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1Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Copyright © 2023 The Korean Society of Coloproctology
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Conflict of interest
In Ja Park is the Editor-in-Chief of Annals of Coloproctology, but was not involved in the review process of this article. No other potential conflict of interest relevant to this article was reported.
Funding
None.
Author contributions
Conceptualization: HSR, IJP; Data curation: all authors; Formal analysis: HSR, IJP; Investigation: all authors; Methodology: HSR, BKA; Project administration: IJP, SBL, JCK; Resources: YIK; Software: MSK, MYP; Supervision: IJP, SBL, JCK; Validation: IJK; Visualization: HSR, YIK; Writing–original draft: HSR; Writing–review & editing: all authors. All authors read and approved the final manuscript.
DFS, disease-free survival; OS overall survival; HR, hazard ratio; CI, confidence interval; WD, well-differentiated; MD, moderately differentiated; PD, poorly differentiated; UD, undifferentiated; LVI, lymphovascular invasion; PNI, perineural invasion; DRM, distal resection margin; CRM, circumferential margin; LNY, lymph node yield.
aThe variable listed first in the parenthesis is the reference category.
DFS, disease-free survival; OS overall survival; HR, hazard ratio; CI, confidence interval; WD, well-differentiated; MD, moderately differentiated; PD, poorly differentiated; UD, undifferentiated; LVI, lymphovascular invasion; PNI, perineural invasion; DRM, distal resection margin; CRM, circumferential margin; LNY, lymph node yield.
aThe variable listed first in the parenthesis is the reference category.
Clinicopathologic parameter | Total (n=1,240) | LNY ≥12 (n=1,037) | LNY <12 (n=203) | P-value |
---|---|---|---|---|
Sex | 0.890 | |||
Male | 830 (66.9) | 695 (67.0) | 135 (66.5) | |
Female | 410 (33.1) | 342 (33.0) | 68 (33.5) | |
Age (yr) | 57.4±10.2 | 56.9±10.4 | 60.0±9.1 | <0.001 |
Clinical T stage | <0.001 | |||
cT2 | 7 (0.6) | 6 (0.6) | 1 (0.5) | |
cT3 | 1,143 (92.2) | 946 (91.2) | 197 (97.0) | |
cT4 | 90 (7.3) | 85 (8.2) | 5 (2.5) | |
Clinical N stage | <0.001 | |||
cN0 | 90 (7.3) | 62 (6.0) | 28 (13.8) | |
cN1 | 390 (31.5) | 309 (29.8) | 81 (39.9) | |
cN2 | 760 (61.3) | 666 (64.2) | 94 (46.3) | |
Tumor location | 0.680 | |||
Low (0–4 cm from the AV) | 789 (63.6) | 660 (63.6) | 129 (63.5) | |
Mid (4–8 cm from the AV) | 419 (33.8) | 353 (34.0) | 66 (32.5) | |
Upper (>8 cm from the AV) | 32 (2.6) | 24 (2.3) | 8 (3.9) | |
Histologic type | ||||
Well-differentiated | 164 (13.2) | 130 (12.5) | 34 (16.7) | |
Moderately differentiated | 1,012 (81.6) | 844 (81.4) | 160 (79.8) | |
Poorly differentiated | 40 (3.2) | 36 (3.5) | 4 (2.0) | |
Mucinous | 17 (1.4) | 15 (1.4) | 2 (1.0) | |
Signet ring cell | 7 (0.6) | 6 (0.6) | 1 (0.5) | |
