Lindegaard Jacob Christian, Petric Primoz, Tan Li-Tee, Hoskin Peter, Schmid Maximilian P, Jürgenliemk-Schulz Ina, Mahantshetty Umesh, Kirisits Christian, Pötter Richard
Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
Department of Radiation Oncology, University Hospital Zürich, Zürich, Switzerland.
Int J Gynecol Cancer. 2024 Dec 2;34(12):1940-1945. doi: 10.1136/ijgc-2024-005572.
Major improvements in radiotherapy over the past two decades in the definitive treatment of locally advanced cervical cancer have significantly improved loco-regional control and survival, whereas little progress has been made with chemotherapy since the implementation of concomitant cisplatin 25 years ago. However, the randomized study INTERLACE (A phase III multicenter trial of weekly induction chemotherapy followed by standard chemoradiation versus standard chemoradiation alone in patients with locally advanced cervical cancer) of neoadjuvant chemotherapy presented recently, has shown significant improvement in survival with the use of six cycles of weekly carboplatin and paclitaxel. Although INTERLACE is yet to be published, neoadjuvant chemotherapy is already being advocated as the new standard, and studies are being designed with neoadjuvant chemotherapy followed by chemoradiation and brachytherapy as the standard arm. It is noteworthy that INTERLACE was initiated before the improvements in radiotherapy mentioned above were broadly implemented. The survival rate in the standard arm of INTERLACE was therefore inferior to the results obtained with the latest state-of-the-art external beam radiotherapy and image guided adaptive brachytherapy (EMBRACE, Magnetic Resonance Imaging (MRI)-Guided Brachytherapy in Locally Advanced Cervical Cancer). Moreover, patient selection impedes the comparison of INTERLACE with other studies as the patients included in INTERLACE were younger, had better performance status, and had less advanced disease than in other studies. Notably patients with involved para-aortic nodes were excluded. In this review, we discuss neoadjuvant chemotherapy in the frame of the EMBRACE studies and show how the impact of modern radiotherapy and patient selection affects the interpretation of the results of INTERLACE. This has led us to conclude that neoadjuvant chemotherapy is not needed for the majority of patients with cervical cancer treated with definitive modern radiotherapy, and may cause harm. However, it is possible that short course neoadjuvant chemotherapy may benefit a minor subgroup of patients who need to be identified. Comprehensive understanding, including cost utility analyses, are needed to draw conclusions regarding the potential benefit of neoadjuvant chemotherapy in low and middle income countries with limited access to modern radiotherapy.
在过去二十年中,局部晚期宫颈癌的确定性治疗在放射治疗方面取得了重大进展,显著改善了局部区域控制和生存率,而自25年前顺铂同步放化疗实施以来,化疗方面进展甚微。然而,最近公布的新辅助化疗随机研究INTERLACE(一项III期多中心试验,对比局部晚期宫颈癌患者每周诱导化疗后进行标准放化疗与单纯标准放化疗的疗效)表明,使用六个周期的每周一次卡铂和紫杉醇可显著提高生存率。尽管INTERLACE尚未发表,但新辅助化疗已被倡导为新标准,并且正在设计以新辅助化疗后进行放化疗和近距离放疗作为标准治疗组的研究。值得注意的是,INTERLACE是在上述放疗改进广泛实施之前启动的。因此,INTERLACE标准治疗组的生存率低于采用最新的先进外照射放疗和图像引导适应性近距离放疗(EMBRACE,局部晚期宫颈癌的磁共振成像(MRI)引导近距离放疗)所获得的结果。此外,患者选择阻碍了将INTERLACE与其他研究进行比较,因为与其他研究相比,纳入INTERLACE的患者更年轻、身体状况更好且疾病分期更晚。值得注意的是,主动脉旁淋巴结受累的患者被排除在外。在本综述中,我们在EMBRACE研究的框架内讨论新辅助化疗,并展示现代放疗和患者选择的影响如何影响对INTERLACE结果的解释。这使我们得出结论,对于大多数接受确定性现代放疗的宫颈癌患者而言,不需要新辅助化疗,而且新辅助化疗可能会造成伤害。然而,短程新辅助化疗可能会使一小部分需要识别的患者受益。需要进行包括成本效益分析在内的全面理解,才能就新辅助化疗在难以获得现代放疗的低收入和中等收入国家的潜在益处得出结论。