Previous studies have suggested that histologic variants may be seen in up to 20% of cystectomy specimens, of which 44% are not primarily diagnosed. These entities include (most commonly) plasmacytoid, micropapillary, nested variant, and small cell variants. Several retrospective series have demonstrated that histologic variants are associated with poorer survival compared to standard urothelial carcinoma. Recently, micropapillary variant has been associated with HER2 gene amplification in 35% of cases, although small studies assessing targeted therapy for these individuals has not proven to improve outcomes. Recent work from the TCGA dataset [1] suggests that subtyping seems to reflect the intrinsic biology of MIBC very well. This includes luminal papillary, luminal, luminal infiltrated, basal squamous, and neuronal/neuroectodermal. The therapeutic implications for this degree of molecular subtyping are vast as Dr. Hartmann highlights:
Furthermore, there is recent evidence suggesting that bladder cancer patients have high levels of PD-L1 immune targets, specifically 22% of tumor cells having >1% of PD-L1 expression. This certainly has the potential as a biomarker and targeted therapy as we move forward in the era of precision medicine.
References:
1. Robertson AG, Kim J, Al-Ahmadie H, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell 2017;171(3):540-556.
Presented by: Arndt Hartmann, University of Erlangen-Nuremberg, Erlangen, Germany
Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark