Chapter 57: Palliative and Supportive Care

Despite significant progress in our understanding of cancer biology and the development of novel therapeutics, most patients with advanced cancer still die of their disease (¹). In addition to the significant mortality, cancer contributes to significant morbidity for cancer patients and their families.

The growth of cancer can result in multiple symptoms by direct invasion, obstruction, compression, inflammation, effusions, and paraneoplastic syndromes. Moreover, cancer predisposes patients to various complications, such as infections, bleeding, thrombosis, and fractures. Cancer treatments such as surgery, radiation, chemotherapy-targeted agents, and immunotherapy can also cause multiple adverse effects involving the cardiac, pulmonary, gastrointestinal, hematologic, musculoskeletal, neurological, endocrine, and dermatologic systems. Living with cancer also means that patients not only have to face their own mortality but also have to deal with many psychosocial stresses related to the uncertainties along the disease trajectory. They have to cope with changes in their bodily function, body image, ability to engage in daily activities, and family dynamics. Finally, many patients and families express significant existential issues and financial concerns. Taken together, the direct cancer effects, cancer treatments, and psychosocial issues all contribute to a large number of physical and psychological symptoms, resulting in a decrease in quality of life and increase in caregiver burden (²).

The literature has consistently demonstrated that cancer patients, particularly those with advanced disease, experience an average of 8 to 12 symptoms (^3,4), suggesting that many symptoms are underrecognized, underdiagnosed, and undertreated. In addition to physical, psychological, and existential concerns, patients and families often have informational and decision-making needs (⁴).

Over the past few decades, palliative care has matured as a discipline that specializes in addressing the multidimensional care needs of patients and their families. Palliative care

The key domains of palliative care include the following: building relationships and rapport, assessing and managing symptoms, addressing coping, establishing illness understanding, discussing cancer treatments, discussing end-of-life planning, and engaging family members (⁶).

Multiple studies have demonstrated improved patient outcomes associated with palliative care. In a meta-analysis, Higginson et al found that palliative care was associated with a significant improvement in pain (odds ratio [OR], 0.38; 95% CI, 0.23-0.64) and other symptoms (OR, 0.51; CI, 0.30-0.88) (⁷). Recent randomized controlled trials also demonstrated that palliative care involvement was associated with improvement in health-related quality of life compared to routine oncologic care (^8,9). Evidence also supports the role of palliative care in enhancing patient satisfaction (¹⁰) and caregiver satisfaction (¹¹). Through facilitating end-of-life discussions, providing spiritual care, and offering an alternative to aggressive care, palliative care also contributes to improved quality of end-of-life care (^12,13,14). This in turn leads to a reduction in the cost of care in the last days of life (¹⁵).

Setting of Palliative Care

Specialist palliative care is provided in four care settings: inpatient consultation teams, acute palliative care units, outpatient clinics, and community-based palliative care. Inpatient consultation teams represent the backbone of palliative care in the United States, with 92% of cancer centers designated by the National Cancer Institute (NCI) and 74% of non–NCI-designated cancer centers reporting their presence (¹⁶). Acute palliative care units provide intensive symptom control for patients and families in severe distress and facilitate transition of care (^17,18,19). The mortality rate varies widely, but the average is approximately 30% (²⁰). Outpatient clinics are present in 59% of NCI-designated cancer centers and in 22% of non–NCI-designated cancer centers (¹⁶). They are key to early palliative care access and provide longitudinal supportive care concurrent with active cancer treatments (²¹). There is growing emphasis to increase the availability of these programs. Finally, the community branch of palliative care is tailored for patients as they approach the end of life (ie, 6 months or less) (²²), when they often have decreased ability to travel back and forth to the hospital. These individuals may benefit from outreach by the palliative care team in the form of home palliative care or a transition to home-based or inpatient hospice programs.

Evidence to Support Early Palliative Care

In the 1990s, several first-generation randomized controlled trials compared palliative care interventions to usual care; however, they did not consistently demonstrate improved outcomes (^23,24,25). A systematic review revealed significant methodological limitations among these studies, such as contamination, underpowered sample size, attrition, and poor adherence (¹¹). The variable timing of introduction of palliative care, the lack of standardization of palliative care programs, the heterogeneous study duration, and the inconsistent outcome measures all made it difficult to clearly identify the intervention effect associated with palliative care.

Over the past decade, second-generation studies with improved designs have provided more evidence to support not only the need for specialist palliative care but also the early involvement for patients with advanced cancer. We review the key studies supporting involvement of palliative care early in the disease trajectory.

