Improvements in the understanding of molecular mechanisms, together with a greater focus on prevention, are key elements to countering gynaecological malignancies
Advances over the last decade have changed the face of gynaecological cancer management, as exemplified by progress made in the prevention and management of the three main tumour types.
The revised FIGO publication in 2023 has completely changed the way we view endometrial cancer (Int J Gynaecol Obstet. 2023;162:383–394). With the incorporation of a variety of histological and molecular parameters, classification now has a greater relationship with the prognosis of patients. Additionally, this revised classification allows the selection of treatment based on molecular classification, for example the use of immunotherapy for patients with microsatellite instability disease or the role of chemotherapy in p53-positive disease, and can help to avoid the unnecessary use of adjuvant treatment in patients unlikely to derive benefit from it. We are now waiting to see if this new molecular classification will change the way patients are staged surgically, and the results from the large ongoing European EUGENIE trial will provide valuable information in this respect (Int J Gynecol Cancer. 2023;33:823–826).
We are also on the verge of a new era in the management of endometrial cancer, based on a more tailored approach. One of the main achievements in recent years has been the demonstration that minimally invasive surgery is the best way to treat these patients, with the recommended approach typically involving sentinel lymph node (SLN) removal. It is now recognised that not all patients require SLN removal. What is more, in those patients that do, the future availability of novel, specific antigen-directed antibody–fluorescence conjugated tracers should enable the accurate identification of nodes that contain metastatic disease, thereby facilitating focussed removal.
Turning to cervical cancer, while discussions continue about the efficacy of immunotherapy and its combination with chemotherapy and radiotherapy, possibly the most promising avenue to pursue is prevention and this is where our efforts for the future should be concentrated. Wide-reaching vaccination programmes, like those conducted in Australia, have the potential to eradicate this disease for coming generations. And this effort will be helped by the finding that single-dose vaccination regimens can be as effective as multi-dose regimens (Lancet Glob Health. 2024;12:e360–e361) – which makes the programmes more achievable globally, even in low-resource settings – and by the recent arrival of novel vaccines targeting more HPV types and with particular relevance for Asian and African populations.
Prevention is also being explored for the most difficult of the major gynaecological cancers to treat, ovarian cancer. Cascade prevention, using molecular evaluation of mutations of BRCA and other genes, first in patients with a family history of ovarian cancer and then in their healthy relatives, is already common practice. However, a more systematic approach could lead to a greater reduction in the incidence of ovarian cancer. In addition, studies are now suggesting that opportunistic salpingectomy in menopausal women undergoing abdominal surgery, even for benign disease, holds great potential for preventing ovarian cancer (JAMA Netw Open. 2022;5:e2147343). In the future, it is likely that with increasing technological advances, for example in the detection of p53-mutated cells or the use of liquid biopsies, it will be possible to identify disease at a very early stage, when patients have the best chance of responding to treatment.
The other major area we need to get to grips with in ovarian cancer is overcoming chemotherapy resistance. One way is by improving our understanding of the molecular mechanisms of resistance to allow the development of systemic agents directed at these targets. Another way is by capitalising on innovations in radio-imaging to guide surgery, which can increase the number of cancer lesions identified compared with normal white light (J Clin Oncol. 2023;41:276–284). This has the potential to turn standard approaches upside down: instead of performing radical surgery with adjuvant chemotherapy to counter residual disease, future treatment may involve initial maximal cytoreduction with neoadjuvant chemotherapy followed by removal of chemoresistant clones using radio-imaging-guided surgery.
By capitalising on increasing improvements in technology, we have the capacity to make even greater strides in the management of gynaecological malignancies in the coming years.
