童綜合醫院 外科部 泌尿科
Neoadjuvant immunotherapy as Nivolumab and Ipilimumab for muscle invasive urothelial bladder cancer: preliminary report of single hospital
Yu-Feng Chuang, Li-Hua Huang, Wei-Chun Weng, Yi-Sheng Lin, Chao-Yu Hsu, Yen-Chuan Ou, Min-Che Tung
Divisions of Urology, Department of Surgery, Tungs’ Taichung Metro Harbor Hospital
Neoadjuvant chemotherapy with following radical cystectomy is the standard treatment for muscle invasive urothelial bladder cancer. The outcome of neoadjuvant immunotherapy as ipilimumab and nivolumab with following partial cystectomy or radical cystsctomy are still under investigation.
Materials & methods:
Total 10 patients with muscle invasive urothelial bladder cancer proved by transurethral resection of bladder tumor were enrolled from Febuary 2019 to June 2020. There were 7 patients finished neoadjuvant immunotherapy with following cystoscopy, partial cystectomy or radical cystectomy. The other 3 patients were still in the neoadjuvant treatment and outcome was temporarily unavailable. This clininal trail was hosted by ONO pharma and investigated outcomes of 4 course neoadjuvant immunotherapy as NIVO 1 mg/kg + IPI 3 mg/kg for 4 doses Q3W with following cystectomy in muscle invasive bladder cancer patient. This study was conducted at Tung's Taichung MetroHarbor Hospital with certification of approval with IRB No.: 107020
There were two patients didn’t complete 4 courses neoadjuvant immunotherapy (1 patient stroke after two courses neoadjuvant and 1 patient had severe hepatic adverse effect). There were 5 patient received radical cystectomy, 1 patient received partial cystectomy and 1 patient who was stroked followed up with cystoscopy (complete response). The pathology reports revealed 3 patients had complete response, 3 patients had partial response and 1 patient had progressive disease. The complete response rate is 42.8% and total response rate is 85.7%. The largest tumor diameter average is 3.49cm (range 1.2~5.3cm) before treatment, and the diameter average became 1.27 cm after neoadjuvant immunotherapy (range 0~5cm including one PD patient). If exculed the only one PD patient whose tumor diameter from 3.5cm to 5cm with prostatic invasion. The tumor diameter reduce rate can elevate to 84% (From 3.49cm to 0.56cm) in other 6 CR/PR patients. The 7 patients all had grade I to grade III adverse effects, most as skin rush (4/7, 57.1%) and diarrhea (3/7, 42.8%). One patient had grade III hepatic adverse effect as liver enzyme elevated over 700 and received only 3 courses neoadjuvant immunotherapy.
The preliminary report of neoadjuvant immunotherapy with following cystectomy showed better oncologic outcome than current standard neoadjuvant chemotherapy. The treatment of neoadjuvant immunotherapy may become one of treatment option for muscle invasive urothelial bladder cancer in the future. In addition to this, universal adverse effects of immunotherapy is also an important issue pending more research and solution.