This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Survival Outcomes and Prognostic Factors in Metastatic Unresectable Appendiceal Adenocarcinoma Treated with Palliative Systemic Chemotherapy: A 10-Year Retrospective Analysis from Australia
by
, and
Jirapat Wonglhow
1,2,*
,
Hui-Li Wong
2,
Michael Michael
2,3,
Alexander Heriot
4,
Glen Guerra
4,
Catherine Mitchell
3,5 and
Jeanne Tie
2,3 1
Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand
2
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
3
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC 3000, Australia
4
Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
5
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
*
Author to whom correspondence should be addressed.
Cancers 2025, 17(20), 3297; https://doi.org/10.3390/cancers17203297 (registering DOI)
Submission received: 31 August 2025
/
Revised: 24 September 2025
/
Accepted: 11 October 2025
/
Published: 11 October 2025
(This article belongs to the Special Issue Clinical Efficacy of Drug Therapy in Gastrointestinal Cancers)
Simple Summary
Appendiceal adenocarcinoma is a rare cancer, and there is limited evidence to guide systemic treatment for metastatic or unresectable cases. This study evaluated real-world outcomes in patients with advanced appendiceal adenocarcinoma who received palliative chemotherapy. The results support fluoropyrimidine-based doublet chemotherapy as an appropriate and preferred option for patients with high disease burden and aggressive tumor features. Single-agent fluoropyrimidine therapy may be a reasonable alternative for frail patients with less aggressive disease. A high incidence of KRAS mutations was observed, which may affect the use of targeted therapies. These findings highlight the need for treatment strategies tailored specifically to appendiceal cancer and suggest that molecular testing may help guide future therapy. This study offers valuable insights to improve care for patients with this rare and understudied disease.
Abstract
Background: Appendiceal adenocarcinoma is a rare malignancy, and data guiding its systemic treatment in metastatic settings are limited. This study aimed to determine the clinical outcomes, treatment efficacy, biomarkers, and prognostic factors in patients with metastatic or unresectable appendiceal adenocarcinoma receiving palliative chemotherapy. Methods: We retrospectively reviewed patients with metastatic appendiceal adenocarcinoma who received first-line palliative systemic chemotherapy at the Peter MacCallum Cancer Centre between January 2015 and December 2024. Results: Of the 40 patients included, fluoropyrimidine-based doublet regimens were most commonly used (82.5%) in first-line setting, achieving an objective response rate of 39.4%. Median overall survival (OS) was 21.6 months, and median first-line progression-free survival (PFS) was 8.9 months. 22 patients (55.0%) received second-line treatment. Median OS and PFS were 21.6 and 8.9 months, respectively, among patients treated with oxaliplatin-based doublet regimens, and 66.4 and 10.8 months, respectively, among those treated with irinotecan-based doublet regimens. Molecular biomarker testing was performed in 35 patients (87.5%). KRAS and NRAS mutations were identified in 68.6% and 2.9% of tested patients, respectively. Factors associated with poorer OS included male sex, elevated carcinoembryonic antigen levels, and overweight status. Bevacizumab use was not clearly associated with survival. Conclusions: Palliative systemic chemotherapy, particularly fluoropyrimidine-based doublet regimens, appears to be a reasonable and effective treatment option for patients with advanced appendiceal adenocarcinoma. Although this study was underpowered for formal comparison, the numerically longer OS and PFS of irinotecan-based regimens are hypothesis-generating and support further prospective evaluation. Molecular profiling emphasizes the need for personalized targeted therapeutic strategies. The identified prognostic factors may help guide risk stratification and patient counseling for treatment planning.
