Affiliations of authors: Department of Surgery (S-YJ, DBC, WDW, JGG), Medical Oncology (DS), Epidemiology and Biostatics (ER), Memorial Sloan-Kettering Cancer Center, New York, NY
Correspondence to: Jose G. Guillem, MD, MPh, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-1077, New York, NY 10021 (e-mail: guillemj{at}mskcc.org).
Stages II and III of the newly revised tumor-node-metastasis staging system for colon cancer (American Joint Committee on Cancer [AJCC] Staging Manual sixth edition) differ from those in the fifth edition (1). In the sixth edition, stage II is subdivided into IIa (T3N0) and IIb (T4N0) and stage III is subdivided into IIIa (T12N1M0), IIIb (T34N1M0), and IIIc (anyTN2M0). This stratified grouping was motivated by the large difference in survival between stage II and III patients noted in the analysis of the National Cancer Data Base registry by Greene et al. (2) and recognition that having a T4 tumor could have a greater impact on prognosis than regional lymph node involvement (3).
Recently, O'Connell et al. (4) reported survival of 119 363 colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) program and demonstrated that survival was worse for the subset of patients with stage IIb (T4N0M0) than for those with stage IIIa (T12N1M0) tumors. The authors attributed this paradoxical survival difference to several potential factors: 1) preferential administration of chemotherapy for stage IIIa patients; 2) understaging of T4N1 tumors as T4N0, thereby resulting in migration of aggressive disease from stage IIIb to stage IIb; 3) greater likelihood of a curative en bloc surgical resection for stage IIIa; and 4) a relative disproportional increase of biologically more aggressive tumors in stage IIb. However, because the SEER program does not contain information on chemotherapy or the extent of resection (R0 versus R1 versus R2), the authors were unable to fully explain this paradox.
Using the Memorial Sloan-Kettering Cancer Center (MSKCC) Tumor Registry Database, we identified patients who had undergone resection of a primary invasive colon adenocarcinoma and for whom at least 3 years of follow-up were available. From this group, we identified 117 stage IIb and 82 stage IIIa patients with colon adenocarcinoma who had undergone a curative resection in whom detailed information on adjuvant chemotherapy was available. Median follow-up for these two groups was 57 months, and median ages were 66 years (range = 3193) and 62 years (range = 3191) for stage IIb and stage IIIa, respectively.
As O'Connell et al. had predicted, patients with stage IIIa tumors received adjuvant chemotherapy more frequently than patients with stage IIb tumors (83% versus 44%, P<.001). We noted that overall, 5-year disease-specific survival (DSS) and 5-year disease-free survival (DFS) in our study were superior for patients with stage IIIA tumors compared with those with IIB tumors, although these differences did not reach statistical significance (Table 1). For the subset of patients who received chemotherapy, those with stage IIIa tumors had a statistically significant improved DFS relative to those with stage IIb tumors. In contrast, for the subset of patients who did not receive adjuvant therapy, earlier stage did indeed correspond to superior prognosis (Table 1).
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Burke recommended in his editorial that until the advent of a revised edition, clinicians and researchers should rely on the earlier fifth edition of the AJCC Staging Manual for colon cancer (5). We agree that the paradoxical survival difference is a definite concern for the sixth edition, as survival should decrease with advancing stages. However, our data suggest that this paradox may be based on a heterogenously treated study population.
REFERENCES
(1) American Joint Committee on Cancer. AJCC cancer staging manual. 6th ed. New York (NY): Springer; 2002.
(2) Greene FL, Stewart AK, Norton HJ. A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50 042 patients. Ann Surg 2002;236:41621.[CrossRef][ISI][Medline]
(3) Shepherd NA, Baxter KJ, Love SB. The prognostic importance of peritoneal involvement in colonic cancer: a prospective evaluation. Gastroenterology 1997;112:1096102.[CrossRef][ISI][Medline]
(4) O'Connell JB, Maggard MA, Ko CY. Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 2004;9:14205.
(5) Burke HB. Outcome prediction and the future of the TNM staging system. J Natl Cancer Inst 2004;96:14089.
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