BCG抵抗性表在性膀胱癌の治療:膀胱温存の立場から

Abstract

膀胱上皮内癌(CIS)診断された93例に, BCG膀胱内注入療法を施行し, 3ヵ月時の治療効果判定で85例にCRを得た.うち17例は平均21.2ヵ月後に再発を来した.初回BCG注入療法で抵抗性があった16例に再注入療法を行ったところ, 初回療法後の残存腫瘍が7例, 再発腫瘍が9例であった.3ヵ月時の治療効果判定で15例がCRを得た.うち6例が平均28.2ヵ月後に膀胱への再発を来したが, 腫瘍進展や上部尿路再発は認めなかった.一方, BCG抵抗性表在性膀胱癌で膀胱全摘出術の適応とならない4例にゲムシタビン膀胱内注入療法を施行したが, 1例は原発性CIS, 2例はCISとT1腫瘍の合併で, BCG療法2～4コース後の再発例であった.残る1例は多発性Ta腫瘍の頻回再発例であるが, 直腸癌に対する化学療法中で, BCG療法の効果が期待できないと判断された.2例でCRが得られ, 15ヵ月および14ヵ月まで無病状態が維持されている.他の2例では乳頭状腫瘍の再発を認めたが, うち1例は高齢と副作用のため注入は6回で中止されていた

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.