Significant symptoms and suffering related to castrate-resistant prostate cancer (CRPC) are associated with the disease and its treatment. Increasingly, with advances in treatment efficacy, men can live with symptoms for long periods. Interdisciplinary palliative care teams (including physicians, nurses, social workers, chaplains, pharmacists, psychologists, physical therapists, and nutritionists) focused on symptom management and patients’ goals of care can collaborate with prostate cancer surgeons, oncologists, and radiation oncologists to provide the best care for men at all stages of treatment, including end of life. This article reviews the benefits of palliative care in helping patients with CRPC manage symptoms and distress.
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Men with castrate-resistant prostate cancer commonly experience distress across physical, emotional, social, and existential realms.
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Interdisciplinary palliative care teams of clinicians (including physicians, nurses, social workers, chaplains, pharmacists, psychologists, physical therapists, and nutritionists) focused on symptom management and patients’ goals of care can collaborate with prostate cancer surgeons, oncologists, and radiation oncologists to provide the best care for men at all stages of cancer treatment, including at the end of life.
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Palliative care should be offered concurrently with disease-directed treatments.
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Basic palliative care interventions include communication, education, and simple emotional support.
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Interdisciplinary palliative care teams can provide necessary assistance with management of complex pain, fatigue depression, anxiety, existential crisis, and caregiver distress.
Introduction
Prostate cancer is the second leading cause of cancer death in men after lung cancer. For patients with metastatic castration-resistant prostate cancer, the median survival in recent phase 3 clinical trials ranges from 12.2 to 21.7 months. Although localized prostate cancer typically is asymptomatic, significant symptoms and suffering are associated with advanced prostate cancer and its treatments. This article reviews the benefits of palliative care comanagement in helping patients with castrate-resistant prostate cancer and their family caregivers manage symptoms and distress. Working to relieve distressing symptoms and improve quality of life (QOL) for patients and family throughout the course of their disease are the goals of palliative care, which should be pursued along with ongoing disease management efforts.
Concurrent palliative and oncologic care
The World Health Organization (WHO) defines palliative care in cancer as an approach that improves QOL of patients and their families facing the problems associated with life-threatening illness, through prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychological, and spiritual. Palliative care improves QOL and reduces unnecessary costs of health care with its focus on management of symptoms, psychological support, and assistance in goal-setting and the decision-making process for patients facing serious illness.
Traditionally, palliative care has been used only late in the course of disease and often delivered only in the hospital setting. Years ago, clinicians viewed palliative care as an alternative to aggressive treatment of cancer and, in fact, hospice regulations require forgoing disease-directed treatments. However, palliative care includes much more than hospice care and comfort-only care for patients at the end of life. Palliative care provides an extra layer of support to improve quality of life for patients with any prognosis that can be offered concurrently with disease-directed treatments. Controlled trials of early palliative care provided concurrently with cancer-directed treatment show its efficacy in improving quality of life for patients undergoing active cancer treatment, and even in prolonging survival. In a randomized trial, Temel and colleagues showed that early palliative care in addition to usual chemotherapy for patients with metastatic non–small cell lung cancer led to significant improvement in quality of life and mood, decreased aggressive care at the end of life, and prolonged survival compared with usual cancer treatment. Patients need not have to choose between curative attempts and palliative care. The American Society of Clinical Oncology (ASCO), the National Cancer Policy Board, and the National Comprehensive Cancer Network (NCCN) all recommend concurrent palliative care as standard of care for all patients undergoing treatment for advanced cancer.
Concurrent palliative and oncologic care
The World Health Organization (WHO) defines palliative care in cancer as an approach that improves QOL of patients and their families facing the problems associated with life-threatening illness, through prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychological, and spiritual. Palliative care improves QOL and reduces unnecessary costs of health care with its focus on management of symptoms, psychological support, and assistance in goal-setting and the decision-making process for patients facing serious illness.
Traditionally, palliative care has been used only late in the course of disease and often delivered only in the hospital setting. Years ago, clinicians viewed palliative care as an alternative to aggressive treatment of cancer and, in fact, hospice regulations require forgoing disease-directed treatments. However, palliative care includes much more than hospice care and comfort-only care for patients at the end of life. Palliative care provides an extra layer of support to improve quality of life for patients with any prognosis that can be offered concurrently with disease-directed treatments. Controlled trials of early palliative care provided concurrently with cancer-directed treatment show its efficacy in improving quality of life for patients undergoing active cancer treatment, and even in prolonging survival. In a randomized trial, Temel and colleagues showed that early palliative care in addition to usual chemotherapy for patients with metastatic non–small cell lung cancer led to significant improvement in quality of life and mood, decreased aggressive care at the end of life, and prolonged survival compared with usual cancer treatment. Patients need not have to choose between curative attempts and palliative care. The American Society of Clinical Oncology (ASCO), the National Cancer Policy Board, and the National Comprehensive Cancer Network (NCCN) all recommend concurrent palliative care as standard of care for all patients undergoing treatment for advanced cancer.
