One thousand four hundred and twenty CRC patients from February 2007 to February 2013 who met the inclusion criteria were evaluated in this study. The clinicopathologic characteristics of 1420 CRC patients are listed in table 1. Of all CRC patients, there were 822 males (57.9%) and 598 females (42.1%); 47.1% of patients were ≤ 60 years of age and 52.9% of patients were > 60 years of age. The number of stages Ⅰ, Ⅱ, and Ⅲ patients were 173, 409, and 838, respectively. Of the 409 stage Ⅱ patients, 144 patients did not receive ACT, 121 patients received FOLFOX regimen, 56 patients received CapeOx regimen, 48 patients received 5-FU/LV regimen and 40 received 5-FU regimen.
In order to avoid the effects of different ACT regimens, among 409 stage Ⅱ patients we chose 121 patients who received FOLFOX regimen and the 144 patients who did not receive ACT as the object of study. Finally, these 265 stage Ⅱ patients were analyzed in this study whose clinicopathologic characteristics were listed in table 1. 100 patients (37.7%) were LVI + and 165 (62.3%) were LVI -. We divided these stage Ⅱ patients into ACT and surgery alone (SA) groups.
Occurrence of LVI in stage Ⅱ CRC patients
As shown in table 2, the incidence of LVI in 265 stage Ⅱ CRC patients is listed based on clinicopathologic characteristics. The LVI status was significantly associated with pT stage, degree of differentiation, tumor stage, serum CEA and CA19-9 levels, perineural invasion and KRAS status. The incidence of LVI in pT3, pT4a, and pT4b stage was 22.9%, 47.7%, and 64.3%, respectively. There was a statistically significant difference between LVI and pT stage. No significant difference existed with respect to sex, age, tumor size, tumor site, and ELNs. We also found that the LVI + rate in the ACT group was significantly higher than the SA group (64.5% vs. 15.3%, P < 0.001).
Overall survival of CRC patients
We divided the 265 stage Ⅱ patients into ELNs < 12 and ELNs ≥ 12 groups. The 5-year OS rate of the ELNs ≥ 12 group (75.2%) was greater than the ELNs < 12 group (68.5%); however, there was no statistically significant difference (Fig. 2). The 5-year OS rate of the LVI - group was greater than the LVI + group (79.4% vs. 61.0%; P < 0.001; Fig. 3a). The 5-year DFS rate of the LVI - group was greater than the LVI + group (78.2% vs. 58.0%; P < 0.001; Fig. 3b). We further compared the OS rates among stage Ⅱ patients with ≥ 12 ELNs, stage Ⅱ LVI - patients with < 12 ELNs, stage Ⅱ LVI + patients with < 12 ELNs, and stages ⅢA, ⅢB, and ⅢC patients (Fig. 4). The 5-year OS rate of stage Ⅱ LVI + patients with < 12 ELNs was 60.4%, which is significantly less than stage Ⅱ LVI - patients with < 12 ELNs and stage Ⅱ patients with ≥ 12 ELNs, respectively (60.4% vs. 75%, P < 0.001; 60.4% vs. 75.2%, P < 0.001); however, the 5-year OS rate of stage Ⅱ LVI + patients with < 12 ELNs was even lower than stage ⅢA. No significant differences existed between stage Ⅱ LVI + patients with < 12 ELNs and stages ⅢA and ⅢB patients (60.4% vs. 65.7% vs. 54.3 %, P = 0.052). The 5-year OS rate of the PNI - group was greater than the PNI + group (74.2% vs. 42.1%; P = 0.003; Fig. 5).
Univariate and multivariate analyses for the prognosis of stage Ⅱ patients with < 12 ELNs
Owing to the specific characteristics of stage Ⅱ patients with < 12 ELNs, the prognostic factors were further analyzed. Univariate analyses showed that LVI, pT-stage, degree of differentiation, and CEA and CA19-9 levels were significant prognostic factors for stage II patients with < 12 ELNs; Further multivariate analysis identified that LVI, pT-stage, degree of differentiation, CEA and CA19-9 levels PNI and KRAS status were significant prognostic factors for stage II patients with < 12 ELNs (all P<0.05) (table 3).
Improvement of the 8th TNM staging system
Because of the similarity in 5-year OS rates between stage Ⅱ LVI + patients with < 12 ELNs and stages ⅢA and ⅢB patients, we combined LVI with the 8th TNM staging system. A comparison was made to estimate the prognostic value between the new system and the 8th TNM staging system (table 4). Stage Ⅱ LVI + patients with < 12 ELNs were upgraded to stage Ⅲ, while stage Ⅱ LVI – patients with < 12 ELNs remained stage Ⅱ. The 8th TNM staging system combined with LVI had a higher C-index than the 8th TNM staging system alone (C-index, 0.895 vs. 0.833), which indicates a better prognostic value for CRC patients.
Relationship between LVI and ACT in stage Ⅱ CRC patients
In addition to analyzing OS, we also analyzed disease-free survival (DFS), especially in stage Ⅱ CRC patients. The 5-year DFS rate of the LVI - group was greater than the LVI + group (78.2% vs. 58.0%; P < 0.001; Fig. 3b). We further divided the stage Ⅱ CRC patients into ACT and SA groups. There was no significant difference in the 5-year OS and DFS between stage II CRC patients in the ACT and SA groups (5-year OS, 81.4% vs. 78.7%, P = 0.738; Fig. 6a and 5-year DFS, 79.1% vs. 77.9%, P = 0.896; Fig. 6b). When LVI + patients were analyzed, however, ACT group patients had significantly higher 5-year OS and DFS rates than the SA group (5-year OS, 66.7% vs. 40.9%, P = 0.004; Fig. 6c and 5-year DFS, 64.1% vs. 36.3%, P = 0.002; Fig. 6d).