Association between Early Palliative Care Referrals,Inpatient Hospice Utilization,and Aggressiveness of Care at the End of Life

Introduction

Anumber of studies suggest that palliative care has a positive effect on many clinical outcomes, including symptom distress, quality of life, satisfaction, and survival.^1–3 In Japan, inpatient hospices play a central role in providing palliative care to cancer patients,^4–6 yet most referrals to palliative care have consistently occurred late in the disease trajectory,^7,8 as in the United States of America.^9–12

Meanwhile, end-of-life (EOL) cancer care has become increasingly aggressive over the past decade, as the therapeutic possibilities for patients with advanced cancer, such as intensive chemotherapy and targeted therapy, have expanded.^13–19 However, aggressive EOL care is not associated with higher-quality care,^20–22 and medical interventions in the last weeks of life, such as emergency department visits, hospital and intensive care unit (ICU) admission, death, and chemotherapy administration are generally considered to be indicators of poor-quality care.^23,24 Additionally, the use of chemotherapy in terminally ill patients with cancer in the last months of life may be associated with an increased risk of undergoing cardiopulmonary resuscitation, mechanical ventilation, or both, and of dying in an intensive care unit (ICU). ²⁵

To the best of our knowledge, there have been no studies investigating the association between early palliative care referrals and aggressive EOL care in Japan. Thus, this study was designed to explore the association between early palliative care referrals (>3 months before death) and inpatient hospice utilization at Osaka City General Hospital (Osaka, Japan), a large hospital with more than 1000 beds, by investigating cancer decedents. We also investigated the relationship between the timing of referrals to palliative care and aggressive EOL care.

Subjects and Methods

This was a retrospective cohort study in a cancer-designated hospital in Japan. The Institutional Review Board approved this study.

Measurements

We chose the association between early palliative care referrals (>3 months before death) and inpatient hospice utilization as primary end points. ¹⁹ This time interval (i.e., 3 months) was ad hoc cutoff point according to a previous study, ¹⁹ and confirmed that other cutoff points such as 1 or 2 months achieved essentially the same results. In addition, we also investigated the relationship between the timing of referrals to palliative care and aggressive EOL care. The aggressiveness of EOL care was examined by a composite measure adapted from Earle et al., ¹⁴ only existing instrument available to quantify the levels of aggressiveness of EOL care. This variable was assessed by six indicators in the last month of life: use of chemotherapy or targeted agent, more than one emergency department visit, more than one hospital admission, more than 14 days of hospitalization, an ICU admission, or death in a hospital. This composite score ranges from 0 to 6, with higher scores indicating more aggressive EOL care.

The principal investigator (K.A.) investigated the cases by chart review using electronic medical records. To confirm the reliability and validity, another attending physician verified all evaluations. These items were routinely recorded by physicians and nurses in our hospital.

Results

A total of 265 patients were divided into an early palliative care referral group (>3 months before death, n=54) and a control group (≤3 months before death, n=211). At baseline, there were no significant differences in patients and clinical characteristics between the groups, except in age (Table 1). The rate of inpatient hospice utilization was significantly higher in the early palliative care referral group (74% [n=40] versus 47% [n=99], adjusted p<0.001; Table 2).

The use of chemotherapy or targeted agent, more than one emergency department visit, more than one hospital admission, more than 14 days of hospitalization, an ICU admission, or death in hospital did not differ significantly between the groups (Table 2). However, the composite aggressive EOL care score was significantly lower in the early palliative care referral group (mean±standard deviation: 1.91±0.59 versus 2.14±0.78, adjusted p<0.001; Table 2). In this study, approximately 22% of patients received chemotherapy or targeted agent within 30 days of death and 71% of them died in general wards or an ICU.

Discussion

This retrospective cohort study revealed that early palliative referrals were associated with more inpatient hospice utilization and less aggressive EOL care. This study is the first to indicate the association between early palliative care referrals and inpatient hospice utilization and the relationship between the timing of referrals to palliative care and aggressive EOL care in Japan. Our findings support the importance of early palliative care for patients with advanced cancer in their disease trajectory and the need to address both the proportion and timing of palliative care referral in Japan, as in other countries. Hui et al indicated that early (>3 months before death) and outpatient palliative care was significantly associated with improved EOL outcomes, ¹⁹ consistent with our finding, while our study did not investigate specifically outpatient palliative care. Similarly, a retrospective cohort study of 100 cancer decedents in one hospital reported that patients who received palliative care consults more than 2 weeks before death had fewer ICU admissions and emergency department visits. ²⁶ Research has revealed that between 20% and 50% of patients with incurable cancers receive chemotherapy within 30 days of death^27,28 similar to our result, 58 of 265 (22%), and that the use of chemotherapy within 2 weeks of death is associated with lower rates of hospice use.^15,29 In addition, oncologists tend to be unwilling to discuss advance care planning while prescribing chemotherapy.^30–32 In a randomized controlled study comparing early palliative care integrated with oncology care versus standard oncology care among patients newly diagnosed as having metastatic lung cancer, patients who received concurrent palliative and oncologic care stopped intravenous chemotherapy an average of 2 months earlier than did those in the standard oncology group, but had longer median overall survival and were more likely to receive at least one week of hospice services.^3,33 The role of early concurrent palliative care in other advanced cancer populations needs to be further explored.

This study is preliminary and has major limitations: retrospective evaluation of outcomes, lack of patient-reported quality of life, lack of an early palliative care referral group, single-institution study, and lack of information about patients who were discharged home or moved to a nursing home or another hospital.

In conclusion, early palliative care integrated with oncology care may improve EOL outcomes and promote patients' attainment of their goals. Future nationwide research should assess the association between early palliative care referrals and aggressive EOL care in Japan.