Symptoms in advanced prostate cancer
Epidemiology of Prostate Cancer Symptoms
Men with advanced prostate cancer experience physical and mental health morbidity and impaired quality of life as a result of both their illness and its treatment. Disease- and treatment-related symptoms include those in all domains of the bio-psycho-socio-spiritual model of comprehensive care.
Disease morbidity
In advanced metastatic prostate cancer that is castrate-resistant, pain is the predominant physical symptom. Prostate cancer most commonly metastasizes to bone (particularly the pelvis and spine), potentially causing debilitating pain and pathologic fractures. Bone metastases occur in 70% of men with advanced disease and 90% of men who die of prostate cancer. Approximately half of patients with bone metastases experience a skeletal complication. Patients with advanced disease are also at risk for lymphedema, urinary tract obstruction, and spinal cord compression. Among men with castrate-resistant disease, 10% develop cord compression.
Fatigue is among the most common and distressing complaints of men with advanced prostate cancer. Prominent psychosocial symptoms include depression and anxiety. Although data are limited, studies have found depression in up to half of men with prostate cancer, with anxiety shown to be even more prevalent. Among men with prostate cancer, suicide has been associated with depression, recent diagnosis, pain, and being foreign-born. Advanced prostate cancer creates numerous challenges to men’s coping ability, including an altered view of self, lack of empowerment, altered view of the future, and disrupted partner intimacy. Very little is known with certainty about existential and spiritual distress among this population.
Treatment morbidity
Ongoing evaluation, treatment decisions, and treatment itself for castrate-resistant prostate cancer also create burdensome symptoms. Many men who received prior treatment for localized disease already may have common symptoms associated with a particular treatment. Radical prostatectomy can lead to pain, erectile dysfunction (ED), and urinary incontinence. Nerve-sparing procedures lessen the risk of ED, but less so in older men. After bilateral nerve-sparing surgery by an experienced surgeon, approximately one-half of men will return to pretreatment erectile functioning. External-beam radiotherapy is associated with ED (approximately 50% of men), urinary incontinence, bowel dysfunction (including rectal urgency and mucus discharge), fatigue, and rectal pain. Brachytherapy is associated with ED (around 25% of men), urinary incontinence and burning, and pain. Depression, anxiety, and impaired QOL are common across treatments. Worsened QOL is clearly associated with sexual and urinary dysfunction and pain.
Androgen deprivation therapy can cause ED, loss of libido, hot flashes, depression, osteoporosis, fatigue, weight gain, and loss of mental acuity. Bisphosphonates for skeletal lesions carry the risk of renal toxicity and osteonecrosis.
Chemotherapy side effects from taxane-based agents can include fatigue, anemia, pancytopenia, pneumonitis, and edema around spinal metastatic lesions that can create cord compression.
Quality of Life and Spiritual Distress
Ultimately, disease- and treatment-related symptoms and distress impact the quality of a patient’s life. Health-related quality of life (HRQOL) may be defined as the impact of illness and health care on a patient’s function, daily activities, and emotional well-being. ASCO considers patient QOL second only to survival in importance. QOL influences treatment satisfaction. Notably, QOL may be predictive of patient disease outcomes, including survival. HRQOL declines during the final year of life for men with advanced prostate cancer.
HRQOL research has mostly focused on physical outcomes, and less so on psychological ones. Little research describes the spiritual distress that the diagnosis or treatment of prostate cancer causes in men and their family caregivers, but most clinicians recognize the potential for and frequency of profound existential issues engendered by the diagnosis of prostate cancer, the complications of its treatment, and the poor prognosis of castrate-resistant prostate cancer.
Limitations of the Evidence Base for and Barriers to Palliative Care
Consensus exists among professional organizations and clinical and academic leaders that patients with cancer face a significant symptom burden that should be a prime focus of management. Given all the morbidities across multiple domains involving both disease and treatment, most patients with advanced prostate cancer require symptom management services and benefit from palliative care. Pain, depression, and quality of life must be assessed and interventions offered to treat, manage, or improve them throughout the course of illness and at the end of life.
