Urothelial Carcinoma Molecular Subtype Could Guide Use of Neoadjuvant Chemotherapy

Tumor classification by gene expression profiling and molecular subtyping can help identify which patients with muscle-invasive bladder cancer are more likely to benefit from chemotherapy before radical cystectomy, according to a study published in European Urology. 

“In this study, we investigated how molecular subtypes in the specimen from the transurethral resection of the bladder impact pathological response and survival in 149 patients receiving preoperative chemotherapy,” explained a team of researchers from Sweden.

Tumor transcriptomic profiling and immunostaining were used to classify patients in the retrospective cohort.

According to the findings, rates of complete pathological response were higher for patients with unstable and urothelial-like tumors compared with the basal/squamous subtype. Following neoadjuvant chemotherapy and radical cystectomy, complete pathological response rates were 52% in patients with genomically unstable tumors, 31% in patients with urothelial-like tumors, and 21% in patients with the basal/squamous tumors.

After adjusting for clinical stage, molecular subtype was independently linked with improved survival for patients with genomically unstable tumors and urothelial-like C tumors compared with basal/squamous tumors.

The study also showed a subtype-dependent effect on chemotherapy response with expression of the gene coding for osteopontin, SPP1.

“Together with other markers for response,” researchers wrote, “molecular subtypes could have a role in selective administration of such chemotherapy.”

Reference: 
Sjödahl G, Abrahamsson J, Holmsten K, et al. Different responses to neoadjuvant chemotherapy in urothelial carcinoma molecular subtypes. Eur Urol. 2022;81(5):523-532. doi:10.1016/j.eururo.2021.10.035