In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Francesco Fanfani to discuss secondary cytoreductive surgery in endometrial cancer. Dr. Francesco Fanfani serves as an associate professor in gynecologic oncology at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS in Rome, Italy.

Highlights:

• Secondary cytoreductive surgery with complete gross resection, has the potential to offer significant survival benefits in recurrent endometrial cancer patients.
• Age <65 years, single site recurrence, and nodal or hematogenous recurrence as predictive factors for complete cytoreduction.
• The study’s findings could influence the decision making process in treatment selection, offering valuable insights for future prospective studies and potential impacts on research and clinical practice.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Domenica Lorusso to discuss KEYNOTE-A18 Overall Survival Results: Pembrolizumab and Chemoradiotherapy. Dr. Domenica Lorusso, MD, PhD, directs the Gynaecological Oncology Unit at Humanitas Hospital, Milan, and holds a Full Professorship in Obstetrics and Gynaecology at Humanitas University, Rozzano, Milan. She has led/participated in approximately 250 phase I-IV clinical trials. Currently overseeing more than 60 studies as Principal Investigator, Dr. Lorusso also chairs the Clinical Trials Committee of the MITO Group. She serves on the Board of Directors of the GCIG and is an active member of ENGOT, where she chairs the Gynecological Cancer Academy. Additionally, she sits on the Board of Directors of the ESGO. With around 300 international oncology publications and contributions to national and international treatment guidelines, her primary objectives are to ensure optimal patient care, foster clinical research, and advance international collaborations and education in the field.

• In a phase 3 trial (ENGOT-cx11/GOG-3047/KEYNOTE-A18), pembrolizumab added to chemoradiotherapy significantly improved progression-free survival and overall survival for patients with locally advanced, high-risk cervical cancer.
• Patient Group: 1060 patients with FIGO 2014 stage IB2–IVA cervical cancer from 30 countries were randomized to receive pembrolizumab with chemoradiotherapy or placebo with chemoradiotherapy.
• Overall Survival: At a median follow-up of 29.9 months, the 36-month overall survival rate was 82.6% in the pembrolizumab group versus 74.8% in the placebo group, with a hazard ratio for death of 0.67 (95% CI 0.50–0.90; p=0.0040).
• Safety Profile: Grade 3 or higher adverse events were reported in 78% of pembrolizumab-treated patients versus 70% in the placebo group, with higher rates of potentially immune-mediated adverse events in the pembrolizumab group (39% vs. 17%).
• Conclusion: These findings confirm pembrolizumab plus chemoradiotherapy as an effective and potentially new standard of care for locally advanced cervical cancer.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Alessandro Santin to discuss Sacituzumab Govitecan (TROPiCS—03) in Advanced Endometrial Cancer. Dr. Alessandro D. Santin, a native of Italy, graduated with honors from the University of Brescia, Italy and received his postgraduate training in Obstetrics & Gynecology at the same University. He served a fellowship in Gynecologic Oncology at the University of California, Irvine and an International Fellowship in the Division of Gynecologic Oncology at the University of Arkansas for Medical Sciences, Little Rock, Arkansas. Dr. Santin joined the faculty in the Section of Gynecologic Oncology in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale University as Professor as of July 2008. Dr. Santin has more than 400 original research and peer-reviewed publications including multiple review articles and book chapters and he has written extensively on various topics, including cancer of the ovary, endometrium and cervix as well as on tumor immunology and immunotherapy. Dr. Santin's clinical interests include the use of immunotherapy in ovarian, cervical and endometrial carcinoma patients with disease resistant/refractory to standard treatment, therapeutic vaccines against Human Papillomavirus (HPV) infected genital tumors, and the development of personalized treatment modalities including monoclonal antibodies and antibody-drug-conjugates (ADC) against chemotherapy resistant gynecologic tumors.

