前導性免疫治療對肌肉侵犯型膀胱泌尿上皮癌之治療結果

邱亮維、張兆祥、黃志平、楊啟瑞、吳錫金、陳冠亨、蔡禮賢、方仁愷、楊有容

中國醫藥大學附設醫院 泌尿部

The outcome of neoadjuvant immunotherapy for muscle-invasive urinary bladder urothelial carcinoma: single-center experience

Liang-Wei Chiu, Chao-Hsiang Chang, Chi-Ping Huang, Chi-Rei Yang, Hsi-Chin Wu, Guan-Heng Chen, Li-Hsien Tsai, Jen-Kai Fang, You-Rong Yang

Department of Urology, China Medical University Hospital, Taichung, Taiwan

Introduction: According to National Comprehensive Cancer Network (NCCN) and European Association of Urology (EAU) guideline, neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) is suggested for cases with muscle-invasive urinary bladder urothelial carcinoma (MIBC) without distal metastasis. NAC increases overall survival (OS) 5-6% and cancer-specific survival (CSS) 5-10% for MIBC compared to RC alone, and cisplatin-base chemotherapy is the first choice. In addition, with development of PD-(L)1 inhibitor in urothelial carcinoma (UC), some clinical trials aim to figure out the role of neoadjuvant treatment with immunotherapy (IO) in MIBC. In ABACUS trial, a phase 2 trial, neoadjuvant IO with atezolizumab has about 31% complete response. In PURE-01 trial, a phase 2 trial, 37% complete response is noted for neoadjuvant IO with Pembrolizumab. And, in a phase 3 trial (NABUCCO trial), neoadjuvant IO with Nivolumab plus Ipilimumab reaches 46% complete response. We aimed to report our experience of neoadjuvant IO in cases with MIBC undergoing RC.

Materials and Methods: From May 2018 to December 2022, in a single center, with at least 7 months follow-up, we recruited 20 cases with MIBC who underwent RC following neoadjuvant IO with/without chemotherapy. MIBC was diagnosed via histology of specimen resected by transurethral resection (TUR). The clinical stage of bladder cancer was defined by computerized tomography (CT) scan or magnetic resonance imaging (MRI). We defined pathologic downstaging as ≤ypT1N0 at RC. The outcome was progression-free survival (PFS) and OS. All the statistical analysis was performed with SPSS 25.0.

Results: Among the patients, the mean age was 69.8±7.36 years, and 60% of cases was male. cT2, cT3 and cT4 were reported as 20%, 55% and 25%, respectively. Only one patient (5%) was cN2. Neoadjuvant IO with Durvalumab was used in most of the patients (n=11; 55%), followed by Nivolumab (n=6; 30%) and Pembrolizumab (n=3; 15%). It may combine with chemotherapy, such as gemcitabine plus cisplatin (n=17; 85%), gemcitabine plus carboplatin (n=1; 5%) and gemcitabine plus oxaliplatin (n=1; 5%). After the last cycles of neoadjuvant treatment and a mean time of 24.8 days, all of patients underwent robotic assisted laparoscopic RC with urinary diversion. Overall, 50%, 15%, 15%, and 20% of the patients were reported as ≦ypT1, ypT2, ypT3, and ypT4, respectively. The mean number of lymph node extraction was 29.5. Seventeen patients (85%) were ypN0; 1 patient (5%) was ypN1; and 2 patients (10%) were ypN3. Ten patients (50%) achieved pathologic downstaging. Eight patients (40%) achieved pathologic complete response (pCR), and 4 patients (20%) had partial response. Five patients (25%) were under stable disease (SD), but 3 patients (15%) had progression disease (PD). LN recurrence companied with distal metastasis occurred in three patients (15%) after a mean postoperative follow-up of 3.3 month. PFS was 27.1 ± 15.75 months, and OS was 29.6 ± 14.39 months.

Conclusions: Neoadjuvant treatment with IO plus cisplatin-based chemotherapy seems to have better pCR than neoadjuvant treat with chemotherapy alone reported in previous systemic review study (40% vs. 25.1-35.2%). It also has similar pathologic downstaging rate to the neoadjuvant chemotherapy alone. Only 15% of patients has PD after neoadjuvant IO plus chemotherapy. Therefore, neoadjuvant IO plus chemotherapy approaches are safe and enhance the efficacy for cases with MIBC undergoing RC.