Enfortumab vedotin 合併 Pembrolizumab 做為高風險上泌尿道及膀胱泌尿道上皮癌之前導性治療：真實世界之療效與安全性分析

張家郡¹、張兆祥^1,2、吳錫金^1,2,3、楊啟瑞¹、黃志平^1,2、張議徽¹、蔡禮賢¹

¹中國醫藥大學附設醫院 泌尿部，²中國醫藥大學 醫學系，³中國醫藥大學北港附設醫院 泌尿部

Real-World Efficacy and Safety of Neoadjuvant Enfortumab Vedotin plus Pembrolizumab in High-Risk Bladder and Upper Tract Urothelial Carcinoma

Jia-Jyun Jhang¹, Chao-Hsiang Chang^1,2, Hsi-Chin Wu^1,2,3, Chi-Rei Yang¹, Chi-Ping Huang^1,2, Yi-Huei Chang¹, Li-Hsien Tsai¹

¹Department of Urology, China Medical University Hospital, Taichung, Taiwan; ² School of Medicine, China Medical University, Taichung, Taiwan; ³Department of Urology, China Medical University Beigang Hospital, Yunlin, Taiwan

Purpose: The combination of Enfortumab Vedotin (EV) and Pembrolizumab has established a new standard of care in metastatic urothelial carcinoma (UC) following landmark phase 3 results. While clinical trials are currently investigating this regimen in the perioperative setting, real-world evidence remains limited. This study aims to evaluate the efficacy and safety of neoadjuvant EV plus Pembrolizumab in a real-world cohort of patients with high-risk bladder and upper tract UC.

Materials and Methods: We retrospectively reviewed UC patients treated with neoadjuvant EV plus Pembrolizumab at a tertiary medical center between September 2023 and February 2026. Inclusion criteria for bladder UC were clinical stage ≥T2 or node-positive (cN+) disease. For upper tract UC (UTUC), inclusion required ≥T3 or cN+ disease. Patients who did not undergo subsequent surgery (cystectomy or radical nephroureterectomy) following neoadjuvant therapy were excluded. Primary outcomes included pathological complete response (pCR, ypT0N0), and event-free survival (EFS). Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE).

Results: 18 patients were included (8 males, 10 females; median age 70 years, IQR 63–78). The cohort comprised 4 patients with UTUC (all cN+ and ≥cT3) and 14 with bladder UC (3cN+; 10 ≥cT3). At baseline, the median creatinine clearance was 54 mL/min (IQR 31.3–67.8). Pathological complete response (pCR, ypT0N0) was achieved in 11 patients (61.1%), while one patient had ypT2, 5 had ypT3, and one had ypT4. At a median follow-up of 18.2 months (IQR 8.5–25.4), the median EFS was not yet reached. Only two events occurred: one disease progression and one mortality due to a pelvic abscess. Regarding safety, grade ≥3 AEs occurred in 5 patients (27.8%). Treatment modifications included dose reductions (n=2), treatment delay (n=1), and one treatment withdrawal due to severe skin rash after the first cycle.

Conclusions: Neoadjuvant EV plus Pembrolizumab demonstrates robust real-world efficacy with a 61.1% pCR rate in high-risk urothelial carcinoma, including node-positive and UTUC cases. The regimen appears feasible and maintains a manageable safety profile, even in patients with borderline renal function. Our findings suggest that EV plus Pembrolizumab is a highly effective neoadjuvant strategy; however, further investigation is warranted to evaluate long-term survival outcomes and to determine whether adjuvant therapy is necessary for patients after surgery.