Urothelial carcinoma of the renal pelvis (UCRP) and the ureter is a rare disease, representing 5% of all urothelial malignancies. The incidence of UCRP in the general US population is estimated to be 1.15 per 100,000 person-years.1 Although radical nephroureterectomy is the therapy of choice for nonmetastatic UCRP, the rate of tumor recurrence is still high. For metastatic UCRP (mUCRP), cisplatin-based chemotherapies are often used as first-line agents with limited response, largely based on experience from urothelial tumors of the bladder.2 However, second-line chemotherapies for urothelial malignancies have significantly lower response rates and no significant survival benefit over supportive care.2
Whole-genome studies of metastatic urothelial cancer have shown profound genomic heterogeneity at the nucleotide and chromosomal levels.3,4 Furthermore, the mutation profiles of histologically similar tumors may vary widely, explaining the variable response to chemotherapy observed in small clinical trials.5 The availability of next-generation sequencing (NGS) has made it feasible for clinicians to analyze genetic profiles of an individual's cancer. When these results are coupled with the continual development of targeted therapies, personalized medicine is possible. However, interpretation of the numerous genetic variants that NGS provides and selection of an appropriate targeted therapy presents a novel challenge to clinicians. This report documents the successful use of NGS coupled with in silico analysis to select a targeted therapy, pazopanib, from numerous potential mutations in a patient with heavily pretreated mUCRP.
Author Contributions: MGM treated the patient and performed in silico analysis; MGM, AWH, and SG wrote the initial manuscript; MGM, AWH, DP, AV, HS, and SG completed all revisions.
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