Original ResearchSystematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life
Introduction
Original studies and qualitative and systematic reviews have confirmed the efficacy and effectiveness of palliative care in oncology, with different levels of evidence [1], [2], [3].
Two main palliative approaches have been identified: ‘End-of-Life’ (EoL) palliative care and early palliative care (EPC). EPC has been suggested as an appropriate health care intervention alongside anticancer treatments to manage cancer patients and is referred to as ‘simultaneous palliative care’ [4], [5], [6], [7], [8], [9]. The impact of EPC has been studied on: (a) patient outcomes (quality of life [QoL] and psychophysical symptom burden); (b) quality of care and treatment aggressiveness near the EoL and (c) costs [4], [5], [6], [7], [8], [9].
The effect of EPC on symptom burden and QoL depends on clinical competence and the ability of the palliative care physician and his/her team to manage psychophysical symptoms during the chemotherapy phase. Conversely, the potential impact of EPC on health care resources and treatment aggressiveness near the EoL lies in the capacity of the palliative care team to actively participate in the ‘early’ shared decision-making process (with patient, family and attending oncologist), and also in the degree to which the patient's oncologist accepts the advice of the palliative care specialist [10], [11], [12], [13].
There is no consistent evidence of the impact of EPC on the above outcomes, and studies focussing on this issue show methodological shortcomings in terms of lack of standardisation of interventions and outcome measures, biased enrolment methods, poor protocol specification, difficulties with protocol adherence, contamination between study groups, insufficient statistical power and notable attrition [1], [10]. The entire body of scientific knowledge tends to support the usefulness of EPC, and the early implementation of palliative care is fast becoming standard practice for patients with advanced cancer [14]. However, further research is needed to confirm and clarify the real role of EPC. In particular, EPC data needs to be collected on different types of cancer, in different settings and, if possible, from different countries. Once the full potential of EPC has been acknowledged, more appropriate modalities for its integration into standard care can be evaluated [15], [16].
Different ways of introducing a patient to palliative care services have been identified: spontaneous request for activation from the patient and/or the attending physician on the basis of a referred symptom; request for intervention following symptom identified by a systematic screening tool [17]; automatic activation in patients in a given situation (i.e. first diagnosis of metastatic disease in solid tumours) or on the basis of natural history of a specific cancer and duration of the advanced phase (i.e. first-line chemotherapy for metastatic or inoperable locally advanced pancreatic cancer, or third-line chemotherapy for metastatic breast cancer) [18].
The present study compares on-request activation of EPC and systematic activation for metastatic disease in patients with pancreatic cancer. We chose this particular setting because very little progress has been made in pancreatic cancer patient management. The 5-year survival for pancreatic cancer patients in the United States of America (USA) has only slightly increased over the last 30 years (from 2% to 6%) [19], making it a persistent big killer. Pancreatic cancer currently occupies the 25th position in worldwide prevalence of cancer, with a 5-year prevalence of around 200,000 cases [20].
With regard to global cancer incidence, 2008 estimates ranked pancreatic cancer as 13th of the 20 most commonly diagnosed cancers worldwide [21]. In 2014, pancreatic cancer showed the lowest 5-year survival rate among 30 categorised malignant tumours in the USA [22]. In Europe, pancreatic cancer is currently the 5th cause of death in males (5.4%) and the 4th in females (6.7%) [23].
When the present study was begun, a ‘no palliative treatment’ control arm was considered unethical. We therefore decided to compare an interventional arm in which standard cancer therapy plus best palliative care was systematically performed from the beginning of chemotherapy in patients with advanced pancreatic cancer (systematic EPC) with a standard arm consisting of standard cancer therapy plus on-demand EPC in which a palliative care consultation was requested by oncologists on the basis of symptoms spontaneously reported by patients. Our previous paper focussing on patient outcome as the primary end-point revealed that QoL and symptom burden were significantly in favour of the interventional arm [24]. The present paper describes the results obtained on the use of health care services, a secondary aim of the original study, in the same patient population.
Section snippets
Patients and methods
One hundred and forty-nine of the 207 outpatients with advanced and/or metastatic pancreatic cancer enrolled onto the multicenter, randomised ‘systematic versus on-demand early palliative care’ study had died by December 2015. However, complete information on the use of health care services is available for this group. The study design, inclusion criteria, randomisation strategy and results on patient outcomes have already been described in detail [24].
Patients were randomised to receive either
Results
Two hundred and seven patients with advanced and/or metastatic pancreatic cancer recruited in 21 Italian centres between October 2012 and February 2015 were considered for the study. Twenty-one (9.9%) patients were excluded from the study, leaving 186 eligible for analysis (89 in the standard arm and 97 in the interventional arm; Fig. 1). The most frequent reason for exclusion after informed consent was non-administration of chemotherapy, mainly due to patient refusal or rapid worsening of
Discussion
A previous paper by our multicenter group described the positive impact of systematic EPC compared to on-demand EPC on patient outcomes, especially QoL and symptom burden [24]. The present work reports on the effect of systematic EPC on quality of care issues. Earle et al. [26] described the following as indicators of low quality care: overuse of chemotherapy very near death, underuse of hospice services and misuse of treatments resulting in high rates of emergency room visits,
Funding
This trial was partially supported by a research grant from the Italian Ministry of Health (RF-2011-02350971). The study sponsor was involved neither in the study design nor in the collection, analysis and interpretation of data. The study sponsor did not provide writing support for the report. All authors had full access to all the data in the study. The corresponding author had the final responsibility to submit for publication.
Contributors
Conception and design: Marco Maltoni, Emanuela Scarpi, Chiara Maria Broglia and Oriana Nanni.
Collection and assembly of data: Marco Maltoni, Emanuela Scarpi, Chiara Maria Broglia, Oriana Nanni, Monia Dall’Agata, Stefania Schiavon, Vittorina Zagonel, Antonella Galiano, Claudia Biasini, Luigi Cavanna, Daris Ferrari, Carla Codecà, Chiara Maria Broglia, Paolo Pedrazzoli, Roberto Bortolussi, Ferdinando Garetto, Luisa Fioretto, Maria Teresa Cattaneo, Alice Giacobino, Massimo Luzzani, Giovanna
Conflict of interest statement
None declared.
Acknowledgement
This trial was partially supported by research grant no. RF-2011-02350971 from the Italian Ministry of Health. This study is registered on ClinicalTrials.gov (NCT01996540).
The authors also thank Cristiano Verna and Laura Lotito for editorial assistance.
References (36)
- et al.
Palliative medicine and medical oncology
Ann Oncol
(2001) - et al.
European Society for Medical Oncology (ESMO) program for the integration of oncology and palliative care: a 5-year review of the designated centers' incentive program
Ann Oncol
(2010) - et al.
Top 10 things palliative care clinicians wished everyone knew about palliative care
Mayo Clin Proc
(2013) - et al.
Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
Eur J Cancer
(2013) - et al.
Systematic versus on demand early palliative care: results from a multicenter, randomized clinical trial
Eur J Cancer
(2016) - et al.
Early palliative care for patients with advanced cancer: a cluster-randomised controlled trial
Lancet
(2014) - et al.
Effectiveness of specialized palliative care: a systematic review
JAMA
(2008) - et al.
What is the evidence that palliative care teams improve outcomes for cancer patients and their families?
Cancer J
(2010) - et al.
Does palliative care improve outcomes for patients with incurable illness? A review of the evidence
J Support Oncol
(2011) - et al.
American Society of Clinical Oncology provisional clinical opinion: the integration of palliative care into standard oncology care
J Clin Oncol
(2012)