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Improving the AJCC/TNM Staging for Adenocarcinomas of the Appendix: The Prognostic Impact of Histological Grade

Overman, Michael J. MD*; Fournier, Keith MD; Hu, Chung-Yuan MPH, PhD; Eng, Cathy MD*; Taggart, Melissa MD; Royal, Richard MD; Mansfield, Paul MD; Chang, George J. MD

doi: 10.1097/SLA.0b013e318269d680
Original Articles

Purpose: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th edition's decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.

Methods: Patients with adenocarcinoma of the appendix diagnosed between 1988 and 2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage, and grade was calculated, and Cox proportional hazards regression analyses were performed.

Results: We analyzed a total of 2469 appendiceal adenocarcinomas, of which 1375 had mucinous histology and 860 had nonmucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female sex, stage IV disease, and well-differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 [95% confidence interval (CI): 1.14–2.34] and 4.94 (95% CI: 3.32–7.35) for mucinous histology, in comparison with 1.44 (95% CI: 0.82–2.52) and 1.90 (95% CI: 0.95–3.80) for nonmucinous histology, respectively.

Conclusions: The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and these data do not support the combination of these 2 histological grades in the recent AJCC Staging Manual 7th edition.

In a Surveillance, Epidemiology, and End Results (SEER) analysis of 2469 appendiceal adenocarcinomas, histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinomas. Moderately and poorly differentiated stage IV mucinous adenocarcinomas hold distinctly different cancer-specific survival, which does not support the combination of these 2 histological grades in the 7th edition of the American Joint Committee on Cancer Staging Manual.

*Departments of Gastrointestinal Medical Oncology

Surgical Oncology

Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Reprints: Michael J. Overman, MD, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Unit 426, 1515 Holcombe Blvd., Houston, TX 77030. E-mail: moverman@mdanderson.org; George J. Chang, MD, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Unit 444, 1515 Holcombe Blvd., Houston, TX 77230–1402. E-mail: gchang@mdanderson.org.

Disclosure: Supported by an American Society of Clinical Oncology Foundation Career Development Award (G.J.C.) and National Institutes of Health/National Cancer Institute grants K07-CA133187 (G.J.C.), the Ric Summers Memorial Appendiceal Cancer Research Fund, and CA016672 (MD Anderson's Cancer Center Support Grant).

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© 2013 Lippincott Williams & Wilkins, Inc.