The gold standard of grading urothelial cancer is pathology which provides grading information, including differentiation and extension of the tumor. Pathology establishes treatment decisions. By using the TNM staging system we can classify carcinomas, helps us decide on management and decide whether we should include patients to clinical trials.
The non-muscle invasive bladder cancer (NMIBC) is the most heterogenous groups of bladder cancer. It includes the pTa low grade, PTa high grade, and carcinoma in situ (CIS). None of these have the same prognosis or treatment. Important information the pathologist should acquire from the surgeon include the tumor size, whether it was uni-or multifocal, and whether this is the first occurrence of the tumor. Information the pathologist should add to the clinician includes the presence of lymphovascular invasion (LVI), and whether there is variant histology (VH) or note.
Whether the patient with muscle invasive bladder cancer (MIBC) had VH, CIS, LVI or positive margins has a significant impact on treatment and prognosis. If there is lymph node involvement, it is important to know the size of the involved lymph node, whether there is extra-nodal extension, and what was the Pt stage.
Dr. Comperat next discussed on what the molecular findings can add to pathological data. First, it provides us with more elaborate knowledge and understanding of urothelial carcinoma. It allows us to personalize treatment and understand the different molecular subtypes that exist. The problem is that there is too much data and very little that has been validated. There are 4 major molecular classifications: MDA, Lund, UNC and TGCA (Figure 1). There are two major subtypes: basal/luminal and different gene expression. There is currently much more data available for MIBC than for NMIBC.
For NMIBC molecular findings will help us understand differences between low grade (LG) and high grade (HG). It will provide us with knowledge regarding basal and luminal like characteristics with different outcomes. Finally, it will help us understand the heterogenous group of T1, and perhaps enable us to understand to whom we should give BCG therapy. For MIBC, more data is needed on positive lymph nodes and hopefully it will help us understand tumor progression in metastatic disease.
Mutational burden (MB) can be measured. Tumors with the highest MB are genomically unstable, and perhaps will be good candidates for immune checkpoint inhibitor (ICI) therapy. Using gene expression profiling (GEP) of tissues from TURBT or radical cystectomy surgeries, will allow us to predict different molecular subtypes, enabling us to understand which subtypes will benefit from neoadjuvant chemotherapy (NAC). This has already enabled us to know that the luminal subtype will have the same outcome with or without chemotherapy, while the basal type will have the improved overall survival (OS) with NAC.
Dr. Comperat concluded her lecture, stating that morphology and classical pathology (PTNM) alone are suboptimal in providing all the required information for the best management. Molecular investigations will add much value to TNM staging, refine diagnosis, and complement pathology significantly. In the future, the pathological report will inform which molecular studies should be performed, thereby improving the treatment decisions, and the patient outcomes.
Figure 1: The 4 major molecular classifications:
Presented by: E. Compérat, Paris, France
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark