What does this research mean for the field?

PIK3CA mutations are more common in early-onset appendiceal adenocarcinoma and are independently associated with worse overall survival. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to investigate the mutational profiles of early-onset appendiceal adenocarcinoma compared to late-onset and their impact on overall survival.

February 21, 2026

PIK3CA Mutations in Early-Onset Appendiceal Adenocarcinoma

Key Points

This study aims to investigate the mutational profiles of early-onset appendiceal adenocarcinoma compared to late-onset and their impact on overall survival.
Conducted a retrospective analysis using patient data from the Memorial Sloan Kettering database.
Stratified patients into early-onset (EOAC, <50 years) and late-onset (LOAC, ≥50 years) groups.
Utilized logistic regression to compare mutational profiles between EOAC and LOAC.
Validated findings with the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange data.
Applied Kaplan-Meier survival analysis and multivariable Cox proportional hazard models to evaluate survival associations.
70 out of 200 patients had early-onset appendiceal adenocarcinoma (35%).
EOAC patients had higher rates of PIK3CA mutations than LOAC (17.1% vs. 7.7%; P = .04).
The association persisted in combined analyses with another dataset (12.3% vs. 5.9%; P < .01).
PIK3CA mutations were predominantly found in metastatic cases (11.8%) and more common in adenocarcinoma NOS than mucinous tumors (63.6% vs. 36.4%; P = .04).
In multivariable analysis, PIK3CA mutations correlated with worse overall survival (hazard ratio, 2.62; P < .01).

Abstract

PURPOSE Approximately one in three patients with appendiceal cancer (AC) is diagnosed before age 50 years. Early-onset appendiceal cancer (EOAC) exhibits distinct clinicopathologic and demographic features compared with late-onset disease, suggesting potential biological differences. However, the molecular differences remain poorly understood. This study aims to compare EOAC and late-onset AC (LOAC, ≥50 years) mutational profiles and evaluate their impact on overall survival (OS). METHODS A retrospective analysis was conducted using the Memorial Sloan Kettering—Metastatic Events and Tropisms database. Patients were stratified by age at the time of surgery into EOAC and LOAC groups. Logistic regression was used to assess differences in mutational profiles between these two groups. Findings were validated using data from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange project. Kaplan-Meier survival analysis and multivariable Cox proportional hazard models were used to evaluate associations with survival. RESULTS The study included 200 patients with appendiceal adenocarcinoma (median age: 55 years, IQR, 47-68), of whom 70 (35%) had EOAC and 130 (65%) had LOAC. Patients with EOAC had higher odds of harboring PIK3CA mutations compared with LOAC (17.1% v 7.7%; odd ratio, 2.65; P = .04), which was consistent when combined with the GENIE data set (12.3% v 5.9%; P < .01). PIK3CA mutations were exclusively observed in patients with metastatic disease (11.8%) and were more common in adenocarcinoma not otherwise specified (NOS) than mucinous tumors (63.6% v 36.4%; P = .04). In multivariable analysis, PIK3CA mutations were independently associated with worse OS (hazard ratio, 2.62 95% CI, 1.32 to 5.20; P < .01). CONCLUSION PIK3CA mutations are more common in EOAC and independently associated with worse OS. These findings suggest incorporating PIK3C A mutation status into prognostic assessments and warrant further investigation of PIK3CA inhibitors as a potential therapeutic strategy for appendiceal adenocarcinoma.

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