Introduction
Prehabilitation has been defined in the literature as “a process on the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment and includes physical and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments.” At the time of cancer diagnosis, functional status among patients may vary significantly. While some patients may be functioning independently and routinely exercising, others may be requiring total assistance with activities of daily living. As a result, patients should be medically and functionally screened at the time of cancer diagnosis in order to properly assess needs for prehabilitation. The overall purpose of prehabilitation is to maximize patients’ahealth and functional status prior to undergoing treatment for cancer, which can include surgery, radiation, and/or systemic chemotherapy or other targeted medications. Ideally, participation in prehabilitation will enable patients to tolerate treatment better, improve function and health during and after treatment, and prevent deleterious complications.
Goals of Prehabilitation
The goals of prehabilitation have been described in different ways in the literature; while there are different proposed models, multimodal interventions provide a comprehensive approach to treatment of patients with cancer. Identification of functional impairments can allow for the design of individual exercise programs to improve functional outcomes and prevent injury. However, while exercise itself is beneficial, it does not fully constitute a prehabilitation program. Additional components should include the assessment and optimization of nutrition, mental health, and smoking cessation. Prior to participation in a prehabilitation program, patients should be screened for other medical comorbidities to prevent injury. Participation in a comprehensive prehabilitation program enables patients with cancer to maintain, if not improve, health, function, and quality of life during and after cancer treatment.
Breast Cancer Prehabilitation
Breast cancer is the most common cancer diagnosed in women in the United States, and survival has been improving for the past few decades. Prognosis is largely based on the cancer stage and the estrogen, progesterone, and human epidermal growth factor receptor 2 receptor status. Increased survival in breast cancer is likely due to improve screening and enhancements in adjuvant therapy. The current overall 5-year survival rate for breast cancer is around 90%. Breast cancer treatment can include neoadjuvant chemotherapy to reduce the size of the tumor prior to surgery, therefore increasing the potential of breast conservation. Postoperative chemotherapy along with endocrine therapy may be required as well. These interventions to treat breast cancer, while effective, may result in adverse effects that can negatively impact function. For example, radiation can result in fibrosis, while mastectomy and lymph node resection frequently lead to postmastectomy pain syndrome (PMPS), restricted range of motion (ROM), cording, and lymphedema. Knowledge of these common impairments can help design a prehabilitation program to prevent further morbidity posttreatment.
Neuropathy
Certain types of chemotherapy such as taxanes and platinum agents are often associated with neuropathy. Symptoms of neuropathy can be classified as positive or “presence” of symptoms in addition to negative or “absence” of symptoms. Positive symptoms can include paresthesia such as burning, tingling, and neuropathic pain while negative symptoms include numbness, weakness, and lack of proprioception. As a result of neuropathy, patients can develop impaired balance and gait and experience frequent falls resulting in further morbidity.
Some of these adverse effects can be partially addressed with medications. Neuropathic oral pain medications such as duloxetine, gabapentin, and pregabalin, as well as topical agents such as lidocaine can be used to treat the positive symptoms of neuropathy. Other medications such as tricyclic antidepressants (TCAs) can also be tried, though these medications often cause more adverse effects. To address the functional impairments from neuropathy, physical and/or occupational therapy along with ambulatory aids can be used. At times, use of compression garments and proprioceptive bracing can assist with numbness and impaired gait.
Lymphedema
Lymphedema affects approximately 40% of women treated for breast cancer. Lymphedema can occur after the removal of lymph nodes or radiation therapy and results from the blockage or disturbance of the lymphatic system. Patients with lymphedema experience a lower quality of life and increased psychosocial complications. Despite increasing amounts of research, a large percentage of women continue to experience lymphedema, and management remains a major challenge. Complete decongestive therapy involves manual lymph drainage by a trained lymphedema therapist, who performs and instructs on compression bandaging; in addition, therapy sessions include exercise with focus on ROM, skin care, and patient education. Intensive therapy can result in 50%–60% long-term volume reduction. Effective treatment of lymphedema can prevent complications such as skin breakdown and cellulitis. Previously, patients were counseled to avoid exercise to prevent lymphedema or prevent worsening of symptoms. However, close evaluation of the available literature has demonstrated no association with the development or worsening of lymphedema with exercise.
