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. 2017 Jun 12;6(6):CD011129.
doi: 10.1002/14651858.CD011129.pub2.

Early palliative care for adults with advanced cancer

Markus W Haun  1 , Stephanie Estel, Gerta Rücker, Hans-Christoph Friederich, Matthias Villalobos, Michael Thomas, Mechthild Hartmann
Affiliations

Early palliative care for adults with advanced cancer

Markus W Haun et al. Cochrane Database Syst Rev. .

Abstract

Background: Incurable cancer, which often constitutes an enormous challenge for patients, their families, and medical professionals, profoundly affects the patient's physical and psychosocial well-being. In standard cancer care, palliative measures generally are initiated when it is evident that disease-modifying treatments have been unsuccessful, no treatments can be offered, or death is anticipated. In contrast, early palliative care is initiated much earlier in the disease trajectory and closer to the diagnosis of incurable cancer.

Objectives: To compare effects of early palliative care interventions versus treatment as usual/standard cancer care on health-related quality of life, depression, symptom intensity, and survival among adults with a diagnosis of advanced cancer.

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, OpenGrey (a database for grey literature), and three clinical trial registers to October 2016. We checked reference lists, searched citations, and contacted study authors to identify additional studies.

Selection criteria: Randomised controlled trials (RCTs) and cluster-randomised controlled trials (cRCTs) on professional palliative care services that provided or co-ordinated comprehensive care for adults at early advanced stages of cancer.

Data collection and analysis: We used standard methodological procedures as expected by Cochrane. We assessed risk of bias, extracted data, and collected information on adverse events. For quantitative synthesis, we combined respective results on our primary outcomes of health-related quality of life, survival (death hazard ratio), depression, and symptom intensity across studies in meta-analyses using an inverse variance random-effects model. We expressed pooled effects as standardised mean differences (SMDs, or Hedges' adjusted g). We assessed certainty of evidence at the outcome level using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) and created a 'Summary of findings' table.

Main results: We included seven randomised and cluster-randomised controlled trials that together recruited 1614 participants. Four studies evaluated interventions delivered by specialised palliative care teams, and the remaining studies assessed models of co-ordinated care. Overall, risk of bias at the study level was mostly low, apart from possible selection bias in three studies and attrition bias in one study, along with insufficient information on blinding of participants and outcome assessment in six studies.Compared with usual/standard cancer care alone, early palliative care significantly improved health-related quality of life at a small effect size (SMD 0.27, 95% confidence interval (CI) 0.15 to 0.38; participants analysed at post treatment = 1028; evidence of low certainty). As re-expressed in natural units (absolute change in Functional Assessment of Cancer Therapy-General (FACT-G) score), health-related quality of life scores increased on average by 4.59 (95% CI 2.55 to 6.46) points more among participants given early palliative care than among control participants. Data on survival, available from four studies enrolling a total of 800 participants, did not indicate differences in efficacy (death hazard ratio 0.85, 95% CI 0.56 to 1.28; evidence of very low certainty). Levels of depressive symptoms among those receiving early palliative care did not differ significantly from levels among those receiving usual/standard cancer care (five studies; SMD -0.11, 95% CI -0.26 to 0.03; participants analysed at post treatment = 762; evidence of very low certainty). Results from seven studies that analysed 1054 participants post treatment suggest a small effect for significantly lower symptom intensity in early palliative care compared with the control condition (SMD -0.23, 95% CI -0.35 to -0.10; evidence of low certainty). The type of model used to provide early palliative care did not affect study results. One RCT reported potential adverse events of early palliative care, such as a higher percentage of participants with severe scores for pain and poor appetite; the remaining six studies did not report adverse events in study publications. For these six studies, principal investigators stated upon request that they had not observed any adverse events.

Authors' conclusions: This systematic review of a small number of trials indicates that early palliative care interventions may have more beneficial effects on quality of life and symptom intensity among patients with advanced cancer than among those given usual/standard cancer care alone. Although we found only small effect sizes, these may be clinically relevant at an advanced disease stage with limited prognosis, at which time further decline in quality of life is very common. At this point, effects on mortality and depression are uncertain. We have to interpret current results with caution owing to very low to low certainty of current evidence and between-study differences regarding participant populations, interventions, and methods. Additional research now under way will present a clearer picture of the effect and specific indication of early palliative care. Upcoming results from several ongoing studies (N = 20) and studies awaiting assessment (N = 10) may increase the certainty of study results and may lead to improved decision making. In perspective, early palliative care is a newly emerging field, and well-conducted studies are needed to explicitly describe the components of early palliative care and control treatments, after blinding of participants and outcome assessors, and to report on possible adverse events.

