Department of Surgical Sciences, Division of Urology, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Department of Urology, Medical University of Vienna, Vienna, Austria.
Curr Opin Urol. 2020 Jul;30(4):542-546. doi: 10.1097/MOU.0000000000000789.
The treatment of bacillus Calmette-Guérin (BCG) unresponsive disease remains a challenge for urooncologists. The search for effective conservative treatments is ongoing and several new agents have been recently tested for this purpose. The aim of this manuscript was to review the last developments in this interesting field.
The advent of systemic immunotherapy in the nonmuscle invasive setting promise to revolutionize the paradigm of treatment of BCG unresponsive disease. The preliminary results of the Keynote-057 trial (3 months complete response of 41% in carcinoma-in-situ patients) have led to the rapid approval of pembrolizumab from the Food and Drug Administration. Interesting results have been reported for gene therapies such as those with CG0700 and Adstiladrin, nonreplicating adenovirus able to increase the 'in situ' antitumor activity. However, larger prospective trials with longer follow-up are needed to confirm the initial findings.
In summary, early radical cystectomy remains the standard treatment for BCG unresponsive patients. However, in case of patients unfit for or refusing radical cystectomy, the bladder-sparing options are continuously increasing. Although BCG-reinduction (with or without interferon) and traditional intravesical chemotherapy may represent the past, the present and the future are characterized by device-assisted therapies, systemic immunotherapy, and gene therapy.
卡介苗(BCG)无应答疾病的治疗仍然是泌尿科肿瘤医生面临的挑战。目前正在寻找有效的保守治疗方法,最近已经有几种新的药物被用于该目的。本文旨在综述该领域的最新进展。
系统免疫疗法在非肌肉浸润性疾病中的应用有望彻底改变 BCG 无应答疾病的治疗模式。Keynote-057 试验的初步结果(原位癌患者的完全缓解率为 41%)导致 pembrolizumab 迅速获得美国食品和药物管理局的批准。基因疗法如 CG0700 和 Adstiladrin 等也取得了有趣的结果,这些疗法使用非复制型腺病毒能够增加“原位”抗肿瘤活性。然而,需要更大规模的前瞻性试验和更长时间的随访来证实最初的发现。
总之,早期根治性膀胱切除术仍然是 BCG 无应答患者的标准治疗方法。然而,对于不适合或拒绝根治性膀胱切除术的患者,保留膀胱的选择不断增加。虽然 BCG 再诱导(联合或不联合干扰素)和传统的膀胱内化疗可能代表过去,但现在和未来的特点是设备辅助治疗、系统免疫疗法和基因疗法。