Lymphovascular invasion (yes) | 162 (13.1) | 143 (13.8) | 19 (9.4) | 0.060 |
Perineural invasion (yes) | 210 (16.9) | 179 (17.3) | 31 (15.3) | 0.480 |
Distal resection margin (≤10 mm) | 271 (21.9) | 230 (22.2) | 41 (20.2) | 0.530 |
Circumferential margin (≤1 mm) | 32 (2.6) | 31 (3.0) | 1 (0.5) | 0.001 |
No. of harvested LN | 17.8±7.6 | 19.7±6.8 | 8.3±2.4 | <0.001 |
Pathologic T stage | <0.001 | |||
ypT0 | 180 (14.5) | 143 (13.8) | 46 (22.7) | |
ypTis | 4 (0.3) | 3 (0.3) | 1 (0.5) | |
ypT1 | 64 (5.2) | 50 (4.8) | 14 (6.9) | |
ypT2 | 333 (26.9) | 274 (26.4) | 59 (29.1) | |
ypT3 | 643 (51.9) | 560 (54.0) | 83 (40.9) | |
ypT4 | 7 (0.6) | 7 (0.7) | 0 (0) | |
Pathologic N stage | <0.001 | |||
ypN0 | 841 (67.8) | 686 (66.2) | 155 (76.4) | |
ypN1 | 308 (24.8) | 265 (25.6) | 43 (21.2) | |
ypN2 | 91 (7.3) | 86 (8.3) | 5 (2.5) | |
ypStage | <0.001 | |||
ypStage 0 | 181 (14.6) | 137 (13.2) | 44 (21.7) | |
ypStage I | 323 (26.0) | 259 (25.0) | 64 (31.5) | |
ypStage IIA | 335 (27.0) | 288 (27.8) | 47 (23.2) | |
ypStage IIB | 2 (0.2) | 2 (0.2) | 0 (0) | |
ypStage IIIA | 82 (6.6) | 70 (6.8) | 12 (5.9) | |
ypStage IIIB | 263 (21.2) | 229 (22.1) | 34 (16.7) | |
ypStage IIIC | 54 (4.4) | 52 (5.0) | 2 (1.0) | |
TRGa | 0.008 | |||
TRG 0 | 189 (15.2) | 143 (13.8) | 46 (22.7) | |
TRG 1 | 280 (22.6) | 240 (23.1) | 40 (19.7) | |
TRG 2 | 575 (46.4) | 481 (46.4) | 94 (46.3) | |
TRG 3 | 196 (15.8) | 173 (16.7) | 23 (11.3) | |
Adjuvant chemotherapy (yes) | 1,215 (98.0) | 1,014 (97.8) | 201 (99.0) | 0.140 |
No. of LNs | Total patients (n=1,240) |
Propensity score–matched patients (n=609) |
||||||||
---|---|---|---|---|---|---|---|---|---|---|
TRG 0 (n=189) | TRG 1 (n=280) | TRG 2 (n=575) | TRG 3 (n=196) | P-value | TRG 0 (n=140) | TRG 1 (n=136) | TRG 2 (n=252) | TRG 3 (n=81) | P-value | |
Harvested LNs | 15.6±6.6 | 18.2±7.8 | 17.9±7.6 | 19.3±7.9 | <0.001 | 15.0±7.3 | 16.8±7.9 | 16.0±7.6 | 18.5±8.7 | 0.010 |
Positive LNs | 0.1±0.6 | 0.6±1.6 | 1.0±2.1 | 1.3±2.5 | <0.001 | 0.1±0.5 | 0.3±1.0 | 0.6±1.2 | 0.6±1.1 | <0.001 |
Good response | Before matching |
After matching |
||||||
---|---|---|---|---|---|---|---|---|
LNY ≥12 (n=383) | LNY <12 (n=86) | P-value | Cohen da | LNY ≥12 (n=172) | LNY <12 (n=86) | P-value | Cohen da | |
Sex | 0.290 | 0.147 | 0.710 | 0.057 | ||||
Male | 235 (61.4) | 58 (67.4) | 112 (65.1) | 58 (67.4) | ||||
Female | 148 (38.6) | 28 (32.6) | 60 (34.9) | 28 (32.6) | ||||
Age (yr) | 57.4±10.3 | 60.3±8.7 | 0.008 | 0.289 | 59.9±8.7 | 60.3±8.7 | 0.700 | 0.046 |
Clinical T stage | 0.360 | 0.087 | > 0.990 | 0 | ||||
cT2 | 4 (1.0) | 0 (0) | 2 (1.2) | 0 (0) | ||||
cT3 | 353 (92.2) | 83 (96.5) | 162 (92.4) | 83 (96.5) | ||||
cT4 | 26 (6.8) | 3 (3.5) | 8 (4.7) | 3 (3.5) | ||||
Clinical N stage | <0.001 | 0.586 | 0.003 | 0.393 | ||||
cN0 | 27 (7.0) | 20 (23.3) | 18 (10.5) | 20 (23.3) | ||||
cN1 | 120 (31.3) | 32 (37.2) | 60 (34.9) | 32 (37.2) | ||||
