Optimal cut-off value for lymph node harvesting in colon cancer based on tumor stage and sidedness: A retrospective analysis of a Japanese nationwide cohort.
Authors: Ito Kazuma , Takahashi Kanae , Kataoka Kozo , Ouchi Akira , Shiozawa Manabu , Akiyoshi Takashi , Yoshida Takeshi , Ikeda Masataka , Shinto Eiji , Takamizawa Yasuyuki , Ajioka Yoichi , Kobayashi Hirotoshi , Kanemitsu Yukihide 
Published: January 2025

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Background:
The presence of fewer than 12 harvested lymph nodes (LN) is currently considered a risk factor in stage II colon cancer (CC). However, this cut-off value does not take into consideration the biological differences associated with tumor sidedness. Moreover, the applicability of this cut-off value to stage III CC is unknown.
Methods:
Patients with pathological stage II/III CC who underwent curative surgical resection were assessed using data from the Japanese Society for Cancer of the Colon and Rectum database (2001–2015). The optimal cut-off value of harvested LN was evaluated by analyzing all cut-off values (i.e., 3–40), taking into account the point estimate of the hazard ratio (HR) and lower limit of the 95% confidence interval (CI), according to the tumor stage (II/III) and sidedness (right/left). A Cox proportional hazards model was used to investigate the impact of the number of harvested LN on overall survival, adjusting for age, sex, T stage, histology, size of tumor, sidedness, adjuvant chemotherapy and extent of colon resection. Multivariate analysis was also conducted.
Results:
From the data, 4249 (left/right; 3248/1001) and 3549 (left/right; 2798/751) patients with stage II and III CC, respectively, were identified. The median number of harvested LN was identical between stage II (18, interquartile range [IQR] (12–15)) and III (18, IQR (13–25)). However, this number was higher in right-sided CC (21, IQR (14–31)) versus left-sided CC (17, IQR (12–24)). In stage II, the conventional cut-off value (i.e., 12 LN) was identified as a prognostic factor in the multivariate analysis (HR 1.45; 95% CI: 1.20–1.75; p<0.001). Nevertheless, the prognostic impact of the number of harvested LN was stronger when the optimal cut-off value was set to 7 (HR 1.88; 95% CI: 1.44–2.44; p<0.001). In stage III, the optimal cut-off value was 12 (HR 1.88; 95% CI: 1.44–2.44; p<0.001). When evaluated based on tumor sidedness, the optimal cut-off value differed, especially for stage III. Data are shown in the table. Similar results were obtained following the exclusion of the extent of bowel resection as variable in Multivariate analysis.
Conclusions:
While the presence of 12 harvested LNs remains a valid prognostic factor, the optimal cut-off value can be further evaluated based on tumor stage and sidedness.

Stage II
Stage III

All
Left
Right
All
Left
Right

Cut-off value
12
12
12
12
12
12

N(>cut-off/<cut-off)
3209/1040
2371/877
838/163
2814/735
2181/617
633/118

HR(>cut-off/<cut-off)(95% CI)
1.45 (1.20-1.75)
1.49 (1.20-1.84)
1.31 (0.85-2.02)
1.30 (1.09-1.55)
1.27 (1.05-1.54)
1.43 (0.97-2.13)

P value
<0.001
<0.001
0.216
<0.003
0.015
0.073

Cut-off value
7
7
10

20
13

N(>cut-off/<cut off)
3930/319
2977/271
889/112

1200/1598
609/142

HR(>cut-off/<cut-off)(95% CI)
1.88 (1.44-2.44)
2.07 (1.56-2.74)
1.39 (0.84-2.27)

1.35 (1.13-1.60)
1.59 (1.11-2.28)

P value
<0.001
<0.001
0.198

<0.001
0.011