GINECO, Paris, France; Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, EMR UCBL/HCL 3738, Lyon, France; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Lyon, France.
GINECO, Paris, France; Université Lyon, Université Claude Bernard Lyon 1, Faculté de Médecine Lyon-Sud, EMR UCBL/HCL 3738, Lyon, France; Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, Lyon, France.
Cancer Treat Rev. 2021 Nov;100:102294. doi: 10.1016/j.ctrv.2021.102294. Epub 2021 Sep 15.
In patients with advanced ovarian carcinomas, the first-line treatment has historically relied on debulking surgery and platinum-based chemotherapy. If the major therapeutic/prognostic role of the surgery part is well understood, and integrated in disease-management algorithms, the impact of chemotherapy efficacy has been insufficiently addressed. This review describes the main indicators of the chemosensitivity reported in the literature (pathological response score & biomarkers; genomic alterations; DNA scars; imaging; and circulating tumor markers), and investigates the respective roles of the debulking surgery and tumor primary chemosensitivity relative to the success of the comprehensive medical-surgical treatment. The tumor primary chemosensitivity exhibits a major independent prognostic impact on the feasibility of complete interval debulking surgery after neoadjuvant chemotherapy, risk of subsequent platinum-resistant relapse, efficacy of subsequent maintenance therapies with bevacizumab or PARP inhibitors, progression-free survival, overall and long-term survival. While both the completeness of the surgery and the tumor primary chemosensitivity are undoubtedly major prognostic factors, the impact of the surgery may differ according to the primary chemosensitivity. This assumption raises a potential new concept: in patients with advanced ovarian carcinomas, the maximum tumor debulking should ideally be both biological (induced by systemic treatments) and physical (induced by surgery) for maximizing patient survival. Besides BRCA and HRD biomarkers, future trials and algorithms may integrate indicator(s) of the tumor primary chemosensitivity for guiding more subtly the surgical and medical management in first-line setting. Moreover, such a parameter would help in the development of novel approaches meant to reverse the resistance to chemotherapy and PARP inhibitors.
在晚期卵巢癌患者中，一线治疗历来依赖于肿瘤细胞减灭术和铂类化疗。如果手术部分的主要治疗/预后作用得到很好的理解，并整合到疾病管理算法中，那么化疗疗效的影响就没有得到充分的解决。这篇综述描述了文献中报道的化疗敏感性的主要指标（病理反应评分和生物标志物；基因组改变；DNA 痕迹；影像学；和循环肿瘤标志物），并研究了肿瘤原发性化疗敏感性相对于新辅助化疗后完全间隔肿瘤细胞减灭术的成功、随后铂类耐药复发的风险、贝伐珠单抗或 PARP 抑制剂维持治疗的疗效、无进展生存期、总生存期和长期生存期的相对作用。尽管肿瘤细胞减灭术的完整性和肿瘤原发性化疗敏感性无疑是主要的预后因素，但手术的影响可能因原发性化疗敏感性而异。这一假设提出了一个潜在的新概念：在晚期卵巢癌患者中，为了最大限度地提高患者的生存，最大程度的肿瘤减灭应该是生物性的（由全身治疗诱导）和物理性的（由手术诱导）。除了 BRCA 和 HRD 生物标志物外，未来的试验和算法可能会整合肿瘤原发性化疗敏感性的指标，以更微妙地指导一线治疗中的手术和医疗管理。此外，这样的参数将有助于开发新的方法，旨在逆转对化疗和 PARP 抑制剂的耐药性。