Axillary Web Syndrome
Axillary web syndrome (AWS) (also known as cording) is the development of a palpable, sometimes painful, rope-like cord in the axilla and/or in the ipsilateral arm after lymph node dissection. The incidence of this phenomenon ranges 10%–85% and is not well defined. AWS can result in significant discomfort along with decreased shoulder ROM. While AWS may resolve within a few months, a course of physical therapy focusing on ROM exercises, gentle stretching, and manual manipulation of the cord along with manual lymph drainage can be beneficial to improve the ROM along with function of the shoulder and arm and reduce pain.
Postmastectomy Pain Syndrome
Unilateral or bilateral mastectomy is one of the main treatments for invasive breast cancer. Approximately 20%–68% of patients who undergo a mastectomy experience PMPS, which is pain described as neuropathic discomfort or aching in the anterior chest, arm, or axilla that persists more than 3 months after surgery. Treatment strategies for PMPS include pharmacologic management with nonsteroidal antiinflammatory drugs (NSAIDs), neuropathic agents (gabapentin, pregabalin, duloxetine, and TCAs), and topical lidocaine, along with physical therapy, acupuncture, and regional nerve blocks. Physical therapy focusing on shoulder ROM and myofascial release has also been shown to have some benefits for PMPS. Understanding the pathophysiology of PMPS along with early recognition and education of patients allows better pain management and improved function.
Mental and Physical Fatigue
Treatment for breast cancer can be extensive and may involve neoadjuvant chemotherapy, surgical intervention, radiation, and postoperative chemotherapy, and/or endocrine therapy. Fatigue is common in patients with breast cancer; between 60%–90% of patients report fatigue during treatment, and 30% of patients with breast cancer report ongoing fatigue after completion of treatment. As discussed previously, in the past, patients were instructed to not participate in strenuous exercise out of safety concerns. However, research has found that not only is physical therapy safe but also is extremely important in patients with breast cancer to treat cancer-related fatigue well into survivorship.
Prehabilitation Recommendations
Currently, rehabilitation for patients with breast cancer is commonly started after completion of treatment to address the previously listed impairments. Increasingly, studies demonstrate that earlier integration of postoperative rehabilitation significantly improves outcomes. With this evidence demonstrating improved outcomes from rehabilitation, prehabilitation for patients with breast cancer is being studied more closely. Prehabilitation in patients with breast cancer includes pretreatment screening of physical function and psychosocial well-being with the intent to address any impairments that may exist before treatment, and to follow the patients closely throughout their treatment period to address any impairments that may occur throughout the duration of the treatment. The focus of prehabilitation in this population is on general conditioning exercise, targeted exercise, nutritional interventions, psychosocial well-being, smoking cessation, and patient education. A metaanalysis of 33 randomized controlled trials examining exercise in breast cancer patients illustrated significant improvement in body composition, emotional well-being (including anxiety and depression), and quality of life in patients who exercised. Studies have also shown that women with breast cancer who engage in physical activity preoperatively compared with sedentary women have an 85% greater chance of reporting improved return to baseline level of function 3 weeks postoperatively. Patients with breast cancer who exercise prior to chemotherapy demonstrate improved cardiovascular health, and a higher likelihood of completing chemotherapy treatment.
During breast cancer treatment the shoulder and upper quadrant are areas that are largely affected. Patients often lose shoulder ROM and function after surgical intervention and radiation treatment. Exercise focusing on shoulder abduction and external rotation can reduce pain and maintain ROM. Breast reconstruction through the use of an abdominal flap may result in reduced core strength and ROM along with lower back pain; as a result, specific exercise to the abdominal wall and postural muscles may lead to the prevention of these symptoms preoperatively.
While exercise is important in breast cancer prehabilitation, patients should be assessed and counseled on adequate protein intake, good glycemic control, appropriate vitamin supplementation, and overall weight loss to reduce postoperative complications and improve functional outcomes. Addressing psychological components of breast cancer is important during a prehabilitation program as well, and elements should include stress reduction, coping strategies, and overall psychological counseling to create long-term positive changes in health behaviors.