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Conflict of interest statement

MWH: none known; MWH is an internal medicine physician (internist) and a junior research group leader in mental health services research.

SE: none known.

GR: none known.

HCF: none known; HCF is a specialist in psychosomatic medicine and internal medicine, and manages psychiatric comorbidity in patients with somatic illnesses.

MV: none known; MV is a specialist oncology and palliative care physician and manages patients with advanced cancer.

MT is a department head of thoracic oncology (Thoraxklinik, University of Heidelberg) and manages patients with malignant thoracic diseases and lung metastases. MT received personal consulting fees from Lilly, Novartis, Roche, AstraZeneca, Pfizer, Boehringer, and BMS in 2014; from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2015; and from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2016 for attending boards. MT received lecture fees from Lilly, Novartis, Roche, AstraZeneca, Pfizer, and Boehringer in 2014; from Lilly, Novartis, Roche, AstraZeneca, BMS, MSD, Pfizer, and Boehringer in 2015; and from Lilly, Novartis, AstraZeneca, BMS, MSD, Pfizer, Boehringer, and Celgene in 2016.

MH: none known.

Figures

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1
Screening process diagram (as recommended by the PRISMA statement).
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
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Forest plot of comparison: 1 Health‐related quality of life, outcome: 1.1 Health‐related quality of life.
5
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Forest plot of comparison: 1 Early palliative care vs TAU, outcome: 1.2 Survival.
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Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.2 Depression.
7
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Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.4 Symptom intensity.
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Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.5 Health‐related quality of life (sensitivity analysis for study design including RCTs only).
9
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Forest plot of comparison: 1 Early palliative care vs standard oncological care, outcome: 1.6 Symptom intensity (sensitivity analysis for study design including RCTs only).
See this image and copyright information in PMC

Update of

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NCT01865396 {published data only}
    1. Vanbutsele G, Pardon K, Geboes K, Laat M, Belle S, Deliens L. Effect of systematic palliative care on quality of life of patients with advanced cancer of the upper gastrointestinal tract: a randomized controlled trial. Palliative Medicine 2014;28:834‐5. [DOI: 10.1177/0269216314532748] - DOI
    1. Vanbutsele G, Belle S, Laat M, Surmont V, Geboes K, Eecloo K, et al. The systematic early integration of palliative care into multidisciplinary oncology care in the hospital setting (IPAC), a randomized controlled trial: the study protocol. BMC Health Services Research 2015;15:554. [DOI: 10.1186/s12913-015-1207-3] - DOI - PMC - PubMed
NCT01885884 {published data only}
    1. A pilot trial of an embedded collaborative model of supportive care for pancreatic cancer. Ongoing study July 2013.
NCT01983956 {published data only}
    1. A structured early palliative care intervention for patients with advanced cancer ‐ a randomized controlled trial with a nested qualitative study (SENS trial). Ongoing study December 2013.
NCT02308865 {published data only}
    1. Impact of early palliative care on quality of life and survival of patients with non‐small‐cell metastatic lung cancer in Northern France. Ongoing study October 2014.
NCT02332317 {published data only}
    1. A randomized, controlled phase III study of integrated, specialized palliative rehabilitation for patients with newly diagnosed non‐resectable cancer. Ongoing study November 2014.
NCT02335619 {published data only}
    1. Early integrated supportive care study for gastrointestinal cancer patients. Ongoing study February 2015.
NCT02349412 {published data only}
    1. Ongoing study April 2015.
NCT02547142 {published data only}
    1. Evaluation of the implementation of an early integrated palliative care program in the esophageal cancer population. Ongoing study October 2015.
NCT02631811 {published data only}
    1. Early palliative care in patients with acute leukaemia (Pablo Hemato). Ongoing study November 2015.
NCT02712229 {published data only}
    1. A primary palliative care intervention for patients with advanced cancer (CONNECT). Ongoing study April 2016.
NCT02730858 {published data only}
    1. Palliative and oncology care model In breast cancer. Ongoing study May 2016.
NCT02853474 {published data only}
    1. Early palliative care in patients with metastatic upper gastrointestinal cancers treated with first‐line chemotherapy (EPIC‐1511). Ongoing study August 2016.

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