[Systemic treatment of metastatic tumors of the upper urinary tract]

Similar to bladder cancer, more than 95% tumors of the upper urinary tract are urothelial carcinoma. At initial diagnosis approximately 60% of the tumors are already invasive. In case of distant metastasis (M+) there is no benefit of radical nephroureterectomy. In those cases, systemic therapy is indicated.

The aim of this article is to present a systematic overview of different therapies in patients with metastatic upper tract urothelial carcinoma (UTUC).

Currently there are insufficient data upon which the recommendations for treatment of locally advanced and metastatic UTUC can be based. Cisplatin-based chemotherapy is the gold standard in first-line treatment of metastatic UTUC. Due to a lower toxicity compared to MVAC (methotrexate, vinblastine, adriamycin plus cisplatin), gemcitabine and cisplatin have become standard. However, carboplatin-based chemotherapies should not be considered interchangeable. Immunomodulatory therapies using checkpoint inhibition, particularly with antibodies directed against PD-1 (programmed cell death 1), PD-L1 (programmed cell death ligand 1) or CTLA-4 (cytotoxic T‑lymphocyte antigen-4) have shown significant antitumor activity with tolerable safety profiles and durable responses in patients with locally advanced and metastatic urothelial carcinoma. In those patients, unfit for cisplatin-based chemotherapy, good response rates have been reported in case of a positive PD-L1 status. However, preliminary data of the KEYNOTE-361 and IMvigor130 studies showed a reduced survival in case of low PD-L1 expression.