Department of Urology, St. Antonius Hospital Nieuwegein/Utrecht, Koekoekslaan 1, 3435CM, Nieuwegein, The Netherlands.
Division Value Based Healthcare, St. Antonius Hospital Nieuwegein/Utrecht, Nieuwegein, The Netherlands.
World J Urol. 2023 Jun;41(6):1551-1562. doi: 10.1007/s00345-023-04408-w. Epub 2023 May 5.
For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder.
From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo).
Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674).
There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.
对于许多恶性肿瘤，临床研究中观察到的疗效与常规实践中的疗效之间存在显著差异（疗效-效果差距）。本研究旨在评估在膀胱癌姑息性一线（1L）化疗治疗（CTx）中存在的疗效-效果差距。
从 7 家荷兰教学医院中，捕获所有被诊断为不可切除的 III 期（cT2-4aN1-3M0）和 IV 期（cT4b 和/或 cM1）疾病的患者，这些患者在 2008 年至 2016 年期间接受了 1L-CTx（包括原发性疾病和根治性膀胱切除术后的复发性疾病）。结果与 7 项随机试验的数据进行了比较，这些试验研究了 1L 吉西他滨+顺铂（GemCis）和/或吉西他滨+卡铂（GemCarbo）。
在纳入的 835 名患者中，有 191 名患者接受了 1L-CTx。GemCis 组（N=88）的中位总生存期（mOS）为 10.4 个月[95%CI 7.9-13.0]，尽管临床特征相似，但比临床试验结果（范围 mOS：12.7-14.3 个月）更短。GemCarbo 组（N=92）的 mOS 为 9.3 个月[95%CI 7.5-11.1]。与 GemCis 患者相比，接受 GemCarbo 的患者具有更差的预后特征（更高的年龄、肾功能受损和更差的表现状态（所有 P 值均<0.001）），但剂量减少的发生率（24.4% vs. 29.5%，P 值=0.453）、早期终止（55.7% vs. 54.1%，P 值=0.839）、临床最佳反应（P 值=0.733）和毒性（68.1% vs. 63.3%，P 值=0.743）相似。多变量回归分析显示，GemCis 并不优于 GemCarbo（HR 0.90[95%CI 0.55-1.47]，P 值=0.674）。
尽管患者具有相似的基线特征，但在 1L GemCis 治疗中似乎存在疗效-效果差距。与临床试验相比，治疗的早期终止更为常见，剂量减少较少，这表明在出现不良事件时会放弃治疗。接受 1L GemCis 治疗的患者的生存率并未优于 GemCarbo 患者，尽管 GemCarbo 患者的基线特征更差。
