According to the American Cancer Society (ACS), almost one-third of women in the United States will develop cancer. Most of these women will survive their cancer diagnosis yet face an uphill battle of maintaining their health as well as to reduce the risk of cancer recurrence. To help women in coordinate, there is a shift toward patient-centered approaches to survivorship with Clinical Integrated Networks (CIMs), Patient-Centered Medical Homes (PCMHs), Accountable Care Organizations (ACOs), and the Patient-Centered Outcomes Research Institute (PCORI; Figure 21-1). The focus of these emerging concepts is to help women make informed health care decisions, improve health care delivery, and implement plans of care using evidence-based information. Ultimately, survivorship is guided by patients, caregivers, and the broader health care community.¹ Ideally, patients as well as members of the public have the information they need to make decisions with their health care professional that reflect desired health outcomes. As health care professionals, we must hear the call of our patients’ desires to improve survivorship through rehabilitation, quality of life (QOL), and symptom management. As the nation moves from physician-centric care to a patient-centered team approach, our patients deserve more active roles in their survivorship.

Cancer survivorship can be improved by participating in rehabilitation, improving QOL, and managing symptoms. With new national guidelines putting the patient at the center of communication between oncologists and primary care providers, we need to ensure all survivorship options are available to them.

Definitions

Gynecologic cancer diagnosis can play havoc on a woman’s body. Oncologists typically use various conventional therapies for treating gynecologic cancers to facilitate a positive prognosis. Unfortunately, these therapies along with a list of comorbidities can reduce the functional ability and QOL of women in survivorship. Rehabilitation is defined as restoring the body for use in life. Oncology rehabilitation specifically addresses a patient’s debilitating adverse events as a result of the therapeutic interventions.² Evidenced-based oncology rehabilitation includes physical strengthening, flexibility, functional assessments, QOL improvement strategies, stress management, lifestyle changes, and nutrition/dietary interventions. While still fairly new, oncology rehabilitation is still underutilized as a tool in survivorship, even as we face a future of patient-centered health care.

Although the potential benefits of oncology rehabilitation are obvious, the optimal frequency, intensity, type, and timing of rehabilitation for patients undergoing treatment or in survivorship still remain unclear.^3,4,5,6 Clinicians struggle to find the balance of challenging gynecologic cancer ­survivorship and encouraging one to make lifestyle changes all at once. However, can patients really afford to be inactive? Encouraging patients to be physically active can improve glucose metabolism, digestive function, immune function, and cardiovascular risk factors.^7,8 The balancing act between cancer recovery and thriving in survivorship can be tricky. Nevertheless, the literature remains clear that physical activity/rehabilitation is necessary to reduce the decline of a patient’s health status and support a full recovery. In fact, several health care practitioner groups have developed oncology survivorship-specific toolkits to help serve as guidance documents to ensure the well being of patients with cancer. These toolkits highlight the conventional approaches to rehabilitation for improving physical capacity as well as encouraging healthy lifestyles. Regardless of the cancer diagnosis, exercise/physical activity is the most important thing that a survivor can do in reducing cancer-related fatigue, cancer-­related stress, and reoccurrence.⁹

