Harvard Medical School, Boston, MA.
Harvard Medical School, Boston, MA; Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA.
Urol Oncol. 2021 Nov;39(11):785.e1-785.e10. doi: 10.1016/j.urolonc.2021.03.017. Epub 2021 Apr 30.
The comparative effectiveness of surgery and radiation therapy for high-grade, clinically localized prostate cancer remains a seminal, open question in urologic oncology, with no randomized controlled trials to inform management. We therefore emulated a hypothetical target clinical trial of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) for high-grade, clinically localized prostate cancer.
We conducted observational analyses using the National Cancer Database from 2006-2015 to emulate a target clinical trial in men 55-69 years with cT1-3cN0cM0, PSA<20 ng/mL, Gleason 8 to 10 prostate adenocarcinoma treated with RP or 75 to 81 Gy EBRT with androgen deprivation therapy (EBRT+ADT). The associations of treatment type with overall survival (OS) were estimated using Cox regression with stabilized inverse probability weights (IPW).
A total of 26,806 men formed the study cohort (RP: 23,990; EBRT+ADT: 2,816). Baseline characteristics were well-balanced after IPW-adjustment. Median follow-up was 48.4 (IQR 25.5-76.2) months. After IPW-reweighting, RP was associated with improved OS compared to EBRT+ADT (HR 0.54;95% CI 0.48-0.62; P<0.001), with 5- and 10-year OS of 93% vs 87%, and 76% vs 60%, respectively. RP was associated with improved OS across all categories of Gleason score, PSA, cT stage, age, and Charlson comorbidity index examined. In sensitivity analyses adjusting for biopsy tumor volume and a biopsy-specific Gleason score, RP remained associated with improved OS compared to EBRT+ADT (HR 0.62;95% CI 0.49-0.78; P<0.001).
In observational analyses designed to emulate a target clinical trial of men with high-grade, clinically localized prostate cancer, RP was associated with improved OS compared with EBRT+ADT.
对于高级别、临床局限性前列腺癌，手术与放疗的相对疗效仍然是泌尿外科肿瘤学中的一个重要且悬而未决的问题，目前尚无随机对照试验来指导治疗。因此，我们模拟了根治性前列腺切除术（RP）与外照射放疗（EBRT）治疗高级别、临床局限性前列腺癌的假设性目标临床试验。
我们利用国家癌症数据库（National Cancer Database），对 2006 年至 2015 年期间的患者进行了观察性分析，以模拟 55-69 岁、cT1-3cN0cM0、PSA<20ng/mL、Gleason 8-10 前列腺腺癌、接受 RP 或 75-81GyEBRT+雄激素剥夺治疗（EBRT+ADT）的患者的目标临床试验。使用 Cox 回归和稳定的逆概率加权（IPW）估计治疗类型与总生存（OS）之间的关联。
共纳入 26806 名患者（RP：23990 例；EBRT+ADT：2816 例）。经 IPW 调整后，基线特征均衡。中位随访时间为 48.4（IQR 25.5-76.2）个月。经过 IPW 重新加权后，RP 与 EBRT+ADT 相比，OS 得到改善（HR 0.54；95%CI 0.48-0.62；P<0.001），5 年和 10 年 OS 分别为 93%和 87%，76%和 60%。RP 与所有 Gleason 评分、PSA、cT 分期、年龄和 Charlson 合并症指数类别中观察到的 OS 改善相关。在调整活检肿瘤体积和特定于活检的 Gleason 评分的敏感性分析中，与 EBRT+ADT 相比，RP 仍与 OS 改善相关（HR 0.62；95%CI 0.49-0.78；P<0.001）。
在旨在模拟高级别、临床局限性前列腺癌男性目标临床试验的观察性分析中，与 EBRT+ADT 相比，RP 与 OS 改善相关。
