Re-evaluation of classical prognostic factors in resectable ductal adenocarcinoma of the pancreas

Table 1 Tumor size and survival for resectable pancreatic cancer

Ref.	Year	n	Tumor size, cut-off	Median OS	Statistical model	HR (95%CI)	P value
Matsumoto et al[38]	2015	968	≥ 3 cm	NR	Multivariable	1.72 (1.16-2.56)	0.006
Jeong et al[39]	2015	276	≤ 2.5 cm	13 mo	Multivariable	1.65 (1.17–2.32)	0.004
			> 2.5 cm	25 mo
Hur et al[17]	2015	18338	In situ	120 mo	Multivariable	1
			≤ 1.0 cm	27 mo		3.09 (2.35-4.07)	< 0.001
			1.1-2.0 cm	17 mo		4.35 (3.42-5.53)	< 0.001
			> 2.0 cm	11 mo		5.69 (4.49-7.21)	< 0.001
Yamamoto et al[40]	2015	195	≤ 2 cm	29 mo (mean)	Multivariable	0.40 (0.17-0.83)	0.012
Elberm et al[41]	2015	1070	< 2 cm	19 mo	Multivariable	0.63 (0.50-0.78)	< 0.001
Liu et al[31]	2015	411	> 2 cm	NR	Univariable	1.46 (1.14-1.88)	0.003
Okada et al[42]	2014	200	≥ 3 cm	NR	Multivariable	3.26 (1.52–7.00)	0.002
Dusch et al[21]	2014	415	< 3 cm	16 mo	Univariable	-	< 0.03
Shin et al[15]	2014	537	≤ 3 cm	22 mo	Multivariable	1.4 (1.13-1.73)	0.002
			> 3 cm	14 mo
Kooby et al[37]	2014	1399	Continuous	20 mo	Multivariable	1.12 (1.06-1.18)	< 0.001
Petermann et al[10]	2013	114	≤ 2 cm	35 mo	Multivariable	0.52 (0.25–1.05)	0.071
			2.1–3.4 cm	16 mo
			3.5–4.5 cm	20 mo
			> 4.5 cm	8 mo
Jamieson et al[43]	2013	217	≤ 3 cm	23 mo	Multivariable	1.28 (0.93–1.76)	0.13
			> 3 cm	16 mo
Franko et al[14]	2013	7135	≤ 1 cm	N0/N1: 38/18 mo	Multivariable	1
			1.1–2 cm	N0/N1: 26/19 mo		1.18 (0.94-1.48)	0.152
			> 2 cm	N0/N1: 19/14 mo		1.67 (1.34-2.07)	< 0.001
Lad et al[44]	2013	382	Continuous	16 mo	Multivariable	1.23 (1.07–1.41)	0.003
Sugiura et al[45]	2013	208	≥ 3 cm	NR	Univariable	NR	0.014
Hong et al[18]	2012	209	< 3 cm	20 mo	Univariable	NR	0.06
			≥ 3 cm	15 mo
Bhatti et al[46]	2010	84	≤ 2 cm	34 mo	Univariable	NR	0.017
			> 2 cm, invasion-	27 mo
			> 2 cm, invasion+	11 mo
Yamada et al[47]	2009	335	> 4 cm	NR	Multivariable	2.69 (1.30-5.56)	< 0.05
Ueda et al[48]	2009	140	< 3 cm	22 mo	Multivariable	1.85 (1.14-3.10)	0.013
			≥ 3 cm	11 mo
Kaneoka et al[49]	2009	84	< 2 cm	NR	Multivariable	1
			2–4 cm	20 mo		1.7 (1.0–3.1)	0.031
			> 4 cm	11 mo		2.3 (1.3–4.5)	0.003
Campbell et al[50]	2009	163	Continuous	14 mo	Multivariable	1.02 (1.00-1.03)	0.049
Doi et al[51]	2007	133	≤ 4 cm	45% dead within 1 yr	Univariable	1.55 (1.06–2.24)	0.02
			> 4 cm	67% dead within 1 yr
Zacharias et al[52]	2007	81	≤ 3 cm	28 mo	Multivariable	1.9 (1.1–3.1)	0.018
			> 3 cm	14 mo
Pawlik et al[6]	2007	905	≥ 2 cm	17 mo	Multivariable	1.24 (1.01-0.51)	0.04
Moon et al[53]	2006	94	< 3 cm	25 mo	Multivariable	0.46 (0.27-0.78)	0.004
Cleary et al[20]	2004	123	Continuous	14 mo	Univariable	1.2 (1.0–1.4)	0.01
Ahmad et al[54]	2001	125	< 2 cm	16 mo	Univariable	1
			2-4 cm			1.05 (0.58-1.89)	0.87
			> 4 cm			1.15 (0.61-2.15)	0.66
Sohn et al[55]	2000	616	< 3 cm	21 mo	Multivariable	0.72 (0.57-0.90)	0.004
			≥ 3 cm	14 mo
Meyer et al[56]	2000	113	≤ 2 cm	28 mo	Multivariable	2.27	< 0.006
			> 2 cm	13 mo