Temel et al conducted a landmark randomized controlled trial involving 151 patients with stage IV non–small cell lung cancer comparing routine oncology care with or without early palliative care referral (⁸). Patients were eligible if they were within 8 weeks of diagnosis of metastatic cancer and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Early palliative care involvement was associated with significant improvement in the primary outcome Trial Outcome Index in the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale at 12 weeks (59 vs 53, P = .009). The secondary outcomes, including the Lung Cancer Subscale (21 vs 19, P = .04); FACT-L total score (98 vs 92, P = .03); Hospital Anxiety and Depression Scale (HADS) depression (16% vs 39%, P = .01); Patient Health Questionnaire 9 (PHQ-9) (4% vs 17%, P = .04); aggressive end-of-life care (33% vs 54%, P = .05); documentation of resuscitation preferences (53% vs 28%, P = .05); and overall survival (11.6 months vs 9.8 months; hazard ratio 0.59, P = .01) also improved significantly. Largely based on this study, the American Society of Clinical Oncology published a provisional clinical opinion in 2012 supporting the integration of palliative care into standard oncologic care (²⁶).

Bakitas et al examined the effect of a nurse-led palliative care intervention in a randomized controlled trial (⁹). A total of 322 patients within 8 to 12 weeks of their diagnosis of advanced lung, gastrointestinal, genitourinary, or breast cancer were randomized to the intervention arm or usual care arm. Specifically, the study intervention was led by advanced practice nurses and consisted of four structured educational and problem-solving sessions followed by monthly telephone follow-up sessions addressing various aspects of care, such as symptom management, crisis prevention, communication strategies, advance care planning, and timely referral to palliative care and hospice teams. Over time, palliative care was associated with a significant improvement in health-related quality of life (Functional Assessment of Chronic Illness Therapy for Palliative Care [FACIT-PC], P = .02), depression (Center for Epidemiological Studies Depression Scale [CES-D], P = .03). However, symptom burden (Edmonton Symptom Assessment Scale [ESAS], P = .06), resource use at the end of life (intensive care unit admission, P > .99; emergency room visits, P = .53), and palliative care team referral (P = .32) were not significant different between the intervention and control groups. Because the study intervention was primarily nursing based, the lack of involvement of other disciplines, such as medicine, may have contributed to the lack of a significant difference in some observed outcomes.

Zimmermann et al randomized, using a cluster randomized design, 461 patients in 24 medical oncology clinics to either early involvement of palliative care or routine oncology care (¹⁰). Unlike the two previous clinical trials that enrolled patients from time of diagnosis, patients in this study had stage III/IV lung, gastrointestinal, genitourinary, breast, or gynecological cancer with an estimated survival of 6-24 months. The primary outcome, Functional Assessment of Chronic Illness Therapy–Spiritual Well-Being (FACIT-Sp) at 3 months, improved in the early palliative care arm (1.6) and decreased in the control arm (−2.0), although the difference was not statistically significant (3.6, P = .07). At 4 months, a significant improvement was observed (2.5 vs −4.0, difference = 6.4, P = .006). Secondary outcomes also favored early palliative care by 4 months, including Quality of Life at the End of Life (QUAL-E) scale (3.0 vs −0.5, difference = 3.5, P = .003), symptom burden measured by the ESAS (−1.3 vs 3.2, difference = −4.4, P = .05), and patient satisfaction with care assessed by FAMCARE-P16 (3.7 vs −2.4, difference = 6.0, P < .0001). The median survival in the early palliative care arm was 340 days, suggesting that these patients accessed palliative care relatively early in the disease trajectory.

Because the studies mentioned compared early palliative care to routine oncologic care, it was unclear if late palliative care was as effective as early palliative care. This question was partly addressed in a recent retrospective cohort study examining the quality of end-of-life care indicators in the last 30 days of life among patients who died of advanced cancer at MD Anderson Cancer Center (¹⁴). Patients referred to palliative care 3 months or more before death had significantly lower rates of emergency room visits (39% vs 68%, P < .001), hospital admission (48% vs 81%, P < .001), and hospital death (17% vs 31%, P = .004) compared with a patient seen by the same palliative care team less than 3 months before death. Similar differences were also reported using 6 months as the cutoff. Moreover, outpatient palliative care consultation was associated with significantly improved outcomes compared with inpatient palliative care consultation (Table 57-1). In multivariate analysis, improved quality of end-of-life care was associated with female gender (OR, 1.63; P = .027), palliative care outpatient referral (OR, 2.4; P < .001), and nonhematologic malignancies (OR, 2.6; P = .02).

