Advances in Surgical Approaches and Targeted Therapies Highlight Progress in Uterine Cancer

As the availability of therapeutic approaches continues to widen in the uterine cancer landscape, acknowledging the gaps that have been addressed is important; however, centering the attention on disparities is also essential, according to John P. Diaz, MD.

He noted that it is an exciting time in the field with new treatments and approaches emerging. Ongoing studies could advance the uterine cancer treatment paradigm, such as the phase 3 GOG-3064/KEYNOTE-C93 trial (NCT05173987), which is examining first-line pembrolizumab (Keytruda) compared with chemotherapy in mismatch repair–deficient advanced or recurrent endometrial cancer.1

Of note, pembrolizumab plus chemotherapy was approved by the FDA in June 2024 for the treatment of patients with primary advanced or recurrent endometrial cancer.2 The regulatory decision was based on data from the phase 3 KEYNOTE-868 trial (NCT03914612).

“We need to continue to educate the public. We’ve made some great breakthroughs, both surgically as well as with targeted therapies, and we continue to build upon those [in uterine cancer],” Diaz said in an interview with OncLive® during Gynecologic Cancer Awareness Month, observed annually in September.

In the interview, Diaz discussed the role of surgery in uterine cancer, including minimally invasive approaches, ongoing challenges and unmet needs within the space, and current studies that could potentially shift clinical practice.

Diaz is the chief of Gynecologic Oncology, Robotic Surgery, and the Center of Excellence in Minimally Invasive Gynecologic Surgery at Baptist Health; as well as the lead physician for Clinical Trials in Gynecologic Oncology at Miami Cancer Institute, director of Ambulatory Surgery Center at Baptist Health Cancer Care | Plantation, and chair of the Department of Obstetrics and Gynecology at Florida International University Herbert Wertheim College of Medicine.

OncLive: Why is it important to emphasize gynecologic cancer awareness to the public?

Diaz: Awareness drives early recognition of symptoms and hopefully timely referrals for patients who can get access to treatment for these cancers, particularly uterine cancer, where we’ve had an increase in the incidence and, unfortunately, mortality here in the United States. We often see this because of disparities, particularly racial disparities. We know that our African American patients don’t do as well with this diagnosis. Therefore, September gives us that opportunity to bring awareness to patients and providers about gynecologic cancers, genetic syndromes [such as] Lynch syndrome with uterine cancer, and what we can do to hopefully prevent these cancers in the future.

How has the role of surgery evolved in the multidisciplinary management of uterine cancer within the past decade?

Surgery remains the cornerstone for the treatment of [patients with] uterine cancer, and it’s evolved over the last 10 years. We’ve now developed a technique called sentinel lymph node mapping, where we can use a tailored approach to evaluate the lymph nodes for evidence of metastatic disease. This has widely replaced routine lymphadenectomy. [Many patients] derive no benefit from that surgery, because they have lymph node–negative disease. By using sentinel lymph nodes, we’re able to have a more tailored approach with less morbidity for patients, and that’s been just one of the developments in this [space]. Additionally, [with] the use of the Enhanced Recovery After Surgery [ERAS] protocols, most of our patients go home the same day after their surgery. Robotics has completely changed the way we perform these surgeries.

Our traditional open approach often leads to a high rate of wound complications and delayed healing for these patients. [However], with the use of robotics, we’ve [mostly] eliminated that complication from the treatment of this disease. [Notably], patients can have their surgery, go home the same day, have a tailored lymph node evaluation, and we can get them started if [they need] adjuvant therapy earlier.

With minimally invasive surgery becoming a common modality in gynecologic cancers, how is it being used in clinical practice?

Minimally invasive surgeries, such as laparoscopy and robotics, have been a game-changer in the treatment of uterine cancer. One of the risk factors for developing cancer is obesity, and that could make surgery more challenging. The traditional approach, through an open technique, often resulted in postoperative complications such as wound infection and deep vein thrombosis. By using a minimally invasive approach, we’ve almost eliminated these complications in the management of this disease. We’re able to do more precise surgery, particularly in our patients [who are obese] and those with complex anatomy. It’s been a game-changer for surgeons and for patients in the management of uterine cancer.

