Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients with High Grade Upper Tract Urothelial Carcinoma.
Data supporting neoadjuvant chemotherapy (NAC) in high-grade (HG) upper-tract urothelial carcinoma (UTUC) is scant. This multi-institution prospective phase II trial investigated pathologic complete response (pCR) after NAC for HG UTUC.Patients with HG UTUC planned for nephroureterectomy (NU) were assigned to 4 NAC cycles of either accelerated methotrexate, vinblastine, doxorubicin, cisplatin (aMVAC) for baseline CrCl>50 mL/min or gemcitabine and carboplatin (GCa) for 303 pCRs (10.7%) in a given arm. Secondary endpoints included safety, renal function, and oncologic outcomes.From 2015-2017, 30 patients enrolled in the aMVAC arm. Six enrolled in the GCa arm, which closed for poor accrual. Of 29 eligible aMVAC patients (23 M, 6F) with median age 65 (40-84), 80% completed all planned treatments, 3 achieved ypT0N0 (10.3%), and a fourth achieved ypT0Nx (pCR=13.8%, 90% CI [4.9-28.8]). One aMVAC patient deferred NU due to grade 4 sepsis. Grade 3-4 toxicity rate was 23% in the aMVAC arm, with no grade 5 events.aMVAC NAC in patients with HG UTUC and CrCl>50 mL/min was safe and demonstrated pre-defined activity with 14% pCR. Final pathologic stage