Quality of End-of-Life Care in Patients With Advanced Cancer
The patient with advanced cancer, his or her family and friends, and the oncology clinicians often are faced with treatment decisions that profoundly affect the patient’s quality of life (QOL). Oncology clinicians are obligated to explore, with the patient and family, the potential impact of continued disease-directed treatments or care directed at the patient’s symptoms and QOL.
This section summarizes the information that will allow oncology clinicians and patients with advanced cancer to create a plan of care to improve QOL at the end of life (EOL) by making informed choices about the potential harms of continued aggressive treatment and the potential benefits of palliative or hospice care. This section:
- Reviews the concept of quality EOL care.
- Summarizes and evaluates the commonly cited indicators of quality EOL care.
- Explores the concept of a good death.
In addition, information about outcomes associated with cardiopulmonary resuscitation (CPR) and admission to the intensive care unit (ICU) at the EOL will allow the oncology clinician to better present options to patients with advanced cancer who are near the EOL.
Quality of EOL Care
Questions relevant to the goal of measuring the quality of EOL care in patients with advanced cancer include the following:
- Which evidence-based guidelines inform assessments of quality?
- What period defines the EOL?
- Are the quality indicators of interest accurate, readily available, and plausibly linked to desired outcomes?
- What constitutes high quality?
- Most important, is the patient’s perspective given precedence?
The patient perspective
Surveys and interviews of patients with life-threatening illnesses, not restricted to cancer, can contribute to the understanding of what constitutes high-quality EOL care. One group of researchers proposed that patients value five main domains of care near the EOL:
- Receiving adequate pain and symptom management.
- Avoiding inappropriate prolongation of dying.
- Achieving a sense of control.
- Relieving burden.
- Strengthening relationships with loved ones.
A 2011 prospective study of QOL in a cohort of patients with advanced cancer seen in outpatient medical oncology clinics provides additional insight into the patient’s perspective of what contributes to a good QOL in advanced cancer. The median survival of the cohort was 10 months, so the results may not reflect the situation for patients closer to death. Nonetheless, the strongest predictors of QOL were age, good performance status, and a survival time longer than 6 months. Patients who were waiting for a new treatment had worse emotional well-being. This experience suggests that QOL is related to factors such as disease progression and its complications, and to patients’ goals relative to any treatment they are receiving. In addition, other researchers have reported that family caregivers often report worse scores than do patients with advanced cancer in self-assessments of the patients’ QOL.
Indicators of EOL care quality
A variety of indicators have been proposed to measure the quality of EOL care in patients with advanced cancer. Several salient criticisms of the proposed indicators include the following:
- Indicators are typically measured in a period before death that is defined retrospectively from death. Clinicians cannot predict whether an intervention will be futile in preventing death; consequently, quality concerns may be exaggerated if the indicator is dependent on the time to death.
- Quality indicators may be insensitive to patient preferences. For example, a patient may prefer to receive chemotherapy close to death and forgo hospice enrollment. Conversely, the failure to deliver treatments consistent with guidelines may reflect patient refusals or medical contraindications to the recommended treatment. One study  demonstrated that adherence to six quality indicators in patients with lung cancer cared for in the Veterans Health Administration (VHA) was compromised by refusal (0% to 14% of the time) or medical contraindications (1% to 30% of the time), depending on the indicator.
- Administrative databases do not capture data for all patients. For example, Centers for Medicare & Medicaid Services databases capture only the Medicare population.
- Many indicators were not deliberately developed as measures of quality and may be insensitive to important outcomes.
Nonetheless, important insights into quality EOL care are provided by studying indicators over time or between different geographic regions, health systems, or subspecialties.
Trends over time in indicators of EOL care quality
Multiple reports are relevant to understanding trends in EOL care quality indicators over time for a variety of cancers. The following observations are supported by a 2004 analysis, with additional supporting citations indicated when relevant:
- Increasing numbers of patients start a new chemotherapy regimen within 30 days of death or continue to receive chemotherapy within 14 days of death.
- Increasing numbers of patients are referred to hospice; however, the length of stay in hospice remains relatively brief, supporting the concern that referrals to hospice may occur too late. For example, a 2011 study of men dying from prostate cancer demonstrated an increased utilization of hospice (approximately 32% to 60%), but there was an increase in the proportion of stays shorter than 7 days.
