Effect of [68Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial.

Those with high clinical risk but non-suspicious or equivocal MRI often undergo prostate biopsy, but have a low likelihood of clinically significant prostate cancer, and a high incidenceof clinically insignificant prostate cancer.

那些临床风险高但MRI检查结果不具可疑性或模棱两可的患者，通常会接受前列腺活检，但其临床显著性前列腺癌的可能性较低，而临床不显著前列腺癌的发生率较高。

We aimed to investigate whether gallium-68 ([68Ga]Ga)-prostate-specific membrane antigen (PSMA)-11 PET-CT could reduce the number of people requiring prostate biopsy and limit biopsy to targeted cores, without compromising clinically significant prostate cancer diagnosis.

我们的目标是研究是否使用镓-68 ([68Ga]Ga)-前列腺特异性膜抗原 (PSMA)-11 PET-CT可以减少需要进行前列腺活检的人数，并将活检限制在目标核心上，同时不损害对临床显著性前列腺癌的诊断。

Methods

In this multicentre, non-inferiority, phase 3, randomised controlled trial, done at at seven Australian hospitals, we recruited biopsy-naive participants with clinical suspicion of significant prostate cancer, equivocal (Prostate Imaging-Reporting and Data System [PI-RADS] 3) or non-suspicious (PI-RADS 2) MRI but high clinical risk (eg, prostate-specific antigen [PSA] density of >0·1 ng/mL/mL, strong family history of prostate cancer, abnormal digital rectal examination, BRCA mutation, PSA >10 ng/mL, PSA doubling time <36 months, or PSA velocity >0·75 ng/mL per year), PSA of 20 ng/mL or less, and clinical T2 disease or less.

在这项多中心、非劣效性、第三阶段、随机对照试验中，我们在七家澳大利亚医院进行，招募了临床怀疑有显著性前列腺癌的活检初学者，他们有可疑（前列腺成像报告和数据系统 [PI-RADS] 3）或非可疑（PI-RADS 2）的MRI结果，但临床风险高（例如，前列腺特异性抗原 [PSA] 密度>0·1 ng/mL/mL，有强烈的前列腺癌家族史，数字直肠检查异常，BRCA突变，PSA >10 ng/mL，PSA倍增时间<36个月，或PSA速度>0·75 ng/mL/年），PSA为20 ng/mL或以下，以及临床T2疾病或更轻。

Participants were randomly assigned (1:1) using a centralised web-based system to undergo [68Ga]Ga-PSMA-11 PET-CT (experimental group) or systematic transperineal prostate biopsy (control group), using block sizes of two or four and stratification by study site.

参与者通过中央网络系统随机分配（1:1），接受[68Ga]Ga-PSMA-11 PET-CT（实验组）或系统性经会阴前列腺活检（对照组），使用大小为两或四的分块，并按研究地点进行分层。

There was no masking for participants or investigators.

参与者或研究人员均未进行盲法处理。

Participants with positive [68Ga]Ga-PSMA-11 PET-CT (PRIMARY score 3-5) underwent PSMA-PET-targeted transperineal prostate biopsies, whereas those with a negative result (PRIMARY score 1-2) avoided biopsy.

具有阳性[68Ga]Ga-PSMA-11 PET-CT（PRIMARY评分3-5）的参与者接受了PSMA-PET靶向经会阴前列腺活检，而阴性结果（PRIMARY评分1-2）的参与者避免了活检。

The co-primary outcomes were the proportion of participants with clinically significant prostate cancer, defined as a Gleason score of 3 + 4 (≥10% pattern 4) or higher, and the proportion of participants in the [68Ga]Ga-PSMA-11 PET-CT group who avoided biopsy within 6 months of random assignment.

主要共研究结果是具有临床显著性前列腺癌的参与者比例，定义为Gleason评分为3+4（≥10%模式4）或更高，以及在随机分配后6个月内避免活检的[68Ga]Ga-PSMA-11 PET-CT组参与者的比例。

A two-sided 95% Wald CI based on a binomial model was used to estimate the risk difference in the proportion of participants with clinically significant prostate cancer (non-inferiority margin 10%) and to estimate the proportion of participants in the experimental group who had avoided biopsy 6 months after random assignment (20% threshold), analysed based on intention to treat.

