Department of Urology, Hadassah Hebrew University Hospital, Jerusalem, Israel.
J Urol. 2010 May;183(5):1678-84. doi: 10.1016/j.juro.2009.12.104. Epub 2010 Mar 17.
In marker lesion experiments a single bladder tumor is deliberately left unresected for later ablation by intravesical instillation of a novel agent. While the benefits are clear, eg the opportunity to examine the effect of therapy on measurable disease, the safety and medical ethics of these experiments are less obvious. We review the goals, inclusion criteria, definition of success, agents used, effectiveness, safety and ethics of marker lesion studies, and suggest a framework for future experiments.
Published bladder cancer studies using the marker lesion concept were identified with a MEDLINE search through March 2009.
A total of 23 well documented marker lesion studies were identified involving more than 1,200 patients. Most agents studied were cytotoxins (mitomycin-C, epirubicin, gemcitabine, valrubicin, apaziquone) or immune response modifiers (bacillus Calmette-Guerin, tumor necrosis factor-alpha, interferon-alpha, granulocyte-macrophage colony-stimulating factor). The highest complete response rate in intermediate risk patients (67%) was attained with apaziquone. Patients who achieved a complete response with this agent also had a prophylactic benefit with a 2-year recurrence-free rate of 45.2% compared to 26.7% in those who did not achieve a complete response. The complete response rate in bacillus Calmette-Guerin trials ranged from 32% to 61%. Marker lesion experiments were deemed safe with progression to T2 disease in only 7 patients (0.6%) and only when high risk patients were selected.
Marker lesion studies are most appropriate for the evaluation of novel anticancer therapeutics. Only patients with multiple recurrent, noninvasive, low grade tumors (intermediate risk) should be recruited. Primary end points should be complete response and recurrence rates after 2 to 3 years.
在标记病变实验中，为了通过膀胱内灌注一种新的药物来对单个膀胱肿瘤进行故意未切除的后续消融，故意留下单个膀胱肿瘤不切除。虽然其好处显而易见，例如有机会检查治疗对可测量疾病的效果，但这些实验的安全性和医学伦理学问题就不那么明显了。我们对标记病变研究的目的、纳入标准、成功定义、使用的药物、疗效、安全性和伦理学进行了回顾，并对未来的实验提出了一个框架。
通过 2009 年 3 月前的 MEDLINE 搜索，确定了使用标记病变概念的膀胱癌研究。
总共确定了 23 项有充分记录的标记病变研究，涉及 1200 多名患者。研究中使用的大多数药物都是细胞毒素（丝裂霉素 C、表柔比星、吉西他滨、戊柔比星、阿帕齐喹酮）或免疫反应调节剂（卡介苗、肿瘤坏死因子-α、干扰素-α、粒细胞-巨噬细胞集落刺激因子）。在中危患者中，阿帕齐喹酮获得的完全缓解率最高（67%）。用这种药物获得完全缓解的患者也有预防作用，2 年无复发生存率为 45.2%，而未获得完全缓解的患者为 26.7%。卡介苗试验的完全缓解率在 32%至 61%之间。只有在选择高危患者时，才会出现 7 例（0.6%）进展为 T2 疾病的进展。
标记病变研究最适合评估新的抗癌治疗方法。只有那些患有多个复发性、非侵袭性、低级别肿瘤（中危）的患者才应被招募。主要终点应该是 2 至 3 年后的完全缓解率和复发率。
