One of the difficulties to convince the most sceptical oncologists about the importance of integrating Palliative Care (PC) into standard cancer care was that they would frequently argue that the amount of benefit has not already been objectively demonstrated. Indeed, when compared to the long-lasting tradition of randomised clinical trials (RCTs) in oncology, PC researchers struggled to implement robust and relevant research, facing barriers that include study design and recruitment, funding and ethical issues. In the last decade, we have been assisting to an increasing amount of evidence-based research favouring the integration of PC early in the cancer trajectory, that prompt recommendations of several cancer organisations. Nevertheless, this seems far from becoming the standard practice.
Kavalieratos and colleagues have recently published the larger systematic review and meta-analysis of RCTs that aimed to determine the association of PC with patient and caregiver outcomes. Nine outcomes were evaluated in a narrative synthesis (quality of life (QoL)), symptom burden, mood, survival, advance care planning, site of death, resource utilisation, health care expenditures and satisfaction with care) and 3 were pre-selected to be evaluated in the meta-analysis (QoL, symptom burden and survival). Pooled effects were summarised as standardised mean differences (SMD), for QoL and symptom burden assessment. Pooled SMDs were translated as units of tools considered by authors to be more familiar by multiplying SMDs by the among-person standard deviation of the FACIT-Pal and ESAS for QoL and symptom burden, respectively. Interventions included those self-described as PC and had to comprise at least 2 of 8 possible domains of PC (structure and processes; physical aspects; psychological and psychiatric aspects; social aspects; spiritual, religious, and existential aspects; cultural aspects; EoL; ethical and legal aspects) and those designed for single symptom treatment or targeting only one PC domain were excluded. The review followed the Cochrane proposed methodology and the search criteria and databases were broad, although limited to English written papers, up to July 2016.
For the narrative synthesis, 43 trials were eligible for inclusion, comprising 12731 patients and 2479 caregivers. Although the study population was not limited to cancer, most of the studies (69.7%) included only this group of patients. The majority of the studies were performed at the United States and were rated as having a high risk of bias (Cochrane Collaboration Tool). Interventions ranged from nurse-led telephone monitoring to face-to-face multidisciplinary assessment, including inpatient to outpatient settings, and the majority (98%) addressed physical aspects of care.
A total of 23 trials were included in the meta-analysis. PC was associated with significant and clinically meaningful improvement in QoL at 1- to 3-month follow-up (SMD, 0.46; 95% CI, 0.08 to 0.83; I2 = 94.8%; mean difference in FACIT-Pal units) and with significant and clinically meaningful reduction in symptom burden at 1- to 3-month (SMD, −0.66; 95% CI, −1.25 to −0.07; I2 = 96.1%; mean difference in ESAS units, −10.30) and 4- to 6-month follow-up (SMD, −0.18; 95% CI, −0.31 to −0.05; I2 = 0.0%; mean difference in ESAS units: −2.80). No difference was found in QoL at 4- to 6-months follow-up. The additional post-hoc analysis according to disease type (cancer vs non-cancer) and setting (home vs hospital vs ambulatory) did not find association between PC and QoL or symptom burden. Regarding survival, 7 trials were pooled in the meta-analysis (2184 patients) and no association with PC was found (0HR, 0.90; 95% CI, 0.69-1.17; I2 = 75.3%)
In a nutshell, this meta-analysis achieved to demonstrate that PC interventions seem to be beneficial regarding patients’ QoL and symptom burden. Nevertheless, this results must be interpreted with caution. The variety of settings, tools and interventions (accounting for clinical diversity) as well as study designs and risk of bias (accounting for methodological diversity) was reflected in the high levels of statistical heterogeneity for all outcomes assessed in the meta-analysis. Even though the authors have accounted for heterogeneity in the statistical analysis performing a random-effects meta-analysis, cross-trial comparison is challenging. Issues regarding which types of intervention, timing and care providers remain obscure.
This study highlights the need to standardise the way we are measuring, more than the degree of benefit of PC. It is crucial to effectively implement a core set of validated outcome measures in all RCTs that include cancer patients comprised within the definition of “palliative” (metastatic setting). Additionally, further research on models of care integration and palliative interventions (including disease-modifying agents) that could benefit the most cancer patients is imperative.
This review has dealt with quality of life, symptom burden and survival in the palliative setting – how would you define core outcome measures that can be used in oncology clinical trials?
The author has no actual, potential, real or apparent interest to declare and has no involvement that might raise the question of bias in the work reported or in the conclusions, implications, or opinions