MRI-targeted fusion-guided prostate cancer diagnostics - strategies to avoid overdiagnosis and overtreatment

前列腺癌（PC）是男性癌症相关发病率和死亡率的主要原因。前列腺癌的诊断依赖于前列腺活检。然而，标准的经直肠超声引导的随机活检可能会遗漏临床上重要的肿瘤，而且也会导致不太可能从诊断中受益的男性发现癌症。由于广泛采用psa检测，发达国家的发病率和死亡率之间存在8倍的差异。虽然高风险肿瘤仍然经常被发现得太晚，但与此同时，大量生物学上无关紧要的低风险肿瘤的过度诊断和过度治疗代表了重要的临床和经济问题。局部PC的最佳管理关键取决于对患者一生中肿瘤进展的个体化风险的准确评估。虽然主动监测现在应该是治疗惰性疾病的选择，但由于重新分类为高风险疾病，仍有高达40%的男性在主动监测期间早期转向主动治疗。为了安全地增加主动监测的广泛使用，需要改进PC诊断，以便从一开始就正确识别侵袭性疾病。越来越多的证据表明，多参数磁共振成像（mp-MRI）可用于提高前列腺活检的表现。在此背景下，我们开发了一种新的前列腺活检系统，该系统融合了介入前mri数据和介入周超声图像引导下的经会阴前列腺活检。该平台能够准确检查前列腺的所有区域，并精确定位癌症可疑病变。本提案的第一个目标是验证mp-MRI和mri靶向融合引导前列腺活检检测临床重要癌症的有效性和准确性，并将其与根治性前列腺切除术获得的标本作为参考标准进行比较。此外，我们的目标是前瞻性地优化图像引导前列腺活检方案和所需的核心数量，以减少惰性肿瘤的过度诊断，同时又不漏诊侵袭性疾病。使用新颖的3d图像引导组织采样，我们希望达到前所未有的诊断准确性。这项建议的结果将提高患者的安全性，并进一步个性化管理PC患者。最终，他们将是有价值的，以防止过度检测和过度治疗男性的惰性疾病。

Prostate cancer (PC) is a leading cause of cancer-related morbidity and mortality in men. PC diagnosis is dependent on prostate biopsy. However, standard transrectal ultrasound-guided random biopsies may miss clinically important tumors and they also result in cancer detection in men who are unlikely to benefit from the diagnosis. Due to widespread adoption of PSA-testing, there is an eightfold difference between incidence- and mortality-rates in developed countries. While high risk tumors are still often detected too late, at the same time overdiagnosis and overtreatment of large numbers of biologically insignificant low risk tumors represent important clinical and economical problems.The optimal management of localized PC is critically dependent on an accurate assessment of the individualized risk of tumor progression within the lifetime of the patient. Although active surveillance should nowadays be the treatment of choice for indolent disease, still up to 40% of men shift to active therapy early during their active surveillance due to reclassification towards higher risk disease. To safely increase widespread use of active surveillance, PC diagnostics need to be refined in order to correctly identify aggressive disease from the start.Evidence is accumulating that multiparametric magnetic resonance imaging (mp-MRI) can be used to improve the performance of prostate biopsy. In this context we have developed a novel prostate biopsy system, which fuses pre-interventional MRI-data with peri-interventional ultrasound for image-guided transperineal prostate biopsies. This platform enables accurate examination of all regions of the prostate and exact targeting of cancer-suspicious lesions. The first goal of this proposal is to validate the efficacy and accuracy of mp-MRI and MRI-targeted fusion-guided prostate biopsies to detect clinically significant cancers as compared to specimen obtained by radical prostatectomy as reference standard. Furthermore, we aim to prospectively optimize image-guided prostate biopsy protocols and numbers of cores needed to reduce overdiagnosis of indolent tumors without underdetecting aggressive disease.Using novel 3D-image-guided tissue sampling we want to achieve unprecedented diagnostic accuracy. The results of this proposal will increase patient safety and further individualise the management of PC patients. Ultimately, they will be valuable to prevent overdetection and overtreatment of men with indolent disease.