By Marcus E. Randall, MD, FACR, FASTRO – Naples Cancer Advisors (NCA)
As September is Gynecologic Cancer Awareness Month, this is a great time to reflect about all the progress that has been made in limiting morbidity and mortality from gynecologic cancers. Most people are aware of the significant decline in the incidence, morbidity, and mortality from cervical cancer. This success story is unparalleled in oncology, especially in developed countries. Patient education regarding screening and prevention is a major vehicle through which we have realized these results. However, this positive news in cervical cancer is offset by the fact that uterine cancers have shown an increase in incidence and even mortality. The bottom line is that we must maintain our awareness of these and other malignancies that arise in the female reproductive system, as this gives us the best chance to make early diagnoses and provide a greater likelihood of cure.
Even as we work to raise awareness and facilitate early diagnosis, it remains the case that we still see, too often, cases of advanced gynecologic cancers of all sites. Although many women have recovered from locally advanced gynecologic cancers, there is still significant room for improvement. In my long career managing gynecologic cancers, I have seen steady but noticeable progress in all aspects of care, from prevention to early diagnosis, to improved outcomes, and, in some cases, limiting morbidity. In this brief article, my goal is to share, in general terms, what I see happening now that gives us hope for further improving outcomes from where we are now. There are two main topics that I am going to cover.
TUMOR BIOMARKERS
As I have often explained to patients and the general public, “cancer” is not one disease, but hundreds, possibly thousands. Even cancers that arise in the same location and look the same under a microscope can have very different molecular features. In some cases, we can evaluate tumors for these various characteristics (we might call them biomarkers). In some cases, the molecular profile (the marker status) can provide predictive and even therapeutically useful information. Endometrial cancer is a great example of a disease in which we increasingly rely on this information to aid in treatment decisions. With proper laboratory analysis using sophisticated techniques, subclassifications of endometrial cancers can be determined. There are obviously other prognostic factors, such as tumor stage, lymph-vascular space invasion, etc. that we have used for a long time, and these are still important. We are beginning to use this information to better tailor treatment, with the goal of limiting, to the extent possible, undertreatment and overtreatment of patients. Lots of work has been done to advance our knowledge in this area, and much remains to be done for us to optimize the use of this new information.
Another promising area where biomarkers are demonstrating promise is in cervical cancer. It turns out that it is possible to measure circulating tumor DNA (ctDNA) in the blood of patients with cervical cancer. A large randomized study has recently shown that the vast majority of cervical cancer patients have detectable ctDNA, and levels of ctDNA at diagnosis appear to correlate with treatment outcomes. Following treatment, data suggests that following ctDNA after treatment can be used as an early sign of tumor progression, before other clinically apparent recurrence is recognized.
Although the use of molecular profiling and biomarkers is exciting, it is important to recognize that there are limitations. It is known that there can be discrepancies between laboratories, making interpretation of results an imperfect science. Furthermore, these are not binary “yes-no” tests, meaning that there will always be gray areas. Further work in this area is needed to better understand how to use this information clinically.
IMMUNOTHERAPY
After many years of “trial and error,” cancer immunotherapy is rapidly becoming an important component of cancer treatment, usually in conjunction with established treatments such as radiation therapy, surgery, and chemotherapy. An example of an immunotherapy drug that has become well established is called pembrolizumab, but there are many others. At present, pembrolizumab is approved by the FDA for use in 18 different cancer types. Initially, these drugs were used mostly in patients with metastatic disease, but increasingly they are finding their way into upfront treatment, often with very promising results. Research is ongoing to better understand how to combine these drugs with standard treatments, and even how to combine different immunotherapy drugs with each other for greatest benefit. As promising as these drugs can be, they are not perfect. In addition to their expense, each drug adds potential toxicities, which can be quite different from older agents.
SUMMARY
The use of tumor biomarkers, molecular profiling, and immunotherapy agents hold tremendous promise in tailoring and optimizing treatment of many cancers, especially gynecologic malignancies.
As always, a close patient-physician partnership is important to making treatment decisions, even with imperfect information. The future of treatment for gynecologic cancers is brighter than ever!
About the Author
Dr. Marcus Randall joined NCA in 2024 as a specialist in gynecological oncology. Dr. Randall earned his medical degree from the University of North Carolina at Chapel Hill in 1982, receiving their Distinguished Medical Alumnus Award in 2017. He completed his residency in Radiation Oncology at the University of Virginia Medical Center. During his first faculty appointment at Wake Forest University he was recruited to Indiana University as Chair of the Department of Radiation Oncology, where he held the William A. Mitchell Distinguished Professorship. Subsequently, he became Chair of the Department of Radiation Oncology at the University of Kentucky, where he held the Markey Foundation Endowed Chair. He is board-certified by the American Board of Radiology and is a Fellow of both the American College of Radiology and the American Society for Therapeutic Radiology and Oncology.
Throughout his distinguished career, Dr. Randall has led national trials in endometrial and ovarian cancers within the Gynecologic Oncology Group (now NRG Oncology). He chaired several large randomized trials in endometrial cancer that were practice-changing, improving our knowledge of the respective roles of chemotherapy and radiation therapy in the management of early stage and locally advanced endometrial cancer. While in the GOG/NRG, he chaired the Radiation Oncology Committee and for over 15 years was co-chair of the Uterine Corpus Committee. His clinical interests include brachytherapy and gynecologic malignancies. Outside of work, Dr. Randall enjoys reading, traveling, and spending time with his family, including his seven grandchildren.
With Dr. Randall’s expertise and NCA’s comprehensive support services, we are making a significant impact in improving outcomes for women in Southwest Florida. By offering platinum-level care and guidance, NCA ensures that no patient faces their cancer journey alone.
239-846-2273 (CARE)
3201 Tamiami Trail N, Suite 112, Naples, FL 34103
naplescanceradvisors.org