Challenges in the treatment of bladder cancer
Challenges in the treatment of bladder cancer
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DOI：
10.1093/annonc/mdj963
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发表时间：
2006-01-01
影响因子：
50.5
通讯作者：
Kaufman, D. S.
中科院分区：
文献类型：
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作者：
Kaufman, D. S.
70%到80%的新诊断的膀胱癌患者会出现浅表肿瘤(Ta、Tis或T-1)。然而，浅表性和肌肉浸润性癌症之间有一个连续体，晚期病例通常与分化较低的组织学和非整倍体有关。常见的转移部位包括区域淋巴结、骨、肺、皮肤和肝脏。从根治性膀胱切除术的低治愈率来看，有强有力的证据表明，膀胱癌从一开始就是一种系统性疾病。局部治疗的局限性是有据可查的：放射治疗的局部控制率为30%，根治性膀胱切除术的局部控制率为50%-70%；术前放射治疗在手术治愈方面没有看到任何改善。在过去的30年里，自从首次报道顺铂治疗晚期膀胱癌的有效性以来，不断有化疗药物单独或联合使用，证明对这种肿瘤的治疗是有效的。虽然联合化疗的有效率和CR率有所提高，但这并没有转化为晚期疾病超过16个月的存活率。在继续寻找更有效的药物和组合的同时，人们也注意到了新辅助和辅助化疗的作用，以努力提高仅通过手术实现的治愈率。尽管在美国，根治性膀胱癌切除、可控性分流或重建新膀胱术仍然是美国肌肉浸润性膀胱癌患者的标准治疗方法，但有几个组织已经探索了旨在保留膀胱的治疗策略。早期以保留膀胱为目标的方法包括作为单一疗法的放射治疗(大部分被放弃)，或对较小的肿瘤进行侵袭性TURBT。在过去的20年里，马萨诸塞州总医院(MGH)和放射治疗肿瘤学小组(RTOG)利用三种治疗方法对肌肉浸润性膀胱癌患者进行了研究：明显完整的经尿道电切，然后放射治疗，同时进行放射增敏化疗，然后进行辅助化疗。因此，化疗被用于两个治疗阶段：(1)作为放射增敏剂，与放射治疗同时给予；(2)作为辅助治疗，认识到只有成功地治疗微转移才能提高存活率。根据吉西他滨/顺铂治疗晚期疾病有效性报告的初步信息，在我们最近完成和报道的早期方案之一中，该联合方案被选为辅助方案。我们目前的方案使用Bellmunt方案作为我们的辅助方案，在晚期疾病中具有最高的RR。这项研究正在进行中，早期关于三种药物方案耐受性的报告令人鼓舞。侵袭性膀胱固有肌瘤的治疗方法大致可分为保留膀胱和切除膀胱。在美国，根治性膀胱切除加盆腔淋巴清扫是治疗这种肿瘤的标准方法。
Seventy to eighty percent of patients with newly-diagnosed bladder cancer will present with superficial tumors (Ta, Tis or T-1). There is, however, a continuum between superficial and muscle-invasive cancer, with the advanced cases usually associated with less-differentiated histology and aneuploidy. Common sites of metastasis include regional lymph nodes, bone, lung, skin and liver. From the low cure rates achieved with radical cystectomy, there is strong evidence that bladder cancer, from the outset, is a systemic disease. The limitations of local treatment are well-documented: a local control rate of 30% with radiation treatment, and 50-70% with radical cystectomy; and no improvement in surgical cure was seen with the use of preoperative radiation. Over the past 30 years, since the initial reports of the effectiveness of cisplatin in the treatment of advanced bladder cancer, there has been a steady flow of chemotherapeutic agents, singly and in combination, shown to be effective in the treatment of this tumor. While response rates and CR rates have increased with the use of combination chemotherapy, this has not translated into survival in advanced disease of greater than 16 months. While the search for more effective agents and combinations continues, attention has also been given to the roles of neoadjuvant and adjuvant chemotherapy in an effort to improve the cure rate achieved with surgery alone. Although radical cystectomy, with continent diversion or neobladder construction in selected cases remains the standard of care in the United States for patients with muscle-invasive bladder cancer, several groups have explored therapeutic strategies that aim at bladder preservation. Early approaches with the goal of bladder preservation consisted of radiation treatment as monotherapy (largely abandoned) or aggressive TURBT for smaller tumors. Over the past 20 years, the Massachusetts General Hospital (MGH) and the Radiation Therapy Oncology Group (RTOG) have studied patients with muscle-invading bladder cancer utilizing tri-modality treatment: a visibly complete transurethral resection followed by radiation with concurrent radiosensitizing chemotherapy and, subsequently, adjuvant chemotherapy. Thus, chemotherapy has been used in two phases of treatment (1) as radiosensitizers, given concurrently with radiation treatment and ( 2) as adjuvant treatment, recognizing that survival will only be improved by the successful treatment of micrometastases. Based on preliminary information from reports of the effectiveness of gemcitabine/cisplatin in advanced disease, that combination was chosen as the adjuvant regimen in one of our earlier protocols, recently completed and reported. Our current protocol utilizes the Bellmunt regimen as our adjuvant program with the highest RR in advanced disease. This study is ongoing, with early reports of tolerance of the three-drug regimen encouraging. The treatment options for muscularis propria-invasive bladder tumors can broadly be divided into those that spare the bladder and those that involve removing it. In the United States, radical cystectomy with pelvic lymph node dissection is the standard method used to treat patients with this tumor.