Re: Cervical cancer in pregnancy: diagnosis, staging and treatment

Dear Editor, We examined the recent review by Howe and colleagues with great interest, and we wish to commend the authors for producing an extremely useful framework for clinicians involved in the care of patients with the considerably challenging diagnosis of cervical cancer during pregnancy. It was with particular attention that we considered the guidance presented for the management of locally advanced disease, International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB3 and above. Locally advanced disease has been treated over the past 20 years with concomitant platinumbased chemotherapy and radiotherapy, with the potential for definitive surgery in some patients with stage IB3 and IIA. More recently, the use of neo-adjuvant chemotherapy (NACT) followed by radical surgery has been a subject of great interest to the gynaecological oncology community. While acknowledging that the evidence basis is limited, Howe and colleagues advise that NACT may provide some benefit to patients with locally advanced disease who wish to prolong their pregnancy prior to definitive treatment, citing a meta-analysis from 2012 examining NACT followed by surgery versus surgery alone. However, a recent randomised controlled trial examining NACT followed by surgery versus concomitant chemoradiotherapy found superior disease-free survival (DFS) among the chemoradiation group in their intention-to-treat analysis, with the main benefit being apparent among the FIGO stage IIB group. Furthermore, the post-hoc analysis showed worse DFS among patients who could not undergo surgery following NACT and crossed over to the chemoradiotherapy arm, as well as among those who underwent surgery following NACT but needed adjuvant treatment. Although by selection these patients will have had poor prognostic factors, the authors raise the possibility of a detrimental effect on disease control in delaying definitive chemoradiotherapy or inducing cross resistance between chemotherapy and radiotherapy. A further point, as alluded to by Howe and colleagues, is the controversial nature of surgical staging with lymphadenectomy prior to definitive treatment. When considering the challenging nature of accurate clinical staging in pregnancy, as discussed by the authors, one can envisage a scenario where a patient wishes to discuss this strategy to potentially guide her decision making regarding prolongation of her pregnancy. However, the very recent results of the UTERUS-11 trial (published after the work of Howe was submitted), examining clinical versus surgical staging in locally advanced cervical cancer, found no difference in DFS except among the FIGO stage IIB group. Furthermore, patients in this trial all underwent chemoradiotherapy following either clinical or surgical staging, with the goal of staging through identification of lymph node metastases being subsequent adjustment of the target volume definition of primary chemoradiation. We would be most interested to hear the authors views, given the recent trial evidence, as to whether we should be prudently counselling women with suspected locally advanced cervical cancer wishing to continue their pregnancy about the safety of NACT as a treatment strategy, and the risks of delaying definitive chemoradiotherapy, especially given the challenging nature of accurate clinical staging in pregnancy and the recently described limitations in surgical staging.