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Research

Gallbladder Tumor Biology May Affect Survival

“Changes inside the cancer cells may help explain why some patients do worse than others, even when they receive similar treatment.”

Gallbladder cancer (GBC) is an extremely aggressive biliary tract malignancy characterized by silent early progression, late-stage diagnosis and poor prognosis. It is one of the most lethal gastrointestinal cancers, with a five-year survival rate often below 10%, partly because only about 10-20% of patients are eligible for curative surgical resection at diagnosis. 

A key focus of molecular research is whether Actionable Genomic Alterations (AGAs) – specific DNA changes in cancer cells – independently impact survival beyond established factors like stage and treatment.

A new study has found that patients with gallbladder cancer who had certain documented gene changes in their tumor had a higher risk of death, even when we compared them with similar patients based on age, sex, race/ethnicity, cancer stage, surgery and chemotherapy.

Genetic changes inside the cancer cells may help explain why some gallbladder patients do worse than others, even when they receive similar treatment.

Eduardo Vega, MD

“Genetic changes inside the cancer cells may help explain why some gallbladder patients do worse than others, even when they receive similar treatment,” says corresponding author Eduardo Vega, MD, assistant professor of surgery at the school.

The researchers studied real-world medical records from a large international database called TriNetX. First, they identified more than 40,000 patients with gallbladder cancer and separated them into two groups according to whether they had, or didn’t have, a documented actionable gene change in their tumor. They then used statistical methods to filter the two groups into individuals with a similar background, including matching them by age, sex, race/ethnicity, whether the cancer had spread, whether they had surgery and whether they received chemotherapy. After that, they compared survival rates between the groups. They found that cancers with AGAs such as KRAS, ERBB2/HER2, PIK3CA, IDH1, FGFR1, TP53, or ARID1A had lower survival rates than those without these genes.

The researchers hope this study helps move gallbladder cancer care toward a more personalized approach, where treatment decisions are guided not only by the stage of the cancer but also by the biology of each patient’s tumor. “Ultimately, we want genomic testing to help identify higher-risk patients earlier, expand access to targeted therapies and clinical trials, and improve outcomes for a disease that remains very difficult to treat,” adds Vega, who also is a hepato-bilio-pancreatic surgeon at Boston Medical Center.

But precision medicine can only help patients if all patients have fair access to testing. According to the researchers, the study found important disparities between those who received genomic testing or had genomic results documented. In the group without a documented actionable genomic alteration, 51.0% of patients had unknown race recorded, compared with only 3.7% in the group with a documented genomic alteration.  Also, white patients were more likely to have genomic results documented. Among patients whose race was known, white patients made up 67.1% of the documented-genomics group compared with 32.6% of the comparison group.

These findings appear online in the journal Cancers.