Highlights:

• In the TROPiCS-03 trial Sacituzumab Govitecan demonstrated encouraging clinical activity in recurrent endometrial cancer patients in progression after chemotherapy and immune check point inhibitors
• Sacituzumab Govitecan toxicity profile was manageable with only 5% of patients discontinuing treatment due to TRAEs
• TROP-2 protein was expressed in over 90% of endometrial cancer patients enrolled in the TROPiCS-03 trial and showed limited correlation with efficacy to Sacituzumab Govitecan

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Drs. Anne Knisely and Nitecki Wilke to discuss Racial and Sociodemographic Disparities with Novel Therapeutics. Dr. Knisely is a 3rd year gynecologic oncology fellow at MD Anderson Cancer Center. She is originally from the New York City area and completed her residency training in Ob/Gyn at Columbia University in 2022 where Dr. Jason Wright served as her primary research mentor. Her current research focuses on early phase clinical trials, minimal residual disease in ovarian cancer, and sociodemographic factors that affect oncologic treatment and outcomes. She is a current SGO/GOG-F BRIDGES Research Scholar. In her free time, she mostly chases around her two toddlers, Zoe (3.5) and Isaiah (2). Dr. Nitecki Wilke is a gynecologic oncologist and assistant professor at the department of gynecologic oncology and reproductive medicine at the University of Texas MD Anderson Cancer Center.

Highlights:

• Of the 6242 patients who met inclusion criteria and were included in the final cohort, 4.4% received a PARP inhibitor, 34% received bevacizumab, and 6% received both.
• On multivariable analysis, non-Hispanic Black patients were 23% less likely than non-Hispanic white patients to receive either targeted therapy
• Most patients in the study were treated in the recurrent setting; we suspect that the potential barriers to guideline-concordant prescription of these therapeutics would persist in the upfront treatment setting, but future studies are required to validate this.
• A key area of focus to reduce disparities in access to targeted therapies should be ensuring adequate reimbursement for genetic/ biomarker testing as well as brainstorming creative solutions to expand access to genetic counseling, including the use of mainstreaming.
• Use of the SEER-Medicare database specifically reduces external validity of this study, but the results are nonetheless hypothesis generating and should spark conversation regarding potential inequitable receipt of PARP inhibitors and bevacizumab in advanced ovarian cancer

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Rongyu Zang and Yulian Chen to discuss the SOC-1 trial. Dr. Rongyu Zang is the Director of the Department of Gynecologic Oncology, Fudan University Zhongshan Hospital, & Institute for Ovarian Cancer, Fudan University and is the Principal investigator of the SOC-1 and SUNNY trials. Dr. Yulian Chen is an Attending Physician at the Department of Gynecologic Oncology, Fudan University Zhongshan Hospital.

Highlights:

• The SOC-1 trial concluded that in patients with platinum-sensitive, relapsed ovarian cancer, surgery did not increase overall survival in the intention-to-treat population, but resulted in a prolongation of survival after adjustment of crossover.
• Surgery may provide an obviously higher proportion of long-term relapse-free survivors than chemotherapy alone.
• An active preoperative evaluation for all patients with platinum-sensitive first relapsed ovarian cancer is suggested in specialized centers.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Drs. Andreas Obermair and Rachel Collings to discuss the impact of surgical complications on surgeons. Dr Obermair is an Australian-based gynaecological oncologist, researcher and leader of innovation. He is the PI of numerous investigator-initiated clinical trials and is never tired of finding more effective and less harmful ways to treat patients diagnosed with gynaecological cancer. Dr Rachel Collings is a gynaecologist and fertility specialist working in private practice in Toowoomba, Australia. She has a particular interest gynaecological surgery and doctor wellbeing.

