Table 2.
Univariate and multivariable analyses of 5-year time to recurrence according to clinicopathological features in the validation set of patients.
|
Stage II |
Stage III |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Univariable analyses |
Multivariable analyses |
Univariable analyses |
Multivariable analyses |
|||||||||
| Variable | Total number | n (%) | HR (95% CI) | P-value | HR (95% CI) | P-value | Total number | n (%) | HR (95% CI) | P-value | HR (95% CI) | P-value |
| Age | 369 | 369 (100%) | 1.00 (0.98–1.03) | 0.78 | 1.00 (0.97–1.03) | 0.97 | 672 | 672 (100%) | 1.00 (0.99–1.01) | 0.98 | 0.99 (0.98–1.01) | 0.39 |
| Gender | 369 | 0.61 | 672 | 0.45 | ||||||||
| Male | 217 (59%) | Ref. | 387 (58%) | Ref. | ||||||||
| Female | 152 (41%) | 0.87 (0.51–1.49) | 285 (42%) | 0.90 (0.68–1.19) | ||||||||
| Randomized adjuvant treatment | 369 | 0.041 | 0.015 | 672 | 0.12 | |||||||
| CAP | 181 (49%) | Ref. | Ref. | 330 (49%) | Ref. | |||||||
| CAP+BEV | 188 (51%) | 1.75 (1.02–3.00) | 2.08 (1.15–3.73) | 342 (51%) | 1.25 (0.95–1.65) | |||||||
| Sidedness | 353 | 0.26 | 640 | 0.12 | ||||||||
| Right | 175 (50%) | Ref. | 394 (62%) | Ref. | ||||||||
| Left | 178 (50%) | 0.73 (0.42–1.27) | 246 (38%) | 1.25 (0.94–1.67) | ||||||||
| pT stage | 354 | 0.062 | 641 | <0.001 | <0.001 | |||||||
| pT1 | 14 (2%) | Ref. | Ref. | |||||||||
| pT2 | 65 (10%) | 1.32 (0.30–5.92) | 1.52 (0.34–6.83) | |||||||||
| pT3 | 177 (50%) | Ref. | 365 (57%) | 1.72 (0.42-6.98) | 1.29 (0.32-5.30) | |||||||
| pT4 | 177 (50%) | 1.69 (0.97–2.96) | 197 (31%) | 4.87 (1.20–19.74) | 3.16 (0.77–12.95) | |||||||
| Number of lymph nodes removed | 354 | 0.018 | 0.015 | 642 | 0.21 | |||||||
| >=12 | 289 (82%) | Ref. | Ref. | 481 (75%) | Ref. | |||||||
| <12 | 65 (18%) | 2.05 (1.12–3.75) | 2.12 (1.16–3.89) | 161 (25%) | 1.22 (0.89–1.66) | |||||||
| pN stage | 644 | <0.001 | <0.001 | |||||||||
| pN1 | 477 (74%) | Ref. | Ref. | |||||||||
| pN2 | 167 (26%) | 3.35 (2.53–4.44) | 2.40 (1.77–3.24) | |||||||||
| Histological grade | 345 | 0.47 | 635 | 0.14 | ||||||||
| Well | 16 (5%) | Ref. | 26 (4%) | Ref. | ||||||||
| Moderate | 264 (77%) | 0.84 (0.26–2.70) | 517 (81%) | 2.05 (0.76–5.54) | ||||||||
| Poor | 65 (19%) | 0.51 (0.13–2.02) | 92 (14%) | 2.62 (0.93–7.41) | ||||||||
| Venous vascular invasion | 350 | 0.81 | 639 | <0.001 | 0.011 | |||||||
| No | 197 (56%) | Ref. | 392 (61%) | Ref. | Ref. | |||||||
| Yes | 153 (44%) | 0.93 (0.54–1.62) | 247 (39%) | 2.10 (1.58–2.79) | 1.48 (1.10–1.99) | |||||||
| Lymphatic invasion | 348 | 0.47 | 633 | <0.001 | 0.002 | |||||||
| No | 317 (91%) | Ref. | 568 (90%) | Ref. | Ref. | |||||||
| Yes | 31 (9%) | 1.37 (0.58–3.21) | 65 (10%) | 2.25 (1.55–3.26) | 1.80 (1.24–2.63) | |||||||
| KRAS | 342 | 0.17 | 615 | 0.89 | ||||||||
| Wild type | 240 (70%) | Ref. | 403 (66%) | Ref. | ||||||||
| Mutated | 102 (30%) | 1.47 (0.84–2.57) | 212 (34%) | 1.02 (0.75–1.39) | ||||||||
| BRAF | 338 | 0.64 | 625 | 0.11 | ||||||||
| Wild type | 291 (86%) | Ref. | 545 (87%) | Ref. | ||||||||
| Mutated | 47 (14%) | 0.82 (0.35–1.91) | 80 (13%) | 1.39 (0.93–2.08) | ||||||||
| Microsatellite instability | 353 | 0.14 | 645 | 0.10 | ||||||||
| MSI-H | 58 (16%) | Ref. | 66 (10%) | Ref. | ||||||||
| MSS | 295 (84%) | 1.96 (0.78–4.93) | 579 (90%) | 1.59 (0.91–2.80) | ||||||||
| CD8+ T-lymphocyte and stroma fraction | 369 | 0.15 | 672 | <0.001 | 0.001 | |||||||
| High CD8+ fraction and low stroma fraction | 186 (50%) | Ref. | 259 (39%) | Ref. | Ref. | |||||||
| Low CD8+ fraction or high stroma fraction | 158 (43%) | 1.57 (0.90–2.74) | 364 (54%) | 1.34 (0.98–1.83) | 1.30 (0.94–1.79) | |||||||
| Low CD8+ fraction and high stroma fraction | 25 (7%) | 2.09 (0.85–5.16) | 49 (7%) | 2.93 (1.86–4.60) | 2.50 (1.57–3.97) | |||||||
| CD8+ T-lymphocyte fraction | 369 | 0.26 | 672 | 0.032 | ||||||||
| High (>2.7%) | 222 (60%) | Ref. | 308 (46%) | Ref. | ||||||||
| Low (<=2.7%) | 147 (40%) | 1.35 (0.80–2.28) | 364 (54%) | 1.36 (1.03–1.81) | ||||||||
| Stroma fraction | 369 | 0.072 | 672 | <0.001 | ||||||||
| Low (<56%) | 308 (83%) | Ref. | 574 (85%) | Ref. | ||||||||
| High (>=56%) | 61 (17%) | 1.73 (0.94–3.17) | 98 (15%) | 1.92 (1.38–2.69) | ||||||||
Abbreviations: HR, hazard risk; CI, confidence interval; Ref, reference; CAP, capecitabine; BEV, bevacizumab; pT stage, pathological tumor stage; pN stage, pathological lymph node stage; MSI-H, microsatellite instability-high; MSS, microsatellite stable.