What are some ongoing challenges in the uterine cancer landscape?

Uterine cancer is a unique and diverse disease, and when we talk about uterine cancer, we are talking about some very different entities. Nevertheless, one of the things that stands out to me in some of the gaps that we have in prevention and early detection. Obesity is one of the leading drivers in the development of endometrial cancer. We haven’t done a good job of educating the public about this. Obesity continues to be an epidemic here in the United States, and the numbers continue to climb. We need to talk about early prevention, nutrition, and all the other health challenges that come with obesity, particularly with uterine cancer.

The other aspect we are looking at is equity. We know that African American women have nearly double the mortality of other ethnicities with uterine cancer, and we don’t understand why. We think part of it might be access. They may not have access to health care when they first develop symptoms such as abnormal bleeding. Additionally, there’s something [going on with disease] biology. When you take stage-for-stage patients, and you compare our African American patients with other ethnicities, they do worse, and we don’t understand why. We’ve had great breakthroughs in the treatment of uterine cancer with immunotherapies and other new targets. However, unfortunately, African American women continue to be underrepresented in these clinical trials. We’re not sure if these [outcomes] are the same benefits that we’ll see in our African American population. We need to do a better job of enrolling African American women and other underrepresented ethnicities into clinical trials.

How do you see the role of combination approaches evolving, particularly with immunotherapy plus targeted therapies?

It’s been an exciting time in cancer treatment, with the onset of immunotherapy and targeted therapies. Immunotherapy uses the body’s own immune system to recognize and attack these cancer cells, and it’s been a great advantage, particularly in uterine cancer, where we’ve seen many trials demonstrate the benefit of using immunotherapy, either alone or in combination with traditional chemotherapy, with improved survival for our patients. Additionally, we now have targeted therapies. The idea in the past was that we treated everyone with the same treatments, and most patients would respond. Where we’re moving is towards having target-driven therapy. In other words, when we look at either the patient or their tumor, [we wonder if] there is a biomarker that tells us which therapy might be most appropriate for them, thereby tailoring their treatments to hopefully decrease their [adverse] effects [AEs] and morbidity, and also improve their outcomes. We’ve seen many new targeted therapies, such as antibody-drug [conjugates] that target a particular receptor, which [could show] benefit in these patients.

What ongoing studies are you most excited about that could potentially shift clinical practice?

It’s been an exciting time in the treatment of [patients with] gynecologic cancers, particularly uterine cancer. We’ve come such a long way. We used to think that chemotherapy wasn’t effective in uterine cancer, and now we’ve learned that it is, but we’ve also tried to improve that. One of the big improvements has been the use of immunotherapy, particularly in patients with mismatch repair–deficient disease who carry a biomarker which [shows that] they’re going to respond to immunotherapy. This has been so successful that now we’re looking at whether we can use immunotherapy instead of traditional chemotherapy for these patients, which may result in better outcomes and fewer AEs. The GOG-3064/KEYNOTE-C93 trial, is [evaluating whether] we can use pembrolizumab instead of traditional chemotherapies for the treatment of [patients with] advanced endometrial cancer, and we’ve seen other disease sites where this transition has happened.1 Therefore, we’re very excited for this.

References

1. Study of pembrolizumab (MK-3475) versus chemotherapy in mismatch repair deficient (dMMR) advanced or recurrent endometrial carcinoma (MK-3475-C93/KEYNOTE-C93/GOG-3064/ENGOT-en15. ClinicalTrials.gov. Updated November 21, 2024. Accessed September 16, 2025. https://www.clinicaltrials.gov/study/NCT05173987
2. FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. FDA. June 17, 2024. Accessed September 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma