Presentation Authors: Andrew Silagy*, New York, NY, Nirmal John, Renzo DiNatale, Roy Mano, Julian Marcon, Kyle Blum, Alejandro Sanchez, Ari Hakimi, Eugene Pietzak, Jonathan Coleman, New York City, NY
Introduction: Few reports compare genomics of Upper tract urothelial carcinoma (UTUC) with outcomes from newer treatment modalities. We reviewed the genomic profile and oncological outcomes in patients treated for UTUC with neoadjuvant chemotherapy (NAC) prior to nephroureterectomy (NU).
Methods: After obtaining IRB approval, we reviewed 243 patients with UTUC and genomic sequencing, treated between 1995 - 2018. 207 patients underwent NU, with 22 receiving cisplatin-based NAC. Baseline clinicopathological factors, treatment and outcomes were recorded. For NAC, response was defined as
Results: The study cohort included 243 patients, 64.6% males, median age of 67 (IQR: 59-75). 110 (45.3%) patients were â‰¥T2. The median survivor follow-up was 34 months. The median time to metastasis was 6 months. The 2- and 5-year survival was 63.5% and 17.5% respectively. 73% of patients had a pathological response to NAC (95% CI 50%, 89%), the common mutations and copy number alterations are depicted in Figure 1. _x000D_
The median TMB in patients receiving NAC was 0.87 (IQR: 0.70-0.95). Of the selected gene panel, only TP53 (75% vs 47%; p < 0.01) and MLL2 (88% vs 35%; p < 0.01) were over-expressed in patients with a TMB >0.9. While an elevated TMB did not confer a statistically significant lower progression free survival (PFS), this may be confounded by TP53 which trended towards prolonged PFS (HR 0.54(95% CI 0.27-1.07); p=0.08) but was associated with N2 disease at surgery (30% vs 7%; p=0.04). TMB was not associated with response to NAC (p=0.64).
Conclusions: Mutational signatures in UTUC and NAC responsiveness are affected by altered biology, however TMB was unable to predict this response. A comprehensive clonality analysis is being done to assess whether specific evolutionary subtypes are associated with divergent clinicopathology or therapeutic efficacy.
Source of Funding: This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748