Recommendations for Palliative and Hospice Care in NCCN Guidelines for Treatment of Cancer

Abstract

Background

Integration of specialist palliative care into routine oncologic care improves patients’ quality of life and survival. National Comprehensive Cancer Network (NCCN) cancer treatment guidelines are instrumental in standardizing cancer care, yet it is unclear how palliative and hospice care are integrated in these guidelines. In this study, we examined the frequency of occurrence of “palliative care” and “hospice care” in NCCN guidelines and compared between solid tumor and hematologic malignancy guidelines.

Materials and Methods

We reviewed all 53 updated NCCN Guidelines for Treatment of Cancer. We documented the frequency of occurrence of “palliative care” and “hospice care,” the definitions for these terms if available, and the recommended timing for these services.

Results

We identified a total of 37 solid tumor and 16 hematologic malignancy guidelines. Palliative care was mentioned in 30 (57%) guidelines (24 solid tumor, 6 hematologic). Palliative care was mentioned more frequently in solid tumor than hematologic guidelines (median, 2 vs. 0; p = .04). Among the guidelines that included palliative care in the treatment recommendation, 25 (83%) only referred to NCCN palliative care guideline. Specialist palliative care referral was specifically mentioned in 5 of 30 (17%) guidelines. Only 14 of 24 (58%) solid tumor guidelines and 2 of 6 (33%) hematologic guidelines recommended palliative care in the front line setting for advanced malignancy. Few guidelines (n = 3/53, 6%) mentioned hospice care.

Conclusion

“Palliative care” was absent in almost half of NCCN cancer treatment guidelines and was rarely discussed in guidelines for hematologic malignancies. Our findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.

Implications for Practice

Integration of specialist palliative care into routine oncologic care is associated with improved patient outcomes. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have an important role to standardize palliative care involvement for cancer patients. It is unclear how often palliative care referral is recommended in these guidelines. In this study involving 53 NCCN Guidelines for Treatment of Cancer, the researchers found that palliative care was not mentioned in over 40% of NCCN guidelines and was rarely discussed in guidelines for hematologic malignancies. These findings underscored opportunities to standardize timely palliative care access across NCCN guidelines.

Short abstract

The timing of palliative care referral is highly variable and often delayed. This article reviews NCCN guidelines for cancer treatment to gain a better understanding of the recommendations for palliative and hospice care.

Introduction

In 2016, there were 17.2 million cancer cases worldwide and 8.9 million deaths. Cancer cases increased by 28% between 2006 and 2016 [1]. Patients with cancer often experience significant physical and psychological distress and have to face many difficult decisions regarding cancer treatments and care planning [2, 3]. Integration of specialist palliative care into routine oncologic care has been found to improve patients’ quality of life, symptom burden, mood, satisfaction with care, survival, and health care cost [4, 5, 6, 7]. Based on existing evidence, the American Society of Clinical Oncology envisions full integration of palliative care into oncologic care by 2020 [8]. However, the timing of palliative care referral is currently highly variable and often delayed [9, 10, 11]. Feld and colleagues found that in practice, oncologists only referred an average of 19% of patients with advanced non‐small‐cell lung cancer at diagnosis [9]. Nitecki et al. reported palliative care referral was only used by 28% of women with ovarian cancer, with 38% referral occurring within 30 days of death and 17% within one week of death. Palliative care referral was independently associated with advanced stage, recurrence, and hospice referral [10].

Clinical guidelines may help to standardize clinical practice and timing of palliative care referral. Widely adopted nationally and internationally, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have a critical role to facilitate knowledge translation and may guide insurance reimbursement [12]. However, it is unclear how often and when NCCN Cancer Treatment Guidelines recommended palliative care for patients with cancer. A better understanding of the recommendations for palliative and hospice care in solid tumor and hematologic malignancy NCCN guidelines may help to identify opportunities to standardize palliative care access and to improve quality of care. In this study, we reviewed all updated NCCN Guidelines for Treatment of Cancer to examine their recommendations for palliative and hospice care and compared the frequency of occurrence of these terms between solid tumor and hematologic malignancy NCCN guidelines.

