Department of Urology, Free University Medical Centre, Amsterdam, The Netherlands.
Anticancer Res. 2013 May;33(5):2099-105.
Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour.
Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania). In Krakow the tumours were treated with incomplete transurethral resection (TUR) leaving a marker tumour of 0.5-1.0-cm followed by IL-2 instillations (3 × 10(6) IU IL-2) on five consecutive days. In Vilnius the tumours were treated with complete TUR, followed by IL-2 instillations (9 × 10(6) IU IL-2) on five consecutive days.
During 30 months follow-up, the recurrence-free survival was 5/10 (50%) and 6/26 (23%) after incomplete and complete TUR, respectively. So, the ratio of the recurrence-free survival after incomplete/complete TUR of 50/23=2.2. The median of the recurrence-free survival is >20.5 months and 7 months after incomplete and complete TUR, respectively. So, this ratio was >20.5/7= >2.9. The hazard ratio which combines both the chance of the disease recurrence and its timing for both censored and uncensored cases was 0.53, again confirming the better outcome after incomplete TUR.
A possible explanation for the better therapeutic effects after incomplete TUR compared with complete TUR is that the marker tumour has tumour-associated antigens (TAA) that could lead to an immune reaction that is stimulated by local application of IL-2. After complete TUR, no TAA are available to initiate and to stimulate an immune reaction; consequently, local IL-2 therapy is less effective after complete TUR. The results of these two pilot studies have led to the recent start of a randomised prospective clinical trial in which therapeutic effects of local IL-2 therapy after complete and incomplete TUR are compared.
比较膀胱内白细胞介素-2（IL-2）灌注治疗存在和不存在标记肿瘤的非肌肉浸润性膀胱癌（NMIBC）的治疗效果。
对 NMIBC 患者进行了两项初步研究。第一项研究（10 例患者）在克拉科夫（波兰）进行，第二项研究（26 例患者）在维尔纽斯（立陶宛）进行。在克拉科夫，肿瘤采用不完全经尿道电切术（TUR）治疗，留下 0.5-1.0 厘米的标记肿瘤，然后连续 5 天进行 IL-2 灌注（3×106 IU IL-2）。在维尔纽斯，肿瘤采用完全 TUR 治疗，然后连续 5 天进行 IL-2 灌注（9×106 IU IL-2）。
在 30 个月的随访期间，不完全 TUR 后无复发生存率为 5/10（50%），完全 TUR 后为 6/26（23%）。因此，不完全/完全 TUR 后无复发生存率之比为 50/23=2.2。不完全和完全 TUR 后无复发生存的中位时间分别为>20.5 个月和 7 个月。因此，该比率为>20.5/7=>2.9。综合考虑疾病复发的可能性和时间因素，对有和无删失病例的风险比为 0.53，再次证实不完全 TUR 的治疗效果更好。
与完全 TUR 相比，不完全 TUR 治疗效果更好的可能解释是，标记肿瘤具有肿瘤相关抗原（TAA），可引发由局部应用 IL-2 刺激的免疫反应。完全 TUR 后，没有 TAA 可用于启动和刺激免疫反应；因此，完全 TUR 后局部 IL-2 治疗效果较差。这两项初步研究的结果促使最近开始了一项随机前瞻性临床试验，比较完全和不完全 TUR 后局部 IL-2 治疗的疗效。
