33 Most patients with localised appendix cancer may be able to safely avoid chemotherapy after surgery, according to a new study from researchers at The University of Texas MD Anderson Cancer Center. Published in JAMA Surgery, the study found that fewer than 10% of patients experienced recurrence after surgery, while chemotherapy given afterward was not associated with improved survival or a lower risk of relapse, even among patients considered higher risk. Researchers also identified specific tumour characteristics and genomic alterations that may help doctors better predict which patients are most likely to see their cancer return. The analysis, led by John Paul Shen, MD, associate professor of Gastrointestinal Medical Oncology, and Sacha El Khoury, MD, a research fellow of Oncology, represents the largest study to date of localised appendix cancer. “For too long, the outdated notion that appendix cancer behaves similarly to colon cancer has driven treatment decisions for our patients,” Shen said. “Our findings demonstrate that appendix cancer has a distinct biology and that, for most patients with localised disease, the risk of relapse is low. Understanding each tumour’s unique characteristics can help us better identify who may benefit from closer monitoring while avoiding unnecessary treatment for others.” Research into appendix cancer treatment and recurrence risk has historically been limited because the disease is rare. As a result, doctors have often relied on evidence from colorectal cancer to guide treatment and follow up care. The new research suggests that appendix cancer has distinct characteristics that may require separate risk factors to determine which patients are most likely to experience a recurrence. The researchers reviewed outcomes for 439 patients with stage 1–3 appendix cancer treated at UT MD Anderson between 2000 and 2024. Of these, 202 patients who underwent surgery were evaluated for cancer recurrence. 19 patients, or 9.4%, experienced a recurrence during a median follow up of more than five years. Recurrence occurred in 6% of patients with stage 2 disease and 19.5% of those with stage 3 disease. Patients whose cancer returned had poorer outcomes, with a five year overall survival rate of 77.2%, compared with 95.7% among those who did not experience recurrence. Researchers found that certain genetic changes were associated with a higher risk of cancer returning. Specifically, TP53 mutations were linked to recurrence in goblet cell tumours, while GNAS mutations were associated with a higher relapse risk in non goblet tumours. “Appendiceal cancers are not all the same,” El Khoury said. “When we consider tumour histology together with its molecular features, we can better identify which patients are truly at a higher risk of recurrence. That’s where tailoring treatment for this disease has to start.” By examining tumour type alongside its genetic features, medical experts may be able to identify patients at greater risk while helping others avoid chemotherapy and its potential side effects. The study’s limitations include the fact that all patients were treated at a single cancer centre, meaning further research is needed to confirm the findings.