Genetics May Predict Treatment Responses But Not Survival in Bladder Cancer

While analysis of molecular subtypes of muscle-invasive bladder cancer using tumor RNA expression can improve the ability to predict the likelihood of response to chemotherapy administered prior to surgery, molecular subtypes were not determined by researchers to be associated with notable differences in overall survival (OS; how long a patient lives following treatment) and progression-free survival (PFS; how long a patient lives following treatment without their disease spreading or worsening), according to findings recently published in the journal Clinical Cancer Research.

“We tested three published subtyping schemes and found a modest improvement in predicting pathologic response but no association with PFS or OS, despite previous studies indicating that the basal/squamous subtype was associated with the most clinical benefit from chemotherapy. These observations support the need to design precision medicine trials for prospective assessment using subtypes to select therapy based on the expression profile for each subtype,” said lead study author Dr. Seth P. Lerner, the Beth and Dave Swalm Chair in Urologic Oncology at Baylor College of Medicine in Houston and an investigator with the SWOG Cancer Research Network, in a news release.

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The study, a secondary analysis of data from the S1314 clinical trial of patients with muscle-invasive bladder cancer, found that COXEN GC, an RNA-based gene expression biomarker, was associated with tumor downstaging (a reduction of tumor size) among patients treated with chemotherapy, and had predictive value for patients who received cisplatin-based chemotherapy treatment prior to surgery, according to the news release.

Muscle-invasive bladder cancer occurs when tumors grow into or through the muscle wall of the bladder, as explained by the Bladder Cancer Advocacy Network, which noted that approximately 25% to 30% of bladder tumors grow into or through the muscle wall of the bladder. Such growth makes tumors more likely to spread further and be more life-threatening, as noted on the Bladder Cancer Advocacy Network’s website.

There will be an estimated 82,290 new cases of bladder cancer and 16,710 deaths from bladder cancer in the United States in 2023, with rates of new cases and deaths from the disease declining recently, according to the American Cancer Society.

Looking forward, researchers are calling for future clinical trials to study the ways in which molecular subtypes are associated with patient outcomes and investigate if therapies based on those subtypes can improve patients’ responses to neoadjuvant therapy (therapy administered prior to the main treatment), with Lerner and some of his co-authors currently developing the SUBTYP trial, which is hoped to be launched in the second half of 2024, the news release stated.

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“Despite a wealth of retrospective cohort studies suggesting that the COXEN score stratified patients into low and high risk of disease progression and death, this was not validated in the prospective S1314 trial testing two cisplatin-based chemotherapy regimens that are standard of care,” Lerner said in the release. “The SUBTYP trial will test a different strategy of using molecular subtypes based on RNA sequencing and a classifier developed by The Cancer Genome Atlas group for subtype directed neoadjuvant treatment.”

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