Adjuvant ChemotherapyImproves Survival in PatientsWith American Joint Committeeon Cancer Stage II Colon Cancer

With great interest we read the article by McKenzie et al,1who demonstrated a survival advantage for adjuvant chemo-therapy in patients with American Joint Committee on Can-cer/International Union Against Cancer (AJCC/UICC) stageII colon cancer in a population-based analysis illustrating thatselect patients with AJCC/UICC stage II disease should begiven adjuvant treatment. In the study by McKenzie et al,1

selection criteria for adjuvant treatment were not defined.However, when grouped according to receipt of adjuvantchemotherapy, patients who received chemotherapy were dis-proportionately younger, had larger tumors located more fre-quently in the descending or sigmoid colon, and were morelikely to have�12 lymph nodes examined.

In our opinion, the pathology report represents thebasis for risk stratification and consequently selection ofpatients for adjuvant treatment. In our recent study pub-lished in this journal,2 we proved that venous invasion wasan independent prognostic variable in patients withAJCC/UICC stage II disease. Inspired by the current pub-lication, we enlarged our multivariable analysis.

Analyzing 108 patients with stage II colorectal can-cer in a Cox regression model, T4 tumors (hazard ratio[HR] 17.51; 95% confidence interval [CI], 4.04-75.80; P< .001), venous invasion (HR, 8.46; 95% CI,2.03-35.12;P ¼ .003), and examination of <12 lymph nodes (HR,3.45; 95% CI, 1.09-10.26; P¼ .035) were associated sig-nificantly with cancer-related death. No impact on out-come was noted for age, sex, tumor size and grade, orlymphatic invasion. With respect to progression-free sur-vival, similar results were obtained (data not shown).

Our data are well in line with the report byMcKenzie et al,1 in which sampling of >12 lymph nodeswas associated significantly with favorable outcome. Stoc-chi et al3 recently presented similar data indicating that<12 examined lymph nodes and T4 tumors are inde-pendent predictors of poor patient outcome, yet they didnot include venous invasion in their analysis.

In conclusion, patients with AJCC/UICC stage IIdisease who have tumors characterized by T4 classifica-tion, venous invasion, or <12 lymph nodes examined aremore likely to die from disease. Thus, these 3 markers,which can be obtained easily during the routine patho-logic work-up of cancer specimens, may well be used toselect patients for adjuvant therapy.

REFERENCES

1. McKenzie S, Nelson R, Mailey B, et al. Adjuvant chemother-apy improves survival in patients with American Joint Com-mittee on Cancer stage II colon cancer [published onlineahead of print June 20, 2011]. Cancer. 2011.

2. Betge J, Pollheimer MJ, Lindtner RA, et al. Intramural andextramural vascular invasion in colorectal cancer—prognosticsignificance and quality of pathology reporting [publishedonline ahead of print July 12, 2011]. Cancer. 2011.

3. Stocchi L, Fazio VW, Lavery I, Hammel J. Individual surgeon,pathologist, and other factors affecting lymph node harvest instage II colon carcinoma. Is a minimum of 12 examined lymphnodes sufficient? Ann Surg Oncol. 2011;18:405-412.

Johannes BetgeCord Langer, MD

Institute of PathologyMedical University of Graz

Graz, Austria

Peter Rehak, PhDDepartment of Surgery

Research Unit for Biomedical Engineering and ComputingMedical University of Graz

Graz, Austria

DOI: 10.1002/cncr.26493, Published online: August 31, 2011 inWiley Online Library (wileyonlinelibrary.com)

Reply to Adjuvant ChemotherapyImproves Survival in PatientsWith American Joint Committeeon Cancer Stage II Colon Cancer

We appreciate the interest in our article1 by Drs. Betge,Rehak, and Langner. Their letter is a microcosm of thegreat worldwide interest in defining the role for adjuvantchemotherapy in patients with American Joint Commit-tee on Cancer (AJCC) stage II colon cancer. Although wecould not identify specific factors that could be used toselect patients for adjuvant chemotherapy, our resultsnevertheless demonstrate a survival benefit in patientswho receive it. The important issue of patient selection israised by Betge et al. In our article, we referred to currentNational Comprehensive Cancer Network guidelines,which suggest that lymph node number and poor prognosticindicators (eg, T4 tumor depth and lymphovascular invasion)must be taken into account when considering adjuvantchemotherapy for these patients.1,2

Betge et al noted that the patients in our cohort whoreceived chemotherapy were more likely to have �12lymph nodes examined. This association is interesting and

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perhaps counterintuitive given current guidelines toconsider adjuvant chemotherapy for patients who have<12 lymph nodes examined. What this may suggest isthat no single factor alone dictates the administration ofadjuvant chemotherapy for patients with stage II diseasein current clinical practice. Several different factors(eg, T classification, number of lymph nodes, lympho-vascular invasion, and others) must be considered, asBetge et al demonstrate.3 Taken together, our collectivefindings indicate that clinicians must continue to use theirbest judgment in selecting patients to receive adjuvanttherapy for stage II colon cancer.

REFERENCES

1. McKenzie S, Nelson R, Mailey B, et al. Adjuvant chemother-apy improves survival in patients with American Joint Com-mittee on Cancer stage II colon cancer [published onlineahead of print June 20, 2011]. Cancer. 2011.

2. Engstrom PF, Arnoletti JP, Benson AB 3rd, et al.; NationalComprehensive Cancer Network. NCCN Clinical PracticeGuidelines in Oncology: colon cancer. J Natl Compr CancNetw. 2009;7:778-831.

3. Betge J, Pollheimer MJ, Lindtner RA, et al. Intramural andextramural vascular invasion in colorectal cancer—prognosticsignificance and quality of pathology reporting [publishedonline ahead of print July 12, 2011]. Cancer. 2011.

Wendy Lee, BAJoseph Kim, MDDepartment of Surgery

City of Hope Comprehensive Cancer CenterDuarte, California

Vincent Chung, MDDepartment of Medical Oncology

City of Hope Comprehensive Cancer CenterDuarte, California

DOI: 10.1002/cncr.26503, Published online: August 31, 2011 inWiley Online Library (wileyonlinelibrary.com)

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