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Survival outcomes used to validate version 9 of the American Joint Committee on Cancer staging system for appendiceal cancer. ​

Literature Information ​

DOI10.3322/caac.21806
PMID37358310
JournalCA: a cancer journal for clinicians
Impact Factor232.4
JCR QuartileQ1
Publication Year2023
Times Cited7
KeywordsAmerican Joint Committee on Cancer (AJCC) staging, appendiceal cancer, mucinous appendix cancer, non-mucinous appendix cancer, signet-ring cell appendix cancer
Literature TypeJournal Article, Review, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural
ISSN0007-9235
Pages590-596
Issue73(6)
AuthorsLauren M Janczewski, Amanda E Browner, Joseph H Cotler, Heidi Nelson, Sanjay Kakar, Norman J Carr, Nader N Hanna, Andreana N Holowatyj, Richard M Goldberg, M Kay Washington, Elliot A Asare, Michael J Overman

TL;DR ​

The study discusses the revisions in the AJCC staging system for appendiceal cancer, highlighting how survival analyses have informed the new version 9 criteria. It emphasizes the importance of differentiating histologies and addressing the challenges of staging rare tumors, thereby enhancing clinical understanding and decision-making in oncology.

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American Joint Committee on Cancer (AJCC) staging · appendiceal cancer · mucinous appendix cancer · non-mucinous appendix cancer · signet-ring cell appendix cancer

Abstract ​

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.

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Primary Questions Addressed ​

  1. How do the survival outcomes for appendiceal cancer in version 9 compare to those in previous AJCC staging versions?
  2. What specific challenges did the incorporation of survival analysis reveal regarding the staging of rare malignancies like appendiceal cancer?
  3. In what ways does the differentiation of histologies in version 9 impact treatment decisions for patients with appendiceal cancer?
  4. How might the limitations of data influence the accuracy of survival analyses for low-grade appendiceal mucinous neoplasms in future AJCC revisions?
  5. What role does prospectively collected data play in enhancing the reliability of the AJCC staging system for appendiceal cancer?

Key Findings ​

Research Background and Purpose ​

Appendiceal cancer is a rare malignancy with an increasing incidence in the U.S. over the past three decades. The American Joint Committee on Cancer (AJCC) staging system is the standard for cancer staging, including appendiceal cancers. This study aimed to validate the AJCC version 9 staging system using survival outcomes from a large dataset, addressing the unique challenges posed by the heterogeneous nature of appendiceal cancers.

Main Methods/Materials/Experimental Design ​

The research utilized data from the National Cancer Database (NCDB), which captures approximately 72% of newly diagnosed cancer cases in the U.S. The study included 11,799 patients with appendiceal cancer, focusing on histological subtypes: non-mucinous, mucinous, and signet-ring cell cancers. Survival analyses were stratified by histology to inform the AJCC version 9 staging system.

Mermaid diagram

Key Results and Findings ​

  • Survival Rates:
    • For non-mucinous appendiceal cancers, 5-year survival rates ranged from 90.34% (stage I) to 14.18% (stage IVC).
    • Mucinous cancers showed a 5-year survival of 92.80% (stage I) to 46.81% (stage IVC).
    • Signet-ring cell cancers had survival rates of 86.67% (stage I) to 10.26% (stage IVA–IVB).
  • Histological Variance: Significant prognostic differences were observed between histological subtypes, with non-mucinous tumors lacking a clear hierarchical survival order by stage, unlike mucinous and signet-ring tumors.

Main Conclusions/Significance/Innovation ​

The study confirmed that while the AJCC version 9 staging system maintained existing definitions, it also highlighted the need for nuanced stratification based on histological subtype due to the observed survival disparities. The findings underscore the complexities in staging rare malignancies and the importance of data-driven approaches to refine cancer staging systems.

Research Limitations and Future Directions ​

  • Limitations: The rarity of appendiceal cancers complicates data collection, particularly for low-grade appendiceal mucinous neoplasms (LAMNs), which were excluded from survival analysis due to insufficient data. Additionally, many appendiceal cancers are diagnosed incidentally, leading to a lack of preoperative staging information.
  • Future Directions: Continued efforts are needed to collect comprehensive data on LAMNs and other rare subtypes. Clinical trials should focus on improving treatment protocols for appendiceal cancers, particularly for patients with advanced disease, to enhance outcomes and inform future AJCC staging revisions.

