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 30<CrCl<50 mL/min. Primary endpoint was pCR (ypT0N0). Accrual goal was 30 patients per arm. Eighteen percent pCR was considered worthy of further study, while 4% pCR would not justify pursuit of this regimen. With 28 eligible patients per arm, success was defined as >3 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 <ypT1 in over 60% of patients is encouraging. Together, the results of this prospective trial support the use of NAC in eligible patients with HG UTUC.

The Journal of urology. 2019 Nov 08 [Epub ahead of print]

Vitaly Margulis, Maneka Puligandla, Edouard J Trabulsi, Elizabeth R Plimack, Elizabeth R Kessler, Surena F Matin, Guilherme Godoy, Ajjai Alva, Noah M Hahn, Michael A Carducci, Jean Hoffman-Censits, Collaborators

Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas., Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania., Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania., Division of Medical Oncology, Department of Internal Medicine, University of Colorado, Aurora, Colorado., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Urology, Baylor College of Medicine, Houston, Texas., Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan., Department of Oncology, Hopkins Kimmel Cancer Center, Baltimore, Maryland.