The multimodal prehabilitation approach described previously, including exercise, nutritional and psychological interventions can improve functional outcomes of breast cancer patients; yet overall, prehabilitation is understudied and underutilized. Generally, patients are neither routinely educated on prehabilitation nor are they aware of the impact these interventions can have on their functional and overall health. In this setting, physiatrists and other rehabilitation providers should be encouraged to be involved with oncology patients’acare to provide education and access to the multimodal strategies of prehabilitation. Ideally, prehabilitation in the breast cancer population would lead to less postoperative complications, higher completion rates of adjuvant treatment, and overall increased survival and functional outcomes for breast cancer patients.
Gynecologic Cancer Prehabilitation
The most common types of gynecologic cancers are uterine, ovarian, and cervical, though cancer can occur in various locations along the reproductive tract. Treatment of gynecologic cancer generally involves surgical management and adjuvant treatment based on multiple factors, including cancer stage and grade. In addition to shared symptoms seen with many different types of cancers such as fatigue, pain, and neuropathy, symptoms after treatment of gynecologic cancers may also include lower limb lymphedema (LLL), pelvic floor dysfunction, bowel/bladder impairment, and reduced quality of life.
Lower Limb Lymphedema
The incidence and prevalence of lymphedema after treatment of gynecologic cancers vary in the literature, with certain studies noting 20%–30% incidence after treatment of all gynecologic cancer, 0%–50% prevalence after treatment of endometrial cancer, and 7%–47% incidence after treatment of uterine cancer. Risk factors for developing lower extremity lymphedema from cancer treatment appear to include treatment-related factors such as extent of lymphadenectomy and use of radiation, as well as patient-related factors such as obesity and age. Lymphedema may be noticed immediately postoperatively, or may take several months to years to develop. Women with LLL after treatment of endometrial cancer have been found to have lower health-related quality of life.
As compared to upper limb lymphedema, LLL presents specific problems related to the dependent edema accrued from standing and walking. Patients who experience LLL may be more inclined to limit physical activity from the fear of worsening lymphedema. Do et al. studied 40 patients with lymphedema after gynecologic cancer surgery, who were randomly assigned to either receive decongestive therapy alone or decongestive therapy and an exercise program consisting of aerobic exercise and strengthening. After 4 weeks of treatment, physical function, leg volume, quality of life, pain, and fatigue were noted to improve in both groups; however, the exercise group was found to have significantly improved fatigue, physical function, and strength compared to those in the control group. Neither group was noted to have exacerbation of LLL. Similarly, another study found that physical activity reduced risk of developing LLL, although this reduction was seen only in patients with a body mass index less than 30 kg/m 2 .
Sexual Dysfunction
Impairments in sexual function may be affected by several variables in the treatment of gynecologic cancers. A study of gynecological cancer patients and breast cancer patients revealed that nearly 42% of patients were interested in discussing sexual care needs, and yet only 7% had sought medical help for these issues. After gynecologic cancer treatment, patients may be left with permanent physical impairments such as difficulty in experiencing orgasm, vaginal dryness, pelvic pain, and dyspareunia. In addition, procedures such as vaginectomies and radical vulvectomies may remove tissues involved in sexual function. Physicians, treating patients with a history of gynecological cancer, should take time to discuss sexual health concerns with their patients. In 2018 Stabile et al. found that among 231 women with gynecological or breast cancer diagnoses, 70% preferred that their medical team raise the issue of sexual dysfunction. In this study, 66% of women were found to prefer written educational material followed by discussion.
Pelvic Floor, Urinary, and Fecal Dysfunction
Because of the closely intertwined anatomy, dysfunction of the pelvic floor related to treatment of gynecologic cancer with surgery and radiation may affect urologic and gastrointestinal function. Injury from surgery and radiation may directly injure the muscles of the pelvic floor, or indirectly affect the function of these muscles through damage to the nerves supplying them. Disruption of the pelvic floor may result in issues in pelvic organ prolapse, continence, and elimination. A recent systematic review article examined the prevalence of pelvic floor symptoms after treatment of cervical cancer and found the prevalence of stress urinary incontinence to range from 4% to 76%, urinary frequency 6% to 71%, and fecal incontinence 2% to 34%. Similarly, among patients with endometrial cancer, prevalence of stress urinary incontinence ranged from 69% to 84%, fecal incontinence 11% to 24%, and pelvic organ prolapse 44%. Urinary incontinence is more common after radical hysterectomies than nerve-sparing radical hysterectomies. In the literature, pelvic floor therapy has been studied and found to improve urinary continence, pelvic pain, and sexual dysfunction. Yang et al. studied 24 patients with gynecologic cancer and randomly assigned them to participate in pelvic floor therapy or a control group without intervention. After 4 weeks of treatment the group that received pelvic floor therapy was noted to have improved pelvic floor strength, sexual, and physical function. Similarly, Rutledge et al. studied women with urinary incontinence after treatment of gynecologic cancer and found that the women assigned to treatment with pelvic floor training noted significant improvement in urinary incontinence symptoms over patients assigned to “usual care.”
