Pye Hayley, Singh Saurabh, Norris Joseph M, Carmona Echeverria Lina M, Stavrinides Vasilis, Grey Alistair, Dinneen Eoin, Pilavachi Elly, Clemente Joey, Heavey Susan, Stopka-Farooqui Urszula, Simpson Benjamin S, Bonet-Carne Elisenda, Patel Dominic, Barker Peter, Burling Keith, Stevens Nicola, Ng Tony, Panagiotaki Eleftheria, Hawkes David, Alexander Daniel C, Rodriguez-Justo Manuel, Haider Aiman, Freeman Alex, Kirkham Alex, Atkinson David, Allen Clare, Shaw Greg, Beeston Teresita, Brizmohun Appayya Mrishta, Latifoltojar Arash, Johnston Edward W, Emberton Mark, Moore Caroline M, Ahmed Hashim U, Punwani Shonit, Whitaker Hayley C
Division of Surgery & Interventional Science, University College London, London WC1E 6BT, UK.
Centre for Medical Imaging, University College London, London WC1E 6BT, UK.
Cancers (Basel). 2021 Apr 20;13(8):1985. doi: 10.3390/cancers13081985.
: To assess the clinical outcomes of mpMRI before biopsy and evaluate the space remaining for novel biomarkers. The INNOVATE study was set up to evaluate the validity of novel fluidic biomarkers in men with suspected prostate cancer who undergo pre-biopsy mpMRI. We report the characteristics of this clinical cohort, the distribution of clinical serum biomarkers, PSA and PSA density (PSAD), and compare the mpMRI Likert scoring system to the Prostate Imaging-Reporting and Data System v2.1 (PI-RADS) in men undergoing biopsy. : 340 men underwent mpMRI to evaluate suspected prostate cancer. 193/340 (57%) men had subsequent MRI-targeted prostate biopsy. Clinically significant prostate cancer (csigPCa), i.e., overall Gleason ≥ 3 + 4 of any length OR maximum cancer core length (MCCL) ≥4 mm of any grade including any 3 + 3, was found in 96/195 (49%) of biopsied patients. Median PSA (and PSAD) was 4.7 (0.20), 8.0 (0.17), and 9.7 (0.31) ng/mL (ng/mL/mL) in mpMRI scored Likert 3,4,5 respectively for men with csigPCa on biopsy. The space for novel biomarkers was shown to be within the group of men with mpMRI scored Likert3 (178/340) and 4 (70/350), in whom an additional of 40% (70/178) men with mpMRI-scored Likert3, and 37% (26/70) Likert4 could have been spared biopsy. PSAD is already considered clinically in this cohort to risk stratify patients for biopsy, despite this 67% (55/82) of men with mpMRI-scored Likert3, and 55% (36/65) Likert4, who underwent prostate biopsy had a PSAD below a clinical threshold of 0.15 (or 0.12 for men aged <50 years). Different thresholds of PSA and PSAD were assessed in mpMRI-scored Likert4 to predict csigPCa on biopsy, to achieve false negative levels of ≤5% the proportion of patients whom who test as above the threshold were unsuitably high at 86 and 92% of patients for PSAD and PSA respectively. When PSA was re tested in a sub cohort of men repeated PSAD showed its poor reproducibility with 43% (41/95) of patients being reclassified. After PI-RADS rescoring of the biopsied lesions, 66% (54/82) of the Likert3 lesions received a different PI-RADS score. : The addition of simple biochemical and radiological markers (Likert and PSAD) facilitate the streamlining of the mpMRI-diagnostic pathway for suspected prostate cancer but there remains scope for improvement, in the introduction of novel biomarkers for risk assessment in Likert3 and 4 patients, future application of novel biomarkers tested in a Likert cohort would also require re-optimization around Likert3/PI-RADS2, as well as reproducibility testing.
评估活检前多参数磁共振成像（mpMRI）的临床结果，并评估新型生物标志物的剩余空间。INNOVATE研究旨在评估新型液体生物标志物在接受活检前mpMRI检查的疑似前列腺癌男性中的有效性。我们报告了该临床队列的特征、临床血清生物标志物、前列腺特异性抗原（PSA）和PSA密度（PSAD）的分布情况，并比较了接受活检男性的mpMRI李克特评分系统与前列腺影像报告和数据系统第2.1版（PI-RADS）。340名男性接受了mpMRI检查以评估疑似前列腺癌。193/340（57%）的男性随后接受了MRI靶向前列腺活检。在96/195（49%）的活检患者中发现了具有临床意义的前列腺癌（csigPCa），即任何长度的总体 Gleason评分≥3+4或任何分级的最大癌芯长度（MCCL）≥4 mm，包括任何3+3。对于活检时患有csigPCa的男性，mpMRI李克特评分为3、4、5时，PSA（和PSAD）的中位数分别为4.7（0.20）、8.0（0.17）和9.7（0.31）ng/mL（ng/mL/mL）。新型生物标志物的空间显示在mpMRI李克特评分为3（178/340）和4（70/350）的男性组中，其中mpMRI李克特评分为3的男性中另外40%（70/178）以及李克特评分为4的男性中37%（26/70）可以避免活检。在该队列中，PSAD已被临床用于对患者进行活检风险分层，尽管如此，接受前列腺活检的mpMRI李克特评分为3的男性中有67%（55/82），李克特评分为4的男性中有55%（36/65）的PSAD低于0.15的临床阈值（年龄<50岁的男性为0.12）。在mpMRI李克特评分为4的患者中评估了不同的PSA和PSAD阈值以预测活检时的csigPCa，为了使假阴性水平≤5%，对于PSAD和PSA，检测结果高于阈值的患者比例分别高达86%和92%，高得不合适。当在一个男性亚组中重新检测PSA时，重复检测的PSAD显示其再现性较差，43%（41/95）的患者被重新分类。对活检病变进行PI-RADS重新评分后，66%（54/82）的李克特评分为3的病变获得了不同的PI-RADS评分。添加简单的生化和放射学标志物（李克特评分和PSAD）有助于简化疑似前列腺癌的mpMRI诊断途径，但仍有改进空间，在李克特评分为3和4的患者中引入新型生物标志物进行风险评估，未来在李克特队列中测试的新型生物标志物的应用也需要围绕李克特3/PI-RADS2进行重新优化以及进行再现性测试。