OS: Overall survival.

Table 2 Prognostic relevance of lymph node ratio

Ref.	Year	n	Cut-off	Detection rate (%)	Median OS with highest LNR (mo)	Survival model	HR (95%CI)	P value
Fouquet et al[34]	2014	166	0.2	76 (46)	NR	Multivariable	2.38 (1.4-4.0)	0.001
Dusch et al[21]	2014	415	Continuous	0.10 (0-0.81)1	NR	Multivariable	1.73 (NR)	0.002
Valsangkar et al[57]	2013	14907	0.3	4038 (27)	NR	Multivariable	2.27 (1.67-3.08)	< 0.001
Lewis et al[58]	2013	424	0.3	83 (20)	16	Multivariable	1.97 (NR)	< 0.001
Robinson et al[59]	2012	131	0.15	70 (53)	NR	Multivariable	4.14 (NR)	< 0.010
La Torre et al[60]	2011	101	0.2	30 (30)	13	Multivariable	4.88 (1.07-22.2)	0.008
Bhatti et al[46]	2010	84	0.3	26 (31)	6	Multivariable	2.7 (1.6–4.4)	0.010
Riediger et al[61]	2009	182	0.3	32 (18)	NR	Multivariable	2.2 (1.4-3.6)	< 0.001
Slidell et al[22]	2008	3868	0.4	602 (16)	10	Multivariable	1.82 (1.59-2.07)	< 0.001
Pawlik et al[6]	2007	905	0.4	154 (17)	12	Multivariable	2.55 (1.75-2.70)	0.001

¹Mean (range). LNR: Lymph node ratio; OS: Overall survival.

Table 3 Para-aortic lymph node involvement and survival

Ref.	Year	n	Detection rate (%)	Median OS with PALN (mo)	Survival model	HR (95%CI)	P value
Sho et al[62]	2015	882	102 (12)	17	Multivariable	1.15 (0.87-1.50)	0.335
Schwarz et al[24]	2014	111	17 (15)	16	Univariable	NR	0.038
Kanda et al[63]	2011	429	49 (11)	8	Univariable	NR	0.006
Murakami et al[64]	2010	103	18 (17)	12	Multivariable	1.84 (0.28-1.07)	0.078
Doi et al[51]	2007	133	19 (14)	5	Multivariable	2.90 (1.60-5.02)	0.001
Shimada et al[65]	2006	133	29 (22)	13	Univariable	NR	< 0.001

OS: Overall survival; PALN: Para-aortic lymph node involvement.

Table 4 Porto-mesenteric vein resection and survival

Ref.	Year	n	VR rate (%)	Median OS without VR/with VR (mo)	Survival model	HR (95%CI)	P value
Jeong et al[39]	2015	276	46 (17)	16/12	Multivariable	1.15 (0.78–1.71)	0.474
Murakami et al[66]	2015	937	435 (46)	26/19	Multivariable	1.16 (0.89-1.53)	0.268
Wang et al[67]	2014	122	64 (53)	31/18	Multivariable	NR	NS
Kelly et al[68]	2013	492	70 (14)	19/12	Multivariable	1.14 (0.83-1.57)	0.410
Gong et al[69]	2013	566	119 (21)	20/13	Univariable	NR	< 0.050
Castleberry et al[70]	2012	3582	281 (8)	Increased 30-d postoperative mortality, 2.9% vs 5.7%	Multivariable	2.1 (1.22-3.73)	0.008
Chakravarty et al[71]	2010	87	12 (14)	10/9	Multivariable	NR	0.591
Ouaissi et al[72]	2010	149	59 (40)	19/18	Multivariable	DFS: 0.43 (0.22-0.82)	0.011
Kaneoka et al[49]	2009	84	42 (50)	26/12	Multivariable	NR	NS
Kurosaki et al[73]	2008	77	35 (45)	20/20	Univariable	NR	0.330
Fukuda et al[30]	2007	121	37 (31)	NR	Univariable	NR	0.550
Carrère et al[74]	2006	133	45 (34)	19/15	Univariable	NR	0.690
Shimada et al[75]	2006	149	86 (58)	35/14	Multivariable	2.25 (1.09–3.62)	NR
Tseng et al[76]	2004	291	110 (38)	27/23	Multivariable	1.13 (0.79-1.63)	0.500
Poon et al[77]	2004	50	12 (24)	21/20	Univariable	NR	0.769
Nakagohri et al[78]	2003	81	33 (41)	10/15	Univariable	NR	NS
Bachellier et al[79]	2001	87	31 (36)	12/12	Univariable	NR	0.480