The American Physical Therapy Association (APTA) provides basic guidelines for treating the adult cancer survivor (Table 21-1). Mainly, the plan of care includes improving physical function (metabolic equivalents of tasks [METs]) during or after various treatments of cancer. Typically, a multisystem approach of improving cognitive, physical, and psychosocial arenas of a patient’s life is also included in the standard plan of care. Specifically, oncology rehabilitation can be beneficial to gynecologic oncology patient at any place on the spectrum of survivorship in various settings of outpatient or inpatient venues.¹⁰ These highly specialized rehabilitation programs have produced promising outcomes in reducing symptoms and in improving physical and psychosocial functioning.^11,12 For example, in a recent Cochrane review on the effects of rehabilitation and cancer-related fatigue,¹³ 56 studies demonstrated a significant impact on the aerobic system and reducing fatigue for patients undergoing oncology rehabilitation compared to controls. However, evidence for increased muscle strength was not significant in regards to overall resistance training and other alternative exercises. Alternatively, targeted resistance training such as strengthening the pelvic floor muscles after pelvic surgery due to gynecologic cancer has been shown to improve muscle strength, QOL, and urethral function. In a prospective, randomized, controlled trial of pelvic-floor exercises (PFRPs) in gynecologic cancer survivors, the intervention group significantly improved pelvic-floor function and QOL domains.¹⁴ The PFRP program consisted of one 45-minute exercise session and a 30-minute counseling session per week for 4 weeks. Overall, the stance of the APTA is to optimize activity by improving functional METs with reduced perception of fatigue allowing for improved activities of daily living (ADLs), knowledge through education, range of motion, and general strength training for ADLs.

The Society of The Society of Gynecologic Oncology (SGO) recently developed recommendations for rehabilitation for cancer survivors to help guide survivorship ­treatment.¹⁵ With similar goals to the APTA, the SGO recommends evidence-based cancer rehabilitation to be a standard of care for survivors. Unfortunately, this is not always the case even though it is widely accepted that exercise and lifestyle changes achieved in rehabilitation will improve survivorship. Specifically, the SGO encourages a healthy lifestyle that engages a healthy diet, stress management, tobacco cessation, and whole system approaches to wellness (see Table 21-1).

The American College of Sports Medicine (ACSM) and the ACS have joint guidelines, which establish detailed exercise prescriptions for cancer survivorship during and after treatment.¹⁶ This is the first time where guidelines have been implemented for survivorship just as emphatic as cancer prevention. Our patients need to have a priority of being physically active and eating a healthy diet in survivorship. The ACSM follows 2008 federal Physical Activity Guidelines for Americans, which states at least 150 minutes per week of moderate-intensity aerobic activity.¹⁷ Generally, moderate-intensity aerobic exercise, resistance exercise, neurocognitive training, and/or combined programs are the most successful.¹⁸ The art and science of exercise prescription in this population should be tailored to each individual’s needs and provide progression using the frequency, intensity, time, and type (FITT) principles of fitness (see Table 21-1).

Overall, the general recommendations of the APTA, ACSM, ACS, and SGO demonstrate that a comprehensive oncology rehabilitation program is a crucial part of recovery for cancer survivors. The balancing act between thriving and surviving should be approached with precaution and a good understanding of contraindications to rehabilitation (Table 21-2). Data from randomized clinical trials indicate that unpleasant symptoms such as fatigue are the largest barrier to exercise and can affect exercise adherence.¹⁹ As a result, the APTA, ACSM, ACS, SGO, and National Comprehensive Cancer Network (NCCN) emphasize the importance of oncology rehabilitation on the management of cancer-related fatigue to assist patients in overcoming this barrier.^20,21 To that end, the benefits of performing rehabilitation should be considered when contraindications do not exist (Table 21-3). With the mulitdisplnary approach, medically supervised oncology rehabilitation can provide a safe atmosphere for a patient and ensure adherence to lifestyle changes in survivorship.

