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

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