Log odds of positive lymph nodes is an excellent prognostic factor for patients with rectal cancer after neoadjuvant chemoradiotherapy

Abstract

Background: Neoadjuvant chemoradiotherapy (NCRT) results in fewer lymph nodes harvested and causes staging migration. Therefore, we compared the prognostic value of the logarithmic odds of positive lymph nodes (LODDS) with the lymph node ratio (LNR) and the American Joint Committee on Cancer (AJCC) ypN stage in patients with locally advanced rectal cancer (LARC) after NCRT.

Methods: A total of 445 patients with LARC who received NCRT and underwent radical surgery between January 2004 and December 2015 were recruited, and data from 4881 patients included in the Surveillance, Epidemiology and End Results (SEER) database between 2010 and 2013 were analyzed to verify our results. The time-dependent area under the receiver operating characteristic curve (TimeROC) was used to evaluate the discriminative ability of the different lymph node staging systems.

Results: ypN staging failed to satisfactorily stratify the patients treated with NCRT [the 3-year disease-free survival (DFS) rates were 65.7% and 55.4% for the ypN1 and ypN2 groups, respectively, P=0.252]. The LODDS classification was significantly associated with DFS, and the 3-year DFS rates for the LODDS0, LODDS1, and LODDS2 groups were 89.9%, 72.4%, and 53.9%, respectively (P<0.05 across all groups). Furthermore, the LODDS classification system was able to subclassify patients with ypN0 stage tumors regardless of whether ≥12 or <12 total lymph nodes (TLNs) were harvested. TimeROC analysis showed that the LODDS classification (AUC, median: 0.722, range: 0.692-0.754) had a higher accuracy for determining the prognosis than the ypN stage (AUC, median: 0.691, range: 0.684-0.712) or the LNR (AUC, median: 0.703, range: 0.685-0.730) classification, regardless of lymph node status. These results were verified using the SEER database.

Conclusions: The LODDS was a better prognostic factor for DFS than ypN staging or the LNR-based approach in patients with LARC after NCRT, particularly those with <12 TLNs harvested or ypN0 stage disease.

Keywords: Logarithmic odds of positive lymph nodes (LODDS); lymph node ratio (LNR); neoadjuvant chemoradiotherapy (NCRT); staging.

Figure 1

Kaplan-Meier analysis of DFS according to the ypN stage, LNR, and LODDS classification in all patients (A,B,C) and TimeROC analysis of ypN, LNR and LODDS in all patients (D). DFS, disease-free survival; LNR, lymph node ratio; LODDS, logarithmic odds of positive lymph nodes; TimeROC, time-dependent area under the receiver operating characteristic curve.

Figure 2

Kaplan-Meier analysis of DFS according to the ypN stage, LNR, and LODDS classification in patients with <12 TLNs harvested (A,B,C) and TimeROC analysis of the ypN, LNR, and LODDS classification in patients with <12 TLNs harvested (D). DFS, disease-free survival; LNR, lymph node ratio; LODDS, logarithmic odds of positive lymph nodes; TLN, total lymph node; TimeROC, time-dependent area under the receiver operating characteristic curve.

Figure 3

Kaplan-Meier analysis of DFS in the ypN0 and ypN+ subgroups according to the LODDS classification (A,B) and TimeROC analysis of the ypN0 and ypN+ subgroups according to the LODDS classification (C,D). DFS, disease-free survival; LODDS, logarithmic odds of positive lymph nodes; TimeROC, time-dependent area under the receiver operating characteristic curve.

Figure 4

Kaplan-Meier analysis of CSS according to the ypN, LNR and LODDS classification for all patients (A,B,C), those in the ≥12 TLNs (D,E,F) subgroup, and those in the <12 TLNs (G,H,I) subgroup in the SEER validation cohort. CSS, cancer-specific survival; LNR, lymph node ratio; LODDS, logarithmic odds of positive lymph nodes; TLN, total lymph node; SEER, Surveillance, Epidemiology and End Results.

Figure 5

Kaplan-Meier analysis of CSS in the in the ypN0 subgroup (A) and ypN+ subgroup (B) according to the LODDS classification in the SEER validation cohort. CSS, cancer-specific survival; LODDS, logarithmic odds of positive lymph nodes; SEER, Surveillance, Epidemiology and End Results.

Figure 6

TimeROC analysis of the ypN, LNR and LODDS classification for all patients (A), the <12 TLNs subgroup (B), the ypN0 subgroup (C), and the ypN+ subgroup (D), respectively, in the SEER validation cohort. TimeROC, time-dependent area under the receiver operating characteristic curve; LNR, lymph node ratio; LODDS, logarithmic odds of positive lymph nodes; TLN, total lymph node; SEER, Surveillance, Epidemiology and End Results.