Division of Hematology and Oncology, Department of Internal Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.
Clin Genitourin Cancer. 2012 Jun;10(2):93-8. doi: 10.1016/j.clgc.2012.01.007. Epub 2012 Feb 28.
Advances in the targeted treatment of renal cell cancer (RCC) have shown improvements in survival in clinical trials and have largely replaced cytokine therapies as the standard of care. However it is unclear if these advances have translated to the general RCC population. We present a retrospective study of a large clinical cancer registry that demonstrates statistically significant improvements in survival in cancer patients, but the causes of this improvement are difficult to determine because of many confounders.
Before 2004, advanced renal cell cancer (RCC) therapy consisted primarily of cytokines such as interferon and/or interleukin-2. Subsequently, randomized trials of targeted therapies have shown a survival benefit, leading to the approval of several new agents since 2004. Whether the survival benefit seen in highly selected patients accrued to these trials has already translated to the general RCC patient population is unclear. To explore this, a large RCC patient registry was evaluated for changes in outcome between the cytokine (1998-2003) and post-cytokine (2004-2007) eras.
Data from the California Cancer Registry (CCR), a population-based cancer surveillance system, was used to retrospectively analyze 28,252 patients with RCC diagnosed between 1998 and 2007. Inter-era differences in clinical variables-including year of diagnosis, histologic characteristics, age, sex, race, stage, nephrectomy status, overall survival (OS), and cause-specific survival (CSS)-were assessed. Univariate and multivariate Cox models were used.
Crude 3-year OS (68.2% vs. 74.6%; 2P < .001) and CSS (78.1% vs. 82.3%; 2P < .001) were significantly higher in the post-cytokine era. In multivariate analysis, the 3 strongest predictors for improved survival were localized disease (hazard ratio [HR], 18.1; 95% confidence interval [CI], 16.6-19.6), nephrectomy (HR, 2.87; 95% CI, 2.68-3.08), and clear cell histologic type (HR, 1.33; 95% CI, 1.22-1.44).
In this analysis of a large RCC registry, there was an apparent increase in crude OS and CSS in the post-cytokine era compared with the cytokine era. Insufficient follow-up time in the post-cytokine era and a higher proportion of localized disease in that era confound the possibility of benefit derived from targeted therapies. Longer follow-up for patients treated in the post-cytokine era is necessary for a more robust comparison of long-term OS.
肾细胞癌(RCC)的靶向治疗进展表明,临床试验中的生存率有所提高,并且在很大程度上取代了细胞因子疗法作为标准治疗方法。 然而,目前尚不清楚这些进展是否已经转化为一般的 RCC 人群。 我们展示了一项大型临床癌症登记处的回顾性研究,该研究表明癌症患者的生存率有统计学意义的提高,但由于存在许多混杂因素,难以确定这种提高的原因。
2004 年之前,晚期肾细胞癌(RCC)的治疗主要包括干扰素和/或白细胞介素-2 等细胞因子。 随后,靶向治疗的随机试验显示出生存获益,导致自 2004 年以来批准了几种新的药物。 在高度选择的患者中看到的生存获益是否已经转化为一般的 RCC 患者人群尚不清楚。 为了探讨这一点,对一个大型 RCC 患者登记处进行了评估,以比较细胞因子(1998-2003 年)和细胞因子后(2004-2007 年)两个时期的结果变化。
使用加利福尼亚癌症登记处(CCR)的数据,这是一个基于人群的癌症监测系统,回顾性分析了 1998 年至 2007 年间诊断为 RCC 的 28,252 名患者。评估了临床变量(包括诊断年份、组织学特征、年龄、性别、种族、分期、肾切除术状态、总生存期(OS)和疾病特异性生存期(CSS))的时代差异。使用单变量和多变量 Cox 模型进行分析。
细胞因子后时代的 3 年 OS(68.2% vs. 74.6%;2P<.001)和 CSS(78.1% vs. 82.3%;2P<.001)明显更高。多变量分析中,提高生存率的 3 个最强预测因素是局部疾病(风险比 [HR],18.1;95%置信区间 [CI],16.6-19.6)、肾切除术(HR,2.87;95%CI,2.68-3.08)和透明细胞组织学类型(HR,1.33;95%CI,1.22-1.44)。
在这项大型 RCC 登记处的分析中,与细胞因子时代相比,细胞因子后时代的 OS 和 CSS 明显增加。细胞因子后时代的随访时间不足以及该时期局部疾病比例较高,使得靶向治疗的获益受到影响。对细胞因子后时代接受治疗的患者进行更长时间的随访,对于更有力地比较长期 OS 是必要的。