cN2 | 236 (61.6) | 34 (39.5) | 94 (54.7) | 34 (39.5) | ||||
Tumor location | 0.850 | 0.022 | 0.670 | 0.057 | ||||
Low (0–4 cm from the AV) | 251 (65.5) | 59 (68.6) | 119 (69.2) | 59 (68.6) | ||||
Mid (4–8 cm from the AV) | 126 (32.9) | 24 (27.9) | 51 (29.7) | 24 (27.9) | ||||
Upper (>8 cm from the AV) | 6 (1.6) | 3 (3.5) | 2 (1.1) | 3 (3.5) | ||||
Histologic type | 0.440 | 0.094 | 0.900 | 0.016 | ||||
Well-differentiated | 83 (21.7) | 24 (27.9) | 43 (25.0) | 24 (27.9) | ||||
Moderately differentiated | 273 (71.3) | 57 (66.3) | 118 (68.6) | 57 (66.3) | ||||
Poorly differentiated | 20 (5.2) | 2 (2.3) | 9 (5.2) | 2 (2.3) | ||||
Mucinous | 5 (1.3) | 2 (2.3) | 1 (0.6) | 2 (2.3) | ||||
Signet ring cell | 2 (0.5) | 1 (1.2) | 1 (0.6) | 1 (1.2) | ||||
Lymphovascular invasion (yes) | 16 (4.2) | 4 (4.7) | 0.850 | 0.062 | 5 (2.9) | 4 (4.7) | 0.480 | 0.269 |
Perineural invasion (yes) | 11 (2.9) | 9 (10.5) | 0.029 | 0.758 | 8 (4.7) | 9 (10.5) | 0.120 | 0.482 |
Distal resection margin (≤10 mm) | 104 (27.2) | 23 (26.7) | 0.940 | 0.012 | 50 (29.1) | 23 (26.7) | 0.700 | 0.064 |
Circumferential margin (≤1 mm) | 3 (0.8) | 1 (1.2) | 0.730 | 0.220 | 1 (0.6) | 1 (1.2) | 0.620 | 0.385 |
Pathologic T stage | 0.001 | 0.378 | 0.670 | 0.049 | ||||
ypT0 | 143 (37.3) | 46 (53.5) | 94 (54.7) | 46 (53.5) | ||||
ypTis | 1 (0.3) | 0 (0) | 1 (0.6) | 0 | ||||
ypT1 | 27 (7.0) | 8 (9.3) | 15 (8.7) | 8 (9.3) | ||||
ypT2 | 122 (31.9) | 22 (25.6) | 48 (27.9) | 22 (25.6) | ||||
ypT3 | 89 (23.2) | 10 (11.6) | 14 (8.1) | 10 (11.6) | ||||
ypT4 | 1 (0.3) | 0 (0) | 0 (0) | 0 (0) | ||||
Pathologic N stage | <0.001 | 0.330 | 0.780 | 0.037 | ||||
ypN0 | 307 (80.2) | 79 (91.9) | 158 (91.9) | 79 (91.9) | ||||
ypN1 | 60 (15.7) | 7 (8.1) | 12 (7.0) | 7 (8.1) | ||||
ypN2 | 16 (4.2) | 0 (0) | 2 (1.2) | 0 (0) | ||||
Adjuvant chemotherapy (yes) | 368 (96.1) | 85 (98.8) | 0.070 | 0.685 | 162 (94.2) | 85 (98.8) | 0.049 | 0.914 |
Poor response | Before matching |
After matching |
||||||
---|---|---|---|---|---|---|---|---|
LNY ≥12 (n=654) | LNY <12 (n=117) | P-value | Cohen da | LNY ≥12 (n=234) | LNY <12 (n=117) | P-value | Cohen da | |
Sex | 0.330 | 0.115 | 0.630 | 0.064 | ||||
Male | 460 (70.3) | 77 (65.8) | 160 (68.4) | 77 (65.8) | ||||
Female | 194 (29.7) | 40 (34.2) | 74 (31.6) | 40 (34.2) | ||||
Age (yr) | 56.5±10.4 | 59.8±9.5 | 0.001 | 0.321 | 59.5±9.8 | 59.8±9.5 | 0.750 | 0.031 |
Clinical T stage | <0.001 | 0.284 | 0.001 | 0.323 | ||||
cT2 | 2 (0.3) | 1 (0.9) | 0 (0) | 1 (0.9) | ||||
cT3 | 593 (90.7) | 114 (97.4) | 213 (91.0) | 114 (97.4) | ||||
cT4 | 59 (9.0) | 2 (1.7) | 21 (9.0) | 2 (1.7) | ||||
Clinical N stage | 0.008 | 0.269 | 0.037 | 0.238 | ||||
cN0 | 35 (5.4) | 8 (6.8) | 11 (4.7) | 8 (6.8) | ||||
cN1 | 189 (28.9) | 49 (41.9) | 75 (32.1) | 49 (41.9) | ||||
cN2 | 430 (65.7) | 60 (51.3) | 148 (63.2) | 60 (51.3) | ||||