Materials and Methods

Literature Search and Review Process

The Institutional Review Board at MD Anderson Cancer Center provided approval to proceed without the need for full committee review. We retrieved all updated NCCN Guidelines for Treatment of Cancer from the NCCN Web site (https://www.nccn.org ) on October 10, 2019. The NCCN testicular cancer guideline was updated on November 20, 2019, and this version was used in our analysis.

Study Measures

For each guideline, we documented the cancer type (solid tumor or hematologic malignancy), version, and date of publication. We counted the number of occurrence of “palliative care” and “hospice care” electronically. We also searched each guideline using the keywords “palliative” or “hospice” to ensure we have captured all mentions of these terms. Palliative cancer therapies were not considered as “palliative care.”

Among the guidelines that mentioned palliative care or hospice care, we extracted the definitions of each term if available and extracted the timing of palliative care in relation to cancer diagnosis and treatment (i.e., localized disease; first line palliative; recurrent, relapse, refractory, progression; and others). We also determined if they specifically recommended specialist palliative care referral or not. Definitions and recommendations for timing of palliative or hospice care involvement in the context of NCCN guidelines were captured and assessed in supplemental online Appendices 1 and 2.

Statistical Analysis

The primary outcome of this study was to compare the frequency of occurrence of the term “palliative care” involvement in NCCN Guidelines for Treatment of Cancer between solid tumor and hematologic malignancy guidelines. The data were summarized by using median, interquartile range (IQR), frequencies, and proportions. We compared between solid tumor and hematologic guidelines using Fisher's exact tests for categorical data and Mann‐Whitney U tests for count data. A p value of <.05 was considered statistically significant for the primary outcome. Secondary comparisons were considered to be hypothesis‐generating only. Statistical analysis was performed using SPSS statistics 24 software (IBM Corporation, Chicago, Illinois)

Results

Recommendations for Palliative Care in NCCN Guidelines

There were a total of 37 solid tumor and 16 hematologic malignancy guidelines (Table 1). Palliative care was mentioned in 30 (57%) NCCN guidelines, including 24 of 37 (65%) solid tumor guidelines and 6 of 16 (38%) hematologic guidelines. The term “palliative care” was used significantly more frequently in solid tumor guidelines than hematologic guidelines (median 2; IQR, 0–6 vs. 0; IQR, 0–2; p = .04; Table 2). Among the guidelines that included palliative care in the treatment recommendation, 25 of 30 (83%) guidelines defined “palliative care” (20 solid tumor and 5 hematologic guidelines). All of them only had a link to NCCN palliative care guideline, and it was unclear if the recommendation was for primary or specialist palliative care (Table 2). Specialist palliative care referral was specifically mentioned in 5 (17%) guidelines (i.e., “pediatric acute lymphoblastic leukemia,” “esophageal and esophagogastric junction cancers,” “gastric cancer,” “ovarian cancer,” and “pancreatic adenocarcinoma”; Tables 1, 2).

Table 1.

