Aarhus University Hospital, Aarhus, Denmark.
Dana-Farber Cancer Institute, Boston, MA, USA.
Eur Urol Oncol. 2020 Aug;3(4):530-539. doi: 10.1016/j.euo.2020.01.001. Epub 2020 Feb 6.
Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised.
To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]).
DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals).
OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors.
Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p < 0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p < 0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p < 0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p < 0.0001). Data were collected retrospectively.
Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC.
We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome.
转移性肾细胞癌 (mRCC) 患者可能表现为原发性转移（同步疾病）或在随访期间发生转移（异时性疾病）。转移时间对患者预后的影响特征描述较差。
描述接受靶向治疗（酪氨酸激酶抑制剂[TKIs]）的 mRCC 患者根据转移时间的总生存期 (OS) 和治疗失败时间 (TTF)。
设计、地点和参与者：我们使用国际转移性肾细胞癌数据库联盟 (IMDC) 将同步（癌症初始诊断后≤3 个月内转移）与异时性疾病（通过>3-12 个月、>1-2 年、>2-7 年和>7 年间隔评估）进行比较。
使用 Kaplan-Meier 曲线评估 OS 和 TFF。Cox 多变量回归分析 (MVA) 对基线因素进行了调整。
在接受一线 TKI 治疗的 7386 例 mRCC 患者中，3906 例（53%）和 3480 例（47%）分别为同步和异时性转移。与异时性疾病相比，更多的同步性疾病患者具有更高的 T 分期（T1-2：19% vs 34%）、N1 疾病（21% vs 6%）、存在肉瘤样分化（15.8% vs 7.9%）、Karnofsky 表现状态<80（25.9% vs 15.1%）、贫血（62.5% vs 42.3%）、中性粒细胞升高（18.9% vs 10.9%）、血小板升高（21.6% vs 11.4%）、骨转移（40.4% vs 29.8%）和 IMDC 不良风险（40.6% vs 11.3%）。间隔>3-12 个月、>1-2 年、>2-7 年和>7 年的同步性疾病与较差的 TTF（5.6 个月 vs 7.3、8.0、10.8 和 13.3 个月，p<0.0001）和较差的 OS（中位 16.7 个月 vs 23.8、30.2、34.8 和 41.7 个月，p<0.0001）相关。在 MVA 中，调整后的危险比（95%置信区间）分别为 1.00（参考）、0.98（0.90-1.06）、0.81（0.73-0.91）、0.74（0.68-0.81）和 0.60（0.54-0.67），分别用于 OS（p<0.0001）和 1.00（参考）、0.99（0.92-1.06）、0.98（0.90-1.07）、0.83（0.77-0.89）和 0.66（0.60-0.72），分别用于 TTF（p<0.0001）。数据是回顾性收集的。
RCC 初始诊断后转移的时间可能会影响 mRCC 患者接受靶向治疗的结果。
我们研究了转移性爆发时间对接受靶向治疗的肾癌患者生存结果的影响。我们发现，转移性发展时间越长，结果越好。
