Development of secondary urothelial carcinoma following complete response to immune checkpoint inhibitors

The management of metastatic urothelial cancer is rapidly evolving since immune checkpoint inhibitors were introduced. We present the case of a patient with metastatic upper tract urothelial cancer who had a complete response to durvalumab and tremelimumab. This patient then developed multiple non-invasive papillary bladder tumours. Next-generation sequencing revealed that the tumours shared ancestry with the upper tract cancer, although there were key differences, most notably the presence of a TP53 missense mutation in the upper tract disease that was absent in the bladder tumours. This illustrates an important practice point in the management of exceptional responders to checkpoint inhibitors.