SUO 2017: Genomic Analysis of Same-Patient Metachronous Upper-Tract and Bladder Urothelial Carcinoma

Washington, DC ( As Firas Petros' team and others have described, upper tract urothelial cancer (UTUC) and bladder cancer (BUC) appears to have distinct clinical, pathologic and genomic profiles and may in fact be two distinct disorders, especially de novo UTUC.

In this study, the authors assess the genomic profile and clinical history of 4 distinct populations in a retrospective manner. The 4 groups were 1) UTUC with metastatic BUC, 2) BUC with metastatic UTUC, 3) Synchronous BUC and UTUC, 4) UTUC with no bladder history (de novo UTUC). Tissue samples / Tumors were macrodissected from unstained formalin-fixed, paraffin-embedded slides. Whole transcriptome RNA sequencing was performed and analyzed using BASE47 panel (includes basal, luminal, p53-like and cell cycle genes) – based on their experience with molecular subtyping of bladder cancer, they proceeded to subtype all these tissues accordingly.

In this very interesting analysis, they identified 95 samples from 40 patients – 61 UTUC samples and 34 BUC samples. Interestingly, they had more UTUC samples than BUC samples. Of the 61 UTUC samples, 33 were from the ureter and 28 from the renal pelvis. Basic demographics: median age was 72 years, 68% male, 76% Caucasian, 60% former smokers. Of the four groups, the breakdown of samples was: 1) UTUC (n=19), mBUC (n=12); 2) BUC (n=12), mUTUC (n=9); 3) Synchronous UTUC/BUC (n=10); and 4) de novo UTUC (n=23). High-grade disease was identified in 33 of the 61 (54%) UTUC tumors, and pTa was found in 34 of the 61 tumors (56%); similarly, HG disease was noted in 56% of BUC tumors and pTa in 79% of BUC tumors.

As with their prior BUC molecular subtyping analysis, unsupervised clustering of the samples resulted in discrimination into basal and luminal subtypes. 87.5% of metachronous tumors displayed conserved subtype membership from their original tumor. For the groups with UTUC and BUC synchronous, only 3/24 (12.5%) clusters (2 patients in Group 2, and 1 patient in Group 3) had unmatched basal/luminal subtypes.

Based on this next-generation sequencing analysis, the authors showed that the majority of metachronous tumors stayed within the same molecular subtype regardless of chronologic development or anatomic origin. However, synchronous tumors did rarely did, suggesting again that UTUC and BUC may be distinct disease processes.

Presented by: Firas Petros
Co-Authors: Yuan Qi, Woonyoung Choi, Roger Li, Xiaoping Su, Charles Guo, Colin Dinney, David McConkey, Surena Matin, MD Anderson Cancer Center, Houston, TX

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, twitter: @tchandra_uromd at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC