Lou David Y, Fong Lawrence
Division of Hematology/Oncology, University of California, San Francisco, CA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
Division of Hematology/Oncology, University of California, San Francisco, CA; UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
Urol Oncol. 2016 Apr;34(4):182-92. doi: 10.1016/j.urolonc.2013.12.001. Epub 2014 Feb 2.
Efforts to improve the clinical outcome for patients with localized high-risk prostate cancer have led to the development of neoadjuvant systemic therapies. We review the different modalities of neoadjuvant therapies for localized prostate cancer and highlight emerging treatment approaches including immunotherapy and targeted therapy.
We performed a PubMed search of clinical trials evaluating preoperative systemic therapies for treating high-risk prostate cancer published after 2000, and those studies with the highest clinical relevance to current treatment approaches were selected for review. The database at clinicaltrials.gov was queried for neoadjuvant studies in high-risk prostate cancer, and those evaluating novel targeted therapies and immunotherapies are spotlighted here.
Neoadjuvant chemotherapy has become standard of care for treating some malignancies, including breast and bladder cancers. In prostate cancer, preoperative hormonal therapy or chemotherapy has failed to demonstrate improvements in overall survival. Nevertheless, the emergence of novel treatment modalities such as targeted small molecules and immunotherapy has spawned neoadjuvant clinical trials that provide a unique vantage from which to study mechanism of action and biological potency. Tissue-based biomarkers are being developed to elucidate the biological efficacy of these treatments. With targeted therapy, these can include phospho-proteomic signatures of target pathway activation and deactivation. With immunotherapies, including sipuleucel-T and ipilimumab, recruitment of immune cells to the tumor microenvironment can also be used as robust markers of a biological effect. Such studies can provide insight not only into mechanism of action for these therapies but can also provide paths forward to improving clinical efficacy like with rationally designed combinations and dose selection.
The use of neoadjuvant androgen-deprivation therapy and chemotherapy either singly or in combination before radical prostatectomy is generally safe and feasible while reducing prostate volume and tumor burden. However, pathologic complete response rates are low and no long-term survival benefit has been observed with the addition of neoadjuvant therapies over surgery alone at present, and therefore preoperative therapy is not the current standard of care in prostate cancer treatment.
为改善局限性高危前列腺癌患者的临床结局所做的努力促使了新辅助全身治疗的发展。我们回顾了局限性前列腺癌新辅助治疗的不同方式，并重点介绍了包括免疫治疗和靶向治疗在内的新兴治疗方法。
我们在PubMed上检索了2000年后发表的评估术前全身治疗高危前列腺癌的临床试验，并选择了与当前治疗方法临床相关性最高的研究进行综述。在clinicaltrials.gov数据库中查询高危前列腺癌的新辅助研究，这里重点介绍那些评估新型靶向治疗和免疫治疗的研究。
新辅助化疗已成为治疗某些恶性肿瘤（包括乳腺癌和膀胱癌）的标准治疗方法。在前列腺癌中，术前激素治疗或化疗未能证明能改善总生存期。然而，诸如靶向小分子和免疫治疗等新型治疗方式的出现催生了新辅助临床试验，这些试验提供了一个独特的视角来研究作用机制和生物学效能。基于组织的生物标志物正在被开发以阐明这些治疗的生物学疗效。对于靶向治疗，这些生物标志物可以包括靶标通路激活和失活的磷酸化蛋白质组学特征。对于免疫治疗，包括sipuleucel-T和伊匹木单抗，免疫细胞向肿瘤微环境的募集也可以用作生物学效应的有力标志物。此类研究不仅可以深入了解这些治疗的作用机制，还可以为通过合理设计联合用药和剂量选择来提高临床疗效提供途径。
在根治性前列腺切除术之前单独或联合使用新辅助雄激素剥夺治疗和化疗通常是安全可行的，同时可减少前列腺体积和肿瘤负荷。然而，病理完全缓解率较低，目前在手术基础上加用新辅助治疗未观察到长期生存获益，因此术前治疗并非目前前列腺癌治疗的标准治疗方法。
