舒尼替尼治疗转移性肾癌的预后因素分析

Prognostic factors of survival in patients with metastatic renal cell carcinoma treated with sunitinib

目的 探讨影响舒尼替尼治疗转移性肾癌的预后因素. 方法 回顾性分析2008年5月至2012年12月82例接受舒尼替尼治疗的转移性肾癌患者的临床资料,男60例,女22例.年龄29～ 82岁,平均（56.1±11.3）岁.52例有血尿、腰痛、肿块等临床症状.肿瘤大小2.0～18.0 cm,平均（8.0±3.0） cm.肾肿瘤位于左侧41例,右侧37例,双侧4例.69例接受了肾切除术,13例未行肾切除术者行穿刺活检获得病理.病理诊断为透明细胞癌75例,乳头状癌、嫌色细胞癌、肉瘤样癌各2例,集合管癌1例.转移部位包括肺50例、肝11例、骨14例、胰腺3例、后腹膜淋巴结31例.美国东部肿瘤协作组（eastern cooperative oncology group,ECOG）评分1～2分52例,≥3分30例.Hb平均（132±24） g/L,治疗开始时59例低于正常值.碱性磷酸酶平均（90±65） U/L,治疗开始时9例异常.乳酸脱氢酶平均（168±114） U/L,治疗开始时6例异常者.WBC平均为（6.4±2.0）×109/L,治疗开始时2例异常.MSKCC风险模型高危组14例,中危组68例.74例在确诊1年内、8例在确诊1年后接受舒尼替尼治疗,59例治疗首月相对剂量密度≥50％.采用Kaplan-Meier生存分析法计算患者的生存率,log-rank检验生存率差异,应用Cox比例回归风险模型分析影响预后的因素. 结果 本组82例的总生存期为2.8264.1个月,平均（21.6±14.1）个月.Kaplan-Meier生存分析结果显示,1年存活率为71％,2年存活率为64％,3年存活率为58％.单因素分析结果显示ECOG评分≥2分（P=0.005）、初次就诊时有临床症状（P=0.031）、未行患肾切除术（P=0.012）、转移部位数目≥2个（P=0.015）、靶向治疗开始时的Hb值（P=0.005）、靶向治疗开始时的碱性磷酸酶值（P=0.007）、MSKCC评分≥3分（P=0.000）、肝转移（P=0.000）、骨转移（P=0.000）、舒尼替尼首月相对剂量密度＜50％（P=0.000）等10项因素对转移性肾癌的预后有影响.Cox多因素分析结果显示ECOG评分≥2分（P=0.136）、初诊时无临床症状（P=0.801）、靶向治疗开始时碱性磷酸酶值＜126 U/L（P=0.618）、无骨转移（P=0.068）、无胰腺转移（P=0.265）等是对预后有益的因素;舒尼替尼首月相对剂量密度≥50％（P=0.000）是影响转移性肾癌预后的独立因素. 结论 靶向药物可使影响转移性肾癌预后的因素发生一定变化.舒尼替尼首月相对剂量密度≥50％是影响转移性肾癌预后的独立因素.

Objective To study the prognostic factors of survival in patients with metastatic renal cell carcinoma （mRCC） treated with sunitinib.Methods From May 2008 to Dec 2012,the clinical data of 82 cases with mRCC adminstered by sunitinib were reviewed retrospectively.The study included 60 male patients and 22 female patients,whose age ranged from 29 to 82 years [mean （56.1±11.3） years].Among them,52 cases presented hematuria,flank pain and palpable mass.The size of renal tumor ranged from 2.0 to 18.0 cm [mean （8.0±3.0） cm].The location of tumor included 41 in left kidney,37 in right kidney and 4 in bilateral kidney.The pathological tissue obtained from the operation in 69 cases and from biopsy in 13 cases.The pathological results demonstrated renal cell carcinoma in 75 cases,papillary cell carcinoma in 2 cases,chromophobe cell carcinoma in 2 cases,sarcomatoid carcinoma in 2 cases,collecting duct carcinoma in one case.The site of metastasis included lung in 50 cases,liver in 11 cases,bone in 14 cases,pancrease in 3 cases,retroperitoneal lymph node in 31 cases.In 52 cases,the ECOG scores ranged from 1 to 2.The others scores were more than 3.The average level of hemoglobin,AKP,LDH and leukocyte were （132±24）g/L,（90±65） U/L,（168±114） U/L and （6.4±2.0）×109/L,respectively.Before treatment,the abnormal cases in those parameters were 59,9,6 and 2,respectively.According to the MSKCC risk model,14 cases were classified into the high risk group and 68 cases into medium risk group.74 cases were accepted the sunitinb therapy within one year after diagnosis and 8 cases were accepted same therapy until one year after diagnosis.The overall survival （OS） rates were calculated by Kaplan-Meier method and Cox regression model was used to analyze the relationship between the influencing factors and the prognosis.Results The average OS was （21.6± 14.1） months （ranged 2.8 to 64.1 months）.The survival rate at 1 st,2nd and 3rd year were 71％,64％ and 58％,respectively.Single factor analysis showed that significant prognostic factors were as follows：ECOG performance status ≥ 2 （P =0.005）,clinical symptom during first clinic visiting （P =0.031）,without nephrectomy （P =0.012）,the number of metastatic sites ≥ 2 （P =0.015）,hemoglobin before treatment （P=0.005）,serum AKP level before treatment （＞126 U/L） （P=0.007）,MSKCC score≥ 3 （P =0.000）,the presence of liver metastases （P =0.000） and bone metastases （P =0.000） and relative dose intensity in the first month （1M-RDI） of sunitinib ≥ 50％ （P=0.000）.Cox regression model showed that the beneficial predictive factors were ECOG performance status＜2 （P=0.136）,no symptom during the first clinic visiting （P=0.801）,serum AKP ＜126 U/L （P=0.618） before treatment,the absence of bone （P =0.068） and pancreas metastases （P =0.265）.Sunitinib 1M-RDI ≥ 50％ was the independent predictive factor （P=0.000）.Conclusions In targeted therapy era,there is some change in the prognostic factors for mRCC and target drug play an important role in the prognosis of mRCC.Sunitinib 1M-RDI ≥50％ is the independent predictive factor for the prognosis of renal carcinoma.