Tumor location | 0.450 | 0.076 | 0.480 | 0.081 | ||||
Low (0–4 cm from the AV) | 408 (62.4) | 70 (59.8) | 147 (62.8) | 70 (59.8) | ||||
Mid (4–8 cm from the AV) | 227 (34.7) | 42 (35.9) | 79 (33.8) | 42 (35.9) | ||||
Upper (>8 cm from the AV) | 18 (2.8) | 5 (4.3) | 7 (3.0) | 5 (4.3) | ||||
Histologic type | 0.120 | 0.158 | 0.380 | 0.100 | ||||
Well-differentiated | 47 (7.2) | 10 (8.5) | 20 (8.5) | 10 (8.5) | ||||
Moderately differentiated | 577 (88.2) | 105 (89.7) | 204 (87.2) | 105 (89.7) | ||||
Poorly differentiated | 16 (2.4) | 2 (1.7) | 8 (3.4) | 2 (1.7) | ||||
Mucinous | 10 (1.5) | 0 (0) | 1 (0.4) | 0 (0) | ||||
Signet ring cell | 4 (0.6) | 0 (0) | 1 (0.4) | 0 (0) | ||||
Lymphovascular invasion (yes) | 127 (19.4) | 15 (12.8) | 0.060 | 0.288 | 40 (17.1) | 15 (12.8) | 0.280 | 0.186 |
Perineural invasion (yes) | 168 (25.7) | 22 (18.8) | 0.090 | 0.221 | 52 (22.2) | 22 (18.8) | 0.460 | 0.116 |
Distal resection margin (≤10 mm) | 126 (19.3) | 18 (15.4) | 0.290 | 0.150 | 48 (20.5) | 18 (15.4) | 0.230 | 0.193 |
Circumferential margin (≤1 mm) | 28 (4.3) | 1 (0.9) | <0.001 | 0.908 | 6 (2.6) | 1 (0.9) | 0.460 | 0.615 |
Pathologic T stage | 0.025 | 0.245 | 0.760 | 0.028 | ||||
ypT0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||||
ypTis | 2 (0.3) | 1 (0.9) | 0 (0) | 1 (0.9) | ||||
ypT1 | 23 (3.5) | 6 (5.1) | 13 (5.6) | 6 (5.1) | ||||
ypT2 | 152 (23.2) | 37 (31.6) | 82 (35.0) | 37 (31.6) | ||||
ypT3 | 471 (72.0) | 73 (62.4) | 139 (59.4) | 73 (62.4) | ||||
ypT4 | 6 (0.9) | 0 (0) | 0 (0) | 0 (0) | ||||
Pathologic N stage | 0.024 | 0.202 | 0.640 | 0.054 | ||||
ypN0 | 379 (58.0) | 76 (65.0) | 157 (67.1) | 76 (65.0) | ||||
ypN1 | 205 (31.3) | 36 (30.8) | 69 (29.5) | 36 (30.8) | ||||
ypN2 | 70 (10.7) | 5 (4.3) | 8 (3.4) | 5 (4.3) | ||||
Adjuvant chemotherapy (yes) | 646 (98.8) | 116 (99.1) | 0.730 | 0.200 | 233 (99.6) | 116 (99.1) | 0.004 | 0.385 |
Variablea | 5-yr DFS |
5-yr OS |
||||||
---|---|---|---|---|---|---|---|---|
Univariate |
Multivariate |
Univariate |
Multivariate |
|||||
HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | |
Histologic type (WD/MD vs. PD/UD) | 2.39 (1.26–4.54) | 0.008 | 2.34 (1.22–4.48) | 0.011 | 3.97 (2.09–7.52) | <0.001 | 4.16 (2.16–8.01) | <0.001 |
LVI (no vs. yes) | 2.16 (0.99–4.68) | 0.050 | - | - | 2.09 (0.84–5.24) | 0.120 | - | - |
PNI (no vs. yes) | 3.43 (1.71–6.86) | 0.001 | 4.67 (2.19–9.98) | <0.001 | 2.51 (1.08–5.84) | 0.033 | 2.97 (1.15–7.66) | 0.025 |
DRM ≤10 mm (no vs. yes) | 0.86 (0.52–1.44) | 0.560 | - | - | 0.67 (0.35–1.28) | 0.670 | - | - |
CRM ≤1 mm (no vs. yes) | 3.59 (0.88–14.65) | 0.070 | - | - | 1.81 (0.25–13.06) | 0.560 | - | - |
LNY (≥12 vs. <12) | 0.91 (0.53–1.58) | 0.740 | - | - | 0.96 (0.52–1.78) | 0.900 | - | - |
ypT stage (ypT0–T2 vs. ypT3–T4) | 3.03 (1.96–4.68) | <0.001 | 2.44 (1.51–3.93) | <0.001 | 2.21 (1.31–3.73) | 0.003 | 1.79 (0.99–3.14) | 0.050 |