- The rates of utilization of ICU stays have also increased. For example, one study  reported that for patients dying from pancreatic cancer, admissions to ICUs increased in two different time periods: from 1992 to 1994, ICU admissions increased from 15.5% to 19.6%; and from 2004 to 2006, ICU admissions increased from 8.1% to 16.4%.
- Rates of do-not-resuscitate (DNR) orders have increased but remain close to death: A 2008 study of the rate and timing of DNR orders at a major cancer center between the years 2000 and 2005 demonstrated that the rates of DNR at the time of death increased from 83% to 86% for in-hospital deaths and from 28% to 52% for out-of-hospital deaths. However, for inpatient deaths, the median time between signing the DNR and death was 0 days; for outpatient deaths, it was 30 days. This suggests that communication about resuscitation preferences is delayed. This delay may negatively affect patient preparation for the EOL.
Regional variations in indicators of EOL care quality
Regional variations in rates of utilization of health care resources near the EOL are of interest because the differences are rarely associated with improved outcomes. While initial findings focused on differences between geographic regions of the United States, subsequent studies have demonstrated potentially meaningful differences between or within health systems. A brief summary of some notable variations follows.
- Compared with men enrolled in a fee-for-service Medicare product, older men with advanced cancer who received treatment through the VHA were less likely to receive chemotherapy within 14 days of death (4.6% vs. 7.5%), less likely to spend time in an ICU within 30 days of death (12.5% vs. 19.7%), and less likely to visit the emergency department more than once (13.1% vs. 14.7%).
- An analysis of data by the Dartmouth Institute for Health Policy & Clinical Practice about the care of Medicare patients with poor prognoses demonstrated significant regional variations in EOL care. The principal findings include the following:
- Variations in the rate of hospitalizations, ICU stays, and aggressive interventions such as CPR and mechanical ventilation.
- Variations in the use of chemotherapy in the last 14 days of life.
- Variations in the use of hospice measured as rates of referral or lengths of stay.
In the opinion of the authors, the observed regional variations were too large to be accounted for by racial or ethnic preferences or illness levels. Factors correlated with the aggressiveness of EOL care include the availability of resources such as the supply of ICU beds or imaging equipment; the number of doctors involved in each patient’s care; and the treatment setting itself.
Factors associated with variations in EOL care
Availability of medical specialists, numbers of hospital beds, physician, and health system characteristics are well-established factors associated with increased expenditures in the final 6 months of life. A 2011 study  utilized data from decedents enrolled in the Health and Retirement Study, Medicare, and the Dartmouth Atlas to identify patient-level factors that may contribute to regional variations. Functional status decline, Hispanic ethnicity, black race, and chronic diseases such as diabetes were associated with higher expenditures, even after controlling for regional characteristics. The patient-level factors accounted for only 10% of variations. EOL practice patterns and number of hospital beds per capita were also associated with higher expenditures. Advance care planning did not influence expenditures.
A potential explanation for regional variations in EOL care is regional variations in patient preferences. The evidence, however, is conflicting.
- One study surveyed 2,515 Medicare beneficiaries about their general preferences for medical care in the event of a serious life-limiting illness with a life expectancy of less than 1 year. The preferences were correlated with EOL spending by hospital referral region. There were no differences between preferences for palliation or life prolongation by region. Thus, it is unlikely that regional variations in preferences account for observed variation in EOL spending.
- Conversely, a secondary analysis of the potential influence of treatment site on the Coping with Cancer study outcomes demonstrated that the effect of treatment site partly resulted from differences in patient preferences.
The Good Death
The health care provider perspective
The concept of a good death is a controversial but potentially useful construct for the oncology clinician to more clearly formulate the goals of timely, compassionate, and effective EOL care. In a 2003 British Medical Journal article about caring for the dying patient, the authors proposed that there were sufficient evidence-based guidelines to facilitate a good death; a commentary that accompanied the article stated, “Nor can professional education convey adequately just how important it is for individuals, both at the time and afterwards, to go through the death of someone they love feeling that they are experiencing a ‘good death.’” Several salient points were made in subsequent letters to the editor:
- The mental health of the patient and family are essential concerns in providing a good death.
- Health care provider beliefs and attitudes may diminish the chances for a good death if they interfere with adequate pain or symptom control.
- Health care providers may risk medical paternalism if they are not respectful of a patient’s perspective and insist on EOL care or refuse to provide comfort measures that may shorten life.
- Religious faith and spiritual beliefs are important for many people near the EOL.
- A good death requires turning one's attention away from prolonging life.
