Role of surgical resection for non-colorectal non-neuroendocrine liver metastases

Table 1 Summary of studies each of which included ≥ 100 patients who underwent hepatectomy for non-colorectal non-neuroendocrine liver metastases (overall survival)

Ref.	Year	Period	No. of patients	Primary tumor (GI/breast/GU/melanoma/sarcoma/others)	MST (mo)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Elias et al[7]	1998	1984-1996	1201	(22/35/31/10/13/9)	NR	NR	362	NR
Yedibela et al[9]	2005	1978-2001	1501	(50/24/11/5/15/45)	232	NR	262	Margin status (R1,2)
Weitz et al[8]	2005	1981-2002	141	(12/29/50/17/0/33)	42	57	NR	Primary tumor type, disease-free interval ≤ 24 mo, margin status (R1,2)
Adam et al[10]	2006	1983-2004	1452	(314/460/332/148/0/198)	35	49	36	Age, primary tumor (ocular melanoma, non-breast), squamous tumor, disease-free interval, extrahepatic disease, major hepatectomy, margin status (R1,2)
Lendoire et al[11]	2007	1989-2006	106	(7/19/40/6/23/11)	27	34	19	Primary tumor (non-breast, non-GU), synchronous metastasis, margin status (R1,2)
O'Rourke et al[12]	2008	1986-2006	102	(27/11/31/20/3/10)	42	56	39	Diameter of liver metastasis > 5 cm, extrahepatic nodal disease
Groeschl et al[13]	2012	1990-2009	420	(13/15/92/31/98/71)	49	50	31	Diameter of liver metastasis ≥ 5 cm, lymphovascular invasion
Takemura et al[14]	2013	1993-2009	145	(91/30/12/1/8/3)	42	55	41	Postoperative complication
Hoffmann et al[15]	2015	2001-2012	150	(30/42/33/15/9/21)	46	NR	42	Primary tumor (melanoma, non-breast), interval < 24 mo, squamous tumor, non-stromal tumor, minor hepatectomy, margin (R2)
Schiergens et al[16]	2016	2003-2013	167	(43/16/61/8/25/14)	35	49	NR	> 3 liver metastases, extrahepatic disease, residual tumor (R1,2), major complications

¹Patients with neuroendocrine tumors were excluded;

²Results including neuroendocrine tumors. GI: Gastrointesti; GU: Genitourinary; MST: Median survival time; ysr: Year survival rate; NR: Not reported.

Table 2 Summary of studies each of which included ≥ 100 patients who underwent hepatectomy for non-colorectal non-neuroendocrine liver metastases (disease-free survival)

Ref.	Year	No. of patients	MDFST (mo)	3-ydfsr (%)	5-ydfsr (%)	Factors associated with worse disease-free survival
Elias et al[7]	1998	1201	NR	NR	282	NR
Yedibela et al[9]	2005	1501	NR	NR	NR	NR
Weitz et al[8]	2005	141	17	30	NR	Primary tumor, diseas-free interval ≤ 24 mo
Adam et al[10]	2006	1452	13	27	21	NR
Lendoire et al[11]	2007	106	NR	NR	NR	NR
O'Rourke et al[12]	2008	102	18	37	27	Diameter of liver metastasis > 5 cm, extrahepatic nodal disease
Groeschl et al[13]	2012	420	NR	NR	NR	NR
Takemura et al[14]	2013	145	10	21	18	Blood transfusuion, preoperative chemotherapy
Hoffmann et al[15]	2015	150	21	36	29	NR
Schiergens et al[16]	2016	167	15	NR	NR	> 3 liver metastases, extrahepatic disease, residual tumor (R1,2)

¹Patients with neuroendocrine tumors were excluded;

²Results including neuroendocrine tumors. MDFST: Median disease-free survival time; ydfsr: Year disease-free survival ratio; NR: Not reported.

Table 3 Summary of studies each of which included ≥ 40 patients who underwent hepatectomy for liver metastasis from gastric cancer

Ref.	Year	Period	No. of patients	MST (mo)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Ambiru et al[17]	2001	1975-1999	40	12	NR	18	Synchronous metastasis
Adam et al[10]1	2006	1983-2004	64	15	NR	27	NR
Cheon et al[18]	2008	1995-2005	41	18	32	21	Multiple liver metastases
Takemura et al[19]	2012	1993-2011	64	34	50	37	Serosal invasion of primary gastric cancer, maximum hepatic metastasis diameter > 5 cm
Aizawa et al[20]	2014	1997-2010	53	27	NR	18	Multiple liver metastases
Kinoshita et al[21]	2014	1990-2010	256	31	42	31	Serosal invasion of primary gastric cancer, > 3 liver metastases, maximum hepatic metastasis diameter > 5 cm
Tiberio et al[22]	2015	1997-2011	53	13	14	9	NR2
Oki et al[23]	2015	2000-2010	69	41	51	42	Multiple liver metastases, > 2 positive regional lymph node metastases of primary gastric cancer

¹As a part of the report of on-colorectal non-neuroendocrine liver metastases;

²Only risk factors including palliative patients were reported. MST: Median survival time; ysr: Year survival rate; NR: Not reported.

