Outcomes of patients with stage II/IIIA urothelial bladder cancer treated with systemic therapy: A 13-year single-center experience.

e16586 Background: Optimal management of stage II/IIIA urothelial bladder cancer (UBC) continues to evolve, with neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) considered a standard approach. We aim to evaluate the impact of various treatment strategies, particularly NAC regimens, on overall survival (OS) and progression-free survival (PFS) in a real-world cohort. Methods: We retrospectively analyzed all patients with stage II/IIIA (T2-4a, N0-1, M0) UBC treated at the Cleveland Clinic from 1/2010-12/2022. Patient demographics, clinical characteristics, and treatment details were collected. Treatment response was assessed using RECIST 1.1 criteria. Cox regression models assessed associations between treatment, patient factors, and survival. Results: We identified 390 patients, with a median age of 68 years (IQR 61-74), 80% males, 92% white, 23% never smokers, and 90% with ECOG 0-1. The treatment approaches were 1. NAC followed by radical cystectomy (RC) (n=248, 64%), 2. bladder preservation with concurrent chemoradiotherapy (CRT) (67, 17%), 3. systemic therapy without definitive local therapy (56, 14%) and 4. surgery followed by adjuvant chemotherapy (19, 4.9%). NAC regimens included: cisplatin/gemcitabine (159, 64%), methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) (48, 19%) and NAC followed by immune therapy (IT) (17, 7.3%). Median follow-up was 62.1 months. The 5-year OS and PFS were 62% and 54%, respectively with an overall response rate of 79%. Table 1 shows OS and PFS by NAC regimen. In multivariable analyses, when compared to cisplatin/gemcitabine, MVAC was associated with improved OS (HR 0.27, 95% CI 0.11-0.68, p<0.001) and PFS (HR 0.39, 95% CI 0.19-0.843, p=0.017). NAC followed by IT did not demonstrate a significant survival advantage compared to NAC cisplatin/gemcitabine. Bladder preservation + CRT and systemic therapy without definitive local therapy were associated with significantly worse OS and PFS compared to NAC+RC (P<0.05). Among patients who underwent surgery, there was no significant difference in OS between those who underwent cystectomy and radical cystectomy (HR 0.64, 95% CI 0.35-1.15, p=0.14), or standard lymph node dissection compared to extended (HR 1.07, 95% CI 0.68-1.70, p=0.8). Conclusions: In this retrospective study, neoadjuvant MVAC followed by RC was associated with significantly improved OS and PFS compared to other treatments in stage II/IIIA UBC. Our study was not powered enough to determine the exact outcomes of NAC followed by IT. We found that type of cystectomy and LN dissection level did not impact OS or PFS. OS and PFS estimates of NAC regimen in stage II/IIIA urothelial bladder cancer. Characteristic 2-year OS 5-year OS 2-year PFS 5-year PFS Neoadjuvant chemo Carboplatin, Gemcitabine 88% 58% 71% 54% Cisplatin, Gemcitabine 82% 73% 76% 68% IT + Chemo 83% 69% 73% 59% MVAC 94% 91% 91% 83%