European Urology Focus Platinum-based Neoadjuvant Chemotherapy Improves Oncological Outcomes in Patients with Locally Advanced Upper Tract Urothelial Carcinoma  Shogo Hosogoe, Shingo Hatakeyama, Ayumu Kusaka, Itsuto Hamano, Hiromichi Iwamura, Naoki Fujita, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama  European Urology Focus  DOI: 10.1016/j.euf.2017.03.013 Copyright © 2017 European Association of Urology Terms and Conditions

Fig. 1 Patient selection and classification. (A) Of the 233 patients who underwent radical nephroureterectomy for locally advanced upper tract urothelial carcinoma (UTUC), 55 received two to four courses of neoadjuvant chemotherapy (NAC group) and 83 patients did not (Ctrl group). Indications for NAC were locally advanced UTUC including cT3–4 disease and/or local lymph node involvement (high-risk patients). Of 138 high-risk patients, we selected 51 pair-matched patients in the Ctrl and NAC groups according to age, sex, Eastern Cooperative Oncology Group performance status (ECOG PS), clinical tumor stage, history of cardiovascular disease (CVD) and diabetes mellitus (DM), and tumor location (renal pelvis or ureter) using propensity score matching. (B) The regimen in the NAC group was GCb for 35 cases (69%) and GCis for 16 cases (31%). In patients on GCis, 94% were eligible for cisplatin. By contrast, 80% of patients were ineligible for cisplatin in the GCb group. GCis=gemcitabine plus cisplatin; GCb=gemcitabine plus carboplatin. European Urology Focus DOI: (10.1016/j.euf.2017.03.013) Copyright © 2017 European Association of Urology Terms and Conditions

Fig. 2 Tumor characteristics and oncological outcomes. (A) The estimated glomerular filtration rate (eGFR) was not significantly different before and after chemotherapy in the neoadjuvant chemotherapy (NAC) group. In addition, eGFR before radical nephroureterectomy was not significantly different between the control (Ctrl) and NAC groups. (B) The median value for pathological downstaging of the primary tumor was significantly higher in the NAC group (1, interquartile range [IQR] 0–2) than in the Ctrl group (0, IQR 0–0). (C) The number of patients with lymphovascular invasion (LVI) in the surgical specimen was significantly lower in the NAC group (25%) than in the Ctrl group (53%). (D) The median MIB1 index was significantly higher in the NAC group (21%, IQR 6.9–44%) than in the Ctrl group (3.3%, IQR 1.9–12%). (E) The median MIB1 index was significantly higher in patients with relapse than in those without relapse in the NAC group (16% vs 39%) but did not differ in the Ctrl group (4.0% vs 2.4%). (F–H) There were significant differences in (F) progression-free survival, (G) cancer-specific survival, and (H) overall survival between the Ctrl and NAC groups. (I) An MIB1 index >20% was significantly associated with poor progression-free survival in the NAC group. European Urology Focus DOI: (10.1016/j.euf.2017.03.013) Copyright © 2017 European Association of Urology Terms and Conditions

Fig. 3 Oncological outcomes in patients by cN− or cN+ status. In cN− patients, neoadjuvant chemotherapy (NAC) was not significantly associated with prolonged (A) progression-free survival (p=0.099) or (B) cancer-specific survival (p=0.149). By contrast, NAC was significantly associated with prolonged (C) progression-free survival (p<0.001) and (D) and cancer-specific survival (p=0.004) in cN+ patients. European Urology Focus DOI: (10.1016/j.euf.2017.03.013) Copyright © 2017 European Association of Urology Terms and Conditions

Fig. 4 Oncological outcomes in patients with neoadjuvant GCis or GCb chemotherapy. (A) The median radiologic tumor response did not significantly differ between the GCis and GCb groups (30% vs 28%; p=0.716). (B) The MIB1 index for surgical specimens did not significantly differ between the GCis (19%) and GCb (22%) groups. (C) Before neoadjuvant chemotherapy (NAC), the mean estimated glomerular filtration rate (eGFR) was significantly lower in the GCb (52 ± 12ml/min/1.73m2) than in the GCis group (72±14ml/min/1.73m2), but did not differ between the GCb and GCis groups after radical nephroureterectomy (44 ± 10 vs 48 ± 6.0ml/min/1.73m2). (D–F) There was no significant difference in (D) progression-free survival, (E) cancer-specific survival, or (F) overall survival between the GCis and GCb groups. GCis=gemcitabine plus cisplatin; GCb=gemcitabine plus carboplatin. European Urology Focus DOI: (10.1016/j.euf.2017.03.013) Copyright © 2017 European Association of Urology Terms and Conditions