Table 4 Summary of studies with relatively large cohort of patients who underwent hepatectomy for liver metastasis from gastrointestinal stromal tumors

Ref.	Year	Period	No. of patients underwent hepatectomy	MST (mo)	3-ysr (%)	5-ysr (%)	3-yPFS (%)	No. of patients with TKI	Factors associated with worse overall survival
DeMatteo et al[26]	2001	1982-2000	341	391	501	301	451	NR	Interval from primary tumor diagnosis ≤ 24 mo2
Nunobe et al[27]	2005	1984-2003	18	36	64	34	NR	3 (17%)	NR
Xia et al[28]	2010	2005	19	33 (mean)	90	NR	NR	19 (100%)	Non-surgical therapy2
Turley et al[29]	2012	1995-2010	39	Not reached at 5 yr	68	NR	NR	27 (73%)3	Non-TKI therapy, extrahepatic disease
Bauer et al[30]	2014	Until 2011	104	96	NR	NR	NR	> 84%	Male4, R2 resection4, progression disease to TKI at the time of surgery4, extrahepatic disease4
Du et al[31]	2014	NR	19	Not reached	NR	NR	88 (2-yr)	19 (100%)	Non-surgical therapy2
Seesing et al[32]	2016	1999-2014	48	90	80	76	67	42 (88%)	Margin status (R1,2)

¹Including gastrointestinal sarcoma;

²Copmarison to the non-operation group;

³Excluding two patients lost to follow-up;

⁴Results including resections of extrahepatic metastasis. GIST: Gastrointestinal stromal tumor; MST: Median survival time; ysr: Year survival rate; PFS: Progression-free survival; TKI: Tyrosine kinase inhibitor; NR: Not reported.

Table 5 Summary of studies with relatively large cohort of patients who underwent hepatectomy for liver metastases from gastrointestinal primaries other than gastric cancer and gastrointestinal stromal tumors

Disease	Ref.	Year	Period	No. of patients	MST (mo)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Peri-ampullary	De Jong et al[34]	2010	1993-2009	40	17 [23 (intestinal), 13 (pancreaticobiliary)]	18	NR	Intestinal type (ampullary or duodenal) tumors
Ampullary	Adam et al[10]1	2006	1983-2004	15	38	NR	46	NR
Small bowel	Adam et al[10]1	2006	1983-2004	28	58	NR	49	NR
Pancreas	Adam et al[10]1	2006	1983-2004	40	20	NR	25	NR
	Schiergens et al[16]1	2016	2003-2013	19	7	17	NR	NR
Esophagous	Adam et al[10]1	2006	1983-2004	20	16	32	NR	NR
	Ichida et al[35]	2013	2003-2005	5	13	NR	NR	NR

¹As a part of the report of on-colorectal non-neuroendocrine liver metastases. MST: Median survival time; ysr: Year survival rate; NR: Not reported.

Table 6 Summary of studies with ≥ 40 patients who underwent hepatectomy for liver metastasis from breast cancer

Ref.	Year	Period	No. of patients	MST (mo)	3-ysr (%)	5-ysr (%)	MDFS (mo)	Factors associated with worse overall survival
Pocard et al[36]	2000	1988-1997	52	42	49	NR	NR	Disesase free interval ≤ 48 mo (univariate)
Elias et al[37]	2003	1986-2000	54	34	50	34	NR	Hormone receptor-negative
Adam et al[38]	2006	1984-2004	85	32	NR	37	20	Poor response to preoperative chemotherapy, R2, no repeat hepatectomy
Adam et al[10]1	2006	1983-2004	454	45	NR	41	NR	NR
Hoffman et al[39]	2010	1999-2008	41	58	68	48	34	Positive resection margin, disease-free interval < 24 mo
Abbott et al[40]	2012	1997-2010	86	57	NR	44	14	ER-negative, disease progression before hepatectomy
Groeschl et al[13]1	2012	1990-2009	115	52	52	27	22	NR
Mariani et al[41]	2013	1988-2007	51	91	NR	NR	NR	Non-hepatectomy3, bone metastasis4
Hoffmann et al[15]1	2015	2001-2012	42	63	NR	53	NR	NR
Sadot et al[42]	2016	1991-2014	692	502	NR	382	29	Lymph node metastasis in the primary tumor, absence of trastuzumab therapy, multiple liver metastases

¹As a part of the report of on-colorectal non-neuroendocrine liver metastases;

²Including 18 patients who underwent percutaneous ablation therapy;

³Comparison to the non-operation group;

⁴Comparison including patients without hepatectomy. MST: Median survival time; ysr: Year survival rate; NR: Not reported.