Lifestyle Approaches to Survivorship Rehabilitation

Today, the majority of research done on rehabilitation programs for oncology patients supports mixed-interventions using strategies to improve body image, aerobic fitness, strength, dietary compliance, weight-loss, stress management, cognitive function, and QOL in concert with reduced fatigue.^{14,15,16,17,18,19,20,21} However, in gynecologic cancer survivorship, weight-loss and weight management are at the forefront of a successful prognosis, yet endometrial cancer survivors are not likely to modify nutritional intake and exercise without supervision or direct intervention.²² Studies conducted in gynecologic cancer survivors using a broad lifestyle management rehabilitation approach demonstrate reduced stress, which, in turn, decreases stress hormone release and improved weight loss. Studies using the cognitive-behavioral intervention (CBI; eg, relaxation exercises, guided imagery, nature sound recordings) in cancer patients (colorectal, lung, prostate, and gynecologic cancers) had immediate symptom improvements from the beginning of the session to the end of the session.²³ Research indicates that elevated levels of stress hormones, such as cortisol and norepinephrine, sustained overtime affect the rate of abdominal fat deposition and the adiponectin-leptin ratio.²⁴ Specifically, Diaz et al²⁴ found that the adiponectin-leptin ratio is significantly linked to disease-specific survival in ovarian cancer patients. Furthermore, in endometrial cancer studies, most women with a larger waist and hip circumferences suffer more than those of normal proportioned survivors.²⁵ When stress hormones are present, weight control appears to be an uphill battle when trying to make lifestyle changes, especially in survivorship. Thus, tackling issues of stress, physical activity, and weight management demonstrates the need for a multidisciplinary approach in oncology rehabilitation.

The National Cancer Institute (NCI) recognizes the need to define patterns of weight, physical activity, and nutrition that contribute to survivorship. From current data, we know the majority of obese cancer survivors are not meeting public health exercise and/or nutrition recommendations. Furthermore, overweight and obese cancer survivors are susceptible to diabetes, coronary heart disease, and premature death.²⁶ Cardiovascular (CVD) comorbidities are the leading cause of death among endometrial cancer survivors. The risk of death from CVD-related causes begins to exceed the risk from cancer-related causes 3.5 years after diagnosis (Figure 21-2).²⁷ Specifically, obesity is the greatest CVD-related risk factor for endometrial cancer. In the prospective study by Ward et al,²⁰ the researchers examined the relationship between cancer, body mass index (BMI), and risk of death, demonstrating a significantly increased risk of death in obese women with endometrial cancer. The relative risk of death for obese endometrial cancer women with a BMI between 30 and 34 kg/m² was 2.53, and BMI above 40 kg/m² was 6.25; the highest of all cancers. It is well established that prevalence of obesity is higher in endometrial cancer survivors than of all the US cancers caused by excess body fat. More than 85% of endometrial cancer patients are overweight and approximately 70% are obese—this number is double the percentage of women with breast cancer.²⁸ Conversely, in a large population-based study of 1423 invasive epithelial ovarian cancer survivors, there were no significant associations between height, weight, or BMI and ovarian cancer-specific mortality.²⁹ However, in a cohort study of 1400 women diagnosed with invasive epithelial endometrial cancer prediagnosis, BMI was associated with a higher risk of all-cause 5-year mortality and an increased risk for 10-year CVD mortality.³⁰ Thus, there are mixed data on the relationships of BMI and gynecologic cancer survivorship. Then again, what we do know from a variety of studies is that obesity is related to an overall decline in survival and increases the risk of CVD-death. These authors conclude that obesity is linked to prognosis and overall survival in gynecologic cancer survivors and medically supervised programs to encourage weight loss is essential.

Several studies have explored the relationship between BMI and gynecologic malignancies, yet evidence surrounding nutrition and diet still remain inconclusive. Using the Health Eating Index, ovarian cancer patients scored very similar to controls identifying no differences in consumption of whole fruit, dark green and orange vegetables, and whole grains.²⁴ The only significant difference between groups was related to meat and beans, which were slightly higher in controls.³¹ Thus, a multidisciplinary approach using nutrition and physical activity seems to be the combination for successful survivorship. von Gruenigen et al³² used a whole systems approach in a randomized clinical trial where early stage overweight and obese (BMI ≥ 25 kg/m²) endometrial cancer survivors followed a 6-month lifestyle intervention program supporting physical activity, dietary compliance of fruits/vegetables, and counseling to improve self-efficacy and QOL. The lifestyle program demonstrated significant increases in physical activity, daily intake of fruits/vegetables, and significant weight loss compared with controls in several cohort studies.^33,34 Maintaining a healthy lifestyle and routine examinations are also key components to fighting recurrence and improving one’s prognosis. Dietary change and increased exercise together are effective for weight loss and improving CVD risk factors. Several concerns have been raised regarding the safety and efficacy of oncology rehabilitation due to increased oxidative stress generation and free radicals from exercise impairing cellular functions (Figure 21-3).³⁵ However, in a systematic review by Ballard-Barbash et al,³⁶ they identified cancer survivors with higher levels of activity were more likely to reduce risk of death from any cause and there may even be a dose-related response to physical activity. Studies encompassing survivors of breast, colon, prostate, ­gastric, ovarian, endometrial, and brain cancer report that physical activity is associated with a reduction of all-cause mortality.

