First-line Treatment of Metastatic Disease

More than 50% of patients with advanced urothelial carcinoma are not eligible for the standard treatment with cisplatin-based chemotherapy. In general, cisplatin-ineligible patients with metastatic urothelial cancer experience poor outcomes with standard treatment, although substantial heterogeneity exists. Baseline variables associated with poor prognosis include borderline performance status, presence of visceral metastases, liver metastases, and low hemoglobin. Although no standard treatment has been defined for cisplatin-ineligible patients, recommendations regarding carboplatin-based combination chemotherapy versus single-agent chemotherapy versus best supportive care are typically based on performance status and renal function. The clinical development of novel agents is of considerable interest.

Key points

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Patients not eligible for cisplatin are defined by one of the following: Eastern Cooperative Oncology Group performance status (PS) greater than or equal to 2, creatinine clearance (glomerular filtration rate [GFR]) less than 60 mL/min, hearing loss greater than or equal to grade 2, peripheral neuropathy greater than or equal to grade 2, heart failure greater than or equal to New York Heart Association class III.
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Patients unfit for cisplatin generally have a poor prognosis. Within this group PS 2, presence of visceral metastases, liver metastases, and low baseline hemoglobin are prognostic factors of poor outcome.
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Treatment decisions in patients who are unfit for cisplatin are mainly based on 2 factors: PS and renal function. In case of PS greater than or equal to 2 and GFR less than 60 mL/min, treatment consists of best supportive care or single-agent chemotherapy. In case of 0 or 1 risk factor, carboplatin-based combination chemotherapy is the preferred option with the highest level of evidence. Patient inclusion in clinical trials is highly recommended.