Characteristics of NCCN guidelines for treatment of cancer

Title of Guideline	Version	Date of publication	Specialist PC referral/consultation	Term present		Definition a		Section to explain
				PC	HC	PC	HC	PC	HC
Guidelines for Hematologic Malignancy (n = 16)
Acute lymphoblastic leukemia (adult and AYA)	Version 2. 2019	May 15, 2019		×		×
Acute myeloid leukemia	Version 2. 2020	Setp 3, 2019		×
B‐cell lymphomas	Version 5. 2019	Sept 23, 2019		×		×
Chronic lymphocytic leukemia small lymphocytic lymphoma	Version 2. 2020	Oct 8, 2019
Chronic myeloid leukemia	Version 2. 2020	Sept 25, 2019
Hairy cell leukemia	Version 1. 2020	Aug 23, 2019
Hodgkin lymphoma	Version 2. 2019	Jul 15, 2019
Multiple myeloma	Version 1. 2020	Sept 6, 2019		×		×
Myeloproliferative neoplasms	Version 3. 2019	Sept 4, 2019
Myelodysplastic syndromes	Version 1. 2020	Aug 27, 2019
Pediatric acute lymphoblastic leukemia	Version 1. 2020	May 30, 2019	×	×		×
Primary cutaneous lymphomas	Version 2. 2020	Dec 17, 2018
Systemic light chain amyloidosis	Version 1. 2019	Jan 11, 2019		×		×
Systemic mastocytosis	Version 2. 2019	Dec 3, 2018
T‐Cell lymphomas	Version 2. 2019	Dec 21, 2018
Waldenström's macroglobulinemia lymphoplasmacytic lymphoma	Version 2. 2019	Oct 12, 2018
Guidelines for solid tumor (n = 37)
AIDS‐related Kaposi sarcoma	Version 2. 2019	Nov 29, 2018
Anal carcinoma	Version 2. 2019	Aug 28, 2019
Basal cell skin cancer	Version 1. 2019	Aug 31, 2018
Bladder cancer	Version 4. 2019	Jul 10, 2019
Bone cancer	Version 1. 2020	Aug 12, 2019
Breast cancer	Version 3. 2019	Sept 6, 2019		×		×
Cervical cancer	Version 5. 2019	Sept 16, 2019		×	×		×
Central nervous system cancers	Version 2. 2019	Sept 16, 2019		×	×	×
Colon cancer	Version 3. 2019	Sept 26, 2019		×
Cutaneous melanoma	Version 2. 2019	Mar 12, 2019		×		×
Dermatofibrosarcoma protuberans	Version 1. 2019	Aug 16, 2018
Esophageal and esophagogastric junction cancers	Version 2. 2019	May 29, 2019	×	×				×
Gastric cancer	Version 2. 2019	Jun 3, 2019	×	×		×		×
Gestational trophoblastic neoplasia	Version 2. 2019	May 6, 2019
Head and neck cancers	Version 3. 2019	Sept 16, 2019		×		×
Hepatobiliary cancers	Version 3. 2019	Aug 1, 2019
Kidney cancer	Version 2. 2020	Aug 5, 2019		×		×
Malignant pleural mesothelioma	Version 2. 2020	Apr 1, 2019		×		×
Merkel cell carcinoma	Version 2. 2019	Jan 18, 2019		×		×
Neuroendocrine and adrenal tumors	Version 1. 2019	Mar 6, 2019
Non‐small cell lung cancer	Version 7. 2019	Oct 10, 2019		×		×
Occult primary	Version 2. 2019	Jan 23, 2019		×	×	×	×
Ovarian cancer	Version 2. 2019	Sept 17, 2019	×	×		×
Pancreatic adenocarcinoma	Version 3. 2019	Jul 2, 2019	×	×		×
Penile cancer	Version 2. 2019	May 13, 2019		×		×
Prostate cancer	Version 4. 2019	Sept 5, 2019
Rectal cancer	Version 3. 2019	Sept 26, 2019		×		×
Small bowel adenocarcinoma	Version 1. 2020	Sept 25, 2019
Small cell lung cancer	Version 2. 2019	Aug 5, 2019		×		×
Soft tissue sarcoma	Version 4.2019	Oct 10, 2019		×
Squamous cell skin cancer	Version 2. 2019	Aug 16, 2018
Testicular cancer	Version 2. 2020	Nov 20, 2019		×		×
Thymomas and thymic carcinomas	Version 2. 2019	Mar 11, 2019
Thyroid carcinoma	Version 2. 2019	Sept 16, 2019		×		×
Uterine neoplasms	Version 4. 2019	Sept 16, 2019		×		×
Uveal melanoma	Version 1. 2019	Jun 14, 2019		×		×
Vulvar cancer (squamous cell carcinoma)	Version 2. 2019	Jan 10, 2019		×		×

^aDefinition only linked to NCCN Guidelines for Palliative Care.