Highlights:

1. While patients are primarily affected by complications, surgeons are second victims when complications develop. Second victim refers to a clinician who experiences emotional trauma when complications develop.
2. Second victims may feel shame, guilt, sadness and a crisis of confidence. In addition, second victims may develop problems with sleep, or develop musculoskeletal and gastrointestinal symptoms.
3. Second victim syndrome is more likely if complications are severe, caused by a perceived mistake, or if the surgeon is concerned that it may attract criticism from colleagues.
4. 89% of respondents reported having impacts on their sleep when they are involved in a surgical complication.
5. Younger age, fewer years in practice, and female respondents had higher impacts of stress related to complications.
6. Female surgeons reported higher levels of physical and mental health impacts and higher levels of impact on sleep compared with male surgeons.

Nadeem Abu-Rustum bio: Dr. Abu-Rustum is a board-certified gynecologic oncologist who specializes in the surgical treatment of gynecologic cancers at Memorial Sloan Kettering Cancer Center. He is also a professor of obstetrics and gynecology at Weill Cornell Medical College. Dr. Abu-Rustum has a special interest in minimally invasive surgery (laparoscopy) for the treatment of cancerous and noncancerous diseases of the female reproductive system, and his clinical research focuses on surgical therapy for gynecologic cancers and innovative surgical approaches to treating gynecologic disorders.

Christian Dagher bio: Christian Dagher is a former research fellow at Memorial Sloan Kettering, and current OBGYN resident at the University of Pennsylvania. He holds a master's degree in clinical epidemiology and health-services research from Weill-Cornel. Before moving to the US, he completed an OBGYN residency at the American University of Beirut and is interested in studying survival biomarkers in endometrial cancer.

Highlights:

• The 2023 FIGO staging system for endometrioid endometrial carcinomas included the extent of lymphovascular invasion as a determinant of stage.
• The new staging system, groups tumors with no lymphovascular space invasion and those with focal invasion (<5 vessels) into one category and upstages those with substantial invasion ( 5 or more vessels).
• This study aimed to evaluate the relationship between the extent of lymphovascular invasion and oncologic outcomes in patients with stage I endometrioid endometrial cancer.
• This study is a retrospective analysis of 1555 patients with FIGO 2009 stage I endometrioid endometrial cancer who underwent total hysterectomy and lymph node assessment at two tertiary centers between 2012 and 2019, categorized by the extent of lymphovascular invasion (no, focal, or substantial invasion as defined by the WHO).
• Key findings showed that both focal and substantial lymphovascular invasion were linked to lower 5-year progression-free survival (68.7% and 70.5% for substantial and focal invasion, respectively, compared to 90.7% for no invasion). This was true even after limiting the analysis to myoinvasive grades 1 and 2.
• In conclusion, focal and no lymphovascular invasion have different prognostic outcomes and should not be combined into a single category as proposed by the FIGO staging system. Focal and substantial lymphovascular invasion were not associated with distinct prognostic outcome that could support upstaging of the latter.

In this episode of the IJGC podcast, Editor-in-Chief Dr. Pedro Ramirez is joined by Dr. Ignace Vergote to discuss Tisotumab Vedotin in Second- & Third-Line Recurrent Cervical Cancer. Prof. Vergote was Chairman of the Department of Gynaecology and Obstetrics at the Catholic University Leuven from 2003-2020. He published more than 1050 papers on gynecologic cancer in peer-reviewed journals, and his work was cited more than 90,000 times. He served as President of IGCS, ESGO, EORTC-GCG and ENGOT.

Highlights:

• Patients with recurrent cervical cancer with progression after platinum/paclitaxel, combined if possible with bevacizumab and anti-PD-(L)1 therapy, have a dismal prognosis
• The antibody-drug -conjugate tisotumab vedotin showed a statistically significant and clinically meaningful improvement in overall survival, demonstrating a 30% reduction in the risk of death compared with standard of care chemotherapy
• Consistent benefit in progression-free survival and confirmed response were also observed and supportive of the observed overall survival benefit with tisotumab vedotin
• The safety profile of tisotumab vedotin was manageable and tolerable, and consistent with previous experience
• Based on these data, tisotumab vedotin should be considered a potential new standard of care for patients with recurrent cervical cancer who have progressed after first-line systemic therapy