High Response Rates to Neoadjuvant Chemotherapy in High-Grade Upper Tract Urothelial Carcinoma



      To evaluate the impact of cisplatin-based neoadjuvant chemotherapy (NAC) in patients who underwent nephroureterectomy for high-grade (HG) upper tract urothelial carcinoma (UTUC).


      Retrospective review was conducted of patients with HG UTUC from 2011 to 2017 who underwent nephroureterectomy at 2 institutions. Patients with eGFR >50 mL/min/1.73 m2 were considered eligible for NAC and were referred for evaluation of NAC prior to nephroureterectomy. Patient demographics, kidney function, clinical and pathologic response rates, and outcomes were analyzed.


      Of 95 patients with HG UTUC meeting inclusion criteria (mean age 72.3 years, mean preop eGFR 57.0 mL/min/1.73 m2), 61 patients were considered eligible for NAC with eGFR >50 mL/min/1.73 m2, of which 25 (41%) received NAC. Of the patients who received NAC, 80% (20/25) of the patients had clinical response on imaging and 80% (20/25) had pathologic response (<pT2N0 disease) on nephroureterectomy. On final pathology, only 20% of the NAC group had ≥pT2 disease compared to 64% of patients who proceeded directly to surgery (P = .001). Patients who received NAC had significantly longer progression free survival (P = .051) and overall survival (P = .052) compared to patients who proceeded directly to surgery. No patients progressed or were deemed ineligible for surgery due to NAC.


      Cisplatin-based NAC demonstrated a high clinical and pathologic response rate in patients with HG UTUC without compromising definitive surgical treatment. Since nephroureterectomy significantly reduces kidney function and eligibility for cisplatin-based chemotherapy after surgery, patients with HG UTUC should be considered for NAC.
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        • Munoz J.J.
        • Ellison L.M.
        Upper tract urothelial neoplasms: incidence and survival during the last 2 decades.
        J Urol. 2000; 164: 1523-1525
        • Siegel R.L.
        • Miller K.D.
        • Jemal A.
        Cancer statistics, 2017.
        CA Cancer J Clin. 2017; 67: 7-30
        • Babjuk M.
        • Burger M.
        • Zigeuner R.
        • et al.
        EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013.
        Eur Urol. 2013; 64: 639-653
        • Perez-Montiel D.
        • Wakely P.E.
        • Hes O.
        • et al.
        High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants.
        Mod Pathol. 2006; 19: 494-503
        • Leow J.J.
        • Orsola A.
        • Chang S.L.
        • et al.
        A contemporary review of management and prognostic factors of upper tract urothelial carcinoma.
        Cancer Treat Rev. 2015; 41: 310-319
        • Brown G.A.
        • Busby J.E.
        • Wood C.G.
        • et al.
        Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: time to change the treatment paradigm?.
        BJU Int. 2006; 98: 1176-1180
        • Eylert M.F.
        • Hounsome L.
        • Verne J.
        • et al.
        Prognosis is deteriorating for upper tract urothelial cancer: data for England 1985-2010.
        BJU Int. 2013; 112 (p. E107-13)
        • Vashistha V.
        • Shabsigh A.
        • Zynger D.L.
        Utility and diagnostic accuracy of ureteroscopic biopsy in upper tract urothelial carcinoma.
        Arch Pathol Lab Med. 2013; 137: 400-407
        • Hall M.C.
        • Womack S.
        • Sagalowsky A.I.
        • et al.
        Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients.
        Urology. 1998; 52: 594-601
        • Margulis V.
        • Shariat S.F.
        • Matin S.F.
        • et al.
        Outcomes of radical nephroureterectomy: a series from the Upper Tract Urothelial Carcinoma Collaboration.
        Cancer. 2009; 115: 1224-1233
        • Leow J.J.
        • Martin-Doyle W.
        • Fay A.P.
        • et al.
        A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma.
        Eur Urol. 2014; 66: 529-541
        • Yin M.
        • Joshi M.
        • Meijer R.P.
        • et al.
        Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis.
        Oncologist. 2016; 21: 708-715
        • McConkey D.J.
        • Choi W
        • Shen Y
        • et al.
        A prognostic gene expression signature in the molecular classification of chemotherapy-naive urothelial cancer is predictive of clinical outcomes from neoadjuvant chemotherapy: a phase 2 trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin with bevacizumab in urothelial cancer.
        Eur Urol. 2016; 69: 855-862
        • Porten S.
        • Siefker-Radtke AO
        • Xiao L
        • et al.
        Neoadjuvant chemotherapy improves survival of patients with upper tract urothelial carcinoma.
        Cancer. 2014; 120: 1794-1799
        • Igawa M.
        • Urakami S
        • Shiina H
        • et al.
        Neoadjuvant chemotherapy for locally advanced urothelial cancer of the upper urinary tract.
        Urol Int. 1995; 55: 74-77
        • Liao R.S.
        • Gupta M
        • Schwen ZR
        • et al.
        Comparison of pathological stage in patients treated with and without neoadjuvant chemotherapy for high risk upper tract urothelial carcinoma.
        J Urol. 2018; 200: 68-73
        • Hoffman-Censits J.
        • Puligandla M
        • Trabulsi E
        • et al.
        LBA26 phase II trial of neoadjuvant chemotherapy followed by extirpative surgery for patients with high grade upper tract urothelial carcinoma (HG UTUC): results from ECOG-ACRIN 8141.
        J Urol. 2018; 199: e1166-e1167
        • Cohen A.
        • Kuchta K.
        • Park S.
        Neoadjuvant and adjuvant chemotherapy use in upper tract urothelial carcinoma.
        Urol Oncol. 2017; 35: 322-327
        • Hosogoe S.
        • Hatakeyama S
        • Kusaka A
        • et al.
        Platinum-based neoadjuvant chemotherapy improves oncological outcomes in patients with locally advanced upper tract urothelial carcinoma.
        Eur Urol Focus. 2017; 4: 946-953
        • Youssef R.F.
        • Shariat SF
        • Lotan Y
        • et al.
        Upper urinary tract urothelial carcinoma with loco-regional nodal metastases: insights from the Upper Tract Urothelial Carcinoma Collaboration.
        BJU Int. 2011; 108: 1286-1291
        • Birtle A.J.
        • Chester JD
        • Jones RJ
        • et al.
        Results of POUT: a phase III randomised trial of perioperative chemotherapy versus surveillance in upper tract urothelial cancer (UTUC).
        J Clin Oncol. 2018; 36: 407
        • Kaag M.G.
        • O'Malley RL
        • O'Malley P
        • et al.
        Changes in renal function following nephroureterectomy may affect the use of perioperative chemotherapy.
        Eur Urol. 2010; 58: 581-587
        • Hoffman-Censits J.H.
        • Trabulsi EJ
        • Chen DYT
        • et al.
        Neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) in patients with high-grade upper-tract urothelial carcinoma.
        J Clin Oncol. 2014; 32: 326