Primary tumor resection in colorectal cancer with unresectable synchronous metastases: A review

Table 1 Median survival (mo) in patients with unresectable metastatic colorectal cancer, according to whether primary tumor resection was performed or not

Ref.	Study period	Resection/No resection	No.of patients	OS(mo)	P value
Scoggins et al[82]	1985-1997	Resection	66	14.5	0.59
		No resection	23	16.6
Tebbutt et al[34]	1990-1999	Resection	280	14	0.08
		No resection	82	8.2
Ruo et al[44]	1996-1999	Resection	127	16	< 0.001
		No resection	103	9
Michel et al[90]	1996-1999	Resection	31	21	0.718
		No resection	23	14
Law et al[35]	1996-1999	Resection	150	7	< 0.001
		No resection	30	3
Benoist et al[79]	1997-2002	Resection	32	23	NS
		No resection	27	22
Stelzner et al[45]	1995-2001	Resection	128	11.4	< 0.0001
		No resection	58	4.6
Konyalian et al[36]	1991-2002	Resection	62	13	< 0.0001
		No resection	47	5
Costi et al[91]	1994-2003	Resection	83	9	< 0.001
		No resection	47	4
Yun et al[37]	1994-2004	Resection	283	15.3	< 0.001
		No resection	93	5.3
Kaufman et al[92]	1998-2003	Resection	115	22	< 0.0001
		No resection	69	3
Galizia et al[38]	1995-2005	Resection	42	15.2	0.03
		No resection	23	12.3
Evans et al[70]	1999-2006	Resection	45	11	< 0.0001
		No resection	57	2
Bajwa et al[39]	1999-2005	Resection	32	14	0.005
		No resection	35	6
Mik et al[40]	1996-2000	Resection	52	21	NS
		No resection	82	14
Frago et al[93]	2004-2008	Resection	12	23.7	0.008
		No resection	43	4.4
Aslam et al[41]	1998-2007	Resection	366	14.5	< 0.005
		No resection	281	5.83
Chan et al[11]	2000-2002	Resection	286	14	< 0.001
		No resection	125	6
Seo et al[94]	2001-2008	Resection	114	22	0.076
		No resection	83	14
Karoui et al[33]	1998-2007	Resection	128	30.7	0.031
		No resection	85	21.9
Ferrand et al[22]	1997-2001	Resection	156	16.3	< 0.0001
		No resection	60	9.5

OS: Overall survival.

Table 2 Prognostic factors associated with overall survival in patients with unresectable metastatic colorectal cancer, according to whether primary tumor resection was performed or not

Ref.	Resection/No resection	No. ofpatients	OS(mo)	P value	PTR on multivariateanalysis [95%CI]	Other independent prognostic factors
Tebbutt et al[34]	Resection	280	14	0.08	No	WHO-PS < 2, no peritoneal dissemination, low phosphatase alkaline and serum albumin levels
	No resection	82	8.2
Law et al[35]	Resection	150	7	< 0.001	OR = 0.42 (0.27–0.66)1P < 0.001	Unilobar LM involvement, no ascites, no chemotherapy
	No resection	30	3
Stelzner et al[45]	Resection	128	11.4	< 0.0001	HR = 0.50 (0.27–0.90) P = 0.0212	No chemotherapy, ASA score < 3, WHO-PS < 2, CEA level, age < 75 yr, extent of metastases, extent of primary tumor
	No resection	58	4.6
Konyalian et al[36]	Resection	62	13	< 0.0001	HR = 0.3 (0.2–0.6) P < 0.00013	Liver involvement < 50%
	No resection	47	5
Yun et al[37]	Resection	283	15.3	< 0.001	HR = 0.53 (0.38–0.73) P < 0.001	Metastatic site ≤ 1, high CEA level, chemotherapy, well-differentiated primary tumor
	No resection	93	5.3
Galizia et al[38]	Resection	42	15.2	0.03	OR = 3.91 (2.83-4.99) 0.26 (0.20-0.35)1P = 0.001	WHO-PS < 2, liver involvement < 50%
	No resection	23	12.3
Bajwa et al[39]	Resection	32	14	0.005	OR = 0.26 (0.13-0.52) P = 0.0001	Left sided primary tumor, unique primary tumor
	No resection	35	6
Mik et al[40]	Resection	52	21	NS	HR = 0.58 (0.36–0.82)1P = 0.004	Unilobar LM involvement
	No resection	82	14
Aslam et al[41]	Resection	366	14.5	< 0.005	P < 0.001	Age < 80 yr, non-locally advanced primary tumor, N + stage
	No resection	281	5.83
Karoui et al[33]	Resection	128	30.7	0.031 -	HR = 0.56 (0.38–0.83)1P = 0.004	Secondary curative resection, well-differentiated primary tumor, anti-VEGF treatment, no extra-hepatic metastases
	No resection	85	21.9
Platell et al[83]	Resection	243	-		HR = 0.51 (0.37–0.69) P = 0.0001	Chemotherapy, radiotherapy, ASA score < 3
	No resection	70	-
Venderbosch et al[12]	Resection	286	14	< 0.001	HR = 0.73 (0.58-0.93) P = 0.01	-
	No resection	125	6
Ferrand et al[22]	Resection	156	16.3	< 0.0001	HR = 0.42 (0.30-0.60) P < 0.0001	WHO-PS < 2, distal colon or rectal primary tumor, one metastatic site and alkaline phosphatase ≤ 300 UI/L
	No resection	60	9.5

