Patient Demographics And Clinicopathologic Data
The patient characteristics are shown in Table 1. There were 245 females (35.4%) and 447 males (64.6%), with a mean age of 61.64 ± 11.39 (range: 22–89) years. The average age at the onset of rectal cancer was 61.43 ± 11.92 years for female patients and 61.75 ± 11.10 years for male patients. There was no significant difference in onset age between female and male patients (F = 0.126, P = 0.723). In total, 98 (14.2%) patients had upper-rectal cancer (10–15 cm), 346 (50%) patients had mid-rectal cancer (5–10 cm from the anal verge), and 248 (35.8%) patients had lower rectal cancer (less than 5 cm from the anal verge) (Table 1).
Table 1
Characteristics of the patients (n = 692)
Characteristics | Number of patients (%) | |
Sex, n (%) | | Age, median, years |
Female | 245 (35.4%) | 61.43 ± 11.92 |
Male | 447 (64.6%) | 61.75 ± 11.10 |
Age, median ± SD (years) | | 61.64 ± 11.39 |
Tumor location (cm) | | |
≤ 5 cm | 248 (35.8%) | |
5–10 cm | 346 (50%) | |
> 10 cm, ≤ 15 cm | 98(14.2%) | |
Pathology, n (%) | | |
Common adenocarcinoma | 639 (92.3%) | |
Mucinous adenocarcinoma | 34 (4.9%) | |
Signet ring cell carcinoma | 7 (1.0%) | |
Neuroendocrine carcinoma | 4 (0.6%) | |
Others | 8 (0.8%) | |
Tumor differentiation grade, n (%) | | |
Moderate-high | 447(64.6%) | |
Low | 245(35.4%) | |
TD, n (%) | | |
Negative | 597 (86.3%) | |
Positive | 95 (13.7%) | |
LVI, n (%) | | |
Negative | 552(79.8%) | |
Positive | 140(20.2%) | |
PNI, n (%) | | |
Negative | 558(80.6%) | |
Positive | 134(19.4%) | |
Pathologic T stage, n (%) | | |
T1 | 51 (7.4%) | |
T2 | 199 (28.8%) | |
T3 | 411 (59.4%) | |
T4 | 31 (4.5%) | |
Pathological N stage, n (%) | | |
N0 | 381 (55.1%) | |
N1 | 189 (27.3%) | |
N2 | 122 (17.6%) | |
TD = tumour deposit, LVI = lymphovascular invasion, PNI = perineural invasion. |
Regarding histological type, 639 (92.3%) tumours were common adenocarcinomas, 34 (4.9%) were mucinous adenocarcinomas, 7 (1.0%) were signet ring cell carcinomas, and 4 (0.6%) were neuroendocrine carcinomas. The histologic diagnoses were moderately differentiated adenocarcinoma in 447 (64.6%) patients and poorly differentiated adenocarcinoma in 245 (35.4%) patients (Table 1).
A total of 86.3% (597/692) of patients were TD negative, and 13.7% (95/692) were positive. A total of 79.8% (552/692) of the patients were LVI negative, and 20.2% (140/692) were LVI positive. PNI was found in 19.4% (134/692) of the patients, while PNI was absent in 80.6% (558/692). With regard to the pathological T and N stages, 51 (7.4%), 199 (28.8%), 411 (59.4%), 31 (4.5%) patients had T1, T2, T3 and T4 disease, while 381 (55.1%), 189 (27.3%), and 122 (17.6%) had N0, N1 and N2 disease.
Association Between Pathological T Stage And N Stage
Table 2 and Figs. 2 and 3 show the associations between each pathological T1-4 stage and N0-3 stage. For pathologic stage T1, the percentages of N0, N1 and N2 were 80.4%, 15.7% and 3.9%, respectively. For pathologic stage T2, the percentages of N0, N1 and N2 were 76.4%, 17.1% and 6.5%, respectively. For pathologic stage T3, the percentages of N0, N1 and N2 were 43.3%, 33.3% and 23.4%, respectively. For pathologic stage T4, the percentages of N0, N1 and N2 were 32.3%, 32.3 and 35.5%, respectively (Table 2). Figure 2 shows that an increased T stage was associated with an increased percentage of N1 and N2. Goodman-Kruskal gamma statistic analysis confirmed this result (gamma = 0.579, P = 0.000).
Table 2
Distribution of T stage and N stages in 692 patients with rectal cancer.
