Division of Hematology/Oncology, Department of Internal Medicine, and University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
Cancer J. 2013 Jan-Feb;19(1):19-24. doi: 10.1097/PPO.0b013e318281197e.
Since 1941, the understanding of prostate cancer pathogenesis and therapy has undergone a significant transformation. Rigorous translational research has identified multiple mechanisms underlying castration resistance, the fatal clinical state of the disease. Therapeutic approaches targeting these mechanisms in metastatic castration-resistant prostate cancer have now been clinically validated in the clinic including high-potency androgen signaling inhibition, novel cytotoxic chemotherapy, and bone-targeted therapies. Despite these advances, cure remains an elusive goal. The natural history of metastatic prostate cancer has evolved particularly in the last 2 decades in step with improved management of age-associated comorbidities, improved imaging, and the expansion of novel therapies, thus providing new opportunities and challenges. It is also important to note that the advent of prostate-specific antigen testing caused a stage shift in the disease spectrum, thus leading to earlier interventions and potentially positively impacting survival. The optimal sequencing and combinations of available therapies, predictive biomarkers, and better understanding of mechanisms of resistance remain high priority. Further refinement of the clinical niche for novel therapies in hormone-sensitive and castration-resistant disease through rationally designed clinical trials incorporating molecular, clinical, and imaging biomarkers and quality-of-life correlatives is of paramount importance.
自 1941 年以来，人们对前列腺癌发病机制和治疗方法的理解发生了重大转变。严格的转化研究已经确定了导致去势抵抗的多种机制，而去势抵抗是该疾病的致命临床状态。针对转移性去势抵抗性前列腺癌中这些机制的治疗方法目前已在临床上得到验证，包括高效雄激素信号抑制、新型细胞毒性化疗和骨靶向治疗。尽管取得了这些进展，但治愈仍然是一个难以实现的目标。转移性前列腺癌的自然病程在过去 20 年中发生了特别的变化，这与年龄相关合并症管理的改善、成像技术的改进以及新型治疗方法的扩展有关，从而提供了新的机遇和挑战。值得注意的是，前列腺特异性抗原检测的出现导致了疾病谱的阶段转移，从而导致更早的干预，并可能对生存产生积极影响。确定现有治疗方法的最佳顺序和组合、预测生物标志物以及更好地了解耐药机制仍然是当务之急。通过合理设计的临床试验，结合分子、临床和影像学生物标志物以及生活质量相关性，进一步完善激素敏感和去势抵抗性疾病中新型治疗方法的临床定位，这一点至关重要。
