Molecular Imaging and Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Department of Surgery, Austin Health, Melbourne, VIC, Australia; Urological Society of Australia and New Zealand, NSW, Australia.
Lancet. 2020 Apr 11;395(10231):1208-1216. doi: 10.1016/S0140-6736(20)30314-7. Epub 2020 Mar 22.
Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.
In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358.
From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT.
PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.
Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.
在对高危局限性前列腺癌患者进行分期时，常规的 CT 和骨扫描敏感性不足。我们旨在研究使用前列腺特异性膜抗原（PSMA）PET-CT 是否可以提高准确性并影响治疗方法。
在这项多中心、两臂、随机研究中，我们招募了澳大利亚十家医院经活检证实患有前列腺癌且具有高危特征的男性患者。患者被随机分配接受 CT 和骨扫描常规成像或镓-68 PSMA-11 PET-CT 检查。在随机分组后 21 天内进行一线成像。除非发现三个或更多远处转移，否则患者将交叉。主要结局是使用包括 6 个月随访时的组织病理学、影像学和生物化学在内的预定参考标准的接受者操作曲线确定一线成像识别骨盆淋巴结或远处转移性疾病的准确性。该试验在澳大利亚和新西兰临床试验注册处注册，ANZCTR12617000005358。
从 2017 年 3 月 22 日至 2018 年 11 月 2 日，对 339 名符合条件的患者进行了评估，其中 302 名患者被随机分配。152 名（50%）患者被随机分配接受常规成像，150 名（50%）接受 PSMA PET-CT。在 295 名（98%）有随访的男性中，87 名（30%）患有骨盆淋巴结或远处转移性疾病。PSMA PET-CT 的准确性比常规成像高 27%（95%CI 23-31）（92%[88-95]比 65%[60-69]；p<0·0001）。与 PSMA PET-CT 相比，常规成像的敏感性（38%[24-52]比 85%[74-96]）和特异性（91%[85-97]比 98%[95-100]）较低。亚组分析也表明 PSMA PET-CT 的优越性（接受者操作特征曲线下面积为 91%比 59%[32%绝对差异；28-35]，用于盆腔淋巴结转移患者；95%比 74%[22%绝对差异；18-26]，用于远处转移患者）。一线常规成像改变管理的频率较低（23[15%]名男性[10-22]比 41[28%]名男性[21-36]；p=0·008），且结果较模糊（23%[17-31]比 7%[4-13]）。与 PSMA PET-CT 相比，常规成像的辐射暴露量更高（10.9 mSv[95%CI 9.8-12.0]比 19.2 mSv[8.4-12.0]；p<0·001）。我们发现 PSMA PET-CT 的报告者一致性很高（淋巴结为 κ=0·87，远处转移为 κ=0·88）。在接受二线成像的患者中，在接受常规成像的 136 名患者中有 7 名（5%），在接受 PSMA PET-CT 的 146 名患者中有 39 名（27%）发生了管理改变。
PSMA PET-CT 是一种合适的替代常规成像的方法，可以提供更高的准确性，与 CT 和骨扫描的综合结果一致。
莫纳罗男人健康基金会和澳大利亚前列腺癌基金会。
视频摘要。
