Clinical Parameters Outperform Molecular Subtypes for Predicting Outcome in Bladder Cancer: Results from Multiple Cohorts, Including TCGA.

PURPOSE: Studies indicate that molecular subtypes in muscle invasive bladder cancer predict the clinical outcome. We evaluated whether subtyping by a simplified method and established classifications could predict the clinical outcome. MATERIALS AND METHODS: We subtyped institutional cohort 1 of 52 patients, including 39 with muscle invasive bladder cancer, an Oncomine™ data set of 151 with muscle invasive bladder cancer and TCGA (The Cancer Genome Atlas) data set of 402 with muscle invasive bladder cancer. Subtyping was done using simplified panels (MCG-1 and MCG-Ext) which included only transcripts common in published studies and were analyzed for predicting metastasis, and cancer specific, overall and recurrence-free survival. TCGA data set was further analyzed using the Lund taxonomy, the Bladder Cancer Molecular Taxonomy Group Consensus and TCGA 2017 mRNA subtype classifications. RESULTS: Muscle invasive bladder cancer specimens from cohort 1 and the Oncomine data set showed intratumor heterogeneity for transcript and protein expression. MCG-1 subtypes did not predict the outcome on univariate or Kaplan-Meier analysis. On multivariate analysis N stage (p ≤0.007), T stage (p ≤0.04), M stage (p=0.007) and/or patient age (p=0.01) predicted metastasis, cancer specific and overall survival, and/or the cisplatin based adjuvant chemotherapy response. In TCGA data set publications showed that subtypes risk stratified patients for overall survival. Consistently the MCG-1 and MCG-Ext subtypes were associated with overall but not recurrence-free survival on univariate and Kaplan-Meier analyses. TCGA data set included 21 low grade specimens of the total of 402 and subtypes associated with tumor grade (p=0.005). However, less than 1% of muscle invasive bladder cancer cases are low grade. In only high grade specimens the MCG-1 and MCG-Ext subtypes could not predict overall survival. On univariate analysis subtypes according to the Bladder Cancer Molecular Taxonomy Group Consensus, TCGA 2017 and the Lund taxonomy were associated with tumor grade (p <0.0001) and overall survival (p=0.01 to <0.0001). Regardless of classification, subtypes had about 50% to 60% sensitivity and specificity to predict overall and recurrence-free survival. On multivariate analyses N stage and lymphovascular invasion consistently predicted recurrence-free and overall survival (p=0.039 and 0.003, respectively). CONCLUSIONS: Molecular subtypes reflect bladder tumor heterogeneity and are associated with tumor grade. In multiple cohorts and subtyping classifications the clinical parameters outperformed subtypes for predicting the outcome.

Renal Cell Carcinoma Presenting as an Isolated Eyelid Metastasis.

Background: Renal cell carcinoma (RCC) has a propensity to metastasize with the most common sites of metastasis being the lungs and bones. Cutaneous metastasis of RCC to the eyelid is exceedingly rare, with only six cases reported in the past decade. We are reporting a case of metastatic renal cell carcinoma (mRCC) that presented with a painless eyelid mass. Case Presentation: We describe a case of a 66-year-old man with a history of chronic kidney disease stage III presenting with a rapidly growing left lower eyelid lesion thought to be a capillary hemangioma. Biopsy revealed polygonal clear cells with small central nuclei with thin-walled vasculature and strong immunostaining with PAX8 consistent with mRCC, clear cell type. Subsequent abdominal CT scan revealed a 5.1 × 4.7 × 4.3 cm heterogeneously enhancing mass with central necrosis in the upper pole of the left kidney. The patient was treated with excision of the eyelid lesion followed by robotic partial nephrectomy of the primary tumor. Follow-up CT scan at 3 and 6 months showed no evidence of recurrence. Conclusion: Isolated eyelid metastasis is an extremely rare form of presentation of mRCC. Interestingly, that patient did not have any other site of metastasis. Cytoreductive partial nephrectomy has been previously reported to be oncologically safe in selected patients.