原发灶手术对比放射治疗在寡转移前列腺癌中的疗效：倾向评分匹配研究

Comparison of clinical outcomes between radical prostatectomy and permanent pros- tate brachytherapy in patients with oligometastatic prostate cancer：A propensity score-matched study

摘要

目的：比较根治性前列腺切除术（radical prostatectomy，RP）与永久性前列腺近距离放疗（permanent pros- tate brachytherapy，PPB）在接受规律雄激素剥夺治疗（androgen deprivation therapy，ADT）的寡转移前列腺癌（oligo-metastatic prostate cancer，omPCa）患者中延缓进展至去势抵抗性前列腺癌（castration-resistant prostate cancer，CRPC）时间的差异。方法：连续选择 2011 年 4 月至 2019 年 8 月于北京大学第三医院诊治的 88 例 omPCa 患者（转移灶 $\leqslant$5 个）的病例资料进行回顾性分析，分为 RP 组（62 例）和 PPB 组（26 例），所有患者术后均接受规律 ADT 治疗。采用倾向性评分匹配法（propensity score matching，PSM）对年龄、前列腺特异性抗原（prostate-specific antigen，PSA）水平、肿瘤 T 分期、肿瘤 N 分期等变量进行1：1匹配，均衡基线差异。主要终点为发生 CRPC。采用 Kaplan-Meier 法和 Log-rank 检验比较生存差异，Cox 比例风险模型分析独立危险因素。结果：PSM 前两组患者在年龄、PSA 及肿瘤N 分期上差异有统计学意义（P 均<0.05），PSM 后成功匹配 36 例患者（每组 18 例），基线特征达到良好均衡（所有协变量 SMD<0.1）。全组中位随访时间 30.5 个月，共观察到 15 例患者发生 CRPC（PPB 组 8 例，RP 组 7 例）。匹配前后结果一致，RP 组无 CRPC 生存期均显著长于 PPB 组（匹配前 $\mathit{H}\mathit{R}=\mathrm{3.38,95}\mathrm{\%}\mathit{C}\mathit{I}:1.10\sim 10.40,\mathit{P}=0.033$ ；匹配后 $\mathit{H}\mathit{R}=\mathrm{4.60,95}\mathrm{\%}\mathit{C}\mathit{I}:1.14\sim 18.49,\text{ }\mathit{P}=0.032$）；PPB 组中位无 CRPC 生存期为 80.0 个月，RP 组尚未达到。多因素 Cox 回归分析显示，调整 T、N 分期后，治疗方式是影响 CRPC 转化的独立预后因素（PPB vs.RP，HR=8.56，$95\mathrm{\%}\mathit{C}\mathit{I}:1.51\sim 48.64,\text{ }\mathit{P}=0.015$）。临床 T 分期 T3 期及以上亦是独立危险因素（$\mathit{H}\mathit{R}=\mathrm{10.29,95}\mathrm{\%}\text{ }\mathit{C}\mathit{I}:1.75\sim 60.57,\text{ }\mathit{P}=0.010)$ 。结论：在接受 ADT 的 omPCa 患者中，RP 较 PPB 更能显著延缓 CRPC 转化，且治疗方式是发生 CRPC 的独立预后因素，提示选择局部治疗方式时需考量其对疾病远期进程的影响，以便为个体化治疗提供循证依据。

Abstract

Objective：To compare radical prostatectomy（RP）versus permanent prostate brachythera- py（PPB）as primary local treatment modalities in delaying disease progression to castration-resistant prostate cancer（CRPC）among patients with oligometastatic prostate cancer（omPCa）receiving standard androgen deprivation therapy（ADT），and to provide clinical evidence for individualized treatment strate- gies. Methods：We performed a retrospective cohort analysis of 88 patients diagnosed with omPCa（de- fined as ⩽5 metastatic lesions）at a single tertiary center between April 2011 and August 2019.All the patients，after receiving either RP(n=62) or PPB(n=26) ，were placed on a regimen of continuous ADT.To address significant baseline disparities-notably in patient age，presenting prostate-specific anti- gen（PSA）levels，and nodal disease burden：A 1 ： 1 propensity score matching（PSM）protocol was im-plemented.Matching variables included age at diagnosis，baseline PSA，clinical T stage（⩽T2c vs.⩾ T3），and nodal status（N0 vs.N1）.The primary study endpoint was the time interval from ADT initia- tion to CRPC development，as defined by the prostate cancer working group 3 （PCWG3）criteria. Survival outcomes were compared using Kaplan-Meier curves and the Log-rank test.Independent risk fac- tors for progression were identified through both univariate and multivariate Cox proportional hazards re- gression analyses. Results：Prior to PSM，the RP and PPB groups exhibited significant differences in key prognostic factors：the PPB group was older（mean 73.2 vs. 68.1 years，P=0.002），had a higher me- dian PSA（31.2 vs. 9.8μ g/L,P=0.002），and had a greater incidence of lymph node involvement （42.3% vs. 12.9%,P=0.006）.Following PSM，a balanced cohort of 36 patients（18 in each group） was achieved.Over a median follow-up of 30.5 months（range： 3.2 to 113. 4 months）， 15 patients （17.0%）developed CRPC，with 8 events occurring in the PPB group and 7 in the RP group.Survival analysis demonstrated a consistent，statistically significant advantage for RP.In the pre-matched cohort， the RP group showed a significantly delayed progression to CRPC（Log-rank P=0.033,HR=3.38 ， 95％CI：1.10-10.40），with a median CRPC-free survival of 80. 0 months for PPB and not reached for RP.In the matched cohort，the survival advantage of RP was more pronounced（Log-rank P=0.032 ， $\mathit{H}\mathit{R}=\mathrm{4.60,95}\mathrm{\%}\mathit{C}\mathit{I}:1.14-18.49)$ ，with a median CRPC-free survival of 80.0 months for PPB and not reached for RP.Multivariate Cox regression，adjusting for T and N stages，confirmed treatment modality as a powerful independent predictor.Patients treated with PPB faced an 8.56 -fold higher risk of progres- sion compared with those treated with $\mathrm{R}\mathrm{P}(\mathit{H}\mathit{R}=\mathrm{8.56,95}\mathrm{\%}\mathit{C}\mathit{I}:1.51-48.64,\mathit{P}=0.015)$.Advanced primary tumor stage（⩾T3）was also identified as a significant independent risk factor（HR=10.29 ， 95％CI：1.75-60.57，P=0.010）. Conclusion：For patients with omPCa receiving ADT，the choice of local therapeutic intervention significantly impacts the time to CRPC.Radical prostatectomy is associated with a markedly longer delay in disease progression to the castration-resistant state compared with permanent prostate brachytherapy，with the treatment modality itself serving as a strong independent prognostic factor.These findings underscore the importance of considering the type of local therapy in the multimodal management of omPCa and provide a rationale for individualized treatment planning.Prospec- tive，randomized trials are necessary to validate these observations and further define optimal therapeutic paradigms.

关键词

寡转移前列腺癌 / 根治性前列腺切除术 / 前列腺癌放射性粒子植人术 / 去势抵抗性前列腺癌 / 倾向性评分匹配

Key words

Oligometastatic prostate cancer / Radical prostatectomy / Permanent prostate brachy- therapy / Castration-resistant prostate cancer / Propensity score matching

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基金资助

国家自然科学基金(82072828)

北京大学第三医院临床重点项目(BYSYFY2021046)