Prognostic Impact of N2 of the Primary Tumour in Surgical Resection for Colorectal Liver Metastases

Patients and Methods

Subjects. Clinical data of 111 patients with colorectal liver metastasis who underwent surgical resection at the Tokyo Medical University Hachioji Medical Center between June 2007 and July 2020 were retrospectively analysed. Patients with extrahepatic metastasis to the lung, lymph nodes, and peritoneal dissemination (N=5) were excluded, leaving 106 patients included in the study. All patients underwent surgical resection for the primary tumour before or at the same time as surgery for liver metastasis. This helped prevent stenosis or bleeding due to the primary tumour.

Pathological definition of the primary tumour. The primary tumour was pathologically diagnosed based on the TNM classification system of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) guidelines. The classification of lymph node metastasis in colorectal cancer was also determined based on these guidelines. All regional lymph nodes were dissected, regardless of the degree of tumour progression. The dissected lymph nodes were removed from the tumour specimen and classified according to the guidelines.

The lymph nodes of the primary tumour were also evaluated using positive lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS). These were calculated as follows:

• LNR=positive lymph node/dissected lymph node,

• LODDS=log [(positive lymph node + 0.5)/(negative lymph node + 0.5)].

The LNR was classified according to a system proposed by Berger et al. (4) and Rosenberg et al. (5), as follows: Berger et al., LNR1<0.05, 0.05≤LNR2<0.19, 0.19≤LNR3<0.39, and 0.39≤ LNR4≤1.00; Rosenberg et al., LNR0=0.00, 0.01≤LNR1≤0.17, 0.18≤LNR2≤0.41, 0.42≤LNR3≤0.69, and LNR4≥0.70. The LODDS was classified according to the classification proposed by Wang et al. (6) and Persiani et al. (7) as follows: Wang et al., LODDS1<–2.2, –2.2≤LODDS2<–1.1, –1.1≤LODDS3<0.0, 0.0≤ LODDS4<1.1, and LODDS5≥1.1; Persiani et al., LODDS1 ≤–1.36, –1.36<LODDS2≤-0.53, and LODDS3 >–0.53.

Treatment strategy for liver metastasis. Surgical resection, with or without preoperative treatment, was performed primarily when the liver metastasis could be resected technically and oncologically. Preoperative treatment was performed in cases wherein the risk of recurrence was high, such as cases of multiple synchronous metastases or difficult resection based on technical or oncological aspects. The surgical procedure used was selected based on anatomical tumour factors. Percutaneous transhepatic portal vein embolization was performed preoperatively when required.

Comparison of overall survival between ≥N1 and ≥N2. Overall survival was compared between the ≥N1 and ≥N2 statuses of the TNM classification of the primary tumour; it was defined as the duration of survival from the beginning of treatment for liver metastasis to the last follow-up or death by any cause. The prognostic factors for overall survival were evaluated using univariate and multivariate analyses. Moreover, prognosis was compared among N0, N1, and N2 of the TNM classification of the primary tumour. Additionally, the prognostic performance of ≥N1 and ≥N2 for 1-, 3-, 5-, and 7-year survival groups was compared.

Statistical analyses. Continuous variables are expressed as median with range (minimum–maximum), and the Mann–Whitney U-test was used for between-group comparisons. Categorical variables are expressed as number (%) and compared using the chi-square test or Fisher’s exact test, as required. Univariate and multivariate analyses were performed using Cox proportional hazards regression analysis with forward selection of the likelihood ratio. The prognosis was evaluated using the Kaplan–Meier method, and statistical differences were evaluated using the log-rank test. All statistical analyses were performed using IBM SPSS Statistics, version 26.0 (IBM Corp., Armonk, NY, USA).

Ethical statements. The procedures followed were in accordance with the ethical standards of the institutional review board of the Tokyo Medical University (T2019-0149). Informed consent was obtained from all individual participants included in the study.