Ovarian Cancer Program Evolves to Improve Outcomes
From previvor to survivor, Sylvester’s ovarian cancer treatment pathway offers genetic testing, less invasive surgery, oral therapies, a range of clinical trials and novel therapeutics for recurrent cancer.
Ovarian cancer is the second most common gynecologic cancer in the United States. It causes more deaths than any other cancer of the female reproductive system, according to the Centers for Disease Control and Prevention.
To change this trajectory, Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine created a program that addresses women who have ovarian cancer, as well as those who don’t but are at risk (previvors). Sylvester’s “previvor to survivor” holistic approach to ovarian cancer care does not resemble the typical care for ovarian cancer patients of the past, according to Abdulrahman K. Sinno, M.D., director of surgical research and education at Sylvester and associate professor of clinical obstetrics, gynecology and reproductive sciences for the Miller School.
“As a National Cancer Institute-designated cancer center, we offer treatment and quality-of-life options that are not available at many hospitals and cancer centers,” he said. “We empower previvors and survivors to have the choice between safe, sound clinical trial options that could potentially change the standard of care but are not yet as available as traditional approaches. Either way, Sylvester offers the safety of an academic setting with a staff of experienced cancer experts and researchers.”
Changes in Ovarian Cancer Treatment
Many women first discover they have advanced ovarian cancer when symptoms send them to a local emergency room.
The ER doctor might find something concerning on a scan. A woman would then see a surgeon, who does surgery to remove the cancer to the best of their abilities before referring her to an oncologist for chemotherapy, according to Dr. Sinno.
The scenario wasn’t optimal care, but that was all most centers could offer and still is the standard at many facilities, he said.
Sylvester has completely revamped that ovarian cancer care pathway to encompass clinical trials specific to the phase of treatment the patient is in. Given that patients enrolled in clinical trials have been shown to have improved overall survival and reduced disparities in care, the goal of this pathway is to offer clinical trials at every step of their care.
“We are challenging and pushing the boundaries of traditional care with precision medicine and radical surgery, in hopes that patients live longer and better,” Dr. Sinno said.
Preventing Ovarian Cancer With Previvor Care
Genetic mutations, like the BRCA1 and BRAC2 genes, are known to increase the probability of developing breast and ovarian cancer. Understanding how genetics impact an individual’s risk for ovarian cancer and how to manage that risk is particularly important in ovarian cancer.
“A BRCA mutation puts one at a 40% risk for getting ovarian cancer,” Dr. Sinno said. “For those women with the BRCA1 gene, the standard of care still offered today is surgery to remove the ovaries and fallopian tubes by age 35 to 40 or completion of childbearing, whichever comes first.”
The approach causes a woman to go into an aggressive type of menopause known as induced menopause. Estrogen levels plummet to zero and patients are left to deal with the onslaught of menopausal side effects, as well as potentially increased risks for heart disease, bone loss, sexual dysfunction and other health concerns.
To safely eliminate the surgical side effects, Sylvester is conducting a clinical trial comparing the traditional approach to a less-invasive surgery.
“It’s a procedure called a prophylactic salpingectomy, where we only remove the fallopian tubes and leave the ovaries intact,” Dr. Sinno said.
Studies have found that most ovarian cancers in women with the BRCA1 mutation start in the fallopian tubes.
“If you remove the fallopian tubes, that should be sufficient to prevent ovarian cancer without the health effects of taking out a woman’s ovaries before natural menopause,” Dr. Sinno said.
Prophylactic salpingectomy, however, should only be done in a clinical trial to ensure adequate and safe follow-up for these patients, he said.
Early Care After a Diagnosis
Sylvester offers clinical trials for women recently diagnosed with ovarian cancer, including one that is studying how to safely reduce the need for cytotoxic chemotherapy with a pill.
Sylvester researchers are examining whether treating some women with a noncytotoxic oral therapy instead—a poly (ADP-ribose) polymerase (PARP) inhibitor called niraparib—sufficiently reduces tumor size, lessening or eliminating the need for chemotherapy before surgery.
“This is a randomized, multi-institutional trial that we are proud to offer,” Dr. Sinno said.
Another trial examines the surgery.
“Surgery for ovarian cancer is classically done through an open incision from the pubic bone to the chest to remove all the cancer,” Dr. Sinno said.
Today, Sylvester is one of nine U.S. cancer centers that have a trial specifically looking at a minimally invasive robotic approach to surgery for ovarian cancer. The less-invasive robotic surgery requires five small incisions (less than a centimeter each), and patients can usually go home from the hospital in a day or two, as opposed to the traditional surgery that requires a significantly longer stay in the hospital.
While robotic surgery is being offered nationally, it has not been validated in a clinical trial, according to Dr. Sinno.
“We believe that a clinical trial is the safest way to adequately ensure the safety of this procedure for ovarian cancer,” he said.