The patient perspective
A landmark study of patients, families, and health care providers  surveyed seriously ill patients, bereaved caregivers, physicians, and other health care providers about what matters at the EOL. Respondents scored the importance of 44 attributes identified in previous interviews and focus groups in which participants were asked to define a good death. There was broad agreement about control of pain and other symptoms, communication, and preparation for death. However, certain attributes such as not being a burden to one’s family or society, or being at peace with God, were ranked as important by patients but less so by physicians. A population-based study in the Netherlands demonstrated a correlation between the respondents’ positive attitudes toward the concept of a good death and preferences that could potentially influence EOL decision making.
The caregiver perspective
In one study, formal and informal caregivers of 396 patients who died from advanced cancer were interviewed about the decedent’s QOL in the last week of life. The QOL was correlated with a variety of factors obtained via baseline interviews of decedents at the time of enrollment into the study and survey measures of coping styles, religious coping, religiousness/spirituality, and EOL preferences. Most variances in the QOL at EOL were unexplained. However, factors negatively correlated with QOL included the following:
- Intensive care in the last week.
- Death in the hospital.
- Feeding tube in the final week.
- Chemotherapy in the final week of life.
Conversely, factors correlated with a higher QOL included the following:
- Prayer or meditation.
- Visits with chaplains.
- The perception that the physician was respectful, open to questions, and trustworthy.
Outcomes After Potentially Life-Prolonging Interventions
CPR was initially developed to restore circulation in patients with predominantly cardiac insults. The outcomes after inpatient CPR in older adults have not improved significantly, in part because of the use of CPR in patients with comorbid life-threatening illnesses. Addressing the limited benefit of CPR during the transition to EOL care is made more difficult because in the United States, patients will undergo CPR unless there is an established DNR order in the medical chart to countermand the procedure. The following is a summary of the evidence that demonstrates the very limited value of CPR in patients with advanced cancer:
- A retrospective chart review of 41 patients who underwent CPR for an out-of-hospital cardiac arrest found that only 18 (43%) survived to be admitted to an ICU, and only 9 patients survived to be discharged (2 to home; 7 to a facility). The authors noted that documentation of the advanced stage of disease and poor prognosis were frequently mentioned in the medical records.
- A meta-analysis of survival after in-hospital CPR found that survival to discharge was 6.2% overall. Patients with advanced-stage disease, with hematological malignancy, and who underwent CPR in the ICU were less likely to survive to be discharged.
- Researchers have described the extremely poor outcomes of patients who were resuscitated in the medical ICU.[22,23] Only 7 of 406 patients resuscitated (2%) survived to be discharged. The remainder died at the time of the arrest (63%) or died within a mean of 4 days (26%).
Admission to an ICU
In addition to CPR, patients may require mechanical ventilation or admission to ICUs. Outcomes are poor for patients with advanced cancer. One study reported that the median survival of 212 patients with advanced cancer (who were referred to a phase I trial) was 3.2 weeks. Patients who required CPR had a median survival of 1 day.
The underlying diagnosis, however, may be a critical variable in predicting patient outcome. Patients with hematologic malignancies may do better than patients with solid tumors. For example, one study reported that patients with newly diagnosed hematologic malignancies had a 60.7% chance of surviving to be discharged and a 1-year survival rate of 43.3%. Multivariate analysis demonstrated that a remission status and early admission to the ICU were favorable risk factors.
