晚期肾癌减瘤性骨转移灶切除患者的预后影响因素分析

Prognostic factors of survival in patients with metastatic renal cell carcinoma after bone metastasectomy

目的探讨晚期肾癌减瘤性骨转移灶切除患者的预后影响因素。方法回顾性分析海军军医大学长征医院2008年1月至2018年12月收治的143例经病理确诊的晚期肾癌骨转移患者的病例资料,男121例,女22例。确诊骨转移时平均年龄(54.8±12.5)(18~85)岁,<60岁91例,≥60岁52例。首次诊断为早期肾癌(无远处转移)81例,晚期肾癌(有远处转移)62例。单纯骨转移86例,骨转移合并其他脏器转移57例。按骨转移灶数量分为骨寡转移81例,骨多发转移62例。按KPS功能状态评分分组,>80分5例,≤80分138例。国际转移性肾癌数据库联盟(IMDC)评分中危组92例、高危组51例。骨转移灶切除术前接受肾癌原发灶切除手术123例,未接受肾癌原发灶切除手术20例。本研究143例均接受骨转移灶切除手术,肾癌原发灶和转移灶均完全切除(无瘤生存组)46例,肾癌原发灶未切除或肾癌原发灶已切除但转移灶未完全切除(带瘤生存组)97例。72例(50.3%)在骨转移灶切除术后联合应用靶向治疗,其中舒尼替尼43例,索拉非尼26例,帕唑帕尼2例,乐伐替尼1例。采用单因素和多因素分析影响患者预后的危险因素。通过Kaplan-Meier法和log-rank检验绘制分析患者的生存曲线。结果本研究143例术后转移灶病理诊断为透明细胞癌132例,非透明细胞癌11例。单因素和多因素Cox分析结果显示,确诊骨转移时年龄≥60岁(HR=1.913,95%CI 1.115~3.284,P<0.05)、骨多发转移(HR=1.887,95%CI 1.003~3.549,P<0.05)是晚期肾癌减瘤性骨转移灶切除患者预后的独立危险因素。143例中位随访时间为49.0个月,中位总生存期(OS)为24.0(1~115)个月,1、3、5年生存率分别为79.2%、59.4%、31.6%。无瘤生存组和带瘤生存组中位OS分别为30.0个月和19.4个月,差异有统计学意义(P=0.030)。IMDC中危组转移灶切除术后联合靶向药物治疗和单纯骨转移灶切除患者的中位OS分别为24.3个月和16.8个月(P=0.027),IMDC高危组患者是否应用靶向药物治疗对生存期无影响(P=0.449)。结论肾癌骨转移患者生存预后差,肾癌原发灶和骨转移灶完全切除患者的无瘤状态可以显著延长生存期。骨转移灶切除后联合靶向药物治疗可以使IMDC中危患者生存获益,而对于IMDC高危患者靶向药物治疗是否能够生存获益尚需进一步研究。

Objective To investigate the factors related to the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy and to provide a reference for the clinical treatment of renal cell carcinoma.Methods The clinical data of 143 patients with metastatic renal cell carcinoma in our center from January 2008 to December 2018 were retrospectively collected.Among 143 patients,121 were male and 22 were female,with the average age of(54.8±12.5)year-old(from 18 to 85 year-old).The KPS scores of 138 patients were no higher than 80%.According to International Metastatic RCC Database Consortium(IMDC)risk model for metastatic renal cell carcinoma,the patients were divided into intermediate risk group(92 patients)and poor risk group(51 patients).The patients who had received complete resection for both primary lesion and metastatic tumor were regarded as tumor-free(47 patients).Otherwise,the patients with unresectable primary tumor or incomplete resection of the metastatic tumor were defined as the patients surviving conversely bone metastases were the only metastatic site,and the other 57 patients also experienced concomitant metastases comparatively.Sixty-two patients only had solitary bone metastasis lesion and 81 patients had multiple bone metastases.Kaplan-Meier survival analysis was used to calculate the 1-year,3-year and 5-year survival rate.The impacts of different variables on the prognosis were examined by log-rank test.Univariate analysis and multivariable Cox proportional hazards regression models were used to identify the independent risk factors.Results The median follow-up time was 49.0 months.The overall survival was 1-115 months,with the median OS was 24.0 months.The 1-year,3-year and 5-year survival rate were 79.2%,59.4%and 31.6%,respectively.All the patients underwent bone metastasectomy and 72 of them were treated with targeted therapy.The pathology results of metastasectomy were clear cell carcinoma for 132 patients and non-clear cell carcinoma for the 11 patients.In tumor-free group,the median OS was 30.0 months and in survival with tumor group,the median OS was 19.4 months,with a significant difference between the two groups(P=0.030).In IMDC intermediate risk group,the prognosis was improved among the patients who received post-surgical targeted therapy after metastasectomy(24.3 months vs.16.8 months,P=0.027),whereas the difference was not significant for IMDC poor risk group(P=0.449).Age≥60 years and multiple bone metastases sites were proved to be the independent risk factors for the prognosis of patients with metastatic renal cell carcinoma after bone metastasectomy.Conclusions The prognosis of RCC patients with bone metastases was generally poor.Metastasectomy could prolong the OS of the patients who had undergone primary nephrectomy and had solitary bone metastasis.Metastasectomy combined with targeted therapy could significantly improve the prognosis of the IMDC intermediate risk patients.However,the effect of targeted therapy among IMDC poor risk patients remained to be further proved.