转移性去势抵抗性前列腺癌应用新型内分泌治疗药物后出现“骨闪烁”二例报告并文献复习

摘要

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.%目的 探讨新型内分泌治疗药物治疗转移性去势抵抗前列腺癌(mCPRC)患者出现“骨闪烁”的临床特点和处理方法.方法 回顾性分析2例服用新型内分泌治疗药物出现“骨闪烁”的mCRPC患者的临床病理资料,结合国内外文献,分析其临床特点和处理方法.病例1,79岁.2013年11月5日因尿频就诊.血PSA 115.900 ng/ml.MRI检查:前列腺右侧外周带T2相可见低信号区,累及包膜(考虑前列腺癌).骨扫描检查:多发骨转移.直肠指检:前列腺右侧叶质硬.行超声引导下经直肠前列腺穿刺活检术,病理诊断:前列腺腺癌,Gleason评分5±5=10分,局部可见肉瘤样分化,可见癌组织侵犯脉管、神经及脂肪组织.初始诊断:前列腺腺癌(cT3 N0M1).2013年11月开始雄激素剥夺治疗,PSA最低降至0.066 ng/ml.2015年1月PSA升至133.400 ng/ml,血清睾酮1.4nmol/L;影像学检查示全身多发骨转移进展.诊断为mCRPC,开始使用恩杂鲁胺治疗.病例2,62岁.2013年2月10日因消瘦伴尿频于外院就诊.PSA＞ 100 ng/ml.MRI检查:前列腺癌可能大,累及双侧精囊腺及邻近膀胱壁.胸部CT检查:纵隔、双肺门多发淋巴结转移.骨扫描检查:多发骨转移.直肠指检:前列腺明显增大,质硬.行超声引导下经直肠前列腺穿刺活检术,病理诊断:前列腺腺癌,Gleason评分4±4=8分,可见癌组织侵犯神经.初始诊断:前列腺腺癌(cT4N1 M1).2013年3月开始雄激素剥夺治疗,PSA最低降至0.517 ng/ml.2015年1月PSA升至43.180 ng/ml,血清睾酮0.9nmol/L;影像学检查示全身多发骨转移进展,诊断为mCRPC,开始使用阿比特龙治疗.结果 病例1使用恩杂鲁胺治疗2个月后PSA降至5.530 ng/ml,但骨扫描显示多发骨转移,部分为新发病灶,经骨科会诊无需骨科处理;治疗6个月时,转移灶数量稳定,部分病灶代谢降低;治疗8个月时,骨转移灶数量开始减少;治疗10个月时,骨转移灶开始重新增加.2016年1月,患者因病情进展停用恩杂鲁胺,开始接受全身化疗,化疗5个周期后出现PSA进展而停止化疗.2016年6月因弥散性血管内凝血、肝衰竭死亡.病例2使用阿比特龙治疗2个月后PSA从54.820 ng/ml降至3.580 ng/ml,骨扫描检查示多发骨转移,部分为新发病灶,经骨科会诊无需骨科处理;治疗6个月时,转移灶数量开始减少;10个月时,转移灶稳定.患者至今持续48个月阿比特龙治疗,病情稳定.结论 对于mCRPC患者,采用恩杂鲁胺及阿比特龙治疗早期可能会出现PSA下降、但骨扫描检查提示进展的“骨闪烁”现象,对其正确合理的评估才能让患者获得充分疗效.