Nature Reviews Urology ( IF 12.1 ) Pub Date : 2024-04-26 , DOI: 10.1038/s41585-024-00875-x Xudong Ni 1, 2, 3 , Yu Wei 1, 2, 3 , Xiaomeng Li 1, 2, 3 , Jian Pan 1, 2, 3 , Bangwei Fang 1, 2, 3 , Tingwei Zhang 1, 2, 3 , Ying Lu 4 , Dingwei Ye 1, 2, 3 , Yao Zhu 1, 2, 3
Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3–10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20–30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET–CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negative results, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group.
中文翻译:
从生物学到临床——探索前列腺癌的肝转移
前列腺癌的肝转移与侵袭性病程和不良预后相关。尸检研究结果表明,晚期前列腺癌患者的肝转移率高达 25%。人口数据估计,约 3-10% 的转移性去势抵抗性前列腺癌患者在基线时存在肝转移,在治疗后队列中上升至 20-30%,这表明新疗法施加的选择性压力可能会促进转移扩散到肝脏。与肺转移相比,肝转移与更具侵袭性的肿瘤生物学相关。肝脏病变的分子谱显示低雄激素受体、神经内分泌表型和高基因组不稳定性的富集。尽管前列腺特异性膜抗原 PET-CT 等分子成像模式和循环肿瘤 DNA 等液体活检标记物取得了进步,但前列腺癌肝转移的早期检测仍然具有挑战性,因为这两种方法都受到假阳性和假阴性结果的阻碍,妨碍了早期肝脏病变的准确识别。目前的治疗策略对该患者群体的疗效有限。新兴的靶向放射性核素疗法、转移导向疗法和新型全身药物已显示出针对肝转移的初步活性,但需要进一步验证。各种新型前列腺癌疗法可能会导致肝转移患病率增加,这凸显了临床前和临床研究人员迫切需要协调努力,以改善前列腺癌肝转移的表征、监测和管理。 阐明肝脏趋向性以及与肝脏微环境相互作用的分子驱动因素可能最终有助于确定可操作的目标,以提高这一高危患者群体的生存率。