Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy

Abstract

Background: A survival paradox between Stage IIB/C and Stage IIIA colon cancers exists. It is unclear how adequate lymph nodes dissection (LN) and post-surgery chemotherapy contribute to the survival paradox. We intended to assess the impact of these two factors on the survival paradox.

Results: We evaluated 34,999 patients diagnosed with stage IIIA or stage IIB/C colon cancer in 2003-2012 from the National Cancer Data Base. The 5-year overall survival (OS) was 73.5 % for stage IIIA and 51.1 % for stage IIB/C (P < 0.0001). The 5-year OS was 84.1 % for stage IIIA with post-surgery chemotherapy, 70.8 % for stage IIB/C with ≥ 12 LNs retrieved with chemotherapy, 53.9 % for stage IIB/C < 12 LNs with chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C ≥ 12 LNs retrieved without chemotherapy, to 27.7 % for stage IIB/C < 12 LNs without chemotherapy. Even among stage IIB/C who had optimal treatment (≥12 LNs retrieved, received chemotherapy), OS remains lower than stage IIIA with chemotherapy. After adjusting LN dissection and chemotherapy in addition to the adjustment of other clinical factors, the survival paradox was reduced from HR = 1.76 (95 % CI: 1.68-1.85) to HR 1.51 (95 % CI: 1.44-1.59).

Conclusions: LN dissection and post-surgery chemotherapy partially explained the survival paradox. More research is warranted to identify other factors that contribute to this paradox. Future iteration of TNM staging system should take this into consideration.

Keywords: Colon cancer; Stage IIB/C colon cancer; Stage IIIA colon cancer.

Fig. 1

Overall Survival for Stage IIB/C and Stage IIIA: Note that there is a statistically significant survival difference between stage IIIA and stage IIB/C (P < 0.0001). However, there is no significant difference between stage IIB and stage IIC (P = 0.46)

Fig. 2

Overall Survival for the Six Subgroups of Patients with Stage IIB/C and Stage IIIA Colon Cancer. The 5-year OS are 84.1 % for stage IIIA plus chemotherapy, 70.8 % for stage IIB/C with ≥ 12 LNs plus chemotherapy, 53.9 % for stage IIB/C < 12 LNs plus chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C ≥ 12 LNs without chemotherapy, and 27.7 % for stage IIB/C < 12 LNs without chemotherapy (P < 0.0001). The median survival has not been reached by the end of follow up (132 months) for stage IIIA with chemotherapy, 122.6 months for stage IIB/C, ≥ 12 LNs with chemotherapy, 72.5 months for stage IIB/C, < 12 LNs with chemotherapy, 58.9 months for stage IIIA without chemotherapy, 46.5 months for stage IIB/C, ≥ 12 LNs without chemotherapy, and 23.0 months for stage IIB/C, < 12 LNs without chemotherapy