGD: Low grade dysplasia; NDBE: Non-dysplastic Barrett’s esophagus; NA: Not application.

Table 8 Recommendations for invasive adenocarcinoma arising from Barrett’s esophagus

Invasive Barrett’s esophagus by stage	Risk of nodal metastases	Recommended management	Risks of intervention	5-yr disease free survival	5-yr overall survival
Intramucosal adenocarcinoma	2%–4%	EET	Stricture 6%; Chest pain 5%; Bleeding 1%; Perforation 1%	NA	Estimated 80%
Submucosal adenocarcinoma	14%–41%	Surgery	Mortality 3%; Adverse events up to 62%; Long-term symptoms due to altered upper gut function	Estimated 70%	Estimated 75%

EET: Endoscopic eradication therapy; NA: Not application.