Management of asymptomatic primary tumours in stage IV colorectal cancer: Review of outcomes

Table 1 Study characteristics

Ref.	Years data collected	Country	Type of study	Total n	% of group receiving chemo	Predominant chemotherapy regime	Targeted agent use
2 arms: PTR vs PC				(PTR n/PC n)	(PTR/PC)
Yun et al[18] (2014)	2000-2008	South Korea	Retrospective, propensity-score matched cohort, single centre	416 (218/198)	66/100	Doublet	ND
Matsumoto et al[19] (2014)	2005-2011	Japan	Retrospective, single centre	88 (41/47)	85/100	Doublet	Approx 50% received targeted agent
Ahmed et al[42] (2014) Subgroup	1992-2005	Canada	Retrospective, multicentre	834	100/100	ND	< 2%
Cetin et al[22] (2013)	2006-2010	Turkey	Retrospective, multi centre	99 (53/46)	100/100	Doublet	100% received bevacizumab
Boselli et al[15] (2013)	2010-2011	Italy	Retrospective, single centre	48 (17/31)	65/100	Doublet	> 50% received bevacizumab 1st line
Seo et al[20] (2010)	2001-2008	South Korea	Retrospective, single centre	227 (144/83)	100/100	Doublet	5%-10% received bevacizumab; 5%-10% received EGFR monoclonal antibody
Galizia et al[25] (2008)	1995-2005	Italy	Retrospective, single centre	65 (42/23)	100/100	Singlet	Nil
Benoist et al[26] (2005)	1997-2002	France	Retrospective, case matched, single centre	59 (32/27)	94/100	Singlet	Nil
Michel et al[21] (2004)	1996-1999	France	Retrospective, single centre	54 (31/23)	97/100	Doublet	Nil
Ruo et al[43] (2003)	1996-1999	United States	Retrospective, single centre	230 (127/103)	ND/83	Singlet	Nil
Scoggins et al[44] (1999)	1985-1997	United States	Retrospective, single centre	89 (66/23)	ND/100	Singlet	Nil
Single arm: Primary chemotherapy				n	% group receiving chemo
Yun et al[23] (2014)	2000-2011	South Korea	Retrospective, single centre	259	100	Doublet	ND
McCahill et al[16] (2012)	2006-2009	United States	Prospective Phase 2	86	100	Doublet	100% received bevacizumab
Clements et al[45] (2009)	2003-2006	United Kingdom	Retrospective, single centre	37	92	Doublet	ND
Bajwa et al[27] (2009)	1999-2005	United Kingdom	Retrospective, single centre	67	100	Doublet	ND
Poultsides et al[24] (2009)	2000-2006	United States	Retrospective, single centre	233	100	Doublet	48% received bevacizumab 1st line
Muratore et al[46] (2007)	2000-2004	Italy	Prospective, single centre	35	100	Doublet	Nil
Sarela et al[47] (2001)	1997-2000	United Kingdom	Retrospective and prospective, single centre	24	87	Singlet	Nil
Single arm: Primary tumour resection				n	% group receiving chemo
Maeda et al[28] (2013)	2001-2009	Japan	Retrospective, single centre	94	85	Doublet	33% received targeted agent
Matsuda et al[17] (2012)	1998-2007	Japan	Retrospective, single centre	40	74	Doublet	ND

PTR: Primary tumour resection; PC: Primary chemotherapy; ND: Not documented.

Table 2 Overall survival

Ref.	Unadjusted median OS (mo)			Adjusted survival outcomes: Is PTR superior?
	PTR	PC	P value
Galizia et al[25] (2008)	15	12	P = 0.03	Yes (HR for death PC = 3.91, 95%CI: 2.83-4.99, P = 0.01)
Ahmed et al[42] (2014) Subgroup	15	8	P < 0.01	Yes (analysis not shown)
Ruo et al[43] (2003)	16	9	P < 0.001	No adjusted survival data
Yun et al[18] (2014) Matched cohort	17	14	P = NS	No (HR for death PC = 1.16, 95%CI: 0.89-1.52, P = 0.27)
Matsumoto et al[19] (2014)	24	23	P = NS	No (HR for death PTR = 0.72, 95%CI: 0.42-1.25, P = NS)
Seo et al[20] (2010)	22	14	P = NS	No (HR for death PC = 1.73, 95%CI: 0.94-3.16, P = 0.07)
Benoist et al[26] (2005) Matched cohort	23	22	P = NS	No (HR not reported, P = 0.753)
Cetin et al[22] (2013)	23	17	P = NS	No adjusted survival data
Michel et al[21] (2004)	21	14	P = NS	No adjusted survival data
Scoggins et al[44] (1999)	14	17	P = NS	No adjusted survival data
Boselli et al[15] (2013)	4	5	P = NS	No (HR for death PTR = 2.1, 95%CI: 1.06-4.5, P = 0.03)

NS: Not significant (P > 0.05); PTR: Primary tumour resection; PC: Primary chemotherapy; HR: Hazard ratio.

