Is salvage treatment necessary after incomplete resection of rectal neuroendocrine tumors: A systematic review and meta-analysis

Table 1 Baseline characteristics

Ref.	Design	Country	Period	Rectal NET cases (n)	Primary endoscopic resection method
					cEMR	mEMR	ESD	Hybrid ESD	CSP	CFP	EC	Missing data
Cha et al[19]	Retrospective	Korea	Between 2008 and 2018	260	126	113	21
Cha et al[20]	Retrospective	Korea	Between January 2005 and December 2016	322	97	122	103
Chatila et al[21]	Retrospective	United States	Between January 2023 and October 2023	10	2					4		4
Cheminel et al[22]	Retrospective	France	Between January 2000 and December 2021	86	14				23	48		1
Cho et al[23]	Retrospective	Korea	Between January 2003 and December 2012	411	300		111
Choi et al[24]	Retrospective	Korea	Between December 2008 and November 2015	134		81	53
Chung et al[25]	Retrospective	Korea	Between January 2013 and April 2018	337	81	143	113
Dell’Unto et al[26]	Retrospective	Italy	Between 2010 and 2021	31		2			14			15
Duan et al[27]	Retrospective	China	Between December 2012 and June 2023	527	213	199	113	2
Heo et al[28]	Retrospective	Korea	Between September 2007 and October 2012	82	34	48
Hwang et al[29]	Retrospective	Korea	Between 2003 and 2014	407	19				68			320
Inoue et al[30]	Retrospective	Japan	Between January 2003 and December 2012	115	43	25	47
Jeon et al[31]	Retrospective	Korea	Between January 2007 and December 2009	31	6				25
Ju et al[32]	Retrospective	Korea	Between January 2018 and December 2022	121	8		2		9	95		7
Kaneko et al[33]	Retrospective	Japan	Between April 2001 and August 2013	46		22	24
Kim et al[34]	Retrospective	Korea	Between October 1999 and November 2010	107	105				2
Kim et al[35]	Retrospective	Korea	Between October 2004 and December 2019	401
Kim et al[36]	Retrospective	Korea	Between January 2012 and October 2021	68	10				11	47
Kim et al[37]	Retrospective	Korea	Between January 1995 and March 2007	30	22	6	2
Kusuhara et al[38]	Retrospective	Japan	Between September 2007 and May 2023	50
Lee et al[39]	Retrospective	Japan	Between 2009 and 2018	346	119	72	155
Li et al[40]	Retrospective	China	Between January 2010 and September 2019	428	211		179			12	26
Moon et al[14]	Retrospective	Korea	Between March 2007 and December 2009	35			35
Moon et al[41]	Retrospective	Korea	Between January 2000 and November 2012	407	211	92	38		66
Nakamura et al[42]	Retrospective	Japan	Between April 2001 and March 2012	170	11	108	51
Oh et al[43]	Retrospective	Korea	Between January 2010 and November 2023	212	103	22	8		35	44
Park et al[44]	Retrospective	Korea	Between January 2020 and August 2023	378	35	5			25	30
Seo et al[45]	Retrospective	Korea	Between 2008 and 2023	202
Sun et al[13]	Retrospective	China	Between January 2010 and December 2016	95			436
Sung et al[46]	Retrospective	Korea	Between January 2000 and June 2010	77	14	58	5
Takita et al[47]	Retrospective	Japan	Between January 2005 and March 2014	139	10	117	12
Wang et al[48]	Retrospective	China	Between February 2011 and September 2018	272			161	111
Zheng et al[49]	Retrospective	China	Between August 2010 and October 2019	98		36	62
Zhuang et al[50]	Retrospective	China	Between January 2013 and December 2021	326	39	6	247		12	32

NET: Neuroendocrine tumor; CSP: Cold snare polypectomy; cEMR: Conventional endoscopic mucosal resection; mEMR: Modified endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; CFP: Cold forceps polypectomy; EC: Electrocoagulation.

Table 2 Clinicopathological characteristics of patients with incomplete resection, mean ± SD

