BACKGROUND 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. METHODS 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. FINDINGS 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. INTERPRETATION PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. FUNDING Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.

中文翻译：

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高危前列腺癌患者行根治性手术或放疗前的前列腺特异性膜抗原 PET-CT (proPSMA)：一项前瞻性、随机、多中心研究。

背景技术使用 CT 和骨扫描的常规成像在对患有高危局限性前列腺癌的男性进行分期时灵敏度不足。我们旨在调查使用前列腺特异性膜抗原 (PSMA) PET-CT 的新型成像是否可以提高准确性并影响管理。方法 在这项多中心、两臂、随机研究中，我们在澳大利亚的 10 家医院招募了经活检证实为前列腺癌且具有高风险特征的男性。患者被随机分配接受 CT 和骨扫描的常规成像或镓 68 PSMA-11 PET-CT。一线成像在随机分组后 21 天内完成。除非确定三个或更多远处转移，否则患者会交叉。主要结果是在 6 个月的随访中，使用预先定义的参考标准（包括组织病理学、影像学和生物化学）确定由接受者操作曲线定义的盆腔淋巴结或远处转移性疾病的一线成像准确性。该试验已在澳大利亚新西兰临床试验注册处注册，ANZCTR12617000005358。结果 从 2017 年 3 月 22 日到 2018 年 11 月 2 日，339 名男性接受了资格评估，302 名男性被随机分配。152 名 (50%) 男性被随机分配到常规成像组，150 名 (50%) 名被随机分配到 PSMA PET-CT。在接受随访的 295 名 (98%) 男性中，87 名 (30%) 患有盆腔淋巴结或远处转移性疾病。PSMA PET-CT 的准确度比传统成像高 27% (95% CI 23-31)（92% [88-95] vs 65% [60-69]；p<0·0001）。我们发现与 PSMA PET-CT 相比，常规成像的敏感性（38% [24-52] vs 85% [74-96]）和特异性（91% [85-97] vs 98% [95-100]）较低. 亚组分析还显示 PSMA PET-CT 的优势（受试者工作特征曲线下面积 91% vs 59% [32% 绝对差异；28-35] 用于盆腔淋巴结转移患者，95% vs 74% [22% 绝对差异；18-26] 用于远处转移患者）。一线常规影像学治疗改变的频率较低（23 [15%] 男性 [10-22] vs 41 [28%] 男性 [21-36]；p=0·008）并且有更多模棱两可的发现（23% [ 17-31] vs 7% [4-13]) 比 PSMA PET-CT 所做的。常规成像的辐射暴露比 PSMA PET-CT 高 10·9 mSv (95% CI 9·8-12·0)（19·2 mSv vs 8·4 mSv；p<0·001）。我们发现 PSMA PET-CT 报告者高度一致（淋巴结转移的 κ=0·87，远处转移的 κ=0·88）。在接受二线影像检查的患者中，136 名患者中的 7 名 (5%) 接受了常规影像检查，而 146 名患者中的 39 名 (27%) 接受了 PSMA PET-CT 治疗。解释 PSMA PET-CT 是传统成像的合适替代品，为 CT 和骨扫描的综合发现提供了卓越的准确性。资助 Movember 和澳大利亚前列腺癌基金会。视频摘要。提供卓越的准确性，CT 和骨扫描的组合结果。资助 Movember 和澳大利亚前列腺癌基金会。视频摘要。提供卓越的准确性，CT 和骨扫描的组合结果。资助 Movember 和澳大利亚前列腺癌基金会。视频摘要。