- Kendall M, Harris F, Boyd K, et al.: Key challenges and ways forward in researching the "good death": qualitative in-depth interview and focus group study. BMJ 334 (7592): 521, 2007. [PUBMED Abstract]
- Singer PA, Martin DK, Kelner M: Quality end-of-life care: patients' perspectives. JAMA 281 (2): 163-8, 1999. [PUBMED Abstract]
- Zimmermann C, Burman D, Swami N, et al.: Determinants of quality of life in patients with advanced cancer. Support Care Cancer 19 (5): 621-9, 2011. [PUBMED Abstract]
- Jones JM, McPherson CJ, Zimmermann C, et al.: Assessing agreement between terminally ill cancer patients' reports of their quality of life and family caregiver and palliative care physician proxy ratings. J Pain Symptom Manage 42 (3): 354-65, 2011. [PUBMED Abstract]
- Ryoo JJ, Ordin DL, Antonio AL, et al.: Patient preference and contraindications in measuring quality of care: what do administrative data miss? J Clin Oncol 31 (21): 2716-23, 2013. [PUBMED Abstract]
- Earle CC, Neville BA, Landrum MB, et al.: Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol 22 (2): 315-21, 2004. [PUBMED Abstract]
- Bergman J, Saigal CS, Lorenz KA, et al.: Hospice use and high-intensity care in men dying of prostate cancer. Arch Intern Med 171 (3): 204-10, 2011. [PUBMED Abstract]
- Sheffield KM, Boyd CA, Benarroch-Gampel J, et al.: End-of-life care in Medicare beneficiaries dying with pancreatic cancer. Cancer 117 (21): 5003-12, 2011. [PUBMED Abstract]
- Levin TT, Li Y, Weiner JS, et al.: How do-not-resuscitate orders are utilized in cancer patients: timing relative to death and communication-training implications. Palliat Support Care 6 (4): 341-8, 2008. [PUBMED Abstract]
- Newhouse JP, Garber AM: Geographic variation in health care spending in the United States: insights from an Institute of Medicine report. JAMA 310 (12): 1227-8, 2013. [PUBMED Abstract]
- Keating NL, Landrum MB, Lamont EB, et al.: End-of-life care for older cancer patients in the Veterans Health Administration versus the private sector. Cancer 116 (15): 3732-9, 2010. [PUBMED Abstract]
- Goodman DC, Morden NE, Chang CH, et al.: Trends in Cancer Care Near the End of Life: A Dartmouth Atlas of Health Care Brief. Lebanon, NH: Dartmouth Institute for Health Policy & Clinical Practice, 2013. Available online. Last accessed March 11, 2015.
- Kelley AS, Ettner SL, Morrison RS, et al.: Determinants of medical expenditures in the last 6 months of life. Ann Intern Med 154 (4): 235-42, 2011. [PUBMED Abstract]
- Barnato AE, Herndon MB, Anthony DL, et al.: Are regional variations in end-of-life care intensity explained by patient preferences?: A Study of the US Medicare Population. Med Care 45 (5): 386-93, 2007. [PUBMED Abstract]
- Wright AA, Mack JW, Kritek PA, et al.: Influence of patients' preferences and treatment site on cancer patients' end-of-life care. Cancer 116 (19): 4656-63, 2010. [PUBMED Abstract]
- Ellershaw J, Ward C: Care of the dying patient: the last hours or days of life. BMJ 326 (7379): 30-4, 2003. [PUBMED Abstract]
- Steinhauser KE, Christakis NA, Clipp EC, et al.: Factors considered important at the end of life by patients, family, physicians, and other care providers. JAMA 284 (19): 2476-82, 2000. [PUBMED Abstract]
- Rietjens JA, van der Heide A, Onwuteaka-Philipsen BD, et al.: Preferences of the Dutch general public for a good death and associations with attitudes towards end-of-life decision-making. Palliat Med 20 (7): 685-92, 2006. [PUBMED Abstract]
- Zhang B, Nilsson ME, Prigerson HG: Factors important to patients' quality of life at the end of life. Arch Intern Med 172 (15): 1133-42, 2012. [PUBMED Abstract]
- Hwang JP, Patlan J, de Achaval S, et al.: Survival in cancer patients after out-of-hospital cardiac arrest. Support Care Cancer 18 (1): 51-5, 2010. [PUBMED Abstract]
- Reisfield GM, Wallace SK, Munsell MF, et al.: Survival in cancer patients undergoing in-hospital cardiopulmonary resuscitation: a meta-analysis. Resuscitation 71 (2): 152-60, 2006. [PUBMED Abstract]
- Ewer MS, Kish SK, Martin CG, et al.: Characteristics of cardiac arrest in cancer patients as a predictor of survival after cardiopulmonary resuscitation. Cancer 92 (7): 1905-12, 2001. [PUBMED Abstract]
- Wallace S, Ewer MS, Price KJ, et al.: Outcome and cost implications of cardiopulmonary resuscitation in the medical intensive care unit of a comprehensive cancer center. Support Care Cancer 10 (5): 425-9, 2002. [PUBMED Abstract]
- Fu S, Hong DS, Naing A, et al.: Outcome analyses after the first admission to an intensive care unit in patients with advanced cancer referred to a phase I clinical trials program. J Clin Oncol 29 (26): 3547-52, 2011. [PUBMED Abstract]
- Azoulay E, Mokart D, Pène F, et al.: Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium--a groupe de recherche respiratoire en réanimation onco-hématologique study. J Clin Oncol 31 (22): 2810-8, 2013. [PUBMED Abstract]