不同抗雄激素药物联合雄激素剥夺疗法治疗激素敏感性局部晚期前列腺癌的真实世界疗效

The real-world efficacy of different anti-androgen drugs combined with ADT in the treatment of hormonesensitive locally advanced prostate cancer

目的探究阿比特龙、阿帕他胺、比卡鲁胺等联合雄激素剥夺疗法(ADT)在治疗激素敏感性局部晚期前列腺癌患者中的疗效差异。方法回顾性纳入78例就诊于兰州大学第二医院的激素敏感性局部晚期前列腺癌患者,包括服用阿帕他胺的患者26例、阿比特龙的患者22例及比卡鲁胺的患者30例,使用卡方检验和非参数检验比较3种药物在基线数据、前列腺特异性抗原(PSA)反应率上的差异,使用Kaplan-Meier生存分析比较阿比特龙、阿帕他胺、比卡鲁胺3组患者在PSA无进展生存、影像学无进展生存、无去势抵抗生存、无转移性去势抵抗生存以及总生存期等方面的差异。结果截至2024年1月,雄激素受体阻滞剂药物+ADT能使85%的患者在用药后3个月达到PSA90状态;治疗后,3组患者PSA降至最低点水平的差异无统计学意义(P=0.528)。此外,与比卡鲁胺组比较,阿帕他胺组和阿比特龙组的患者,其PSA到达最低点时间显著短于比卡鲁胺组(P=0.001);阿帕他胺组患者在用药后第3个月达到PSA深度缓解的患者占比显著高于阿比特龙组与比卡鲁胺组(P=0.005);在用药后的第6、12个月,3组患者到达PSA深度缓解与PSA90的占比差异无统计学意义。26.9%(21/78)的患者PSA有进展,其中阿比特龙组与阿帕他胺组发生PSA进展的患者占比显著少于比卡鲁胺组(P=0.012);16.7%(13/78)患者发生了全身转移(包括骨骼、内脏和远处淋巴结),其中阿比特龙与阿帕他胺组的患者发生全身转移的占比显著低于服用比卡鲁胺的患者(P=0.032);26.9%(21/78)的患者发生了去势抵抗,其中包括转移性去势抵抗的前列腺癌患者12例和非转移性去势抵抗性前列腺癌患者7例,与比卡鲁胺比较,阿比特龙和阿帕他胺能显著降低患者发生去势抵抗的风险(P=0.01)。随访过程中共有10例患者死亡,3组药物影响患者总生存期的差异无统计学意义。此外,3组患者在整体不良事件发生情况上的差异无统计学意义。结论在激素敏感性局部晚期前列腺癌患者中,与比卡鲁胺联合ADT治疗相比,阿比特龙与阿帕他胺联合ADT的双联疗法治疗能有效降低患者发生PSA进展和全身转移的风险,并延缓患者发生去势抵抗的时间。此外,阿帕他胺联合ADT治疗能更快地降低患者PSA水平,并使患者更快达到PSA深度缓解。3种不同抗雄激素药物联合ADT治疗在不良事件发生方面的差异无统计学意义。

Objective To investigate the difference in efficacy of anti-androgen drugs such as abiraterone,apalutamide and bicalutamide in combination with androgen-depri-vation therapy in the treatment of hormone-sensitive localised advanced prostate cancer.Method A total of 78 patients with limited advanced prostate cancer who attended The Second Hospital of Lanzhou University were retrospectively included in the study.Of these,26 patients were on apalutamide,22 on abiraterone,and 30 on bicalutamide.The study compared the four drugs using the chi-square test to analyze baseline data and prostate-specific antigen(PSA)response rate.The Kaplan-Meier survival analysis and non-parametric test were used to compare the four patient groups in terms of PSA progression-free survival,imaging progression-free survival,metastatic denudation-resistant survival,and overall survival.Result At the latest follow-up time,the combination of androgen receptor signaling inhibitors drug and ADT treatment allowed 85%of patients to achieve PSA90 status within 3 months of drug administration.Additionally,there was no significant difference in PSA nadir levels between the three groups after treatment(P=0.528).In addition,the time to PSA nadir was significantly shorter in patients treated with apalutamide or abiraterone compared to those treated with bicalutamide(P=0.001).Furthermore,a significantly higher proportion of patients in the apalutamide group,in contrast with other groups experienced this effect.At month 3 post-dose,a higher proportion of patients in the abiraterone group achieved deep PSA remission compared to the bicalutamide group(P=0.005).However,there was no significant difference in the proportion of patients achieving PSA deep remission versus PSA90 among the three groups at month 6 and 12 after drug administration.Approximately 26.9%(21/78)of patients experienced PSA progression,with a significantly lower proportion of patients in the abiraterone and apalutamide group experiencing PSA progression than those in the bicalutamide group(P=0.012);and systemic metastases(including bone,viscera and distant lymph nodes)occurred in approximately 16.7%(13/78)of patients.The proportion of patients in the abiraterone and apalutamide group who developed systemic metastases was significantly lower than that of patients taking bicalutamide(P=0.032);in addition,approximately 26.9%(21/78)of patients developed denervation resistance,including 12 patients with mCRPC and 7 patients with nmCRPC,and in contrast to bicalutamide,the proportion of patients who developed systemic metastases was significantly lower in the abiraterone and apalutamide group.Abiraterone and apalutamide significantly reduced the risk of patients developing depot resistance(P=0.010).During followup,10 patients experienced a fatal event,and there was no significant difference in the overall survival between the three drug groups.Furthermore,there were no notable differences in the overall incidence of adverse events between the three groups.Conclusion In patients with hormone-sensitive limited-advanced prostate cancer,dual-therapy treatment with abiraterone and apalutamide in combination with ADT effectively reduces the risk of PSA progression and systemic metastases and delays the onset of de-escalation resistance compared to bicalutamide+ADT treatment.Additionally,treatment with abatacept in combination with ADT reduces patients'PSA levels more rapidly and allows them to achieve deep PSA remission more quickly.No significant difference was found in the occurrence of adverse events among the three anti-androgen drugs used in combination with ADT therapy.