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e24151Background: Confirmation of prostate cancer in men with elevated PSA and suspicious digital rectal exams currently requires a core needle biopsy, which is associated with risks such as infect...

12070Background: Bladder cancer patients are routinely monitored after treatment by cystoscopy due to a high rate of recurrence. In the absence of an accurate non-invasive screening test to monitor...

605 Background: Clear cell renal cell carcinoma (ccRCC) is among the most highly infiltrated tumors despite a relatively low mutation burden. Despite success in treating subsets of these patients with immunotherapy, the high immune-infiltration of ccRCC remains a conundrum that has not been sufficiently addressed. Methods: We utilized an original RNAseq-based aggregate immune score (Senbabaoglu Y, bioRxiv, 2015) to compare immune infiltration levels across 20 tumor types profiled in The Cancer Genome Atlas (TCGA) and validated our results with an independent cohort of ccRCC patients (Sato Y, Nat Genet, 2013). We also evaluated the immunogenic effect of intratumoral heterogeneity (ITH) through an analysis of clonal architecture in ccRCC tumors from both of the aforementioned data sets using the SciClone (Miller C, PLoS Comput Biol, 2014) algorithm. Results: We identified ccRCC as an immunogenic outlier that is unique from other highly infiltrated tumors in its exceptional overexpression of antigen presentation machinery compared to normal tissue. In a focused decomposition of immune cell levels within the 415 ccRCC tumors from TCGA, three unique clusters of tumors emerged primarily separated by varying degrees of T cell infiltration; termed (1) T-cell-enriched, (2) heterogeneous, and (3) non-infiltrated groups. These clusters were validated in an independent ccRCC cohort of 101 patients. A comparison of the degree of clonality with immune infiltration levels revealed that tumors with less ITH (i.e. fewer subclones) had significantly higher immune infiltration in both the TCGA and the validation cohort . Conclusions: Our findings provide novel insight into the immune landscape of ccRCC tumors and explore a potential mechanism for the immunogenicity of these tumors. Such information can potentially be used to aid in predicting therapeutic response to immunomodulatory agents.

512 Background: Recently clear cell papillary renal cell carcinoma (cpRCC) has been recognized as new histologic subtype with immunohistochemical profiles that differentiate it from clear cell (ccRCC) and papillary (pRCC) RCC. Several previous studies highlighted the indolent behaviour of this entity in the reported cases. Our primary objective is to further elucidate the genomic and clinical characteristics of cpRCC. Methods: 44 patients with cpRCC were selected from the MSKCC database with surgery performed between 2007 and 2014. Only tumors with appropriate histological configuration and immunohistochemically confirmed CAIX and CK7 positivity and CD10 negativity were included. Whole exome sequencing (WES) was performed on 5 cpRCC tumor samples and one sample was analyzed by next-generation sequencing (MSK-IMPACT). A further comparison was made to 825 ccRCC and 219 pRCC tumors with initial pT1 diagnosis from our institutional database. Differences in the variables across groups were analyzed with the Chi-Square and the Kruskal–Wallis tests. To visualize and test the survival distribution differences, we used Kaplan–Meier plots and Log-rank tests. Results: Sequencing did not reveal VHL mutations or other known driver mutations commonly seen in ccRCC or pRCC and no recurrent mutations were identified. The median follow up period for cpRCC was 27 months, for ccRCC 59 months and for pRCC 63 months. cpRCC frequently co-occured with ccRCC or other RCC subtypes (17/44 cases). Female patients developed cpRCC significantly more frequently than ccRCC or pRCC (47.7% P

406 Background: Proteomics represents the ultimate convergence of DNA and expression alterations. We therefore sought to leverage TCGA reverse phase protein array (RPPA) data with an independent proteomic platform to identify druggable targets and pathways associated with prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Unsupervised hierarchical consensus clustering was performed and differentially expressed proteins were identified for pathway analysis. Associations with clinicogenomic factors were assessed and Cox proportional hazards models were performed for disease-specific survival (DSS). Results: RPPA clustering of 324 patients from the ccRCC TCGA revealed 5 robust clusters characterized by alterations in specific pathways and divergent prognoses. Cluster 1 was characterized by poor DSS, decreased expression of receptor tyrosine kinases (RTK) and upregulation of the mTOR pathway. It was also associated with mTOR pathway genomic alterations, sarcomatoid histology and the ccb prognostic mRNA signature (all p 3 proteins were associated with improved DSS (HR 0.19, 95% CI 0.05-0.082; p=0.03). Patients with mTOR pathway activation segregated to those with coincident RTK activation (n=83) and those without (n=13). Conclusions: We have identified and validated proteomic signatures which cluster ccRCC patients into 5 prognostic groups. Furthermore, two distinct mTOR-activated clusters—one with high RTK activity and one with increased mTOR pathway genomic alterations were revealed, which may have prognostic and therapeutic implications.

358 Background: Patients treated for urothelial carcinoma of the urinary bladder treated with radical cystectomy and pelvic lymph node dissection have worse clinical outcomes if they receive perioperative blood transfusion. We evaluated the impact of perioperative blood transfusion on oncologic outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: We conducted a single-center, retrospective review of 405 patients treated with RNU for UTUC. Clinicopathologic characteristics were recorded. Hospital charts were reviewed to determine if patients received perioperative blood transfusion. Characteristics were compared between groups based on transfusion status using Chi-square analyses. Survival was assessed using the Kaplan-Meier method. Cox regression analysis addressed cancer-specific mortality (CSM). Results: Median age was 71.4 years (IQR 63.7-76.5) and the majority of patients were male (64%). Median follow up was 43.4 months (IQR 16.7-86.6). CSM occurred in 26.2% of patients. Perioperative transfusion was associated with higher rates of invasive T stage (>/=T2), (62% vs. 47%, p=0.019) and lymph node positive disease (23% vs. 10.3%, p=0.029). Three year disease-specific survival (DSS) was 80% for the entire cohort. DSS was significantly shorter (p=0.003) for patients receiving transfusion (66.3%, 95% CI 53.7%-76.3%) than those who did not (83.3%, 95% CI 78.3%-87.3%). Transfusion was an independent predictor of CSM on multivariable analysis including gender, grade, invasive T stage, nodal status, and transfusion (Table 1). Conclusions: Perioperative blood transfusion may be associated with adverse pathologic and oncologic outcomes in patients undergoing RNU for UTUC. [Table: see text]