McElree Ian M, Packiam Vignesh T, Steinberg Ryan L, Hougen Helen Y, Abou Chakra Mohamad, Mott Sarah L, O'Donnell Michael A
Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Division of Urology, Department of Surgery, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA.
Cancers (Basel). 2024 Dec 10;16(24):4126. doi: 10.3390/cancers16244126.
After first-line treatment failure, patients with non-muscle invasive urothelial carcinoma (NMIUC) are recommended to undergo radical cystectomy. However, those unable to pursue radical surgery or desiring bladder preservation require effective salvage therapies. Multi-agent treatment regimens are particularly useful for targeting the complex resistance mechanisms of recurrent UC. Herein, we report a regimen of sequential doxorubicin and gemcitabine alternating weekly with sequential docetaxel and mitomycin (Quad Chemo) for patients with recurrent high-risk NMIUC. We retrospectively identified all patients sequentially treated with 50 mg of doxorubicin followed by 1000 mg of gemcitabine alternating weekly with sequential 37.5 mg of docetaxel followed by 40 mg mitomycin-C between 2007-2024. Induction consisted of 8 weekly treatments, and, if disease-free, patients were initiated on monthly maintenance treatments for 2 years. In total, 29 patients (39 treated units; 26 lower urinary tract, 13 upper urinary tract) with high-grade NMIUC were included in the final analysis. The cohort had high-risk features with a median of three prior induction therapies and with 38 (97%) units presented with either biopsy-proven CIS or presumed CIS in the context of high-grade urine cytology in the absence of tumorous lesions. There were 26 recurrences during follow-up, 17 in the lower tract and 9 in the upper tract. Among all of the treated units, the complete response rate was 80%, and 1- and 2-year recurrence-free survival was 60% and 43%, respectively. In total, 10 patients experienced disease progression yielding a 5-year progression-free survival of 57%. Five patients ultimately died due to bladder cancer yielding a 5-year cancer-specific survival of 83%. A total of 19 (66%) patients reported side effects during treatment, and 7 (24%) stopped treatment secondary to side effects. In a high-risk heavily pre-treated cohort, Quad Chemo rescued a significant portion of patients with recurrent NMIUC from disease relapse. However, progression events were considerable in the long term. Further prospective evaluation of this treatment regimen is warranted.
在一线治疗失败后，非肌层浸润性尿路上皮癌（NMIUC）患者建议接受根治性膀胱切除术。然而，那些无法进行根治性手术或希望保留膀胱的患者需要有效的挽救治疗。多药治疗方案对于针对复发性尿路上皮癌的复杂耐药机制特别有用。在此，我们报告了一种序贯阿霉素和吉西他滨每周交替联合序贯多西他赛和丝裂霉素（四联化疗）的方案，用于复发性高危NMIUC患者。我们回顾性地确定了2007年至2024年间所有依次接受50mg阿霉素，随后1000mg吉西他滨每周交替，接着依次接受37.5mg多西他赛，随后40mg丝裂霉素-C治疗的患者。诱导治疗包括8周的每周治疗，如果无疾病进展，患者开始每月维持治疗2年。最终分析纳入了29例（39个治疗单元；26例下尿路，13例上尿路）高级别NMIUC患者。该队列具有高危特征，中位接受过三次先前的诱导治疗，38个（97%）单元在无肿瘤性病变的情况下，经活检证实为原位癌（CIS）或在高级别尿细胞学背景下推测为CIS。随访期间有26例复发，17例在下尿路，9例在上尿路。在所有治疗单元中，完全缓解率为80%，1年和2年无复发生存率分别为60%和43%。共有10例患者疾病进展，5年无进展生存率为57%。5例患者最终死于膀胱癌，5年癌症特异性生存率为83%。共有19例（66%）患者在治疗期间报告有副作用，7例（24%）因副作用停止治疗。在一个高危且接受过大量预处理的队列中，四联化疗使相当一部分复发性NMIUC患者免于疾病复发。然而，从长期来看，进展事件相当可观。有必要对该治疗方案进行进一步的前瞻性评估。