T stage | N stage |
N0 | N1 | N2 |
T1 | 80.4% (41/51) | 15.7% ( 8/51) | 3.9% (2/51) |
T2 | 76.4% (152/199) | 17.1% (34/199) | 6.5% (13/199) |
T3 | 43.3% (178/411) | 33.3% (137/411) | 23.4% (96/411) |
T4 | 32.3% (10/31) | 32.3% (10/31) | 35.5% (11/31) |
Figure 3 shows the average number of metastatic LNs for each pathologic T stage. The mean numbers of metastatic LNs in patients with T1, T2, T3, and T4 disease were 0.59 ± 2.22, 0.62 ± 1.391, 2.41 ± 3.796, and 3.26 ± 4.719, respectively. Multiple comparisons by analysis of variance (ANOVA) showed that there was no significant difference in the average number of metastatic LNs between T1 and T2 (P = 0.953) or T3 and T4 (P = 0.160). However, significant differences were observed between T1 and T3 (P = 0.000), T1 and T4 (P = 0.000), T2 and T3 (P = 0.000), and T2 and T4 (P = 0.000).
Clinicopathologic variables that correlate with the T stage
We analysed the clinicopathological factors that could be correlated with the pathological T stage, as shown in Table 3. On univariate analysis, tumour location (P = 0.004), PNI (P = 0.000), LVI (P = 0.000), TD (P = 0.000), and differentiation grade (P = 0.000) were significantly correlated with the pathological T stage, but sex was not (p = 0.192).
Table 3
Associations between clinicopathological variables and pathological T stage
| | | Χ2 | P | Exp | 95% CI | P |
| PNI(n) | | | | | |
| Negative | positive | 58.728 | 0.000 | | | |
T1 | 51 | 0 | | | -- | | |
T2 | 187 | 12 | | | 1 | | |
T3 | 293 | 118 | | | 6.2376 | 3.371–11.685 | 0.000 |
T4 | 27 | 4 | | | 2.309 | 0.694–7.676 | 0.172 |
| LVI (n) | | | | | |
| Negative | Positive | 34.053 | 0.000 | | | |
T1 | 46 | 5 | | | 1 | | |
T2 | 183 | 16 | | | 0.804 | 0.280–2.310 | 0.686 |
T3 | 300 | 111 | | | 3.404 | 1.319–8.787 | 0.011 |
T4 | 23 | 8 | | | 3.200 | 0.941–10.886 | 0.063 |
| TD (n) | 42.704 | 0.000 | | | |
| Negative | positive | | | | | |
T1 | 49 | 2 | | | 1 | | |
T2 | 195 | 4 | | | 0.503 | 0.089–2.824 | 0.435 |
T3 | 329 | 82 | | | 6.106 | 1.455–25.631 | 0.013 |
T4 | 24 | 7 | | | 7.146 | 1.378–37.044 | 0.019 |
| Differentiation (n) | 19.996 | 0.000 | | | |
| High grade | Low grade | | | | | |
T1 | 42 | 9 | | | 1 | | |
T2 | 143 | 56 | | | 1.828 | 0.835−4.000 | 0.131 |
T3 | 248 | 163 | | | 3.067 | 1.454–6.471 | 0.003 |
T4 | 14 | 17 | | | 5.667 | 2.065–15.547 | 0.001 |
| Sex (n) | 4.741 | 0.192 | | | |
| Male | Female | | | | | |
| | | Χ2 | P | Exp | 95% CI | P |
T1 | 26 | 25 | | | | | |
T2 | 128 | 71 | | | | | |
T3 | 273 | 138 | | | | | |
T4 | 20 | 11 | | | | | |
| Tumor location (n) | 13.065 | 0.004 | | | |
| ≤ 5 cm | > 5cm | | | | | |
T1 | 13 | 38 | | | 1.196 | 0.440–3.247 | 0.726 |
T2 | 91 | 108 | | | 0.486 | 0.213–1.107 | 0.486 |
T3 | 135 | 276 | | | 0.836 | 0.375–1.866 | 0.836 |
T4 | 9 | 22 | | | 1 | | |
Logistic regression analysis revealed relationships between T stage and these significant pathologic factors. Regarding LVI, compared to T1 patients, a significantly higher proportion of T3 patients were positive for LVI (OR = 3.404, 95% CI: 1.319–8.787, P = 0.011); however, the same result was not observed in T2 patients (P = 0.686, OR = 0.804, 95% CI: 0.280–2.310). T4 patients had a tendency towards a greater probability of positive LVI, but the difference was not significant (P = 0.063, OR = 3.200, 95% CI: 0.941–10.886).