Table 3 Primary tumour related complications in patients undergoing primary chemotherapy

Ref.	% of patients requiring intervention for primary tumour related complications	Most common complication	Comment
Yun et al[18] (2014)	3%	Obstruction > perforation	Mean onset of complications = 8 mo
Cetin et al[22] (2013)	4%	Obstruction > rectovesical fistula	-
Muratore et al[46] (2007)	6%	Obstruction > haemorrhage	-
Clements et al[45] (2009)	8%	All obstruction	-
Scoggins et al[44] (1999)	9%	All obstruction	Mean onset of complications = 3 mo
Poultsides et al[24] (2009)	11%	Obstruction > perforation > pain	-
Seo et al[20] (2010)	14%	Obstruction > bleeding	-
Benoist et al[26] (2005)	15%	All obstruction	-
McCahill et al[16] (2012)	16%	Obstruction > perforation, pain	Majority onset of complications < 12 mo
Michel et al[21] (2004)	22%	All obstruction	Mean onset of complications = 4 mo
Yun et al[23] (2014)	22%	Obstruction > perforation	Mean onset of complications = 7 mo
Matsumoto et al[19] (2014)	26%	Majority obstruction	-
Ruo et al[43] (2003)	29%	All obstruction	Majority onset of complications < 6 mo
Galizia et al[25] (2008)	30%	Obstruction> perforation > haemorrhage	Mean onset of complication = 11 mo
Sarela et al[47] (2001)	33%	Obstruction > pain > tenesmus	Mean onset of complication = 9 mo
Bajwa et al[27] (2009)	40%	Obstruction > bleeding

Table 4 Complications in patients undergoing primary tumour resection

Ref.	Post-operative (30 d) mortality %	Post-operative morbidity		Requiring subsequent surgical intervention (%)
		%	Most common complication
Cetin et al[22] (2013)	0	ND	ND	6% (all rectovesical fistula)
Benoist et al[26] (2005)	0	19	Wound infection, cardio-respiratory, intra-abdominal abscess, UTI	ND
Galizia et al[25] (2008)	0	21	All minor	0%
Maeda et al[28] (2013)	0	21	Wound infection, ileus, anastomotic leak	ND
Michel et al[21] (2004)	0	ND	ND	ND
Seo et al[20] (2010)	0	35	Urine retention, wound complication, ileus.	2%
Yun et al[18] (2014)	1	10	Ileus, wound infection, anastomotic leak	ND
Matsuda et al[17] (2012)	2	15	Wound infection, ileus	11%
Ruo et al[43] (2003)	2	21	Wound infection, ileus, intra-abdominal infection	3%
Matsumoto et al[19] (2014)	2	20	ND	ND
Scoggins et al[44] (1999)	5	30	Wound infection, UTI, sepsis	ND
Boselli et al[15] (2013)	29	35	Wound infection, UTI, pneumonia	ND

ND: Not documented; UTI: Urinary tract infection;

Table 5 Independent prognostic factors influencing overall survival on multivariate analysis, with hazard ratios or odds ratios for death

Ref.	Age	Sex	ECOG PS≥2	Tumour location: Right colon	Tumour differentiation	T stage	N stage	M1b(vs M1a)	Presence of liver mets	Extent of hepatic involvement	Pre treatment CEA	Chemotherapy regime: Non use of Oxaliplatin/Irinotecan
Cetin et al[22] (2013)	a	a									a
Yun et al[18] (2014)1	a	a		a	a	a	a	HR 1.39	HR 1.31		a
Galizia et al[25] (2008)	a	a	HR 3.18	a	a	a	a			HR 5.792	a
Matsuda et al[17] (2013)	a	a		a	a		a		a		a	HR 2.57
Bajwa et al[27] (2009)	a		a	OR 2.61	a					a	a
Maeda et al[28] (2013)	a	a	OR 2.73	a	a	a	a	OR 1.66			a
Seo et al[20] (2010)	a	a	a	a	HR 2.824			a		HR 2.415	a	HR 1.896
Michel et al[21] (2004)										a

a: Factor investigated by authors and found to be non-significant on multivariate analysis;

¹Unmatched cohort;

²> 50% hepatic replacement (vs < 50% hepatic replacement);

³ECOG PS ≥ 1 (vs 0);

⁴High grade (vs low grade);

⁵> 5 liver metastases (vs < 5);

⁶Oxaliplatin use only. ECOG: Eastern Co-operative.