背景:下一代成像方法和分子生物标志物(“放射性基因组学”)的临床引入彻底改变了前列腺癌(PCa)领域。虽然这些测试的临床有效性已经过彻底审查,他们的临床效用仍然是一个调查问题。
目的:系统回顾迄今为止关于正电子发射断层扫描(PET)成像和基于组织的预后生物标志物的影响的证据,包括解密,Prolaris,和OncotypeDx,关于风险分层,治疗选择,以及新诊断的PCa或生化衰竭(BCF)男性的肿瘤结局。
方法:我们使用MEDLINE对文献进行了定量系统回顾,EMBASE,和WebofScience数据库(2010-2022)遵循系统审查和荟萃分析声明指南的首选报告项目。使用经过验证的诊断准确性研究2的质量评估评分系统来评估偏倚风险。
结果:共纳入148项研究(130项关于PET,18项关于生物标志物)。在主PCa设置中,前列腺特异性膜抗原(PSMA)PET成像对改善T分期没有帮助,对改善N分期中等有用,但在改善国家综合癌症网络(NCCN)不利的中至极高危PCa患者的M分期方面始终有用。它的使用导致20-30%的患者管理发生变化。然而,这些治疗改变对生存结局的影响尚不清楚.同样,治疗前原发性PCa设置中的生物标志物增加并降低了风险,分别,在7-30%和32-36%的NCCN低危患者中,31-65%和4-15%的NCCN有利中危患者被考虑进行主动监测。多达65%的患者发生了管理变化,这种变化符合基于分子风险的重新分类,但同样,这些变化对生存结局的影响尚不清楚.值得注意的是,在术后原发性PCa设置中,生物标记物引导的辅助放射治疗(RT)与肿瘤控制改善相关:Δ丨2年BCF降低22%(2b级).在BCF设置中,数据更加成熟。PSMAPET在改善T的疾病定位方面一直很有用。N,M分期为13-32%,19-58%,9-29%,分别。29%至73%的患者改变了管理方式。最重要的是,在三项试验中,这些管理方式的改变与生存结局的改善相关:Δ^4年无病生存率降低了24.3%,Δ^6个月无转移生存率(MFS)下降46.7%,接受PET一致RT(1b-2b级)的患者无雄激素剥夺治疗生存8mo。这些患者的生物标志物测试似乎也有助于风险分层和指导早期抢救RT(sRT)和伴随激素治疗的使用。具有高基因组风险评分的患者受益于强化治疗:使用早期sRT的Δ^8年MFS减少20%,使用激素治疗和早期sRT的Δ^12年MFS减少11.2%,而低基因组风险评分患者在最初的保守治疗(3级)中表现同样良好.
结论:PSMAPET成像和肿瘤分子谱分析均为原发性PCa患者和BCF患者的治疗提供了可行的信息。新的数据表明,放射性基因组学指导治疗转化为患者的直接生存益处,然而,等待更多的前瞻性数据.
结果:在这篇综述中,我们评估了前列腺特异性膜抗原正电子发射断层扫描和肿瘤分子谱分析在指导男性前列腺癌(PCa)治疗中的实用性.我们发现这些测试增强了风险分层,改变管理,并改善了新诊断为PCa的男性或复发患者的癌症控制。
BACKGROUND: The clinical introduction of next-generation imaging methods and molecular biomarkers (\"radiogenomics\") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation.
OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF).
METHODS: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias.
RESULTS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3).
CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited.
RESULTS: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.