Pain
Pain in patients with gynecologic cancers is related to extent of disease and treatment of disease. Hacker et al. noted “gynecologic oncology patients frequently have higher rates of moderate to severe pain and opioid use than patients diagnosed with other cancers.” Though mechanisms behind cancer-related pain are poorly understood, cytokine secretion and local tissue invasion are thought to be important factors. Pain from treatment may be related to surgery (acute postoperative pain), chemotherapy, and radiation. Patients may develop pain after surgery, which may be nociceptive and related to incisional or myofascial pain, and/or neuropathic pain related to nerve dysfunction from treatment. In addition, with radiation patients may develop complications such as radiation cystitis and postradiation vaginal strictures/atrophy. Obtaining an accurate and detailed pain history is imperative for better pain management assessment and treatment.
Prehabilitation Recommendations
No studies on prehabilitation exist in the gynecologic oncology patient population. However, screening patients for the earlier listed and other impairments along with counseling patients about the importance of exercise should be part of a general prehabilitation program in this population. In addition, addressing nutrition, stress reduction, and smoking cessation should also be a part of a prehabilitation program for the gynecology oncology population.
Recommendations for Prehabilitation and Future Directions
There are no studies on prehabilitation in the gynecologic oncology population, and only a few studies conducted on the breast cancer population. In one breast cancer prehabilitation study, Baima et al. studied the feasibility of prehabilitation by providing upper extremity exercises to 60 patients with breast cancer via instructional videos or in-person training. The patients were scheduled to have surgery within 1–4 weeks of the intervention. The study found no difference in adherence to exercises between groups, and no increased risk of seroma formation in the prehabilitation participants. A systematic review by Tsimopoulou et al. examined preoperative psychological intervention in the cancer population, with four of the seven studies reviewed involving breast cancer patients. The review noted improvement in several patient-reported outcomes such as quality of life, anxiety, and depression.
Santa Mina et al. recommended five components for breast cancer prehabilitation, including “total body exercise, loco-regional exercise pertinent to treatment-related deficits, nutritional optimization, stress reduction/psychosocial support, and smoking cessation.” Cardiovascular fitness and conditioning are thought to improve surgical oncology outcomes by reducing perioperative complications, reducing length of stay, and improving postoperative pain and function. By improving preintervention fitness a patient may be less affected by cardiotoxic effects of chemotherapy and better able to tolerate treatment. The goal of targeted exercise is to strengthen an area of particular vulnerability for patients with specific types of cancer. As described earlier in this chapter, upper extremity dysfunction is common after treatment of breast cancer. By understanding this tendency and treating any preexisting impairments in strength or ROM, a patient may experience less upper extremity morbidity after treatment.
Nutritional support for breast and gynecologic cancer patients is critical, as there are risks associated with being malnourished as well as being overweight or obese during and prior to treatment. Patients who are overweight are more likely to have poor prognoses, with reduced disease-free recurrence and increased mortality. Similarly, patients with sarcopenia may be more prone to experiencing adverse side effects from cancer treatment. As alluded to earlier, there is literature that suggests that psychological intervention prior to cancer treatment may reduce severity of several patient-reported outcomes. Smoking cessation counseling should be provided throughout all stages of prehabilitation, as patients who smoke throughout cancer treatment are at increased risk for surgical and postoperative complications, disease recurrence, development of second primary tumor, mortality, and reduced quality of life.
Though there are several gaps in knowledge on the topics of breast cancer and gynecologic cancer prehabilitation, by drawing from prehabilitation studies on available cancer populations, multimodal approaches to prehabilitation appear to be feasible and appear to improve surgical and patient-reported outcomes. Further research is needed to better delineate the best time-frame, patient population, and interventions for prehabilitation.
References
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