ypN stage (ypN0 vs. ypN1–N2) | 2.85 (1.81–4.49) | <0.001 | 2.20 (1.32–3.69) | 0.003 | 2.49 (1.45–4.25) | 0.001 | 1.88 (1.02–3.46) | 0.043 |
Variablea | 5-yr DFS |
5-yr OS |
||||||
---|---|---|---|---|---|---|---|---|
Univariate |
Multivariate |
Univariate |
Multivariate |
|||||
HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | HR (95% CI) | P-value | |
Histologic type (WD/MD vs. PD/UD) | 1.97 (1.19–3.27) | 0.009 | 1.57 (0.93–2.65) | 0.090 | 2.28 (1.27–4.10) | 0.006 | 1.69 (0.92–3.09) | 0.090 |
LVI (no vs. yes) | 1.88 (1.42–2.47) | <0.001 | 1.25 (0.93–1.68) | 0.130 | 1.93 (1.39–2.68) | <0.001 | 1.26 (0.89–1.77) | 0.190 |
PNI (no vs. yes) | 2.30 (1.78–2.96) | <0.001 | 1.59 (1.21–2.09) | 0.001 | 2.41 (1.78–3.25) | <0.001 | 1.64 (1.19–2.25) | 0.002 |
DRM ≤10 mm (no vs. yes) | 0.85 (0.61–1.18) | 0.320 | - | - | 0.90 (0.60–1.33) | 0.590 | - | - |
CRM ≤1 mm (no vs. yes) | 2.29 (1.40–3.75) | 0.001 | 1.35 (0.81–2.25) | 0.250 | 2.83 (1.64–4.89) | <0.001 | 1.68 (0.95–2.96) | 0.070 |
LNY (≥12 vs. <12) | 1.30 (0.95–1.79) | 0.100 | - | - | 1.27 (0.88–1.84) | 0.210 | - | - |
ypT stage (ypT0–T2 vs. ypT3–T4) | 2.64 (1.88–3.72) | <0.001 | 1.79 (1.24–2.58) | 0.002 | 3.19 (2.06–4.94) | <0.001 | 2.04 (1.28–3.24) | 0.003 |
ypN stage (ypN0 vs. ypN1–N2) | 2.43 (1.90–3.11) | <0.001 | 1.85 (1.42–2.41) | <0.001 | 2.70 (1.20–3.65) | <0.001 | 2.06 (1.50–2.82) | <0.001 |
Values are presented as number (%) or mean±standard deviation. LNY, lymph node yield; AV, anal verge; LN, lymph node; TRG, tumor regression grade. aAmerican Joint Committee on Cancer/College of American Pathologists.
Values are presented as mean±standard deviation. LN, lymph node; TRG, tumor regression grade. aTRG 0, complete response; TRG 1, moderate response; TRG 2, minimal response; TRG 3, poor response.
Values are presented as number (%) or mean±standard deviation. LNY, lymph node yield; AV, anal verge. aStandardized mean difference.
Values are presented as number (%) or mean±standard deviation. LNY, lymph node yield; AV, anal verge. aStandardized mean difference.
DFS, disease-free survival; OS overall survival; HR, hazard ratio; CI, confidence interval; WD, well-differentiated; MD, moderately differentiated; PD, poorly differentiated; UD, undifferentiated; LVI, lymphovascular invasion; PNI, perineural invasion; DRM, distal resection margin; CRM, circumferential margin; LNY, lymph node yield. aThe variable listed first in the parenthesis is the reference category.
DFS, disease-free survival; OS overall survival; HR, hazard ratio; CI, confidence interval; WD, well-differentiated; MD, moderately differentiated; PD, poorly differentiated; UD, undifferentiated; LVI, lymphovascular invasion; PNI, perineural invasion; DRM, distal resection margin; CRM, circumferential margin; LNY, lymph node yield. aThe variable listed first in the parenthesis is the reference category.