OS: Overall survival; PALN: Para-aortic lymph node involvement; NS: Not significant.

Table 5 Prognostic role of perineural invasion

Ref.	Year	n	Detection rate (%)	Median OS with PNI (mo)	Survival model	HR (95%CI)	P value
Kondo et al[36]	2015	209	197 (94)	15	Multivariable	No of PNIs:	< 0.001
						< 14: 1
						14-40: 1.96 (1.01-3.93)
						> 40: 5.81 (3.17-11.35)
Fouquet et al[34]	2014	166	133 (81)	NR	Multivariable	2.77 (1.40-5.26)	0.001
Chatterjee et al[80]	2012	212	123 (58)	29	Multivariable	1.70 (1.18-2.45)	0.005
Takahashi et al[81]	2012	110	56 (51)	NR	Multivariable	2.48 (1.11-5.52)	0.026
Sahin et al[82]	2012	544	473 (87)	29	Multivariable	1.60 (1.08-2.36)	0.019
Robinson et al[59]	2012	134	128 (96)	NR	Multivariable	5.52 (NR)	< 0.050
Kanda et al[63]	2011	429	148 (34)	NR	Multivariable	1.72 (1.15-2.58)	< 0.001
Shimada et al[35]	2011	153	146 (94)	7 (DFS)	Multivariable	2.19 (1.36-3.52)	0.001
Murakami et al[64]	2010	103	31 (30)	NR	Multivariable	1.93 (1.03–3.62)	0.041
Kazanjan et al[83]	2008	182	112 (62)	20	Multivariable	2.66 (1.74-4.06)	< 0.001

OS: Overall survival; PNI: Perineural invasion.

Table 6 Radicality of resection and survival

Ref.	Year	n	R1 definition	R1 rate (%)	Median OS	Survival model	HR (95% CI)	P value
					R0/R1 (mo)
Kooby et al[37]	2014	1399	1 mm	R0 (86)	21	Multivariable	1	0.009
				R1→R0 (5)	12		1.55 (1.11-2.16)	0.004
				R1 (9)	14		1.46 (1.13-1.90)
Konstantinidis et al[84]	2013	554	1 mm	157 (28)	35/14	Univariable	NR	< 0.001
Kimbrough et al[85]	2013	283	0 mm	76 (27)	22/15	Multivariable	NR	NS
Gnerlich et al[86]	2012	285	1 mm	97 (34)	22/16	Univariable	NR	0.010
Jamieson et al[11]	2010	148	1 mm	110 (74)	27/15	Multivariable	1.76 (1.15–2.28)	0.009
Van den Broeck et al[87]	2009	144	1 mm	48 (33)	24/12	Univariable	NR	< 0.001
Chang et al[88]	2009	365	0 mm	131 (36)	20/13	Multivariable	1.48 (1.15–1.89)	0.002
Campbell et al[50]	2009	163	1 mm	128 (79)	25/13	Multivariable	1.44 (0.90-2.32)	0.132
Westgaard et al[89]	2008	40	1 mm	18 (45)	16/11	Univariable	NR	0.300
Esposito et al[90]	2008	111	1 mm	84 (76)	NR	Univariable	NR	0.370
Raut et al[91]	2007	360	0 mm	61 (17)	28/22	Multivariable	NR	NS
Verbeke et al[92]	2006	26	1 mm	22 (85)	37/11	Multivariable	NR	0.790
Howard et al[93]	2006	226	0 mm	68 (30)	NR	Multivariable	1.39 (1.02-1.90)	0.030

NS: Not significant; OS: Overall survival.