Prehabilitation During the Neoadjuvant Window of Opportunity in Older Women With Ovarian Cancer

Ovarian cancer is the deadliest gynecologic cancer with 5-year survival rates of approximately 48%. Standard of care treatment is grueling, requiring a radical "debulking" surgery and 5 months of chemotherapy. Cytoreductive surgery for ovarian cancer is often extensive, due to the necessary removal of all visible cancer. This radical surgery results in major postoperative complication rates as high as 50% in prospective clinical trials, and 75% occur within 2 weeks of surgery. Half of women are greater than 60 years-old and have high rates of hospital readmission and postoperative complications. Aside from immediate morbidity and mortality related to surgery itself, postoperative complications, such as anastomotic leak, sepsis, or pelvic abscess, can delay the onset of adjuvant chemotherapy, resulting in decreased survival. These postoperative complications also lead to increased discharge to a non-home setting, decreased quality of life, increased costs, and mortality.

Although all patients with ovarian cancer undergo this treatment schedule, older women are at particularly high risk for adverse events. Among women with ovarian cancer, more than 50% are over the age of 60 and up to 40% of these older women are defined as frail. Both age and frailty have been shown to be independent predictors of surgical complications, chemotherapy complications, as well as under-treatment with chemotherapy, resulting in inferior cancer-specific survival. Additionally, the definition of aging contains mechanisms beyond the chronological age of the patient. Both a cancer diagnosis and receipt of chemotherapy lead to synergistic biologic and physiologic changes that accelerate aging and increase frailty. Many older women with ovarian cancer are treated with neoadjuvant chemotherapy which is delivered in 3-4 cycles prior to surgery and this time period provides an optimal window to intervene to improve high-risk older patients' surgical outcomes.

Prehabilitation is the process of enhancing an individual's functional capacity prior to a forthcoming stressor, such as a major surgery, with the goal of improving postoperative outcomes. Prehabilitation programs are multimodal and can involve medical optimization, preoperative physical exercise, nutritional support and stress/anxiety reduction. Benefits of prehabilitation include reduced length of stay, fewer postoperative complications and improved postoperative pain. Even small increases in light physical activity or reducing sedentary time has been shown to slow or halt functional decline and improve quality of life. Among advanced cancer patients, physical activity interventions have been shown to be safe and feasible. They have also been associated with improved aerobic capacity, increased strength, and increased physical function. These parameters are important in older ovarian cancer patients to prevent functional decline, reduce frailty, and decrease surgical morbidity.

However, not all prehabilitation interventions or physical activity interventions are effective. There are populations that do not have sufficient time prior to surgery to have a meaningful change in activity or nutrition, this is especially true for cancer patients who often have a short window between diagnosis and surgery. Furthermore, many physical activity interventions in the pre-operative period have used structured, in-person, professionally-led programs with high intensity activity that may not be appropriate for the changing symptom burden of older ovarian cancer patients undergoing chemotherapy.

Instead of a one-size fits all approach, the American Cancer Society recommends that patients with advanced cancer engage in physical activity tailored to their capability. A recent systematic review and meta-analysis of prehabilitation in cancer patients undergoing abdominal operations noted that data specific to older patients are sparse. This study seeks to address this critical research gap by testing a home-based, patient-tailored, physical activity prehabilitation program (FIT4SURGERY) among older women with ovarian cancer undergoing neoadjuvant chemotherapy.

Physical activity has been shown to improve functional health and energy balance as well as decrease rates of frailty and sarcopenia, important prognostic factors prior to surgery, especially for older adults, and important prognostic factors for ovarian cancer. Increasing physical activity and motivating behavior change is difficult and many preoperative physical activity interventions have not utilized techniques and frameworks which have been successfully used among patients with chronic diseases. Social cognitive theory (SCT) is a framework which has been successfully used to design physical activity inventions that lead to behavior change. SCT has three main components, self-monitoring, self-judgment and self-evaluation which all contribute to self-regulation which is ultimately what drives behavior change. Behavioral interventions using SCT frameworks have been studied in healthy participants including cancer survivors, and have been shown to increase physical activity. Among women with metastatic breast cancer undergoing chemotherapy, an mHealth behavioral physical activity intervention consisting of a wearable activity tracker to provide direct feedback and a mobile app with motivational messaging, has been implemented by our research group. This study examines a modified version of this intervention, as prehabilitation, for the older ovarian cancer patient, as SCT-driven physical activity interventions have not been studied in a preoperative population.

Compared to the gold standard of professionally led, physical activity interventions, interventions via phone and email have been shown to be potentially as effective as more resource intensive interventions at increasing physical activity. Interventions using mHealth app-based platforms have also been shown to increase physical activity. Specifically, for older patients with ovarian cancer undergoing chemotherapy, interventions using wearable devices may be useful because they are home-based, easy to use, give immediate feedback, and use technology most patients already own. Caregivers can also be enlisted to help patients; activating social support for physical activity. Wearable devices allow for remote monitoring of participants and prevent the need for in-person visits which may be difficult for patients undergoing chemotherapy particularly during the COVID-19 pandemic. Furthermore, Fit4Surgery incorporates daily reported symptom burden into activity goals as symptoms can wax and wane during treatment. Such a tailored, home-based, patient-specific approach that facilitates the gradual and safe adoption of physical activity that can be supported by caregivers is ideal for older ovarian cancer patients.