AUA 2017: Molecular subtypes of muscle invasive bladder cancer are related to benefit from neoadjuvant chemotherapy: Development of a single sample patient assay

Boston, MA ( Molecular gene-expression profiling of bladder cancer by several groups (UNC, MDA, TCGA, Lund) has led to a better understanding that histologically similar bladder cancers can have distinct subgroups of biology. These subgroups have been found to have different prognoses at baseline and even different responses to cisplatin-based neoadjuvant chemotherapy.

However the clinical implementation of a genome-wide assay is difficult due to high cost, labor intensive analysis, and requirement of normalization of the entire cohort in order to make subtype calls. To circumvent this, the authors tried to define a subset of genes and a bioinformatics approach that would allow easier implementation of subtype classification. Using both publicly available datasets they pared down their assay to 149 genes which demonstrated an AUC of 0.85 and classified tumors into four consensus molecular subtypes termed claudin-low, basal, luminal-infiltrated, and luminal. They hypothesized that subtype classification would correlate with prognosis and response to cisplatin-based neoadjuvant chemotherapy. Confirming preliminary data from prior reports, patients with luminal tumors had the best outcomes with 3-year OS rates of 75%. The prognosis of patients with luminal-infiltrated tumors was inferior to that of luminal tumors and did not improve with NAC. Patients with claudin-low tumors had poor OS irrespective of treatment regimen. Patients with basal tumors had a 3-year OS rate of 49.2% in the non-NAC cohort compared to 77.8% in the NAC cohort.

These preliminary findings are similar to other groups' prior findings and suggest that this molecular classification is implementable and generalizable in the clinic. There certainly seems to be an emerging understanding that tumors with the basal subtype are highly chemosensitive, while luminal tumors are relatively chemoresistant. Prospective clinical trials with subtype classifiers of TURBT specimens driving choice of neoadjuvant therapy will be needed to confirm that this approach improves patient outcomes, and surrogate pathologic endpoints at cystectomy could offer early insights into the success of this approach.

Presented by: Roland Seiler, Vancouver CA

Contributed by: Jed Ferguson, MD/PhD and Ashish Kamat, MD. MD Anderson Cancer Center, Department of Urology.

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 – Boston, Massachusetts, USA