Regarding PNI, compared to T2 patients, a significantly higher proportion of T3 patients had PNI (OR = 6.2376, 95% CI: 3.371–11.685, P = 0.000); however, the same result was not observed in T4 patients (OR = 2.309, 95% CI: 0.694–7.676, P = 0.172).
Regarding TD, compared to T1 patients, there was a significantly higher proportion of T3 and T4 but not T2 patients with TD (OR = 6.106, 95% CI: 1.455–25.631, P = 0.013; OR = 7.146, 95% CI: 1.378–37.044, P = 0.019; OR = 0.503, 95% CI: 0.089–2.824, P = 0.435, respectively).
Regarding tumour differentiation grade, compared to T1 patients, a significantly higher chance of T3 and T4 but not T2 patients had poorly differentiated disease (OR = 3.067, 95% CI: 1.454–6.471, P = 0.003; OR = 5.667, 95% CI: 2.065–15.547, P = 0.001; OR = 1.828, 95% CI: 0.835-4.000, P = 0.131).
Regarding tumour location, there were no differences between patients with T4 disease and those with T1 (P = 0.726), T2 (P = 0.486) and T3 (P = 0.836) disease.
Clinicopathologic variables that may be correlated with LNM
We also analysed the clinicopathologic factors that could be correlated with pathologic lymph node metastasis (LNM), as shown in Table 4. Based on univariate analysis, patient age, sex, and tumour location did not significantly affect LNM. However, LVI, PNI, pathologic T stage, tumour differentiation grade, and TD (all P = 0.000) were significantly correlated with LNM. When these factors were entered into a multivariate analysis using a logistic regression model, LVI (OR = 3.882, 95% CI = 2.338–6.440, P = 0.000), pathological T stage (OR = 1.969, 95% CI = 1.471–2.635, P = 0.00), tumour differentiation grade (OR = 2.255, 95% CI = 1.544–3.293, P = 0.000), and TD (OR = 27.645, 95% CI = 9.805–77.947, P = 0.000) retained significance as risk factors for LNM. However, PNI (P = 0.452, OR = 1.213, 95% CI = 0.734–2.003) was not a risk factor for LNM based on the multivariate analysis.
Table 4
Associations between clinicopathologic variables and lymph node metastasis (LNM)
| LNM Negative (381) | LNM positive (311) | | Univariate analysis (P) | Exp | Adjusted odds ratio (95% CI) | Multivariate analysis (P) |
Sex | | | Χ2=0.886 | 0.380 | | | |
Male | 252 | 195 | | | | | |
Female | 129 | 116 | | | | | |
Age | 61.92 ± 11.25 (381) | 61.29 ± 11.57 (311) | F = 0.078 | 0.780 | | | |
Tumor location | | | Χ2=1.445 | 0.229 | | | |
≤ 5 cm | 129 | 119 | | | | | |
> 5cm | 252 | 192 | | | | | |
PNI | | | Χ2=28.859 | 0.000 | 1.213 | 0.734–2.003 | 0.452 |
Negative | 335 | 223 | | | | | |
Positive | 46 | 88 | | | | | |
LVI | | | Χ2=83.659 | 0.000 | 3.882 | 2.338–6.440 | 0.000 |
Negative | 352 | 200 | | | | | |
Positive | 29 | 111 | | | | | |
Pathological T stage | | | Χ2=79.238 | 0.000 | 1.969 | 1.471–2.635 | 0.000 |
T1 | 41 | 10 | | | 1 | | |
T2 | 152 | 47 | | | 1.309 | 0.559–3.065 | 0.535 |
T3 | 178 | 233 | | | 3.126 | 1.380–7.082 | 0.006 |
T4 | 10 | 21 | | | 4.730 | 1.499–14.927 | 0.008 |
Differentiation | | | Χ2=42.700 | 0.000 | 2.255 | 1.544–3.293 | 0.000 |
High | 287 | 160 | | | | | |
Low | 94 | 151 | | | | | |
TD | | | Χ2=131.791 | 0.000 | 27.645 | 9.805–77.947 | 0.000 |
Negative | 377 | 220 | | | | | |
Positive | 0 | 95 | | | | | |
As shown in Table 2, Fig. 2 and Fig. 3, we further confirmed the correlation between the primary tumour (T) and nodule status (N) by a binary logistic regression model. Compared with T1, the HRs of LNM for T2, T3, and T4 patients were 1.309 (95% CI: 0.559–3.065, P = 0.535), 3.126 (95% CI: 1.380–7.082, P = 0.006) and 4.730 (95% CI: 1.499–14.927, P = 0.008), respectively. More advanced T stages (T3 and T4) were significantly associated with a higher incidence of LNM.