¹For readability of the Table, some ORs and HRs have been recalculated with “ No resection” as reference for the multivariate analysis of survival;

²excluding postoperative mortality and complicated primary tumor;

³PTR was independently associated with increased survival probability, while adjusting on patient’s age, sex and degree of hepatic tumor involvement. OS: Overall survival; PTR: Primary tumor resection; OR: Odds ratio; HR: Hazard ratio; LM: Liver metastases; ASA: American society of anesthesiology; CEA: Carcinoembryonic antigen; VEGF: Vascular-endothelial growth factor; WHO-PS: World health organization performance status; NS: Not significant.

Table 3 Prognostic factors after primary tumor resection on multivariate analyzes

Ref.	Metastatic spread	No. of patients	Prognostic factors or predictive factors of postoperative morbimortality
Rosen et al[43]	Liver, Peritoneum	125	Age < 65 yr, limited LM, no peritoneal carcinomatosis
Ruo et al[44]	Liver, peritoneum, retroperitoneal lymph nodes, lung, bone, brain	123	Liver involvement < 25%
Stelzner et al[45]	Mainly liver	186	WHO-PS, ASA grade, low CEA level, metastatic load, chemotherapy
Vibert et al[47]	Liver	80	Serum AST level < 50 IU/l, age < 75 yr
Yun et al[37]	Liver, peritoneum, lung	503	CEA level, well-differentiated primary tumor, chemotherapy
Kleespies et al[46]	Mainly liver, lung, peritoneum	233	Liver involvement < 50%, chemotherapy, pT4 and/or N+ stage
Costi et al[48]	Mainly liver, peritoneum	71	Age < 80 yr, nodal stage
Stillwell et al[31]	Liver and extra-hepatic	379	Nodal stage < N2, well-differentiated primary tumor, no postoperative complications, no apical lymph-node

LM: Liver metastases; ASA: American society of anesthesiology; CEA: Carcinoembryonic antigen; WHO-PS: World health organization performance status.

Table 4 Complications related to in situ tumor in patients with unresectable stage IV colorectal cancer treated with chemotherapy as initial management n (%)

Ref.	No. of patients	Primary tumor-related complications (%)	Type of complication during chemotherapy			Surgery required for complication (%)
			Obstruction	Bleeding	Perforation
Scoggins et al[82]	23	9	2 (9)	0	0	9
Sarela et al[71]	24	29	4 (17)	0	0	21
Ruo et al[44]	103	29	30 (29)	0	0	29
Tebbut et al[34]	82	23	11 (13)	3 (4%)	5 (6)	10
Michel et al[90]	23	22	5 (22)	0	0	22
Benoist et al[79]	27	15	4 (15)	0	0	15
Muratore et al[75]	35	8.5	2 (6)	1 (3%)	0	3
Galizia et al[38]	23	30	4 (17)	1 (4%)	2 (9)	17
Evans et al[70]	52	23	3 (6)	9 (17%)	0	2
Poultsides et al[76]	233	11	18 (8)	0	5 (2)	7
Karoui et al[33]	123	19	21 (17)	0	2 (2)	12
McCahill et al[77]	86	16	10 (12)	0	1 (1)	12

Table 5 Postoperative outcome after primary tumor resection in patients with unresectable stage IV colorectal cancer

Ref.	Study period	No.of patients	Mortality(%)	Morbidity(%)
Scoggins et al[82]	1985-1997	66	5	30
Rosen et al[43]	1984-1998	120	6	22.5
Tebbutt et al[34]	1990-1999	280	NM	13
Ruo et al[44]	1996-1999	127	2	21
Michel et al[90]	1996-1999	31	0	NM
Benoist et al[79]	1997-2002	32	0	19
Stelzner et al[45]	1995-2001	128	11.7	-
Galizia et al[38]	1995-2005	42	0	21
Evans et al[70]	1999-2006	45	16	NM
Bajwa et al[39]	1999-2005	32	3	22
Kleespies et al[46]	1996-2002	233	4.7	46
Mik et al[40]	1996-2000	52	7.7	40
Costi et al[48]	1994-2003	71	8.5	24
Stillwell et al[31]	1984-2004	379	9.2	48.3

NM: Not mentioned.