使用基于二项模型的双侧95% Wald置信区间来估计具有临床显著性前列腺癌的参与者比例的风险差异（非劣效性边界为10%），并估计实验组中在随机分配后6个月避免活检的参与者的比例（20%阈值），基于意向治疗分析。

This trial is registered with ClinicalTrials.gov, NCT05154162, and participant follow-up is ongoing.

该试验已在ClinicalTrials.gov上注册，编号为NCT05154162，参与者的随访正在进行中。

Results

Between March 2, 2022, and Aug 24, 2025, 660 eligible male participants were enrolled and had a median age of 61 years (IQR 56-66), a median PSA of 5·2 ng/mL (4·0-7·0), and a median PSA density of 0·13 ng/mL/mL (0·09-0·17).

在2022年3月2日至2025年8月24日期间，共有660名符合条件的男性参与者入组，他们的中位年龄为61岁（四分位数间距56-66岁），中位前列腺特异性抗原（PSA）水平为5.2 ng/mL（范围4.0-7.0 ng/mL），中位PSA密度为0.13 ng/mL/mL（范围0.09-0.17 ng/mL/mL）。

There were PI-RADS 2 in 335 (51%) participants and PI-RADS 3 in 325 (49%) participants.

在参与者中，有335名（51%）的PI-RADS评分为2，325名（49%）的PI-RADS评分为3。

Ethnicity data were not collected. 329 (50%) were assigned to the control group with systematic transperineal prostate biopsy, and 331 (50%) were assigned to the experimental group with [68Ga]Ga-PSMA-11 PET-CT.

未收集种族数据。329名（50%）被分配到对照组，接受系统性经会阴前列腺活检，331名（50%）被分配到实验组，接受[68Ga]Ga-PSMA-11 PET-CT。

The proportion of participants with clinically significant prostate cancer in the experimental group (39 [12%] of 331) was non-inferior to the control (51 [16%] of 329; difference -3·7% [95% CI -8·9 to 1·5%]; p=0·0093).

实验组中具有临床显著性前列腺癌的参与者比例（331名中的39名，占12%）不劣于对照组（329名中的51名，占16%；差异-3.7% [95% 置信区间-8.9至1.5%]；p=0.0093）。

Use of [68Ga]Ga-PSMA-11 PET-CT avoided biopsy in 163 (49%) of 331 participants (95% CI 44 to 55%; p <0·0001).

在331名参与者中，使用[68Ga]Ga-PSMA-11 PET-CT避免了163名（49%）的活检（95%置信区间44%至55%；p<0.0001）。

After prostate biopsy, participants reported similar proportions of pain (33 [21%] in the experimental group vs 62 [21%] in the control group), haematuria (60 [38%] vs 126 [43%]), and haematospermia (77 [48%] vs 133 [45%]).

前列腺活检后，参与者报告了相似的疼痛比例（实验组33名[21%]对比对照组62名[21%]），血尿（实验组60名[38%]对比对照组126名[43%]），以及血精（实验组77名[48%]对比对照组133名[45%]）。

interpretation

[68Ga]Ga-PSMA-11 PET-CT could have the potential to improve the diagnostic pathway of patients with a high clinical risk but non-suspicious or equivocal prostate MRI.

[68Ga]Ga-PSMA-11 PET-CT可能有潜力改善临床风险高但前列腺MRI无异常或可疑的患者的诊断途径。

Further research, including health-economic analyses and validation with other PSMA radiopharmaceuticals, are needed to confirm the clinical implementation and generalisability of this approach.

需要进一步的研究，包括健康经济分析和与其他PSMA放射性药物的验证，以确认这种方法的临床实施和普遍适用性。

funding

Prostate Cancer Foundation, National Health and Medical Research Council, St Vincent's Curran Foundation, and Peter MacCallum Cancer Foundation.

前列腺癌基金会、国家健康与医学研究委员会、圣文森特Curran基金会和彼得·麦克卡勒姆癌症基金会。