案例報告: 讓局部晚期合併鱗狀上皮細胞分化之膀胱癌，能夠保留膀胱的治療選擇

葉星佐、羅浩倫

高雄長庚紀念醫院泌尿科

Case Report: A Bladder Preserving Alternative for Locally Advanced Bladder Cancer with Squamous Differentiation

Hsing-Tsuo, Yeh, Hao-Lun Luo

Kaohsiung Chang Gung Memorial Hospital, Department of Urology

Introduction: Neoadjuvant chemotherapy followed by radical cystectomy is the standard treatment for muscle-invasive bladder cancer (MIBC). Despite receiving aggressive treatments, more than 40% of MIBC patients still underwent recurrence or death within 3 years. Growing evidence has shown improved complete response rate and survival with neoadjuvant chemoimmunotherapy. Here, we present a case of MIBC, cT3N1 with squamous differentiation, who responded incredibly well to neoadjuvant Gencitabine, Cisplatin, and Pembrolizumab and partial cystectomy.

Case Report:  This 54-year-old man has no known underlying disease. He was presented with urinary frequency, urgency, nocturia (4-5 times per night), dysuria, and blood clots in urine for months. Thus, he went to local medical department for first aid, where bladder sonography revealed bladder mass, then was referred to our outpatient department for further managements. Physical exams were unremarkable. Urine analysis showed hematuria (RBC>500/uL), blood tests reported hypokalemia (K 3.4 mEq/L). CT urography showed bladder tumor over left anterior wall up to 1.9cm with perivesicular invasion and left pelvic lymph node metastasis, cT3N1 (AJCC 8^th edition).

Transurethral resection of bladder tumor(TURBT) was done, and pathology revealed high grade urothelial carcinoma with squamous differentiation and muscle invasion. In the next 2 months, he received 4 cycles of neoadjuvant chemoimmunotherapy with Gencitabine + Cisplatin + Pembrolizumab and experienced little side effects of only mild nausea and decreased appetite. CT urography followed up in the 3^rd month showed regression of bladder mass and pelvic lymph node. Second TURBT and partial cystectomy with pelvic lymph nodes dissection were arranged in the same month, with pathology revealing negative for malignancy. Throughout the next following 2.5 years, no recurrence was noted under routine examinations with fibrocystoscopy and CT urography. This patient has achieved complete response of bladder cancer so far.

Discussion: There is an increased interest in bladder-preserving strategies such as partial cystectomy with neoadjuvant therapy due to downsides of radical cystectomy. According to literature review, it not only effect quality of life, but also has high rates of short-term complications (27–32%), long-term complications (64%), and mortality (1.5–5%). In highly selected patients, PC may provide reasonable oncological outcomes. The ideal candidates for partial cystectomy are patients with a solitary lesion < 3–4 cm, where excision of 2 cm margins is feasible (such as the bladder dome), and there is no concomitant CIS, no need for ureteral re-implantation, and no hyper-contractility of the bladder.

        Several single armed studies have shown a high response rate of chemoimmunotherapy in MIBC in the neoadjuvant era, with pathological complete response rates of 30-44% and downstaging to non-muscle invasive disease in 50-66%. Furthermore, several large ongoing randomized trial investigating combination chemoimmunotherapy in MIBC are being conducted. No previous research has directly compared outcomes between partial cystectomy and radical cystectomy after neoadjuvant chemo-immunotherapy. In carefully selected patients, partial cystectomy following neoadjuvant chemo-immunotherapy is a feasible choice for those seeking quality of life or patients unsuitable for radical cystectomy. Here, we present one of the many cases in Kaohsiung Chang Gung Memorial Hospital, who underwent neoadjuvant chemoimmunotherapy with partial cystectomy and result in good oncologic outcome to date. Further investigation regarding tumor recurrence rate and overall survival is still needed with long term follow up.