McElree Ian M, Packiam Vignesh T, Steinberg Ryan L, Mott Sarah L, Gellhaus Paul T, Nepple Kenneth G, O'Donnell Michael A
Carver College of Medicine, University of Iowa, Iowa City, Iowa.
Department of Urology, University of Iowa, Iowa City, Iowa.
J Urol. 2022 Nov;208(5):969-977. doi: 10.1097/JU.0000000000002848. Epub 2022 Jul 5.
Intravesical gemcitabine-docetaxel has emerged as an efficacious and well-tolerated salvage therapy for non-muscle-invasive bladder cancer. However, further rescue therapies are needed for subsequent recurrences or intolerance, particularly when cystectomy is refused or precluded. Valrubicin is a U.S. Food and Drug Administration-approved agent for bacillus Calmette-Guérin unresponsive disease, yet as monotherapy has demonstrated poor efficacy. We report our experience with sequential intravesical valrubicin and docetaxel as a rescue therapy for non-muscle-invasive bladder cancer.
We retrospectively identified all patients with recurrent non-muscle-invasive bladder cancer treated with valrubicin and docetaxel between April 2013 and June 2021. Patients received weekly sequential intravesical instillations of 800 mg valrubicin and 37.5 mg docetaxel for 6 weeks. If disease-free at first follow-up, monthly maintenance of 2 years was initiated. The primary outcome was recurrence-free survival, assessed using the Kaplan-Meier method.
The analysis included 75 patients with median follow-up of 21 months (IQR: 13-37). Twelve patients with low-grade disease had a 73% recurrence-free survival at 2 years. Sixty-three patients with recurrent high-grade disease had a 38% 2-year high-grade recurrence-free survival. Forty-two (56%) patients had carcinoma in situ present; recurrence-free survival was similar for those with and without carcinoma in situ ( = .63). Two patients died of metastatic bladder cancer while 10 underwent cystectomy. Among patients with high-grade disease, overall, cancer-specific, and cystectomy-free survivals were 87%, 96%, and 84% at 2 years, respectively. Adverse events included bladder spasms (n = 18), urinary frequency (n = 10), and dysuria (n = 8). Two patients could not tolerate valrubicin and docetaxel induction.
In a heavily pretreated population, our results suggest valrubicin and docetaxel is an effective rescue treatment for patients with recurrent non-muscle-invasive bladder cancer. Further prospective evaluation is needed.
膀胱内注射吉西他滨-多西他赛已成为一种治疗非肌层浸润性膀胱癌的有效且耐受性良好的挽救疗法。然而，对于后续复发或不耐受的情况，尤其是当患者拒绝或不适合进行膀胱切除术时，还需要进一步的挽救治疗。表柔比星是一种经美国食品药品监督管理局批准用于卡介苗无反应性疾病的药物，但作为单一疗法疗效不佳。我们报告了我们使用序贯膀胱内注射表柔比星和多西他赛作为非肌层浸润性膀胱癌挽救治疗的经验。
我们回顾性确定了2013年4月至2021年6月期间所有接受表柔比星和多西他赛治疗的复发性非肌层浸润性膀胱癌患者。患者每周序贯膀胱内灌注800毫克表柔比星和37.5毫克多西他赛，持续6周。如果首次随访时无疾病复发，则开始为期2年的每月维持治疗。主要结局是无复发生存率，采用Kaplan-Meier方法进行评估。
分析纳入了75例患者，中位随访时间为21个月（四分位间距：13 - 37个月）。12例低级别疾病患者2年无复发生存率为73%。63例复发性高级别疾病患者2年高级别无复发生存率为38%。42例（56%）患者存在原位癌；有原位癌和无原位癌患者的无复发生存率相似（P = 0.63）。2例患者死于转移性膀胱癌，10例接受了膀胱切除术。在高级别疾病患者中，总体、癌症特异性和无膀胱切除生存率在2年时分别为87%、96%和84%。不良事件包括膀胱痉挛（n = 18）、尿频（n = 10）和排尿困难（n = 8）。2例患者无法耐受表柔比星和多西他赛诱导治疗。
在经过大量预处理的患者群体中，我们的结果表明表柔比星和多西他赛是复发性非肌层浸润性膀胱癌患者的一种有效挽救治疗方法。需要进一步进行前瞻性评估。