Exercise is medicine and can provide a protective shield for gynecologic cancer survivors. From a landmark study conducted by Blair and Cooper in 1998,³⁰ morbidity and mortality rates were directly related to physical functioning or metabolic capacity. Most notably, they demonstrated a linear reduction of risk with increasing levels of maximal METs achieved on functional capacity evaluations. Based on these data, the goals of oncology rehabilitation should be to improve patient functional capacity to be between 5 and 8 METs. These moderate-to-high activity levels will double the odds of survival compared with those individuals who have lower maximal MET levels.³⁷ Gynecologic cancer survivors are no exception. In a small study of obese endometrial cancer patients, functional capacity was significantly worse compared with normal obese controls.³⁸ In this instance, regardless of the cancer status, self-reported exercise for both groups was associated with improving health status. This emphasizes the point that peak exercise capacity is a stronger predictor of death than any other risk factors, such as hypertension, diabetes, obesity, heart arrhythmia, high cholesterol, and even smoking.

Oncology rehabilitation does not only provide benefits to maximal oxygen consumption, it also reduces the risk of frailty, especially after cancer treatments. In a study of frail elderly women recovering from gynecologic cancers, BMI was significantly different (P = .02) between groups women who were categorized as not frail (26.1 kg/m²), intermediately frail (31.5 kg/m²), and frail (36.0 kg/m²).³⁹ The risk of frailty is directly related to the excess weight of most gynecologic cancer patients as a result of not meeting public health guidelines for physical activity. The importance for survivors to engage in regular physical activity is plentiful even in various forms of rehabilitation. For example, in a randomized control study of 110 patients, the intervention group performed supervised, home-based training program shortly after chemotherapy. The program included flexibility training, both low- and moderate-intensity exercises over several months after treatment. As a result, the intervention group significantly improved cancer-related fatigue and increased maximal functional capacity compared with the control group.⁴⁰ Therefore, it is feasible and beneficial for cancer survivors to engage in supervised home-training programs or medically based supervised rehabilitation programs.

Research evidence suggests that individuals with cancer who follow recommended guidelines and observe specific precautions can safely exercise during cancer treatment and in survivorship. However, is there an optimal dose of physical activity to improve survivorship prognosis? Studies show that physical activity and obesity may predict cancer survivorship. There is some evidence suggesting a dose–response effect of increasing risk reduction with increasing physical activity levels.⁴¹ In a review by Litterini et al,⁴² patients are likely to benefit from an oncology rehabilitation exercise program approximately 12 weeks long; however, studies revealed a wide variety of frequency, duration, and intensity of exercise. In these studies, most oncology rehabilitation programs took a multiple mode approach along with a healthy lifestyle education curriculum. Further research is needed to determine the best type, timing, and intensity of exercise for the different types and stages of cancer. Despite these limitations, for the most part, exercise prescriptions have closely followed the published guidelines of the ACSM and ACS joint recommendations. Without reservation, gynecologic cancer survivors should be referred to oncology rehabilitation programs to assist women in making lifestyle changes. It is important to get survivors into supervised exercise and lifestyle programs because most gynecologic cancer survivors do not make spontaneous lifestyle changes. The effectiveness of interventions such as oncology rehabilitation among cancer survivors has demonstrated long-term health benefits and survival.⁴³ In addition, research studies testing the effectiveness of various types of rehabilitation and training regimens for cancer survivors found that exercise was effective in preventing or reducing cancer-related fatigue.⁴⁴ Thus, physicians have a responsibility to ensure patients get referred to rehabilitation programs to assist a patient’s well being and provide support on the journey of survivorship.

