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。PC的诊断依赖于前列腺活检。然而，标准的经直肠超声引导随机活检可能会错过临床上重要的肿瘤，并且它们也会导致不太可能从诊断中受益的男性癌症检测。由于广泛采用PSA测试，发达国家的发病率和死亡率之间存在八倍的差异。虽然高风险的肿瘤仍然经常被发现为时已晚，在同一时间过度诊断和过度治疗的大量的生物学上无关紧要的低风险的肿瘤代表重要的临床和经济problems.The最佳管理本地PC是至关重要的依赖于一个准确的评估的个体化风险的肿瘤进展的患者的一生。虽然积极监测现在应该是惰性疾病的治疗选择，但由于重新分类为高风险疾病，仍有高达40%的男性在积极监测期间早期转向积极治疗。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。证据正在积累，多参数磁共振成像（mp-MRI）可用于提高前列腺活检的性能。在这种情况下，我们已经开发了一种新的前列腺活检系统，融合介入前的MRI数据与围介入超声图像引导经会阴前列腺活检。该平台能够准确检查前列腺的所有区域，并准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显著癌症的有效性和准确性，并与通过根治性前列腺切除术获得的样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的前列腺活检方案和所需的核心数量，以减少对惰性肿瘤的过度诊断，而不会低估侵袭性疾病。该提案的结果将提高患者安全性，并进一步个性化PC患者的管理。最终，它们对于防止对患有惰性疾病的男性进行过度检测和过度治疗将很有价值。

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.