deVere White Ralph W, Lara Primo N, Goldman Bryan, Tangen Cathy M, Smith David C, Wood David P, Hussain Maha H A, Crawford E David
University of California at Davis, Sacramento, California 95817, USA.
J Urol. 2009 Jun;181(6):2476-80; discussion 2480-1. doi: 10.1016/j.juro.2009.01.115. Epub 2009 Apr 16.
We conducted a phase II trial of neoadjuvant paclitaxel, carboplatin and gemcitabine as well as transurethral resection of bladder tumor to evaluate the clinical T0 (cT0) rate with paclitaxel, carboplatin and gemcitabine, and to study cystoscopic surveillance or immediate cystectomy for patients with cT0 status following chemotherapy.
Patients with T2-T4a chemotherapy and radiation naive urothelial cancer were eligible. T2+ tumor had to be diagnosed by transurethral bladder tumor resection followed by a second transurethral bladder tumor resection to confirm persistent disease within 16 weeks of the first resection. Three cycles of paclitaxel, carboplatin and gemcitabine were administered within 8 weeks of the second transurethral bladder tumor resection. Patients with cT0 status after paclitaxel, carboplatin and gemcitabine therapy could elect immediate cystectomy or cystoscopic surveillance, and those with greater than cT0 status were to undergo immediate cystectomy.
Of 77 patients 74 were assessable, and cT0 status after paclitaxel, carboplatin and gemcitabine was achieved in 34 of 74 patients (46%). Of the 34 patients with cT0 status 10 underwent immediate cystectomy, 6 of whom had persistent cancer. Persistent tumor at transurethral bladder tumor resection was seen in 28 patients (38%) and 21 underwent cystectomy. Thus, 35 of 74 patients underwent cystectomy. With a median followup of 22 months 2-year overall survival was 59% (95% CI 45, 72) and among cT0 cases it was 75% (95% CI 57, 93).
Although neoadjuvant paclitaxel, carboplatin and gemcitabine had a promising 46% cT0 rate, the study failed to meet the primary objective as there was an unacceptably high rate (60%) of persistent cancer at cystectomy in patients presumed to have pT0 status. Patients completing neoadjuvant chemotherapy should strongly consider definitive local therapy rather than cystoscopic surveillance regardless of post-chemotherapy cT0 status.
我们开展了一项关于新辅助紫杉醇、卡铂和吉西他滨以及经尿道膀胱肿瘤切除术的II期试验，以评估紫杉醇、卡铂和吉西他滨治疗后的临床T0（cT0）率，并研究化疗后cT0状态患者的膀胱镜监测或即刻膀胱切除术。
纳入未经化疗和放疗的T2 - T4a期尿路上皮癌患者。T2 + 期肿瘤必须通过经尿道膀胱肿瘤切除术诊断，随后在首次切除术后16周内进行第二次经尿道膀胱肿瘤切除术以确认疾病持续存在。在第二次经尿道膀胱肿瘤切除术后8周内给予三个周期的紫杉醇、卡铂和吉西他滨治疗。紫杉醇、卡铂和吉西他滨治疗后处于cT0状态的患者可选择即刻膀胱切除术或膀胱镜监测，而cT0状态以上的患者则接受即刻膀胱切除术。
77例患者中74例可评估，74例患者中有34例（46%）在接受紫杉醇、卡铂和吉西他滨治疗后达到cT0状态。在34例cT0状态的患者中，10例接受了即刻膀胱切除术，其中6例有持续性癌症。28例患者（38%）经尿道膀胱肿瘤切除术中发现有持续性肿瘤，21例接受了膀胱切除术。因此，74例患者中有35例接受了膀胱切除术。中位随访22个月，2年总生存率为59%（95%CI 45, 72），cT0病例中为75%（95%CI 57, 93）。
尽管新辅助紫杉醇、卡铂和吉西他滨的cT0率达46%，前景良好，但该研究未达到主要目标，因为在推测为pT0状态的患者中，膀胱切除术中持续性癌症的发生率高得令人无法接受（60%）。完成新辅助化疗的患者，无论化疗后cT0状态如何，都应强烈考虑确定性局部治疗而非膀胱镜监测。
