Prostate-Specific Membrane Antigen PET-Guided Intensification of Salvage Radiotherapy After Radical Prostatectomy: A Phase 2 Randomized Clinical Trial.

Background

To evaluate whether intensification of salvage RT (SRT) after radical prostatectomy (RP) guided by PSMA-PET (PSMAiSRT) is associated with improved failure-free survival (FFS).

评估在根治性前列腺切除术（RP）后，通过PSMA-PET引导的挽救性放射治疗（SRT）加强（PSMAiSRT）是否与改善无失败生存（FFS）相关。

DESIGN, SETTING, AND PARTICIPANTS: PSMAiSRT was a stratified cohort within a larger PSMA-guided intensification of radiotherapy (PSMAgRT) trial, a phase 2, two-center, registry-based randomized clinical trial. Patients with biochemical recurrence following RP who were eligible for standard-of-care (SOC) SRT from May 2018 to February 2021, were eligible for randomization in the PSMAiSRT stratum.

设计、设置和参与者：PSMAiSRT是在一个更大的PSMA指导的放射治疗加强（PSMAgRT）试验中的一个分层队列，这是一个2期、双中心、基于注册的随机临床试验。从2018年5月到2021年2月，对于那些在根治性前列腺切除术（RP）后出现生化复发并且符合标准治疗（SOC）立体定向放射治疗（SRT）条件的患者，有资格在PSMAiSRT分层中进行随机分组。

A total of 130 patients were randomized, with 2 who did not proceed to radiotherapy (RT).

共有130名患者被随机分组，其中2人未进行放射治疗（RT）。

The cutoff date for the primary analysis was October 26, 2023.

主要分析的截止日期是2023年10月26日。

intervention

Patients were randomized in a 1:1 ratio to receive either SOC SRT to the prostate bed, with or without elective pelvic RT, with or without adjuvant hormonal therapy (HT), or PSMA-PET/CT-guided SRT, intensified to detected sites of disease.

患者以1:1的比例随机分配，接受标准治疗（SOC）的前列腺床SRT，可能伴有选择性盆腔RT，可能伴有辅助性激素治疗（HT），或者接受PSMA-PET/CT引导的SRT，加强到检测到的疾病部位。

main_outcome_and_measures

The primary end point was FFS, defined as PSA progression (PSA nadir >0.2 ng/mL), radiological progression, next-line therapy initiation, or death.

主要终点是无进展生存期(FFS)，定义为前列腺特异性抗原(PSA)进展(PSA最低值>0.2 ng/mL)，放射学进展，下一阶段治疗的开始，或死亡。

Results

Among 128 patients (median [IQR] age, 71 [64-74] years), median (range) PSA at enrollment was 0.3 (0.1-3.0) ng/mL.

在128名患者中（中位年龄[四分位数间距]为71[64-74]岁），入组时中位前列腺特异性抗原(PSA)水平为0.3（0.1-3.0）ng/mL。

In the PSMAiSRT group, 33 of 64 patients (52%) received intensified SRT; with addition of pelvic RT (n = 16 [25%]), metastasis-directed RT (n = 2 [3%]), lymph node boost (n = 19 [30%]), or prostate bed boost (n = 15).

在PSMAiSRT组中，64名患者中有33名（52%）接受了加强的SRT；其中增加了盆腔RT（n = 16 [25%]），转移灶定向RT（n = 2 [3%]），淋巴结增强（n = 19 [30%]）或前列腺床增强（n = 15）。

Adjuvant hormone therapy was equally prevalent in both arms (55 [86%] control vs 54 [84%] PSMAiSRT).

两组中辅助性激素治疗的普及程度相同（对照组55 [86%] vs PSMAiSRT组54 [84%]）。

At a median (range) follow-up of 37 (7-60) months, PSMAiSRT improved FFS (hazard ratio[HR], 0.50; 95% CI, 0.27-0.94; P = .04) and eugonadal FFS (HR, 0.45; 95% CI, 0.21-0.96; P = .03), with its greatest benefit in the subgroup with PSA of 0.3 ng/mL or more (HR, 0.17; 95% CI, 0.04-0.79; P = .01).

在中位随访时间为37（7-60）个月时，PSMAiSRT改善了无进展生存期（风险比[HR]，0.50；95%置信区间，0.27-0.94；P = .04）和正常睾酮水平的无进展生存期（HR，0.45；95%置信区间，0.21-0.96；P = .03），其最大的益处在PSA为0.3 ng/mL或更多的亚组中（HR，0.17；95%置信区间，0.04-0.79；P = .01）。

Fewer next-line treatment events occurred in the PSMAiSRT arm (4 vs 12; HR, 0.32; 95% CI, 0.11-1.02; P = .04).

在PSMAiSRT组中，较少发生后续治疗事件（4 vs 12；HR，0.32；95%置信区间，0.11-1.02；P = .04）。

There were no significant differences in toxic effects or quality of life between arms.

两组间在毒性效应或生活质量方面没有显著差异。

conclusion_and_relevance

This phase 2 trial demonstrated an isotoxic improvement in cancer control with PSMA-PET-guided intensification of SRT after RP.

这项II期试验显示，在RP后，通过PSMA-PET引导的SRT增强治疗，实现了等毒性改善的癌症控制效果。

Confirmatory evidence is awaited from a subsequently accrued phase 3 trial.

后续积累的第三阶段试验正在等待确认性证据。

trial_registration

ClinicalTrials.gov NCT03525288.

ClinicalTrials.gov NCT03525288。