Gynaecological oncology: present and future

During the ESMO Congress on Gynaecological Cancers, Prof. Scambia analysed developments in the field, and what's next in the coming decade.

Endometrial cancer: a long story

Endometrial cancer presents a paradox: despite decreasing mortality rates, incidence continues to rise, primarily due to the global obesity epidemic. One of the most significant advancements in recent years has been the genomic characterization of endometrial cancer, identifying 4 distinct molecular subtypes. Additionally, minimally invasive surgical techniques and advancements in medical therapies have improved patient outcomes.

Today there are several ongoing studies that will answer some clinical questions:

  1. Adjuvant treatment based on TCGA classification? RAINBO trial NCT05255653 (refining Adjuvant treatment IN endometrial cancer Based On molecular profile).
  2. Extent of the surgical staging based on TCGA classification? EUGENIE trial NCT06354738 (Improving Endometrial cancer assessment by combining the new techniqUe of GENomic profiling with the known valuable surgical extra-uterIne disEase assessment).
  3. Neadjuvant chemo-immuno-approach before surgery to increase surgical cytoreduction? CIAREC trial MITO proposal (Cytoreduction vs chemotherapy + immunotherapy only in advanced or recurrent endometrial cancer).
  4. Conservative treatment for early EC based on TCGA? Immuno FERT MITO proposal (A phase II, open label, single-arm study of pembrolizumab as fertility sparing treatment in G1 endometrioid EC or atypical complex hyperplasia and MMRd).

Another significant advancement is sentinel lymph node (SLN) mapping, which enhances the quality of life by reducing the need for extensive lymphadenectomy. In the future, radiomics might replace SLN mapping, further improving patient outcomes.

Prevention of endometrial cancer also requires robust support for WHO initiatives to combat obesity and the use of risk-reducing surgery, particularly in patients with Lynch syndrome.

 “We are in Florence, so I think that everybody of you will go to the Uffizi Museum. You will understand my metaphor. In the past we have identified the Annunciation topic. Now we are going to see the colour of the Annunciation. I think that the future will be to look at the perspective of the Annunciation”.

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Copyright: Scambia G. (2024)

Cervical cancer: a (potentially) successful story

Cervical cancer represents a potentially successful story due to advancements in treatment and, most importantly, vaccination. Vaccination can prevent cervical cancer entirely, but we observe an increased incidence. The WHO aims to reduce mortality by 33% in low- and middle-income countries within the next decade and by nearly 99% over the next century through vaccination.

What can we do now for those who will get the disease? For patients with precancerous lesions, immunotherapy may reduce disease progression. In advanced cases, CAR-T cell therapies and radiomics can enhance patient selection and risk prediction.

Today there are several ongoing studies that will answer some clinical questions:

  1. Can Minimally invasive surgery be re-introduced in early stage disease? RACC trial (NCT03719547), ROCC/GOG-3043 trial (NCT04831580), LASH trial (NCT06416748).
  2. Can sentinel node biopsy (SLNB) be the only approach to assess N status? SENTIX trial (NCT02494063), PHENIX trial (NCT02642471), SENTICOL III trial (NCT03386734).
  3. Can conservative treatment be safely extended to 2-4 cm cervical cancer? CONTESSA trial (NCT04016389).

According to Prof. Scambia, the incidence of this cancer is not acceptable when an effective vaccine is available. We have to make all the efforts for prevention of the disease by vaccination.

Ovarian cancer: a never-ending story

Ovarian cancer remains one of the most challenging gynaecological malignancies to treat. However, significant progress has been made. BRCA and HRD testing, the introduction of PARP inhibitors, and the role of secondary cytoreductive surgery have all contributed to improved outcomes. Hyperthermic intraperitoneal chemotherapy (HIPEC) also shows promise in reducing mortality.

Several ongoing studies have the potential to change clinical practice:

  1. Is MIS non-inferior to lpt (NACT+IDS)? LANCE.
  2. Is PCS better than NACT + IDS? TRUST (ENGOT OV33/AGO-OVAR OP7).
  3. Might HIPEC improve OS? OVHIPEC-2.
  4. Which maintenance is better according to HRD status? MITO-25, NIRVANA, AGO-OVAR 28/ENGOTOV57.

Prof. Scambia stressed the importance of changing perspective, trying to imagine, for example, that this cancer could be prevented. Future strategies will include opportunistic salpingectomy during non-gynecological pelvic surgeries and the potential for Pap smear-based genomic instability analysis to detect ovarian cancer up to nine years before diagnosis.

Future Perspectives

The combination of surgery and chemotherapy, aiming for no residual tumour, remains a key objective. Technology, such as targeted fluorescent agents, can enhance intraoperative tumour detection.

The future will likely see the integration of radiomics and artificial intelligence to identify and treat chemotherapy-resistant clones. The operating room of the future will incorporate diagnostics and treatment, with pre- and post-operative data guiding precision surgery.

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The next-generation hybrid operating room integrating artificial intelligence and robotics for diagnostic imaging, procedure planning and execution: the operating room of the future is envisioned as the centre of a technology ecosystem. (Copyright Barbara Seeliger/Carlos Amato; Chengyuan Yang; Niloofar Badihi; IHU Strasbourg and Cannon Design USA - Pavone et al. 2024. Ultrasound guided robotic procedures. Surg End).

Additional innovations include telesurgery, which will democratise access to treatments, and autonomous robotic systems that may perform procedures without human intervention. Theranostics, combining diagnosis and treatment with radioactive isotopes, represents one of the most promising advances.

Over the past decade, advancements in gynaecological oncology have significantly improved prognosis and quality of life for patients. Looking forward, the integration of new technologies, prevention, and personalised treatments will be crucial in continuing to enhance outcomes.

Source:

Scambia G. 10 years of success in gynaecological malignancies treatment: Moving forward into a brilliant future. ESMO Gynaecological Cancers Congress 2024. Keynote Lecture, 21.06.2024, h. 12:00 – 12:30, Auditorium