Abbreviations: AYA, adolescent and young adult; HC, hospice care; NCCN, National Comprehensive Cancer Network; PC, palliative care.

Table 2.

Comparison of frequency, definition, and timing for palliative care involvement in NCCN guidelines for treatment of cancer

Characteristics of Palliative Care Recommendation	Solid tumor NCCN guidelines, n = 37	Hematologic NCCN guidelines, n = 16
Number of times “palliative care” was mentioned,median (IQR); primary outcome	2 (0–6) a	0 (0–2) a
“Palliative care” term present, n (%)	24 (65)	6 (38)
Definition of “palliative care” provided, b n (%)	20 (83)	5 (83)
Section to explain palliative, care b n (%)	2 (8)	0 (0)
Specialist palliative care referral/consultation, b n (%)	4 (17)	1 (17)
Timing for palliative care involvement, c n (%)
First line	14 (58)	2 (33)
Recurrent, relapse, refractory, progression	12 (50)	5 (83)
Others d	7 (29)	1 (17)
Solid ‐ localized disease	2 (8)

^a p = .04.

^bAmong the guidelines that mentioned palliative care.

^cAmong the guidelines that mentioned palliative care. Some guidelines discussed palliative care involvement on more than one occasion, and thus the total percentage was greater than 100%.

^dOther timing for palliative care involvement included (a) poor physical status, (b) patients who do not desire further therapy, (c) symptom management (i.e., pain, dysphagia, obstruction, pain, bleeding, nausea/vomiting), (d) end‐organ status and preexisting toxicities from prior regiments, and (e) when establish goal of therapy (i.e., discuss palliative care option).

Abbreviations: IQR, interquartile range; NCCN, National Comprehensive Cancer Network.

Recommendations for Timing of Palliative Care in NCCN Guidelines

Among the guidelines that mentioned palliative care, only a small proportion recommended palliative care in the front line setting for advanced malignancy (solid tumor: n = 14/24, 58%; hematologic: n = 2/6, 33%; Table 2). About 50% of solid tumor (n = 12/24) and 83% of hematologic (n = 5/6) guidelines recommended palliative care in the late stage for advanced cancer (i.e., recurrent, relapse, refractory, progression setting). A few NCCN guidelines mentioned that palliative care should be considered in patients with care needs (n = 7/30, 23%; i.e., “pediatric acute lymphoblastic leukemia,” “central nervous system cancers,” “esophageal and esophagogastric junction cancers,” “gastric cancer,” “ovarian cancer,” “pancreatic adenocarcinoma,” and “small cell lung cancer”), including (a) poor physical status; (b) symptom management (i.e., pain, dysphagia, obstruction, pain, bleeding, nausea/vomiting); and (c) when establishing goals of therapy (i.e., discuss palliative care option). Two (7%) guidelines recommended palliative care when patients did not desire further therapy or had end‐organ failure (i.e., “ovarian cancer” and “thyroid carcinoma”).

Recommendations for Hospice Care in NCCN Guidelines

Only 3 (8%) solid tumor guidelines mentioned hospice care (i.e., “central nervous system cancers,” “cervical cancer,” and “occult primary”; Tables 1, 3). In two guidelines (i.e., “cervical cancer,” “occult primary”), “hospice care” was followed by a link to the NCCN palliative care guideline (Table 3). None of the hematologic malignancy guidelines mentioned hospice care.

Table 3.