Taken together, these studies suggest that early outpatient palliative care is associated with improved health-care outcomes. Table 57-2 summarizes some key questions related to palliative care delivery.

Access to Palliative Care

The delivery of palliative care can be categorized as primary, secondary, and tertiary (^27,28). Primary palliative care is the provision of basic symptom management and psychosocial care by oncology teams and primary care clinicians. Because these clinicians see patients in the frontline setting, it is crucial that they are all equipped with core palliative care competencies. Secondary palliative care refers to consultation services provided by interdisciplinary specialist palliative care teams. Often, patients have more complex supportive care needs, such as severe pain not relieved by first-line strong opioids. A growing number of countries, such as the United Kingdom, the United States, and Canada, have formal board accreditation for palliative medicine (²⁹). Tertiary palliative care denotes the situation when palliative care becomes the primary coordinating team. For example, patients admitted to acute palliative care units are followed by tertiary palliative care teams. Tertiary palliative care teams are often actively involved in education and research.

In delivering primary palliative care, oncologists generally feel the need for their active involvement in the provision of symptom management and supportive care (³⁰). A 1998 survey of 3,227 medical, radiation, surgical, and pediatric oncologists revealed that 90% learned palliative care by trial and error. A majority also reported that they had inadequate coaching in discussing prognosis and symptom control (³¹). In another survey of 895 medical oncologists in Europe, only 36% agreed that a palliative care specialist is the best person to coordinate palliative care of patients with advanced cancer; however, only 37% reported that most medical oncologists they know are expert in symptom management (³⁰). A more recent survey of US oncology trainees showed they still received limited core palliative care training, with less than half reporting having explicit training in the management of depression at the end of life and opioid rotation (³²). To date, only approximately 25% of oncology fellows have routine palliative care rotations (^16,32). To enhance the level of primary palliative care delivery, oncology fellowships should incorporate a greater degree of didactic and clinical training related to palliative care, ideally with role modeling and clinical rotations. Recognizing this important gap in knowledge, multiple organizations, such as the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO), are taking active measures to increase the level of core palliative care skills among oncology professionals through conferences, continuing medication education, and web-based learning (³³).

For secondary and tertiary palliative care, access to specialized teams can be measured in several ways: (1) What is the level of availability of palliative care in cancer centers? (2) Among cancer centers that offer palliative care programs, how many patients with advanced cancer see palliative care before they die? (3) Among patients who have had a palliative care consultation, when was the time of referral?

Although most US cancer centers reported having a palliative care service, the infrastructure of these programs varied widely, ranging from a single nurse practitioner to a comprehensive interdisciplinary team (³⁴). Cancer center executives, particularly in NCI-designated cancer centers, generally supported the expansion of palliative care in their centers. On a global scale, the development of palliative care has recently been outlined in the Worldwide Hospice Palliative Care Alliance (WPCA) Global Atlas of Palliative Care, demonstrating higher level of development in developed nations and areas for improvement in developing nations (³⁵).

The proportion of cancer patients who had palliative care consultations is another measure of access, although the denominator is not easily defined because not all patients may benefit from palliative care. We examined the timing of referral for patients who died of advanced cancer at MD Anderson Cancer Center during a 6-month period and found that only 366 of 816 (45%) had a palliative care consultation (³⁶). The percentage of referral varied significantly among tumor types. Over 60% of patients with gynecology malignancies had a palliative care consultation before death compared to only slightly over 30% in patients with hematologic malignancies. Older patients and those who were married were more likely to have a referral (³⁶). The timing of palliative care referral was also examined in this study. A majority of patients were referred to palliative care late in the disease trajectory, ranging from 1 to 2 months before death for patients with solid tumors to 0.4 months before death for hematologic malignancies (³⁶). In a US national survey, the median time from referral to death was 90 days for outpatient palliative care clinics and 7 days for inpatient palliative care programs (¹⁶).

Overcoming Barriers to Palliative Care Access

Despite the evidence to support early palliative care, there remain significant barriers to accessing specialist palliative care. These barriers can be categorized as oncology team–related barriers, patient-related barriers, and health-care system–related barriers (Table 57-3) (^36,37,38,39). In particular, the lack of emphasis of supportive care needs and the stigma associated with palliative care represent barriers common to both patients and oncology teams. A number of interventions, such as routine symptom screening, use of the goals of car analogy (discussed further in the chapter), and name change to supportive care may facilitate early palliative care access early in the disease trajectory.