Quality of Life

The NCI recognizes that there are few national measures available to accurately measure health-related QOL for cancer survivors.⁴⁵ The American Association for Cancer Research (AACR) states that obesity can interfere with a survivor’s recovery and subsequent QOL. QOL measures, an example of patient-reported outcomes (PROs), are becoming a common component in patient-centered approaches to survivorship with CIMs, PCMHs, ACOs, and the PCORI. QOL encompasses subjective and objective life conditions as well as personal aspirations and values.^46,47 The multiple dimensions of QOL include physical, mental, social, emotional well-being, and development/activity. Within the last 4 decades, QOL has become an important end point relating to the treatment of cancer. Specifically, QOL in endometrial cancer patients are at the forefront of cancer-related QOL due to the early age of diagnosis and number of survivors. Obesity is not only the most significant risk factor for the development of endometrial cancer; obesity also reduces the QOL of endometrial cancer survivors. In a prospective ancillary analysis of women with endometrial cancer, results revealed that increasing BMI correlated with decreasing health-related QOL scores, specifically physical and functional well being.⁴⁸ Previous work in a meta-analysis from 30 randomized controlled trials in the European Organization for Research and Treatment of Cancer (EORTC) confirmed that QOL could predict survival.⁴⁹ Thus, QOL measures can provide significant prognostic value of cancer survivors and interventions such as oncology rehabilitation can influence QOL in survivorship.

Recently, a review of the most commonly applied QOL tools for women with ovarian, cervical, endometrial, and vulvar cancers revealed that disease-specific questionnaires are available, but there is little evidence to support the superior sensitivity and responsiveness of cancer-specific versus generic QOL questionnaires.⁵⁰ Several studies explored this point of QOL symptom-specific and cancer-specific questionnaire to more accurately reflect the QOL domains directly related to survival.⁴⁹ One study attempted to advance the understanding of QOL in ovarian cancer patients by assessing the top 10 symptoms important to women and their related QOL scores.⁵¹ Symptom management, the preservation of functionality, a sense of hope, sleep quality, and the maintenance/improvement of QOL all emerged as important components; however, choosing the right QOL tool is essential to capture the multidimensional experience of ovarian cancer patients stages of their survival. Thus, the specificity of symptoms for each patient should be carefully correlated with an appropriate QOL tool (eg, FACT-O, FACT-G, EORTC QLQ-C30). The psychometric properties of these tools can be beneficial when assessing a woman for QOL concerns, especially after pelvic surgery—meaning that not all QOL tools are created equal. Most notably, a small study of women (n = 50) who underwent pelvic surgery for vulvar, cervical, or endometrial cancer reported significant reduction in sexual frequency, vaginal lubrication, and ability to achieve orgasm; in spite of these results, no differences were noted in QOL/depression between sexual dysfunction groups.⁵² The results of these studies indicate the importance of engaging women in oncology rehabilitation programs that focus on QOL improvement initiatives specific to each woman guided by a multidisciplinary team of health care professionals. A Cochrane review of 40 trials with 3694 cancer patients revealed positive effects on QOL, specifically body image/self-esteem, emotional well-being, sexuality, sleep disturbance, social functioning, anxiety, fatigue, and pain for those patients participating in a formal intervention program.⁵³ Consequently, interventions facilitating women to improve QOL can greatly benefit women in any stage of treatment for gynecologic cancers.