Comparison of Frequency, definition, and timing for hospice care involvement in NCCN guidelines for treatment of cancer

Characteristics of Hospice Care Recommendation	Solid Tumor NCCN Guidelines, n = 37	Hematologic NCCN Guidelines, n = 16
Number of times hospice care was mentioned, median (IQR)	0 (0–0)	0 (0–0)
“Hospice care” term present, n (%)	3 (8)	0 (0)
Definition of hospice care provided, a n (%)	2 (67)	0 (0)
Section to explain hospice care, a n (%)	0 (0)	0 (0)

^aAmong the guidelines that mentioned hospice care.

Abbreviations: IQR, interquartile range; NCCN, National Comprehensive Cancer Network.

Discussion

In this study, we found that palliative care was absent in almost half of the NCCN cancer treatment guidelines. Palliative care was mentioned more frequently in solid tumor guidelines than hematologic guidelines. When mentioned, it was often unclear if the guidelines recommended primary or specialist palliative care and the timing for introduction of palliative care was often late in the disease trajectory. Few guidelines mentioned hospice care. Taken together, our study highlights significant variations in the recommendations regarding palliative care and underscores important opportunities to standardize timely palliative care access across NCCN guidelines.

Patients with cancer often encounter many unmet palliative care needs during their illness, including physical, psychosocial, spiritual, communication, decision making, and financial concerns [13, 14, 15, 16, 17, 18]. Comprehensive oncologic care includes not only diagnosis and treatment of cancer but also provision of timely supportive care for patients and families. In the NCCN palliative care guideline, palliative care was defined as “an approach to patient/family/caregiver‐centered health care that focuses on optimal management of distressing symptoms, while incorporating psychosocial and spiritual care according to patient/family/caregiver needs, values, beliefs, and cultures… Institutions should develop processes for integrating palliative care into cancer care, both as part of usual oncology care and for patients with specialty palliative care needs.” [19]

In this study, we found that almost half of NCCN guidelines did not mention palliative care, despite the body of evidence to support its integration and the importance of supportive care in oncology. There may be several reasons for this omission. First, the emphasis of these oncology guidelines is on cancer therapeutics, and supportive or palliative care may not be prioritized. The NCCN guideline panels consist predominantly of oncologists and may not have adequate representation from palliative care specialists to ensure this aspect is consistently included. Inclusion of key representatives of specialist palliative care teams in guideline committee may help to better integrate palliative care along the cancer care continuum. Second, there remains a lot of stigma associated with palliative care [20, 21, 22]. Third, some oncologists may see themselves providing most of the palliative care and thus rarely think of the need for referral to specialist palliative care [21]. Fourth, the term “supportive care” appeared to be used more frequently in NCCN cancer treatment guidelines than “palliative care,” and this warrants further research.

Even when palliative care was mentioned, there was often only a link to NCCN palliative care guideline without further clarification, making it difficult to know if these guidelines were recommending specialist palliative care referral and/or primary palliative care delivered by the oncology team. Only five NCCN guidelines mentioned specialist palliative care referral. In a landmark randomized trial, Temel et al. found that early palliative care integrated into routine oncologic care led to significant improvements in both quality of life and survival for patients with metastatic non‐small cell lung cancer [6]. Although the NCCN guideline for non‐small cell lung cancer cited this paper, it only mentioned “palliative care” twice and did not explicitly recommend specialist palliative care referral. Because the evidence supports that specialist palliative care improves cancer patients’ quality of life, symptom burden, costs of care, and survival when added onto primary palliative care [4, 5, 23, 24, 25, 26, 27, 28], endorsement of timely specialist palliative care referral by NCCN cancer treatment guidelines would facilitate knowledge translation toward improved patient outcomes.

