Background

Both imaging and several prognostic factors inform the planning of salvage radiotherapy (SRT). Prostate-specific membrane antigen positron emission tomography (PSMA-PET) can localize disease unseen by other imaging modalities.

Objective

To evaluate the impact of PSMA-PET on biochemical recurrence–free survival rate after SRT.

Design, setting, and participants

This prospective randomized, controlled, phase 3 clinical trial randomized 193 patients with biochemical recurrence of prostate cancer after radical prostatectomy to proceed with SRT (control arm, n = 90) or undergo a PSMA-PET/computed tomography (CT) scan prior to SRT planning (investigational arm, n = 103) from June 2018 to August 2020. Any other approved imaging modalities were allowed in both arms (including fluciclovine-PET).

Outcome measurements and statistical analysis

This is a secondary endpoint analysis: impact of PSMA-PET on SRT planning. Case-report forms were sent to referring radiation oncologists to collect the management plans before randomization and after completion of SRT. The relative frequency (%) of management changes within each arm were compared using chi-square and Fisher’s exact tests.

Results and limitations

The delivered SRT plan was available in 178/193 patients (92.2%; 76/90 control [84.4%] and 102/103 PSMA-PET [99%]). Median prostate-specific antigen levels at enrollment was 0.30 ng/ml (interquartile range [IQR] 0.19–0.91) in the control arm and 0.23 ng/ml (IQR 0.15–0.54) in the PSMA-PET arm. Fluciclovine-PET was used in 33/76 (43%) in the control arm. PSMA-PET localized recurrence(s) in 38/102 (37%): nine of 102 (9%) outside of the pelvis (M1), 16/102 (16%) in the pelvic LNs (N1, with or without local recurrence), and 13/102 (13%) in the prostate fossa only. There was a 23% difference (95% confidence interval [CI] 9–35%, p = 0.002) of frequency of major changes between the control arm (22% [17/76]) and the PSMA-PET intervention arm (45% [46/102]). Of the major changes in the intervention group, 33/46 (72%) were deemed related to PSMA-PET. There was a 17.6% difference (95% CI 5.4–28.5%, p = 0.005) of treatment escalation frequency between the control arm (nine of 76 [12%]) and the intervention arm (30/102 [29%]). Treatment de-escalation occurred in the control and intervention arms in eight of 76 (10.5%) and 12/102 (11.8%) patients, and mixed changes in zero of 76 (0%) and four of 102 (3.9%) patients, respectively.

Conclusions

In this prospective randomized phase 3 study, PSMA-PET findings provided information that initiated major management changes to SRT planning in 33/102 (33%) patients. The final readout of the primary endpoint planned in 2025 may provide evidence on whether these changes result in improved outcomes.

Patient summary

Prostate-specific membrane antigen positron emission tomography leads to management changes in one-third of patients receiving salvage radiotherapy for post-radical prostatectomy biochemical recurrence of prostate cancer.

中文翻译：

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前列腺特异性膜抗原正电子发射断层扫描/计算机断层扫描对前列腺癌挽救性放射治疗管理的影响：前瞻性多中心随机 3 期试验的结果 (PSMA-SRT NCT03582774)

背景

影像学和一些预后因素均可为挽救性放射治疗 (SRT) 的规划提供信息。前列腺特异性膜抗原正电子发射断层扫描 (PSMA-PET) 可以定位其他成像方式无法发现的疾病。

客观的

评估 PSMA-PET 对 SRT 后生化无复发生存率的影响。

设计、设置和参与者

这项前瞻性随机对照 3 期临床试验将 193 名根治性前列腺切除术后前列腺癌生化复发的患者随机分组，分别接受 SRT（对照组，n  = 90）或在 SRT 之前接受 PSMA-PET/计算机断层扫描 (CT) 扫描计划（研究组，n  = 103）从 2018 年 6 月至 2020 年 8 月。两个组都允许使用任何其他批准的成像方式（包括氟昔洛韦 - PET）。

结果测量和统计分析

这是次要终点分析：PSMA-PET 对 SRT 计划的影响。病例报告表被发送给转诊放射肿瘤科医生，以在随机分组前和 SRT 完成后收集管理计划。使用卡方检验和 Fisher 精确检验比较各组内管理变更的相对频率 (%)。

结果和局限性

178/193 名患者（92.2%；76/90 对照 [84.4%] 和 102/103 PSMA-PET [99%]）可使用已交付的 SRT 计划。对照组的入组时前列腺特异性抗原水平中位数为 0.30 ng/ml（四分位距 [IQR] 0.19-0.91），PSMA-PET 组为 0.23 ng/ml（IQR 0.15-0.54）。对照组中 33/76 (43%) 的患者使用了氟昔洛芬-PET。PSMA-PET 局部复发率为 38/102 (37%)：102 例中有 9 例 (9%) 位于骨盆外 (M1)，16/102 (16%) 位于骨盆淋巴结 (N1，有或没有局部复发)复发），13/102（13%）仅发生在前列腺窝。对照组 (22 % [ 17/76  ]) 和 PSMA-PET 干预组 (45 ％[46/102]）。在干预组的主要变化中，33/46 (72%) 被认为与 PSMA-PET 有关。 对照组（76 例中的 9 例 [12%]）和干预组（30/102 [29%]）之间的治疗升级频率存在 17.6% 的差异（95% CI 5.4–28.5%，p = 0.005）。76 名患者中的 8 名 (10.5%) 和 12/102 名 (11.8%) 患者中对照组和干预组发生了治疗降级，76 名患者中的 0 名 (0%) 和 102 名患者中的 4 名 (3.9%) 出现了混合变化。分别。

结论

在这项前瞻性随机 3 期研究中，PSMA-PET 结果提供的信息启动了对 33/102 (33%) 患者的 SRT 计划进行重大管理改变。计划于 2025 年公布的主要终点的最终结果可能会提供证据，证明这些变化是否会改善结果。

患者总结

前列腺特异性膜抗原正电子发射断层扫描导致三分之一因前列腺癌根治术后生化复发而接受挽救性放射治疗的患者的治疗发生变化。