A genome-wide query of somatic copy number alterations to predict lymph node metastases and survival in patients with muscle-invasive bladder cancer.

Abstract

325 Background: Patients with muscle-invasive bladder cancer (MIBC) have a poor prognosis if the cancer has metastasized to surrounding lymph nodes (LN). Adding tumor-based genomic tests that improve prediction of LN status and prognosis over clinical variables alone would be useful to clinicians in making treatment decisions, potentially improving outcomes for these patients. Methods: We performed a genome-wide query of copy number alterations (CNAs) in MIBC tumors from 237 patients in The Cancer Genome Atlas who had radical cystectomy and lymphadenectomy ( ≥ 10 nodes) without neoadjuvant treatment. We independently analyzed pathology reports and copy number data to confirm LN status and gene-level CNAs. Using elastic net and logistic regression models, we sought to identify a set of genes with CNAs that predict LN status. We also tested for association between CNAs and survival. Results: We identified 26 genes with CNAs that predicted LN status. Those located on chr3p25 and chr11p11 had gains associated with LN positivity after adjusting for age, gender, race, pathological tumor stage, histology, and number of nodes examined (p = 0.03). CNAs at these loci were also associated with one-year survival in the cohort overall (p < 0.01), as well as in LN-positive patients after adjusting for node stage, LN density, and extracapsular extension (p < 0.01). Conclusions: We have identified a small set of genes with CNAs in MIBC tumors that robustly predict LN status and one-year survival. A simple copy number-based test based on these genes could potentially improve preoperative LN status determination and help inform adjuvant treatment decisions to improve outcomes in MIBC patients.