BackgroundThe prognostic impact of early metabolic response by fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) after 2 cycles of first-line chemotherapy is still unrecognized in metastatic transitional cell carcinoma (TCC). Patients and MethodsPatients with metastatic TCC receiving the modified combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), according to institutional protocol, underwent computed tomography (CT) and FDG-PET imaging at baseline, a restaging with PET imaging after 2 cycles only (PET2), and a CT (± FDG-PET) scan at the end of treatment and during follow-up. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan–Meier method; univariate (UVA) and multivariate (MVA) Cox models were fitted. Prespecified variables were the presence of visceral metastases, nodal or soft tissue disease, and early PET response. ResultsIn the period from May 2010 to October 2012, 31 patients with Eastern Cooperative Oncology Group performance status 0 received the modified MVAC regimen every 3 weeks. In all, 6 patients (19.3%) had a complete response (CR) and 17 (54.8%) a partial metabolic response (PR), 4 had stable disease (SD), and 4 progressed. PET2 responders had a median PFS of 8 months (95 % CI, 7-11 mo) compared with 3 months (95 % CI, 2-5 mo) of patients without response (P = .024). They also had a significant benefit in 8-month PFS (P < .001 via Klein test) and 15-month OS (P = .016). PET2 response was significant for PFS in both UVA and MVA Cox models (P = .027 and P = .023, respectively). ConclusionPET response after 2 cycles of first-line chemotherapy, compared with detection by early CT, was associated with longer PFS and OS in advanced TCC and warrants further investigation in the field.