Clinical outcomes for neoadjuvant chemotherapy (NAC) vary by molecular subtype in muscle-invasive bladder cancer, investigators report.

Researchers classified the subtypes in 223 patients with muscle-invasive bladder cancer (luminal, basal, claudin-low, and luminal-infiltrated) and found response to neoadjuvant cisplatin-based chemotherapy varied by subtype (P = .0001).

“Neoadjuvant chemotherapy improves outcomes in muscle-invasive bladder cancer, but only at 5%-7% for overall survival at 5 years,” study author Roland Seiler, MD, of the University of British Columbia, Vancouver, said in a press briefing held at the 2017 genitourinary cancers symposium sponsored by the American Society of Clinical Oncology, ASTRO, and the Society of Urologic Oncology. “About 60% of patients still have invasive disease at cystectomy so they are therefore nonresponders, but they still suffer from unnecessary side effects.”

Dr. Seiler explained that molecular subtypes of muscle-invasive bladder cancers had been identified that were based on gene expression. They decided to investigate the impact of different subtyping methods on patient response to NAC with the goal of developing a single sample model for subtyping.

A transcriptome-wide microarray analysis was conducted, using bladder tumor transurethral resection specimens that were obtained from 223 patients prior to receipt of NAC and cystectomy. The specimens were then classified according to four published methods for molecular subtype: University of North Carolina (UNC) dataset, MD Anderson (MDA) dataset, The Cancer Genome Atlas (TCGA) dataset, and the Lund dataset.

A validation set of 82 pre-NAC specimens also was done, with the results compared to non-NAC cohorts in the public domain including 179 cases from TCGA dataset, 107 from the MDA dataset, and 190 from the Lund dataset.

Finally, a genomic classifier was trained to predict the different subtypes in a single sample model and was then validated in both independent NAC and non-NAC datasets.

Investigators found that patients with luminal tumors had the best overall survival and it was independent of NAC. Patients with tumors classified as UNC basal, MDA basal, and TCGA cluster III achieved the greatest improvement in overall survival following NAC as compared with cystectomy alone.

Patients with tumors that were classified as UNC basal, MDA basal and TCGA cluster III achieved the greatest survival benefit following NAC, compared to surgery alone. Tumors that were assigned as UNC claudin-low had the worst overall survival regardless of the type of treatment regimen (P = .005).

“Basal tumors showed the most improvement with neoadjuvant therapy and should be prioritized with this treatment,” said Dr. Seiler. “Whereas for other subtypes we may need novel therapies.”

As discussant for the presentation, Jonathan Rosenberg, MD, of Memorial Sloan Kettering Cancer Center in New York, said that cisplatin “is a toxic therapy and we would love to have a great biomarker to select the right group of patients. Currently using present data, anywhere from 10 to 20 patients need to be treated to save one life.”

He reiterated that these findings confirm that basal tumors appear to benefit significantly from platinum-based chemotherapy and this benefit appears to exist regardless of downstaging.

“However it does not automatically follow that other subtypes do not benefit, and we are not ready to change clinical practice just yet,” Dr. Rosenberg said. “We need to prospectively validate these findings before we implement them into clinical practice.”


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