多西他赛联合内分泌疗法治疗转移性激素敏感性前列腺癌的疗效研究

A retrospective study of docetaxel combined with ADT therapy in the treatment of metastatic hormone-sensitive prostate cancer

目的探讨多西他赛联合内分泌疗法治疗转移性激素敏感性前列腺癌的临床疗效。方法回顾性分析长海医院2004年1月至2018年7月收治的497例转移性激素敏感性前列腺癌患者的病例资料。患者确诊年龄为(72.1±8.7)岁。治疗前中位PSA为100.0(42.3~999.0)ng/ml。TNM临床分期分别为:T2期213例(42.9%)、T3期160例(32.2%)、T4期124例(24.9%);N0期319例(64.2%)、N1期144例(29.0%)、Nx期34例(6.8%);M0期100例(20.1%)、M1a期51例(10.3%)、M1b期332例(66.8%),M1c期9例(1.8%)、Mx期5例(1.0%)。穿刺Gleason评分≤7分146例(29.4%)、8分103例(20.7%)、≥9分248例(49.9%)。根据治疗方式分为2组,采用单独内分泌治疗(单独治疗组)459例,多西他赛联合内分泌治疗(联合治疗组)38例。采用倾向评分匹配方法,卡钳值设置为0.02,对两组数据实行1∶1匹配。共37对匹配成功,匹配后两组的年龄(P=0.102)、PSA(P=0.713)、T分期(P=0.113)、N分期(P=0.226)、M分期(P=0.514)、Gleason评分(P=0.612)、肿瘤负荷(P=0.812)比较差异均无统计学意义。采用log-rank和Breslow-wilcoxon检验比较两组的无进展生存期和肿瘤特异性生存期。绘制两组患者年龄、临床TNM分期、Gleason评分、肿瘤负荷及是否接受过姑息性电切手术等各亚组生存情况的森林图,并针对高肿瘤负荷亚组比较两组间的无进展生存期差异。结果匹配后单独治疗组和联合治疗组的中位随访时间分别为22.6个月和13.7个月;发生去势抵抗的患者例数分别为23例和17例;死亡患者例数分别为3例和6例。单独治疗组和联合治疗组患者进展为去势抵抗的中位时间差异无统计学意义(10.3个月与16.5个月,P>0.05);平均前列腺癌特异性生存期分别为21.9个月和14.8个月,但均未达到中位生存期,且差异无统计学意义(P>0.05)。高肿瘤负荷亚组中,联合治疗组的中位无进展生存期明显优于单独治疗组(10.6个月与7.2个月,P=0.044),但低肿瘤负荷亚组中两组平均无进展生存期分别为10.5个月和12.6个月,均未达到中位生存期,且差异无统计学意义(P>0.05)。结论多西他赛联合内分泌治疗可以延长高肿瘤负荷激素敏感性前列腺癌患者的无进展生存期,但低肿瘤负荷患者无明显获益。

Objective To investigte the efficacy of docetaxel combined with androgen deprivation therapy for the treatment of metastatic hormone-sensitive prostate cancer based on Chinese population.Methods A total of 497 patients were enrolled from January 2004 to July 2018 in the Changhai Hospital.459 patients received androgen deprivation therapy alone and 38 patients received androgen deprivation therapy combined with docetaxel.The mean age was(72.1±8.7)years.The median PSA level was 100.0 ng/ml,ranging 42.3-999.0 ng/ml.Patients of clinical T2,T3,T4 stage were 213(42.9%),160(32.2%),124(24.9%),respectively.Patients of clinical N0,N1,Nx stage were 319(64.2%),144(29.0%),34(6.8%),respectively.Patients of clinical M0,M1a,M1b,M1c,Mx stage were 100(20.1%),51(10.3%),332(66.8%),9(1.8%),5(1.0%),respectively.Gleason scores of biopsy showed that 146(29.4%)patients was≤7,103(20.7%)was 8 and 248(49.9%)was≥9.Propensity score matching was used to match the baseline between groups.Caliper value was set at 0.02.SPSS 22 software was used to achieve a 1∶1 match between the two groups.There were no statistical difference in the age(P=0.102),PSA(P=0.713),T stage(P=0.113),N stage(P=0.226),M stage(P=0.514),Gleason score(P=0.612),tumor loading(P=0.812)between the two groups.The castration resistance-free rate and cancer specific survival rate of the two groups were compared by log-rank and breslow-wilcoxon test.Furthermore,forest plots were used to display the analysis results of different subgroups such as age,PSA,clinical stage,Gleason score,tumor load,whether patients had received palliative resection,and the differences in castration resistance-free rate were compared between the subgroups with high tumor load.Results The median follow-up time was 22.6 months in the androgen deprivation therapy group and 13.7 months in the combined therapy group.The number of patients with castration resistance in the two groups was 23 and 17,respectively.There were 3 and 6 deaths,respectively.There was no statistically significant difference in the overall progression time to castration resistance between the two groups(10.3 m vs.16.5 m,P>0.05),and no statistically significant difference in the prostate cancer specific survival rate(21.9 m vs.14.8 m,P>0.05).When subgroup analysis was performed,it was found that patients in the high-metastasis-volume subgroup who received the combination therapy had a significantly longer castration resistance free lifetime(10.6 m vs.7.2 m,P=0.044),but there was no significant difference in the low-metastasis-volume subgroup(10.5 m vs.12.6 m,P>0.05).Conclusion Docetaxel combined with androgen deprivation therapy can improve the castration resistance free rate in patients with high metastasis volume,but not in low metastasis volume group.