Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA; UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, Los Angeles, CA, USA.
Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
Eur Urol. 2024 Jul;86(1):52-60. doi: 10.1016/j.eururo.2024.01.012. Epub 2024 Jan 29.
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. The main objective of the study was to evaluate the impact of PSMA-PET on biochemical recurrence-free survival rate after SRT.
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). 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.
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.
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.
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.
影像学检查和多种预后因素均有助于制定挽救性放疗（SRT）计划。前列腺特异性膜抗原正电子发射断层扫描（PSMA-PET）可以定位其他影像学检查方法无法发现的疾病。本研究的主要目的是评估 PSMA-PET 对 SRT 后生化无复发生存率的影响。
本前瞻性随机对照 III 期临床试验于 2018 年 6 月至 2020 年 8 月期间将 193 例前列腺癌根治术后生化复发的患者随机分为 SRT 组（对照组，n=90）或 PSMA-PET/计算机断层扫描（CT）扫描组（研究组，n=103）。允许两组患者使用任何其他批准的影像学检查方法（包括氟膦酸镓-PET）。这是一项次要终点分析：PSMA-PET 对 SRT 计划的影响。病例报告表被发送给转诊放射肿瘤学家，以收集随机分组前和 SRT 完成后的管理计划。使用卡方检验和 Fisher 精确检验比较每组内管理方案变化的相对频率（%）。
178/193 例患者（92.2%；90 例对照组中有 76 例[84.4%]，103 例 PSMA-PET 组中有 102 例[99%]）可获得 SRT 计划。对照组中位前列腺特异性抗原水平为 0.30ng/ml（四分位距[IQR]0.19-0.91），PSMA-PET 组为 0.23ng/ml（IQR 0.15-0.54）。对照组中有 33 例（43%）患者使用氟膦酸镓-PET。PSMA-PET 定位复发（102 例患者中有 38 例[37%]）：9 例（9%）位于骨盆外（M1），16 例（16%）位于骨盆淋巴结（N1，伴或不伴局部复发），13 例（13%）仅位于前列腺窝。对照组（22%[76 例中有 17 例]）和 PSMA-PET 干预组（45%[102 例中有 46 例]）之间主要改变的频率差异为 23%（95%CI 9-35%，p=0.002）。干预组的主要改变中有 33/46（72%）被认为与 PSMA-PET 相关。对照组（9/76[12%]）和干预组（30/102[29%]）之间治疗升级频率的差异为 17.6%（95%CI 5.4-28.5%，p=0.005）。对照组和干预组分别有 8/76（10.5%）和 12/102（11.8%）例患者发生治疗降级，对照组和干预组分别有 0/76（0%）和 4/102（3.9%）例患者发生混合改变。
在这项前瞻性随机 III 期研究中，PSMA-PET 检查结果为 33/102（33%）患者的 SRT 计划提供了信息，这些患者的管理方案发生了重大改变。计划于 2025 年得出的主要终点最终结果可能提供这些改变是否会改善结局的证据。
前列腺特异性膜抗原正电子发射断层扫描导致三分之一接受前列腺癌根治术后生化复发的挽救性放疗的患者的管理方案发生改变。
