New treatment options in cervical cancer

With an estimated incidence of 528.000 new cases per year worldwide, cervical cancer remains among the most common cancers in women, despite the large efforts for cervical cancer screening and the promotion of the HPV-vaccination. Therefore, it is obvious that further research to find new treatments stays necessary. In this doctoral thesis we tried to evaluate new treatments and compare these to already existing ones and thereby confirm and introduce new treatment options. The first part of this doctoral thesis contained the exploration of neoadjuvant chemotherapy in fertility sparing surgery and locally advanced cervical cancer. We showed that neoadjuvant chemotherapy followed by a reconization is a safe and successful possibility of fertility sparing treatment. We also proved that neoadjuvant chemotherapy followed by a radical hysterectomy is an equally effective treatment compared to chemoradiation, but with a different toxicity profile. The neoadjuvant group showed more toxicity related to the chemotherapy, while the chemoradiation group has more local toxicity like vaginal fibrosis, radio cystitis, radio enteritis and fistulas. Besides these research topics, we also focused on different neoadjuvant chemotherapy regimens. We established that paclitaxel/carboplatin is as effective as TIP, but with less hematologic and non-hematologic toxicity. Furthermore, we tried to explore the addition of bevacizumab to paclitaxel/carboplatin, since this combination has also showed benefit in metastatic cervical cancer. Unfortunately, our results did not validate the benefit of adding bevacizumab to paclitaxel and carboplatin for neoadjuvant chemotherapy in locally advanced cervical cancer. In the second part of this doctoral thesis we evaluated new surgical techniques. We started with the analysis of our own experiences with the use of fluorescence indocyanine green for sentinel node mapping, and showed a high bilateral detection rate with a low false negative rate. We also examined the robotic assisted para-aortic lymph node staging and showed it to have less blood loss, a higher median number of removed para-aortic lymph nodes and a lower mean length of postoperative hospital stay. In addition, the number of positive para-aortic lymph nodes tended to be higher for the robot-assisted procedure. Based on these results, we have changed several aspects of our treatment protocol for cervical cancer, at the university hospital of Leuven. Neoadjuvant chemotherapy followed by conization as fertility sparing surgery is now offered in specific cases. Patients with locally advanced cervical cancer are treated with both neoadjuvant chemotherapy followed by a radical hysterectomy and chemoradiation, depending on the patients characteristics. We also changed our neoadjuvant chemotherapy regimen: we switched from TIP to a less toxic paclitaxel/carboplatin weekly regimen. Besides these alterations with regard to neoadjuvant chemotherapy, the robotic assisted para-aortic lymph node staging and the sentinel lymph node mapping with indocyanine green has become standard of treatment. Besides the investigation of the possibilities of neoadjuvant chemotherapy and new surgical treatments, we will focus on the use of a PD-L1 inhibitor for cervical cancer in our recently started randomized multicenter trial. This study will be the first of its kind. Recently the Keynote study published its preliminary data showing good results of a PD-1 inhibitor in recurrent cervical cancer. Hopefully these studies can introduce immunotherapy as a new treatment for cervical cancer. Further studies will be conducted as new data about cervical cancer will be published, hopefully finding new therapies for these patients.status: publishe