Summary Table of Survival Outcomes by Histology ​

Histology TypeStage I SurvivalStage II SurvivalStage III SurvivalStage IV Survival
Non-mucinous90.34%87.97%82.02% (IIIA)14.18%
Mucinous92.80%84.32%58.01% (IIIA–IIIC)46.81%
Signet-ring cell86.67%60.82%10.26% (IVA–IVB)12.81%

This structured summary encapsulates the critical aspects of the research, providing insights into the AJCC staging system's validation for appendiceal cancer based on survival outcomes.

References ​

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  2. Primary malignant neoplasms of the appendix: a population-based study from the surveillance, epidemiology and end-results program, 1973-1998. - Margaret E McCusker;Timothy R Coté;Limin X Clegg;Leslie H Sobin - Cancer (2002)
  3. The rise in appendiceal cancer incidence: 2000-2009. - Schelomo Marmor;Pamela R Portschy;Todd M Tuttle;Beth A Virnig - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (2015)
  4. Grading and staging mucinous neoplasms of the appendix: a case series and review of the literature. - Sarah E Umetsu;Nafis Shafizadeh;Sanjay Kakar - Human pathology (2017)
  5. Continued increasing incidence of malignant appendiceal tumors in Canada and the United States: A population-based study. - Harminder Singh;Ananda S Koomson;Kathleen M Decker;Jason Park;Alain A Demers - Cancer (2020)
  6. Staging of appendiceal mucinous neoplasms: challenges and recent updates. - Sarah E Umetsu;Sanjay Kakar - Human pathology (2023)
  7. Appendiceal mucinous neoplasms: clinicopathologic study of 116 cases with analysis of factors predicting recurrence. - Reetesh K Pai;Andrew H Beck;Jeffrey A Norton;Teri A Longacre - The American journal of surgical pathology (2009)
  8. Appendiceal mucinous neoplasms: a clinicopathologic analysis of 107 cases. - Joseph Misdraji;Rhonda K Yantiss;Fiona M Graeme-Cook;Ulysses J Balis;Robert H Young - The American journal of surgical pathology (2003)
  9. Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade. - Michael J Overman;Keith Fournier;Chung-Yuan Hu;Cathy Eng;Melissa Taggart;Richard Royal;Paul Mansfield;George J Chang - Annals of surgery (2013)
  10. Adenocarcinoma of the appendix is rarely detected by colonoscopy. - Apurva N Trivedi;Edward A Levine;Girish Mishra - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract (2009)

Literatures Citing This Work ​

  1. AJCC Cancer Staging System Version 9: Appendiceal Adenocarcinoma. - Nader Hanna;Andrew N Hanna;David N Hanna - Annals of surgical oncology (2024)
  2. Current Status of Treatment among Patients with Appendiceal Tumors-Old Challenges and New Solutions? - Katarzyna Chawrylak;Magdalena Leśniewska;Katarzyna Mielniczek;Katarzyna Sędłak;Zuzanna Pelc;Sebastian Kobiałka;Timothy M Pawlik;Wojciech P Polkowski;Karol Rawicz-Pruszyński - Cancers (2024)
  3. Mucinous neoplasm of the appendix: A case report and review of literature. - Hao-Cheng Chang;Jung-Cheng Kang;Ta-Wei Pu;Ruei-Yu Su;Chao-Yang Chen;Je-Ming Hu - World journal of gastrointestinal surgery (2024)
  4. Analysis of survival and prognostic factors in appendix adenocarcinoma and mucinous carcinoma. - Bilal Turan;Ahmet Necati Sanli;Serdar Acar - Updates in surgery (2025)
  5. Defining a 'cells to society' research framework for appendiceal tumours. - Andreana N Holowatyj;Michael J Overman;Konstantinos I Votanopoulos;Andrew M Lowy;Patrick Wagner;Mary K Washington;Cathy Eng;Wai Chin Foo;Richard M Goldberg;Mojgan Hosseini;Kamran Idrees;Douglas B Johnson;Ardaman Shergill;Erin Ward;Nicholas C Zachos;Deborah Shelton; - Nature reviews. Cancer (2025)
  6. Fusobacterium nucleatum Is Associated with Tumor Characteristics, Immune Microenvironment, and Survival in Appendiceal Cancer. - Christopher Sherry;Neda Dadgar;Hyun Park;Chelsea Knotts;Erin Grayhack;Rose Blodgett;Kunhong Xiao;Ashten N Omstead;Albert D Donnenberg;David L Bartlett;Vera Donnenberg;Ajay Goel;Ali H Zaidi;Patrick L Wagner - Microorganisms (2025)
  7. Prognosis Prediction and Surgical Benefit Subgroup Analysis in Anal Squamous Cell Carcinoma Patients Undergoing Concurrent Chemoradiotherapy. - Quan Wang;Guangmin Wan;Lu Yang;Gang Xu - Cancer medicine (2025)

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