The current system has major limitations to providing this care, and inadequately proven models proposed to remedy the situation. These limitations include the lack of data about what types of care are best, the limited ability of cancer clinicians to implement symptom management care, and the lack of data about the feasibility and efficacy of care delivery models for improving symptom management. The evidence base for treatment of many physical, emotional, and existential prostate cancer morbidities is limited. The ability of prostate cancer clinicians to provide optimal symptom management is hampered by time constraints, lack of training in providing expert symptom management, and patient expectations and willingness to discuss symptom issues with their cancer physician. Even with the recognition that cancer symptom management is likely best performed in an oncologic/palliative care comanagement model, numerous elements of this model have yet to be evaluated rigorously, including feasibility, efficacy of interventions, staffing, health care use, and costs.
Symptom management and palliative care strategies in castrate-resistant prostate cancer
Principles of symptom management are analogous to those for other treatment goals. First, symptom assessment requires identifying the bothersome symptoms with a good history and physical examination. Second, identifying the underlying cause of the symptom to treat it is a primary goal. Third, symptom-directed treatment is a priority even while correctable underlying causes are still being sought. Fourth, anticipating symptoms and preparing for them and their treatment is necessary. Fifth, symptoms that are continuous should be treated with round-the-clock medication dosing, rather than as-needed dosing. In general, it is easier to keep a patient’s symptoms controlled than to get control of a symptom. Sixth, symptom treatments can create their own symptoms. The classic example is constipation from opioid analgesics used for pain. Seventh, many symptoms are best treated through a coordination of modalities, including pharmacologic and nonpharmacologic interventions. Eighth, preparation and education are key to help patients cope with the burden of symptoms. Information needs are paramount for most patients.
Principles and Tools of Palliative Care for Prostate Cancer
The first step in symptom management is to accurately identify the presence and severity of symptoms. In general, a 2-step approach to symptom identification and assessment is reasonable—brief, initial screening followed by more extensive, targeted evaluation. Brief screening questions to assess symptoms can be asked during routine oncologic visits. Some practices include these screening questions as part of routine previsit or waiting-room surveys. Normalizing the possibility of symptoms can help alleviate patient embarrassment about pain, sexual dysfunction, or relationship distress. Simple screening questions for common symptoms in prostate cancer and treatment are given in Table 1 .
| Symptom | Screening Questions |
|---|---|
| Pain | Are you having any pain? |
| Fatigue | How is your energy level? |
| Urinary incontinence | Do you have trouble with leaking urine? |
| Bowel dysfunction | Do you have trouble with your bowels? |
| Erectile dysfunction | Many men have difficulty with getting or maintaining erections; how have things been for you? |
| Loss of libido | Are you satisfied with your sex life? How is your interest in sex? |
| Anxiety | Many men worry about various things when they get prostate cancer; are you feeling anxious or stressed? |
| Depression | How is your mood? Are you feeling sad or depressed? Have you lost interest in things that used to give you pleasure? |
| Relationship strain | How are things at home? |
| Spiritual distress | Are you at peace spiritually? |
| Poor quality of life | How is your quality of life overall? |
Bothersome symptoms (as defined by patients themselves or by pre-determined survey thresholds) can be further assessed in detail. In general, symptoms can be assessed in terms of their severity, the level of bother they create, and the impact of the symptom on patient functioning. A simple 0 to 10 severity scale (such as the Edmonton Symptom Assessment Scale) or a “distress thermometer” are readily understood by most patients, useful for tracking patients’ symptoms over time, and recommended by specialty organizations. Several validated symptom surveys have proven feasible in clinical settings. Examples of validated symptom assessment tools are given in Table 2 .
| Symptom | Scale |
|---|---|
| Pain | 0–10 scale Distress Thermometer Brief Pain Inventory |
| Fatigue | Functional Assessment of Chronic Illness Therapy–Fatigue |
| Urinary function | UCLA Prostate Cancer Index International Prostate Symptom Score |
| Erectile dysfunction | UCLA Prostate Cancer Index |
| Bowel function | UCLA Prostate Cancer Index |
| Anxiety | Hospital Anxiety and Depression Scale Distress thermometer Generalized Anxiety Disorder-7 (GAD-7) |
| Depression | Hospital Anxiety and Depression Scale Distress Thermometer Patient Health Questionnaire-9 (PHQ-9) |
| Spiritual distress | Spiritual Well-Being Scale Functional Assessment of Chronic Illness Therapy–Spirituality (FACIT-Sp-12) |
| Poor quality of life | UCLA Prostate Cancer Index European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) |
Although screening for psychosocial distress for men with cancer is widely recommended (including by the Institute of Medicine and NCCN ), treating clinicians often do not follow these recommendations, citing lack of time and limited referral resources more commonly than patients’ unwillingness to discuss distress.
