Novel Treatment Concepts for Cervical Cancer-Moving Towards Personalized Therapy

In recent years, several randomized controlled trials have been published regarding cervical cancer therapy and significantly changed the treatment landscape. Recent advances have improved the treatment options and allow personalized treatment concepts with escalation of treatment in high-risk disease and de-escalation with reduction in morbidity in selected low-risk patients. This review aims to provide a comprehensive analysis of the latest landmark studies that are poised to significantly influence clinical practice. Personalized treatment concepts with careful patient selection allow de-escalation in the surgical treatment of cervical cancer. In low-risk cervical cancer patients (lesions of ≤2 cm with limited stromal invasion), simple hysterectomy (SH) was non-inferior to radical hysterectomy in terms of 3-year incidence of pelvic recurrence and was associated with a lower risk of urinary incontinence or retention and improved sexual health and quality of life. Furthermore, sentinel lymphadenectomy is constantly replacing systematic pelvic lymphadenectomy in patients with low-risk cervical cancer. In addition, further studies are necessary to clarify the role of postoperative therapy for patients with intermediate-risk cervical cancer. Starting in 2008, the EMBRACE studies assess the role of Image guided adaptive brachytherapy (IGABT) in LACC in addition to modern external beam radiotherapy concurrent to chemotherapy. The publication of the results of the EMBRACE I prospective study established MRI guided IGABT as state-of-the-art brachytherapy for LACC. EMBRACE II and additional prospective studies emerging from this consortium will address important questions in modern radiotherapy for LACC. Immune checkpoint inhibitors (CPIs) have been evaluated across various clinical settings and are expected to be utilized in numerous scenarios due to several positive randomized trials. Particularly, the combination of platinum-based chemotherapy and pembrolizumab, with or without bevacizumab, has been established as the new standard treatment for primary metastatic or recurrent PD-L1 positive high-risk cervical cancer. In locally advanced cervical cancer, two new treatment escalation regimens-neoadjuvant chemotherapy and adjuvant CPI therapy-have been evaluated in addition to chemoradiation. Furthermore, antibody-drug conjugates, such as tisotumab-vedotin, represent a promising future therapeutic option for recurrent cervical cancer.