Evaluation of Patient and Tumor Features to Optimize Urothelial Metastasis Treatment

Abstract

<h3>Purpose/Objective(s)</h3> The treatment of oligometastatic disease is an evolving area of research in oncology. This study characterizes urothelial metastases to identify tumor and clinical features which may be used in patient selection. <h3>Materials/Methods</h3> We evaluated a prospectively collected institutional biorepository for patients with urothelial carcinoma metastases. Metastatic tissue was collected and profiled with Affymetrix GeneChips and the ESTIMATE and CIBERSOFT algorithms were used to infer the immune composition of metastases. Gene set enrichment analysis with select hallmark MSigDB pathways related to DNA damage repair were evaluated. Medical charts were queried for patient demographics as well as tumor and treatment characteristics. Univariable analysis (UVA) with Kaplan-Meier methods was used for time-to-event analysis for overall survival from metastatic collection (OSMC) and time to recurrence at site of MC (TTRMC) and compared by log-rank testing. Cox regression was used to assess ability of variable to predict outcome in a multivariable (MVA) model. <h3>Results</h3> A total of 24 patients were identified between 2006 and 2009 with urothelial metastases profiled for gene expression with adequate records for chart query. The majority were male (75%) and the media age at MC was 69 years (range 52-89). Twelve patients had synchronous metastases with 29% having >1 metastatic range (range 1-3). The median BMI was 25.3 and 8 patients had diabetes or hypercholesteremia. Five patients were on an ACE-inhibitor. Twenty-one patients received definitive local surgery and 15 had ≥ pT3 or N+ disease. Eleven received chemotherapy and 3 received RT prior to MC. After MC, 58% received chemotherapy and 46% received radiation at the MC site. A total of 17 patients recurred after MC with 10 being at the original MC site. Increased immune cell presence at the MC site had increased TTRMC (9.9 months vs 8.1 months, p=0.04). No specific immune cell type was associated with TTRMC. Receipt of definitive local therapy to the primary tumor (p= 0.015), chemotherapy after MC (p= 0.001) and immune cell presence (HR: 0.9; 95% CI: 0.99-1.0, p=0.019) were associated with OSMC. Enrichment of dendritic cells at the MC site was associated with inferior OSMC (8.32 vs 34.3 months, p <0.001). Only immune cell presence remained predictive (p= 0.04) for OSMC on MVA. Neither DNA damage repair pathways nor presence of patient metabolic dysregulation were associated with outcomes. <h3>Conclusion</h3> Not all oligometastatic sites are equivalent and may require tailored approaches. Here we find that immune cell enrichment may provide better local metastatic control and survival.