To increase the awareness of supportive care needs, routine symptom screening using validated questionnaires in the oncology setting is essential. The ESAS examines 10 symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, well-being, dyspnea, and sleep). The intensity of each symptom is documented using a one-item numeric rating scale that ranges from 0 to 10 (0 is no symptom, 10 is worst possible intensity) (^40,41). Other symptom batteries include the Memorial Symptom Assessment Scale and Palliative Care Outcome Scale (^42,43). Routine symptom screening allows the oncology team to obtain patient-reported outcomes, which would help bring significant symptoms to their attention that would otherwise be missed. Once symptoms are identified, the oncology team may initiate treatments or make a referral to specialist palliative care. Repeat screening in future visits allows symptoms to be monitored longitudinally and symptom response to be assessed (⁴⁴).

Another approach to increase the awareness of supportive care needs is to educate patients using the analogy of the goals of the use of a car (Fig. 57-1) (⁴⁵). Some patients focus on seeking cancer treatments and do not want to worry about addressing their supportive care issues, such as symptom management, psychological distress, and advance care planning. This is similar to a hopeful and unrealistic driver who only wants to get to the destination without worrying about the potential hazards on the road and the possibility of accidents. In contrast, a hopeful and realistic driver knows the need to prepare for the road trip ahead—seat belts, insurance policies, suspensions, and cushions are essential to help arrive at the destination comfortably and safely. Because patients with advanced cancer inevitably develop symptom burden along the disease trajectory, it is important for the hopeful and realistic patient to maximize supportive care while receiving cancer treatments. Optimal supportive care would help to maximize symptom control and function, which may help in tolerating cancer treatments and deriving a treatment response.

Because palliative care is often felt to be synonymous with hospice care and end-of-life care, many clinicians and patients may have the impression that palliative care is not compatible with early referrals. To overcome this misconception, the term supportive care has been proposed to facilitate early palliative care referral. Supportive care is defined as “the provision of the necessary services for those living with or affected by cancer to meet their informational, emotional, spiritual, social or physical needs during their diagnostic, treatment, or follow-up phases encompassing issues of health promotion and prevention, survivorship, palliation and bereavement” (²⁸). Thus, palliative care is, by definition, supportive care for patients with advanced diseases. We previously conducted a survey of oncology specialists at our cancer center to examine clinicians’ beliefs toward the palliative care and supportive care. Compared to supportive care, oncology specialists were significantly more likely to feel that the service name palliative care decreases hope in patients and families, is synonymous with hospice and end of life, and is a barrier for referral (Table 57-4) (⁴⁶). This led our program to change its name from Palliative Care to Supportive Care in 2007. We found an increased number of referrals and earlier referral among outpatients after the name change, supporting the hypothesis that supportive care facilitates palliative care access (Table 57-5) (⁴⁷).

Finally, it is important to help oncologists understand how integration of palliative care with oncology can help them care for their patients. The everyday oncology practice consists of management of cancer, such as diagnosis, staging, and treatment decisions, as well as management of supportive care issues such as pain, fatigue, anxiety, and care planning. There are three approaches to address these increasingly complex issues (Fig. 57-2). In the solo practice model, the oncologist manages all the issues. Because of lack of time to conduct routine symptom screening, inability to keep up with the growing literature on supportive care, and absence of an interdisciplinary team, those in solo practice may not provide the optimal level of supportive care. In the congress model, the oncologist focuses on cancer-related issues and involves many different services, each focusing on one particular aspect of supportive care. This could potentially result in fragmentation of care, sometimes-conflicting recommendations, and added care costs. In the integrated care model, the oncologist addresses cancer management and involves the supportive/palliative team early in the disease trajectory. Patients thus would receive timely and comprehensive supportive care. A study showed that consultation to palliative care saves the oncologist on average 170 minutes of patient encounter (⁴⁸).

In summary, cancer patients experience significant symptom burden and have information and decision-making needs. Palliative care is now an accredited discipline that addresses these issues to improve patients’ quality of life. There is a growing body of evidence to support that early referral to palliative care improves patient outcomes, including symptom control, quality of life, quality of end-of-life care, patient and caregiver satisfaction, and possibly survival. However, there remain many barriers to palliative care access. Innovative models and approaches are needed to overcome these barriers and to maximize patient outcomes.