Treatment of Physical Symptoms
This section provides specific treatment strategies for common physical symptoms experienced by men with castrate-resistant prostate cancer, including pain, fatigue, hot flashes, osteoporosis and skeletal events, and nausea and vomiting. ED and incontinence are also considered, because they are common complications associated with the treatment of localized prostate cancer that likely persist through the end of life for men with castration-resistant disease.
Pain
Pain is typically from bony metastases. Severe radicular pain with sensory/motor deficits or neurogenic bladder suggests cord compression and must be evaluated emergently for more definitive treatment. Several general pain management principles can direct the team’s interventions:
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A good history and physical examination is important to identify treatable causes of the pain and the type of pain present. In particular, nociceptive pain (“dull,” “pounding,” “aching” pain from tissue injury) must be distinguished from neuropathic pain (“shooting,” “stabbing,” “burning,” or “electrical” pain from nerve injury or dysfunction).
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Patients’ pain is a subjective experience that cannot be verified by clinicians. Patients ultimately must determine what level of pain management is acceptable to them.
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Given the side effects of pain medications, patients typically must balance sedation and pain control. Improved function and control of pain adequate to participate in important life activities is the goal for most patients.
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Typically, the experience of pain includes the physiologic experience (which may have gender and racial determinants) and the cultural, existential, and psychological implications of pain, pain tolerance, and pain treatment. This concept of physiologic distress plus emotional and existential suffering is known as “total pain.”
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It is easier to keep a patient out of pain than to get a patient out of pain. For round-the-clock pain, round-the-clock pain treatment is necessary, preferably with a long-acting analgesic.
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Pain management requires frequent assessment and reassessment, focusing on patients’ evaluation of the severity of their pain, side effects, QOL, and function.
Many nonpharmacologic pain treatments are safe and can be recommended to almost all patients, including ice, heat, massage, physical therapy, transcutaneous electrical nerve stimulation, visualization, and acupuncture. Intensive nonpharmacologic treatments, such as radiation and surgery, are particularly important for bony metastases causing pain, cord compression, and imminent fractures requiring stabilization.
Pharmacologic pain treatments include 4 broad categories: nonopioid, opioid, neuropathic, and other analgesic medications. Chemotherapy that reduces tumor bulk may also be considered a symptomatic treatment.
Nonopioid medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are often used for mild pain. Each has a significant side-effect profile that may limit their use. However, NSAIDs may be uniquely beneficial for bony pain. NSAIDs, including cyclooxygenase (COX)-2 inhibitors, carry the risk of gastrointestinal bleeding and renal and cardiac toxicity. Proton-pump inhibitors may help patients avoid gastric upset and bleeding. Acetaminophen carries the risk of hepatic toxicity with dosages greater than 3 g/d (2 g/d for the elderly). When NSAIDs or acetaminophen are combined with opioids (in formulations such as acetaminophen with codeine or hydrocodone with acetaminophen), dosing will be limited by these nonopioid toxicities.
Opioid agonists are the mainstay of treatment for moderate to severe pain. There is no maximum dose of opioids. Opioid are available in short-acting and long-acting formulations. Short-acting medications (eg, immediate-release morphine sulfate, oxycodone, hydromorphone) typically are dosed every 4 hours. However, once a medication has reached its maximum concentration (usually after approximately 45–60 minutes for oral administration), short-acting medications can be redosed if a patient is still experiencing significant pain. Long-acting medications include methadone and controlled release formulations of morphine sulfate, oxycodone, and oxymorphone. Fentanyl is available intravenously, as a short-acting oral transmucosal or buccal formulation, or as a very long-acting transdermal formulation that is dosed every 3 days. Typically, a long-acting pain medication should be combined with a short-acting medication for “breakthrough” pain. Breakthrough dosing can be approximated as 10% of the total daily dose of morphine equivalent. When stable, the total 24-hour need for breakthrough pain medication can be calculated and used to adjust the long-acting medication dose. A useful listing of opioid medications, dosing, routes of administration, and widely promoted practice guidelines is available at http://www.nccn.org/ .
A key principle is the concept of equianalgesic dosing—the dosing of any one opioid may be translated into the dosing of another opioid using the equivalencies in Table 3 . Because of incomplete cross-tolerance, starting with 50% to 75% of the calculated equianalgesic dose is prudent.
Related posts:
Targeting the Androgen Receptor
Moving Toward Personalized Medicine in Castration-Resistant Prostate Cancer
Quality of Life with Advanced Metastatic Prostate Cancer
The Experience with Cytotoxic Chemotherapy in Metastatic Castration-Resistant Prostate Cancer
Management of Docetaxel Failures in Metastatic Castrate-Resistant Prostate Cancer
Targeting Angiogenesis as a Promising Modality for the Treatment of Prostate Cancer
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