Table 7 Summary of studies with ≥ 40 patients who underwent hepatectomy for liver metastasis from melanoma

Ref.	Year	Period	No. of patients	Ocular/cutaneous	MST (mo) (ocular/cutaneous)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Adam et al[10]1	2006	1983-2004	148	104/44	19/27	NR	21 (ocular)/22 (cutaneous)	NR
Pawlik et al[44]	2006	1988-2004	40	16/24	28 [29 (ocular)/24 (cutaneous)]	62 (ocular)/48 (cutaneous) (2-yr)	11 (21 (ocular)/0 (cutaneous))	Cutaneous melanoma, no preoperative chemotherapy (in cutaneous melanoma) (univariable)
Mariani et al[45]	2009	1991-2007	255 (R2 = 157)	255/0	14 (27 mo after R0 resection)	NR	7	Interval from primary tumor diagnosis ≤ 24 mo, R1 and R2, number of the metastases > 4, miliary disease
Mariani et al[46]	2016	2000-2013	70 (inclding 13 concomitant with RFA)	70/0	27 (hepatectomy), 28 (+RFA)	NR	NR	NR

¹As a part of the report of on-colorectal non-neuroendocrine liver metastases. MST: Median survival time; ysr: Year survival rate; NR: Not reported.

Table 8 Summary of studies with relatively large cohort of patients who underwent hepatectomy for liver metastasis from sarcoma

Ref.	Year	Period	No. of patients	MST (mo)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Lang et al[48]	2000	1982-1996	26 (including 9 second, 2 third resection)	32 (R0 first resection), 21 (R1,2 resection)	NR	13	NR
DeMatteo et al[26]1	2001	1982-2000	561	391	501	301	Time to liver metastasis from the primary tumor diagnosis ≤ 24 mo
Pawlik et al[49]	2006	1996-2005	53 (35Hx, 18RF + Hx, and 13RF), (including 36 GISTs)	472	652	272	Non-GIST
Marudanayagam et al[50]	2011	1997-2009	361 (including 5 GISTs)	24	48	32	Primaly leiomyosarcoma
Groeschl et al[13]3	2012	1990-2009	98	72	60	32	NR
Zhang et al[51]	2015	2000-2009	27	NR	NR	46	Interval from primary tumor diagnosis ≤ 24 mo, extrahepatic disease, positive margins

¹Including some patients with GIST before 1993, GISTs were considered as leiomyosarcomas;

²Including results of RF and patients with GIST;

³As a part of the report of on-colorectal non-neuroendocrine liver metastases. GIST: Gastrointestinal stromal tumor; MST: Median survival time; ysr: Year survival rate; NR: Not reported; Hx: Hepatectomy; RF: Radiofrequency ablation.

Table 9 Summary of studies with relatively large cohort of the patients who underwent hepatectomy for liver metastasis from genitourinary primary tumor

Disease	Ref.	Year	Period	No. of patients	MST (mo)	3-ysr (%)	5-ysr (%)	Factors associated with worse overall survival
Renal cell carcinoma	Adam et al[10]1	2006	1983-2004	85	36	NR	38	NR
	Thelen et al[52]	2007	1988-2006	31	48	54	39	Resection margin (R1,2)
	Staehler et al[53]	2010	1995-2006	68	142	NR	62	High-grade primary renal cell carcinoma, performance status ≥ 1, lymph node status
	Ruys et al[54]	2011	1990-2008	29	33	47	43	Synchronous metastases, R1,2 resection margin (univariate)
	Hatzaras et al[55]	2012	1994-2011	43	Not reached	62	NR	Disease-free interval ≤ 12 mo, exrahepatic disease (univariate)
	Schiergens et al[16]1	2016	2003-2013	28	50	68	NR	NR
Gyneclogic primary	Kamel et al[56]	2011	1990-2010	52	53	57	41	NR
Ovarian cancer	Merideth et al[57]	2003	1976-1999	262	26	NR	NR	Interval from the primary diagnosis < 12 mo, residual disease > 1 cm (univariate)
	Adam et al[10]1	2006	1983-2004	65	98	NR	50	NR
	Lim et al[58]	2009	2001-2008	142	Not reached	NR	51	Hematogeneous liver metastasis < hepatic parenchymal metastasis from peritoneal seeding5
	Neumann et al[59]	2012	1991-2007	41	42(R0 resection)	NR	NR	R1,2 resection, pre-operative ascites, bilobular liver metastasis
	Niu et al[60]	2012	2000-2011	60	39	NR	30	R1,2 resection
	Kolev et al[61]	2014	1988-2012	273	56	NR	NR	Interval from the primary surgery ≤ 24 mo, residual disease ≥ 1 cm
	Bacalbasa et al[62]	2015	2002-2014	3124	16 (metastasis from seeding), 13 (hematogeneous)	NR	NR	No significant risk factor
	Schiergens et al[16]1	2016	2003-2013	24	33	43	NR	NR
Testicular cancer	Hahn et al[63]	1999	1974-1996	57	NR	97 (2-yr)	NR	NR
	Adam et al[10]1	2006	1983-2004	78	82	NR	51	NR

¹As a part of the report of on-colorectal non-neuroendocrine liver metastases;

²As a part of debulking surgery;

³Hepatectomy as secondary cytoreduction;

⁴Including 2^nd (n = 15), 3^rd (3) and 4^th (2) cytoreduction operations;

⁵Only risk factors that included patients undergoing palliative treatment were reported. MST: Median survival time; ysr: Year survival rate; NR: Not reported.