Hematologic guidelines mentioned palliative care less frequently compared with solid tumor guidelines. This is consistent with the observation that palliative and hospice care were underused in patients with hematologic malignancies [29, 30, 31, 32]. Instead, patients with hematologic malignancies were more likely to be treated more intensively in the last month of life, including cancer treatments, intensive care unit admissions, and prolonged hospital stays [29, 33, 34, 35, 36]. Because patients with hematological malignancies have significant supportive care needs, involvement of palliative care teams can be beneficial [26, 37, 38]. Recently, El‐Jawahri et al. reported in a randomized clinical trial that inpatient palliative care referral significantly improved quality of life, symptom burden, depression, and anxiety among patients undergoing hematopoietic stem cell transplantation and already receiving a high level of supportive care from their hematologic oncologists [26]. Our findings underscore the need to introduce more palliative care to hematologic malignancy guidelines.

The literature supports that earlier involvement of specialist palliative care was generally associated with better outcomes relative to late referrals [4]. Timing of palliative care involvement in NCCN guidelines varied widely, with some guidelines limiting palliative care only to patients with refractory disease or no more cancer treatment options, whereas a few promoted earlier referral. In a Delphi study, international experts in palliative oncology reached consensus that palliative care referral would be most appropriate for patients with a prognosis of 6–24 months [39]. In addition to timing, the panel also strongly endorsed referral based on patient care needs. Specifically, a specialist palliative care consultation may be considered in patients who fulfill any one of the following criteria: severe physical, emotional, and spiritual symptoms; request for hastened death; request for referral; assistance with decision making or care planning; delirium; spinal cord compression; or brain or leptomeningeal metastases [39]. Given the limited availability of palliative care teams [40], the use of these criteria may facilitate more targeted and timelier referrals [41].

Hospice care was rarely mentioned in NCCN guidelines as an alternative to cancer treatments for patients with advanced cancer approaching the end‐of‐life. Exceptions included the “central nervous system cancers,” “cervical cancer,” and “occult primary” guidelines. The median time from hospice referral to death was approximately 2 weeks for patients with cancer, suggesting very late referral. Importantly, timelier hospice use was associated with improved end‐of‐life care outcomes [42, 43]. Inclusion of hospice in NCCN treatment guidelines may remind oncology providers that this may be an appropriate care option for patients with a prognosis of 6 months or less. Enriching the content of hospice care in NCCN guidelines will help oncologists to recognize hospice care referral as part of routine cancer care and facilitate the timely referral of appropriate patients to hospice [44].

This study included all NCCN cancer treatment guidelines in the most up‐to‐date format. However, an important limitation of this study is that the total number of guidelines was small, limiting our ability to compare between groups. Thus, we limited our comparison with the primary outcome to minimize the chance of false discovery.

Conclusion

Our study highlights the limited and variable discussion of palliative and hospice care in NCCN cancer treatment guidelines. Given the growing body of evidence to support the role of timely specialist palliative care in oncology practice, greater inclusion of palliative care in both solid tumor and hematologic NCCN guidelines will improve palliative care access and standardize the timing of referral. Similarly, hospice care can be presented as an option for patients with far advanced cancer. Palliative care specialists and/or palliative oncologists can actively contribute to NCCN cancer treatment panels by sharing their expertise related to the latest scientific advances in supportive and palliative care while promoting greater integration toward improved patient and caregiver outcomes.

Author Contributions

Conception/design: David Hui, Li Mo

Provision of study material or patients: David Hui, Li Mo

Collection and/or assembly of data: David Hui, Li Mo, Diana L Urbauer, Eduardo Bruera

Data analysis and interpretation: David Hui, Li Mo, Diana L Urbauer, Eduardo Bruera

Manuscript writing: David Hui, Li Mo

Final approval of manuscript: David Hui, Li Mo, Diana L Urbauer, Eduardo Bruera.

Disclosures

The authors indicated no financial relationships.

Supporting information

See http://www.TheOncologist.com for supplemental material available online.

Appendix 1 Definitions and Recommendation for Timing of “Palliative Care” Involvement in the Context of NCCN Guidelines

Appendix 2. Definitions and Recommendation for Timing of “Hospice Care” Involvement in the Context of NCCN Guidelines