First-line treatment with standard chemotherapy regimens offers limited clinical benefit in patients with metastatic urothelial carcinoma of the bladder (mUCB). Treatment options beyond the first line have historically been unclear for mUCB patients, but recent clinical trial findings suggest later-line options could be coming into view. Researchers reviewed the recent trials and available evidence to propose a treatment algorithm for later lines that incorporates newer agents, particularly immune checkpoint inhibitors (ICIs).1The findings were published online in Clinical and Translational Oncology on September 4, 2018.

The proposed treatment algorithm took into account certain features, like patient fitness and tumor burden. For fit patients who progress on standard first-line chemotherapy, the authors proposed rechallenging platinum-sensitive tumors with platinum-based regimens and advancing to other treatment options for platinum-resistant tumors. Patients with platinum-resistant tumors that have low disease burden should be treated with an IC I— with pembrolizumab being the preferred option, according to researchers. Patients with platinum-resistant tumors that have high disease burden should not be treated with ICIs; instead combination regimens, preferably, or single-agent chemotherapy was recommended.

The authors proposed ramucirumab plus docetaxel or single-agent chemotherapy as third-line options for fit patients who progress while on an ICI. For platinum-refractory patients (progression within 3 months of treatment) who are ineligible for treatment with an ICI, ramucirumab plus docetaxel was advised in the second-line setting.

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For patients deemed unfit by investigator-defined parameters, ICI was proposed as a frontline treatment option and if progression occurs, chemotherapy — preferably metronomic cyclophosphamide — was recommended; the alternative to chemotherapy was best supportive care. The authors cautioned, “Continuing ICI beyond progression or switching ICI should be limited to clinical trials.” 


  1. El Rassy E, Assi T, Bakouny Z, Pavlidis N, and Kattan J. Beyond first-line systemic treatment for metastatic urothelial carcinoma of the bladder[published online September 4, 2018]. Clin Transl Oncol. doi: 10.1007/s12094-018-1935-z