Population-Based Prostate Cancer Screening With Magnetic Resonance Imaging or Ultrasonography, 2018-2019

Importance Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations. Objective To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer. Design, Setting, and Participants This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019. Interventions All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion–targeted biopsies were performed if the MRI or ultrasonography results were positive. Main Outcomes and Measures The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher. Results A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases. Conclusions and Relevance In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.<p>IP1-PROSTAGRAM was a population-based screening study evaluating magnetic resonance imaging (MRI), ultrasound, and prostate-specific antigen (PSA) for detection of prostate cancer. In this cohort study in which 408 men underwent 3 screening tests, an MRI score of 4 or 5 was associated with improved detection of clinically significant prostate cancer without an increase in the number of men who underwent biopsy or were overdiagnosed with clinically insignificant prostate cancer if prostate-specific antigen testing alone was used. Ultrasonography was not associated with improved screening performance. Making the dataset open access, including image files from the screening tests, will facilitate future advancement and discovery in prostate cancer diagnosis and treatment. The trial was sponsored by Imperial College London and funded by grant 204998/Z/16/Z from the Wellcome Trust Programme, a BMA Foundation for Medical Research grant, grant RESCH18 from a Urology Foundation Research Scholarship, a Royal College of Surgeons of England Research Fellowship, and a grant from UK National Institute of Health Research Imperial Biomedical Research Centre.</p>研究背景：采用前列腺特异性抗原（prostate-specific antigen, PSA）检测进行前列腺癌筛查，可能会出现诊断不足与过度诊断的问题。短时长无对比剂磁共振成像（magnetic resonance imaging, MRI）或经直肠超声检查或可克服这些局限。 研究目的：比较PSA检测、MRI与经直肠超声检查作为前列腺癌筛查手段的筛查性能。 研究设计、场景与对象：本项基于人群的前瞻性盲法队列研究于英国的7家初级保健机构与2家影像中心开展。2018年10月10日至2019年5月15日期间，招募50~69岁男性参与前列腺癌筛查。 干预措施：所有参与者均接受PSA检测、MRI（T2加权成像与弥散加权成像）以及经直肠超声检查（B型超声与剪切波弹性成像）筛查。各项检测独立判读，不参考其他检测结果。两项影像检查均采用经过验证的5级可疑度评分标准进行报告。若任意一项检测结果为阳性，则实施标准12针前列腺活检；若MRI或经直肠超声检查结果为阳性，则额外实施影像融合靶向活检。 主要结局与测量指标：主要结局为MRI或经直肠超声检查结果阳性（定义为评分3~5分或4~5分）、PSA检测结果阳性（定义为PSA≥3 μg/L）的男性占比。关键次要结局为若单独使用各项检测时，检出的临床有意义前列腺癌与临床无意义前列腺癌的数量。临床有意义前列腺癌定义为格里森评分（Gleason score）≥3+4的前列腺癌。 研究结果：共计招募2034名男性参与筛查；其中411名男性到场接受筛查，408名同意完成全部筛查项目。MRI结果阳性（评分3~5分）的占比高于PSA检测阳性占比[72例（17.7%；95%置信区间：14.3%~21.8%）相较于40例（9.9%；95%置信区间：7.3%~13.2%）；P<0.001]。经直肠超声检查结果阳性（评分3~5分）的占比同样高于PSA检测阳性占比[96例（23.7%；95%置信区间：19.8%~28.1%）；P<0.001]。若将影像检查阳性阈值设为4~5分，则MRI结果阳性占比与PSA检测阳性占比无显著差异[43例（10.6%；95%置信区间：7.9%~14.0%）；P=0.71]，经直肠超声检查结果阳性占比亦与PSA检测阳性占比无显著差异[52例（12.8%；95%置信区间：9.9%~16.5%）；P=0.15]。PSA检测（≥3 ng/mL）检出7例临床有意义前列腺癌，MRI评分3~5分检出14例，MRI评分4~5分检出11例，经直肠超声评分3~5分检出9例，经直肠超声评分4~5分检出4例。PSA检测确诊6例临床无意义前列腺癌，MRI评分3~5分确诊7例，MRI评分4~5分确诊5例，经直肠超声评分3~5分确诊13例，经直肠超声评分4~5分确诊7例。 研究结论与意义：本项队列研究显示，在普通人群前列腺癌筛查中，以4~5分作为阳性阈值的MRI筛查，相较于单独采用≥3 ng/mL的PSA检测，可检出更多临床有意义前列腺癌，且未增加需接受活检的男性人数或过度诊断临床无意义前列腺癌的人数。未发现经直肠超声检查的筛查性能优于PSA检测的证据。 IP1-PROSTAGRAM是一项基于人群的前列腺癌筛查研究，旨在评估磁共振成像（MRI）、经直肠超声检查与前列腺特异性抗原（PSA）的检出效能。本项队列研究共纳入408名完成全部三项筛查的男性，结果显示，以4~5分作为阳性判定阈值的MRI方案，相较单独采用≥3 ng/mL的PSA检测，可更有效地检出临床有意义前列腺癌，且未增加需接受活检的男性人数，亦未提升临床无意义前列腺癌的过度诊断率。经直肠超声检查未展现出优于PSA检测的筛查性能。将该数据集开放获取（包含筛查试验的影像文件），将为前列腺癌诊疗领域的后续研究与技术进步提供有力支撑。本试验由帝国理工学院（Imperial College London）赞助，资助方包括惠康信托基金（Wellcome Trust）项目（编号204998/Z/16/Z）、英国医学协会医学研究基金会（BMA Foundation for Medical Research）、泌尿外科基金会研究奖学金项目（编号RESCH18）、英格兰皇家外科医学院（Royal College of Surgeons of England）研究奖学金，以及英国国家卫生与保健研究院帝国生物医学研究中心（UK National Institute of Health Research Imperial Biomedical Research Centre）的项目资助。