The LANCE clinical trial is one of multiple surgical trials that aim to improve perioperative outcomes and reduce recovery time for patients undergoing surgery for ovarian cancer.
TEAL Looks at Diet, Exercise and Chemotherapy
Sylvester’s researchers are conducting several other clinical trials. In one example, the cancer center is collaborating with Yale Cancer Center on the NCI-funded TEAL study, part of the Exercise and Nutrition Interventions to Improve Cancer Treatment-Related Outcomes (ENICTO) consortium.
“In TEAL, we’re studying whether diet and exercise can improve chemotherapy completion, or how much of the overall prescribed dose of chemotherapy someone receives, by reducing treatment-related toxicities,” said TEAL’s co-principal investigator Tracy Crane, Ph.D., RDN, co-lead of the cancer control research program and director of lifestyle medicine, prevention and digital health at Sylvester.
Completing treatment on time and receiving the prescribed dose is particularly important in ovarian cancer, as studies have shown that ovarian cancer patients who do not receive and/or complete all cycles of chemotherapy on time have much worse outcomes.
Medical nutrition and targeted exercise therapy may prevent symptoms from happening, according to TEAL study co-investigator Matthew Schlumbrecht, M.D., medical co-director of the cancer survivorship program and co-lead of the Gynecologic Oncology Site Disease Group at Sylvester.
“We know, for example, that markers of inflammation and stress go down when people exercise. We also know that those same markers can actually promote cancer growth,” Dr. Schlumbrecht said.
By introducing exercise early, specifically during the initial treatment for ovarian cancer, researchers hope to see improvement in compliance and ability to complete the initial chemotherapy regimen, which is the most important thing to try and achieve a cure, said Dr. Schlumbrecht, who is also a professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at the Miller School.
TEAL is the only trial in the NCI’s consortium of research offered in Spanish and the only one that has a comprehensive dietary and exercise intervention in ovarian cancer.
While TEAL is ongoing, Dr. Sinno said he has already seen positive results.
“My patients in the trial are telling me they’ve never felt stronger,” he said. “Usually, patients receiving chemotherapy feel weak and unwell.”
LIVES Clinical Trial and Ovarian Cancer Progression
At the forefront of research in ovarian cancer, Dr. Crane also co-led the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) clinical trial, which included clinical sites from 48 states (as part of NRG Oncology) and included more than 1,200 women with ovarian cancer. The study examined whether a 24-month diet and exercise intervention could impact the time to disease progression for women who had recently completed treatment for ovarian cancer. The LIVES trial concluded in August 2020 with results forthcoming.
“When we were conducting the LIVES trial, we routinely heard from women that they wished there had been a trial like LIVES while they were undergoing treatment. This feedback is part of what led to the development of TEAL,” Dr. Crane said.
There is little research in ovarian cancer focused on diet and exercise, and LIVES is the largest non-pharmacologic trial to date for women with ovarian cancer.
This gap in the literature for ovarian cancer was apparent to Dr. Crane when writing the American Cancer Society (ACS) nutrition and physical activity guidelines a few years ago.
“When we wrote the ACS guidelines, we could not say there was evidence of diet and exercise trials for women with ovarian cancer. Now, we at Sylvester and other top cancer centers are developing the evidence we need to support using diet and exercise as part of ovarian cancer patients’ journeys to not only improve survival but also live their best lives,” Dr. Crane said.
Living WELL Studies Mindfulness and Ovarian Cancer
Following patients long into their survivorship journey is an important part of their care. And for that, Dr. Schlumbrecht points to the NCI-funded Living WELL trial for ovarian cancer survivors.
“Living WELL looks at healthy lifestyles versus mindfulness. It is an inclusive study for anybody who has gone through ovarian cancer treatment and even people who have had one recurrence. It’s really a way to take what we’ve done in TEAL and make sure that we’re providing patients with the skills that they need to continue healthy modifications to their lifestyles as they transition into the survivorship phase of their lives,” said Dr. Schlumbrecht, the co-investigator on the Living WELL grant.
Attending to psychological stressors is not just a feel-good approach—it’s scientifically proven to reduce the chances that the cancer will come back, said Dr. Schlumbrecht as he highlighted Sylvester’s growing portfolio of clinical trial options that address recurrent cancer.
“We are offering trials that are reflective of changes, including specific genetic changes, in the patient’s tumor, as well as expanding opportunities for participation in phase 1 studies looking at novel therapeutics for recurrent ovarian cancer,” Dr. Schlumbrecht said.
The previvor to survivor holistic approach is a novel way to think about disease treatment, Dr. Sinno said.
“We have changed the traditional approach of doing surgery and chemo, and telling patients to come back if there are any problems, to care that addresses prevention, offers the newest options in treatment and helps women live well and long after cancer,” Dr. Sinno said.