Department of Surgery/Urology, Tor Vergata University, Rome, Italy.
Lancet Oncol. 2011 Sep;12(9):871-9. doi: 10.1016/S1470-2045(11)70190-5. Epub 2011 Aug 8.
The clinical effect of intravesical instillation of chemotherapy immediately after transurethral resection of bladder tumours (TURBT) has recently been questioned, despite its recommendation in guidelines. Our aim was to compare TURBT alone with immediate post-TURBT intravesical passive diffusion (PD) of mitomycin and immediate pre-TURBT intravesical electromotive drug administration (EMDA) of mitomycin in non-muscle invasive bladder cancer.
We did a multicentre, randomised, parallel-group study in patients with primary non-muscle invasive bladder cancer in three centres in Italy between Jan 1, 1994, and Dec 31, 2003. Patients were randomly assigned to receive treatment by means of stratified blocked randomisation across six strata. Patients and physicians giving the interventions were aware of assignment, but it was masked from outcome assessors and data analysts. Patients were randomly assigned to receive TURBT alone, immediate post-TURBT instillation of 40 mg PD mitomycin dissolved in 50 mL sterile water infused over 60 min, or immediate pre-TURBT instillation of 40 mg EMDA mitomycin dissolved in 100 mL sterile water with intravesical 20 mA pulsed electric current for 30 min. Our primary endpoints were recurrence rate and disease-free interval. Analyses were done by intention to treat. Follow-up for our trial is complete. This study is registered with ClinicalTrials.gov, number NCT01149174.
124 patients were randomly assigned to receive TURBT alone, 126 to receive immediate post-TURBT PD mitomycin, and 124 to receive immediate pre-TURBT EMDA mitomycin. 22 patients were excluded from our analyses because they did meet our eligibility criteria after TURBT: 11 had stage pT2 disease and 11 had carcinoma in situ. Median follow-up was 86 months (IQR 57-125). Patients assigned to receive EMDA mitomycin before TURBT had a lower rate of recurrence (44 [38%] of 117) than those assigned to receive PD mitomycin after TURBT (70 [59%] of 119) and TURBT alone (74 [64%] of 116; log-rank p<0·0001). Patients assigned to receive EMDA mitomycin before TURBT also had a higher disease-free interval (52 months, IQR 32-184) than those assigned to receive PD mitomycin after TURBT (16 months, 12-168) and TURBT alone (12 months, 12-37; log-rank p<0·0001). We recorded persistent bladder symptoms after TURBT in 18 (16%) of 116 patients in the TURBT-alone group (duration 3-7 days), 37 (31%) of 119 in the PD mitomycin post-TURBT group (duration 20-30 days), and 24 (21%) of 117 in the EMDA mitomycin pre-TURBT group (duration 7-12 days); haematuria after TURBT in eight (7%) of 116 patients in the TURBT-alone group, 16 (13%) of 119 in the PD mitomycin post-TURBT group, and 11 (9%) of 117 in the EMDA mitomycin pre-TURBT group; and bladder perforation after TURBT in five (4%) of 116 patients in the TURBT-alone group, nine (8%) of 119 in the PD mitomycin post-TURBT group, and seven (6%) of 117 in the EMDA mitomycin pre-TURBT group.
Intravesical EMDA mitomycin before TURBT is feasible and safe; moreover, it reduces recurrence rates and enhances the disease-free interval compared with intravesical PD mitomycin after TURBT and TURBT alone.
None.
尽管指南推荐，但经尿道膀胱肿瘤切除术（TURBT）后即刻膀胱内化疗的临床效果最近受到了质疑。我们的目的是比较 TURBT 单独治疗与 TURBT 后即刻膀胱内被动扩散（PD）丝裂霉素和 TURBT 前即刻膀胱内电动力药物给药（EMDA）丝裂霉素在非肌肉浸润性膀胱癌中的作用。
我们在意大利的三个中心进行了一项多中心、随机、平行组研究，纳入了原发性非肌肉浸润性膀胱癌患者。患者按照分层随机分组，分为 6 个组。患者和给予干预措施的医生知道分组情况，但结果评估者和数据分析者对此不知情。患者被随机分配接受 TURBT 单独治疗、TURBT 后即刻膀胱内 40mg PD 丝裂霉素（溶于 50ml 无菌水，60 分钟内注入）或 TURBT 前即刻膀胱内 40mg EMDA 丝裂霉素（溶于 100ml 无菌水，20mA 脉冲电流 30 分钟）。我们的主要终点是复发率和无病间隔。分析采用意向治疗。我们的试验随访已经完成。本研究在 ClinicalTrials.gov 注册，编号为 NCT01149174。
124 例患者被随机分配接受 TURBT 单独治疗，126 例接受 TURBT 后即刻 PD 丝裂霉素膀胱内灌注，124 例接受 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注。22 例患者在 TURBT 后因不符合我们的纳入标准而被排除出我们的分析：11 例患者为 pT2 期疾病，11 例患者为原位癌。中位随访时间为 86 个月（IQR 57-125）。与接受 TURBT 后即刻 PD 丝裂霉素膀胱内灌注的患者（70[59%]例）和 TURBT 单独治疗的患者（74[64%]例）相比，接受 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注的患者（44[38%]例）复发率更低（对数秩检验 p<0.0001）。与接受 TURBT 后即刻 PD 丝裂霉素膀胱内灌注的患者（16 个月，12-168）和 TURBT 单独治疗的患者（12 个月，12-37）相比，接受 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注的患者无病间隔更长（52 个月，32-184）（对数秩检验 p<0.0001）。我们记录了 TURBT 后膀胱持续存在的症状（18[16%]例），在 TURBT 单独治疗组（持续 3-7 天），在 TURBT 后即刻 PD 丝裂霉素膀胱内灌注组（持续 20-30 天），在 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注组（持续 7-12 天）； TURBT 后血尿（8[7%]例），在 TURBT 单独治疗组，在 TURBT 后即刻 PD 丝裂霉素膀胱内灌注组，在 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注组； TURBT 后膀胱穿孔（5[4%]例），在 TURBT 单独治疗组，在 TURBT 后即刻 PD 丝裂霉素膀胱内灌注组，在 TURBT 前即刻 EMDA 丝裂霉素膀胱内灌注组。
与 TURBT 后即刻膀胱内 PD 丝裂霉素相比，TURBT 前即刻膀胱内 EMDA 丝裂霉素是可行且安全的；此外，与 TURBT 后即刻膀胱内 PD 丝裂霉素和 TURBT 单独治疗相比，它可降低复发率并延长无病间隔。
无。