Ref.	Incomplete resection	Resection margin				Salvage treatment	Observation	Sex (M/F)	Age
		Positive	Indeterminate	LVI	Missing data
Cha et al[19]	77	25	5	4	43	21	10	19/12	54 (range: 27-84)
Cha et al[20]	87	57	19	11		44	43	52/35	48.6 ± 11.3
Chatila et al[21]	10	10				10	0	4/6	53.4
Cheminel et al[22]	86					86	0	51/35	54 (range: 18-87)
Cho et al[23]	67					5	62		49.6 ± 11.3
Choi et al[24]	20	6	13	1		1	19	13/6	50.8 ± 11.3
Chung et al[25]	19					9	8		47.5 (range: 39.6-57.1)
Dell’Unto et al[26]	31	31				16	15	18/31	60.5 (range: 22-85)
Duan et al[27]	181					76	105	109/72	59 (range: 50-66)
Heo et al[28]	7	6	0	1		0	7	4/3	49.8 ± 11.6
Hwang et al[29]	87					0	87	55/32	51.7 ± 11.7
Inoue et al[30]	23	7	16			7	16	14/9	62 (range: 27-85)
Jeon et al[31]	31	6	24		1	31	0	21/10	52.0 ± 11.8
Ju et al[32]	121	20	2		99	121	0	73/48	49 (range: 39-58)
Kaneko et al[33]	11					2	6	7/4	58 ± 12
Kim et al[34]	54	17	37	0		0	4	5/4	49.7
Kim et al[35]	118		34	84			54	31/23	55 (range: 27-82)
Kim et al[36]	68	59				9			68
Kim et al[37]	9	9				0			5
Kusuhara et al[38]	50		50	0			0	49/19	49.53 ± 11.20
Lee et al[39]	64	41				12	10	1	7
Li et al[40]	54	54	0			0	57	38/26	50.4 ± 10.8
Moon et al[14]	9		1	8	6/3	49.0 (range: 32-74)	54	33/21	49.9 ± 10.9
Moon et al[41]	148	20				14	7	107	14
Nakamura et al[42]	24	24	0			7	134	88/60	49.7 ± 10.9
Oh et al[43]	212		212	0			17	16/8	56.84 ± 13.27
Park et al[44]	146					95	48	79/44	43 (range: 21-76)
Seo et al[45]	202					76	126
Sun et al[13]	116	76				0	3	37	43
Sung et al[46]	19		6	13	12/7	52.3 ± 12.0	73	63/53	55.8 ± 11.3
Takita et al[47]	10					7	3
Wang et al[48]	22	22				0			3
Zheng et al[49]	13	13	0			0	19	13/9	49.3 ± 10.7
Zhuang et al[50]	83	70	13			18	13	8/5	48.3 ± 12.1

LVI: Lymphovascular invasion; M: Male; F: Female.

Table 3 Additional treatment modalities and follow-up duration, mean ± SD

Ref.	Tumor size (mm)	Additional treatment method							Follow-up duration (month)
		cEMR	mEMR	ESD	Hybrid ESD	EFTR	Surgery	APC
Cha et al[19]	5.2 ± 1.7		16				5		39.8 (range: 24.2-119.7)
Cha et al[20]	4.72		33				11		40.5 (range: 4.27-102.7)
Chatila et al[21]	8.6			10
Cheminel et al[22]	5 (range: 2-10)	19	15	44	1	7			24 (range: 2-216)
Cho et al[23]	5.8 ± 3.2
Choi et al[24]	5.5 ± 2.4								27.4 ± 16.5
Chung et al[25]	4.0 (range: 3.0-6.0)		3	2			4		35 (range: 24.4-48.8)
Dell’Unto et al[26]	6 (range: 1.0-16.0)								36
Duan et al[27]	8.4 (range: 7.5-10.8)								72
Heo et al[28]	6.1 ± 2.7								13 (range: 3-57)
Hwang et al[29]	8.6 ± 3.6								29.1 ± 31.3
Inoue et al[30]	5 (range: 3-13)								24.5 (range: 6-108)
Jeon et al[31]	8.9 ± 3.2	31							12
Ju et al[32]	4 (range: 2-6)	27		94
Kaneko et al[33]	6.4								61.6 (range: 12-150)
Kim et al[34]	5.0 (range: 1.0-10.0)								31 (range: 13-121)
Kim et al[35]									39.3
Kim et al[36]	4.46 ± 2.11								51.85 ± 22.92
Kim et al[37]	6.3 ± 3.1								19.3 (range: 0-122)
Kusuhara et al[38]	5 (range: 2-10)	2							27
Lee et al[39]	5.4 ± 3.1			21					39
Li et al[40]			38 (range: 10-110)	3			4		48.8 (range: 12-131)
Moon et al[14]	4.7 (range: 1-9)								25 (range: 12-43)
Moon et al[41]	5.7 ± 3.1	2							1
Nakamura et al[42]	5.6 ± 2.4		48.3	2			7	2	56.8 (range: 24-227.7)
Oh et al[43]
Park et al[44]	4.7 ± 2.7	1							71
Seo et al[45]			35.0 ± 37.6	16			7		19.0 (range: 1.2-57.5)
Sun et al[13]	9.0 ± 4.0
Sung et al[46]	7.0 ± 2.8			43					61.4 (range: 33.4-125.3)
Takita et al[47]	5.7						4	2	18.5 (range: 5-107)
Wang et al[48]	6.9 ± 3.3								31 (range: 6-97)
Zheng et al[49]	6.3 ± 2.9								28.3 (range: 6-98)
Zhuang et al[50]	6.5

cEMR: Conventional endoscopic mucosal resection; mEMR: Modified endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; EFTR: Endoscopic full-thickness resection; APC: Argon plasma coagulation.

Table 4 Grading of recommendations assessment, development, and evaluation summary of findings

Outcome	Number of participants (studies)	Effect (95%CI)	Risk of Bias	Inconsistency	Indirectness	Imprecision	Publication Bias	Certainty of evidence (GRADE)
Residual tumor after salvage treatment	1223 (19 studies)	Approximately 25% (12%-40%)	Serious	Serious	Not serious	Not serious	Not detected	Very low
Recurrence (salvage vs observation)	2022 (9 studies)	OR = 0.84 (0.42-1.68)	Serious	Not serious	Not serious	Serious	Not detected	Low

GRADE: Grading of recommendations assessment, development, and evaluation; OR: Odds ratio; CI: Confidence interval.