How does lymph node yield affect survival outcomes of stage I and II colon cancer?

Abstract

Background: According to the American Joint Committee on Cancer staging for cancer of the colon, a minimum of 12 lymph nodes (LN) has to be sampled for accurate staging. This has bearing on the long-term prognosis and the need for adjuvant chemotherapy. The aim of this study was to revisit the association of lymph node yield and the long-term survival in patients with stages I and II, i.e. node-negative, colon cancer. Method: Consecutive patients who underwent elective or emergency curative resections for cancer of colon between the years 2003 and 2012 were retrospectively reviewed. Only patients with stage I or II diseases (AJCC 8th edition) were included. They were analysed in three groups, LN<12, LN12-19 and LN≥20. Their clinic-pathological characteristics were compared. The disease-free (DFS) and overall survival (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. Results: There was a total of 659 patients included in the analysis. Twelve or more LN were found in 65.6% of the specimens. The mean follow-up was 83.9 months. LN≥20 had significantly better DFS (p = 0.015) and OS (p = 0.036), whereas LN<12 had similar DFS and OS when compared to LN12-19. The advantage in DFS and OS were mainly seen in those with stage II diseases. A lymph node yield of greater than 20 was one of the predictors of favourable DFS, hazard ratio 0.358; 95% CI 0.170-.756, p = 0.007. Conclusion: The lymph node yield had a significant association with survival outcomes. A lymph node yield of 20 or more was associated with better survival outcomes. On the other hand, lymph node yield less than 12 was not shown to have inferior survival outcomes when compared to those between 12 and 19.

Pathological Features and Prognostication in Colorectal Cancer

“…Lymph node yield (LNY), defined as the number of lymph nodes retrieved following specimen dissection, [ 136 ] is a strong prognostic factor, particularly in non-metastatic CRC [ 38 , 39 , 41 , 212 , 213 , 214 ]. Inadequate LNY may be a factor in decision-making for adjuvant chemotherapy [ 1 , 7 ].…”

“…Several studies have demonstrated that a higher LNY, regardless of status (positive or negative) is associated with improved OS, DFS, and reduced risk of recurrence [ 39 , 41 , 215 , 216 ]. LNY has been established as an important prognostic factor in stage II and III colorectal cancer [ 39 , 41 , 212 , 214 ] and while its utility in stage I CRC is less clear [ 214 ], emerging evidence suggests that there is a prognostic association in stage I CRC [ 38 , 39 , 213 ].…”

“…A systematic review by Chang et al in 2007 concluded that increased LNY was associated with improved survival in stage II and III CRC [ 39 ]. A retrospective study by Foo et al examining 659 stage I and II CRC patients showed that a lymph node yield of ≥20 was associated with improved DFS (HR 0.358, p = 0.007) and 5-year OS (78.9% vs. 68.2%, LNY ≥ 20 vs. LNY < 20 respectively, p = 0.036) [ 213 ]. Foo et al also showed that improved survival with higher LNY was most pronounced in the stage II cohort.…”

Comparative effectiveness of pathological techniques to improve lymph node yield from colorectal cancer specimens: a systematic review and network meta‐analysis

“…A higher lymph node yield may improve overall and disease-free survival, especially in patients with stage II colon cancer. 1,2 A risk of understaging the disease and withholding necessary chemotherapy is present when a small number of lymph nodes is sampled. 3,4 The minimum number of lymph nodes to be examined is controversial, but 12 has been suggested as a standard for an adequate excision.…”

“…5,6 There is a high variability on reported lymph node yield between centres, but a significant number of colorectal cancer specimens remain that fail to reach this threshold. 1,7,8 Many factors may affect the nodal yield, such as age, gender, location of the tumour, tumour stage and body mass index, but the two modifiable ones are the extent of lymphadenectomy and the quality of the pathological examination. [9][10][11][12] The standard approach to identify lymph nodes is through manual palpation of the specimen; however, this may result in some lymph nodes being missed, particularly those smaller than 5 mm.…”