Radiographic predictors of pathologic response to neoadjuvant chemotherapy with gemcitabine and cisplatin in patients with high-grade upper tract urothelial carcinoma.

Abstract

522 Background: Neoadjuvant chemotherapy (NAC) has established survival benefits prior to radical cystectomy for bladder cancer, yet its role in upper tract urothelial carcinoma (UTUC) prior to nephroureterectomy (NU) is less clear. We performed a phase II clinical trial of NAC with gemcitabine and cisplatin (GC) in patients with UTUC to evaluate pathologic response. We investigated if radiographic responses could predict pathologic response. Methods: Patients with high-risk localized UTUC (high grade on biopsy and/or radiographic evidence of cT2-4 disease with positive select cytology) were recruited to receive 4 cycles of GC prior to NU with the primary objective of the phase 2 study being pathologic response rate, defined as ≤pT1N0. All patients underwent CT imaging at before and after chemotherapy. All baseline imaging studies were categorized as: (i) no abnormality, (ii) focal mass or (iii) thickening without discrete mass. Post-chemotherapy imaging studies were categorized as: (i) stable disease, (ii) progression of disease, (iii) partial response or (iv) complete response. Radiographic responses were correlated with final pathologic staging. Results: 43 patients (pT0N0 = 9, ≤pT1N0 = 18 and >pT1N0 = 16) had CT performed pre- and post-chemotherapy. All patients had a visible lesion seen (mass = 34 and thickening = 9). The median pre-chemotherapy mass size was 3.1cm (IQR 1.8, 4.1). Approximately 60.5% of patients (N = 26) had evidence of hydronephrosis prior to chemotherapy. Following chemotherapy, 10 patients had a complete response, 20 had a partial response and 13 had stable disease. No patients progressed radiographically while on chemotherapy. Patients who had a complete radiographic response were more likely to have a pathologic response (≤pT1N0 = 90%), compared to a partial response (90% vs 65%, P = 0.21) and stable disease (90% vs 38%, P = 0.01). Conclusions: Radiographic response following NAC for UTUC appears to be correlated with pathologic response at time of surgery. Radiographic response, in addition to other pre-operative predictors, may play a useful role in counselling and optimizing management of patients with UTUC.