Introduction

According to the World Health Organisation, palliative care (PC) is defined as an approach that improves the quality of life (QoL) of patients and their families facing problems associated with life-threatening illness, through the prevention and relief of suffering and treatment of pain and other problems, e.g. physical, psychosocial and spiritual ones [1]. Early palliative care (EPC) in advanced incurable illness has been suggested to improve QoL, reduces symptoms, hospitalizations, aggressive end-of-life (EoL) care and healthcare costs [2–6].

Despite the growing evidence, one of the main challenges in clinical practice is determining the appropriate moment to initiate PC. This uncertainty may lead to delayed referrals, missed opportunities for symptom management and reduced support during the earlier stages of serious illness [7, 8]. Moreover, multiple barriers limit routine integration, particularly persistent stigma and treatment withdrawal, delaying referrals [9]. A key challenge is insufficient professional training, as well as structural limitations [10, 11].

Advanced cancer refers to malignancies that have evolved beyond the potential for cure with current medical interventions. This typically encompasses stage III (locally advanced) and stage IV (metastatic) disease, as classified by the TNM staging system (tumour-node-metastasis) where stage III indicates significant local growth and/or lymph node involvement (T1–4, N2–3, M0) and stage IV denotes the spread of cancer to distant organs (M1) [12].

According to the American Society of Clinical Oncology Guidelines, EPC should be offered within eight weeks of diagnosis to patients with advanced cancer, alongside standard oncologic care [13, 14]. In a position paper, the European Society for Medical Oncology stated that PC should begin at the time of diagnosis and be provided alongside treatments aimed at modifying the disease, rather than being restricted to EoL care [15].

Although major oncological societies advocate for the early integration of PC in advanced cancer, its implementation in clinical practice remains inconsistent.

This study aims to address this need through the following research question, structured using the PICO framework: in adult patients with advanced oncological disease (P), does early initiation of PC (I), compared to late initiation (C), improve quality of life, survival, healthcare resource utilisation and patient and/or family satisfaction (O)?

Hypothesis

Early initiation of PC in adult patients with cancer leads to significant improvements in QoL and reductions in healthcare resource utilisation compared to late initiation. Incorporating EPC during the advanced stages of oncological management may enhance patient-centred outcomes while contributing to more efficient healthcare delivery.

Aims

General: evaluate the impact of early vs. late PC initiation in adult patients with cancer.

Specific: compare the effects of early and late PC on QoL and overall survival (OS); analyse differences in healthcare resource utilisation between early and late PC groups; identify differences in patient and family satisfaction based on the timing of PC interventions.

Material and methods

Study design

This is a systematic review aimed at evaluating the impact of early vs. late PC initiation in adult patients with advanced oncological disease. The review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines to ensure methodological rigour and transparency.

Systematic literature search

A systematic literature search was conducted using the electronic databases PubMed, Scopus and the Cochrane Library. The search included studies published in English and Spanish from January 2010 onwards, with no geographical limitations.

Search terms included a combination of Medical Subject Headings (MeSH) and relevant keywords related to the following concepts: “Palliative Care”, “Early Palliative Care”, “Terminal Care”, “Timing of Care”, “Initiation of Palliative Care”, “Advanced Cancer”, “Metastatic Cancer”, “Stage III Cancer”, “Stage IV Cancer”, “Quality of Life”, “Survival”, “Health Resources”, “Health Services Accessibility”, “Patient Satisfaction”, “Advance Care Planning”, “Healthcare utilisation” and “Emergency Department Use”.

The search strategy was adapted to the indexing terms and syntax of each database. Reference lists of all included articles were reviewed and forward citation tracking was conducted to ensure completeness.

Eligibility criteria

Studies included met the following conditions:

• study design: primary studies (randomised controlled trials, cohort studies, case-control studies or cross-sectional studies) and secondary studies (systematic reviews and meta-analyses),

• population: adult patients (≥ 18 years) with advanced oncological diseases (stage III–IV according to the TNM classification),

• intervention and comparison: explicit comparison between early and late initiation of PC,

• publication date: studies published from 2010 onwards,

• language: studies published in English or Spanish.

• Studies were considered to be excluded if they meet any of the following:

• focused exclusively on paediatric populations,

• lack of a comparison group between early and late PC,

• editorials, opinion pieces, narrative reviews, individual case reports or conference abstracts,

• secondary analyses from primary studies or reviews including fewer than 3 studies/articles,

• do not report on relevant outcomes of interest.

Study selection

The selection process followed the PRISMA Guidelines. All search results first underwent automatic and manual duplicate removal.

Titles and abstracts were then screened independently by two reviewers to assess initial eligibility based on the inclusion and exclusion criteria. Articles that met the criteria or raise uncertainty proceeded to full-text review, which was also conducted independently by both reviewers. Discrepancies at any stage were resolved through discussion or, where necessary, consultation with a third reviewer.

Data extraction

Data extraction was conducted using a standardised form created in Microsoft Excel, specifically designed to align with the objectives of this systematic review. This form allowed for the systematic collection of all relevant information from each included study.

The data to be extracted included general study characteristics (such as author, year of publication, country, study design and setting), as well as detailed information on the population (sample size, age, diagnosis), the intervention and comparison (timing and definition of early vs. late PC), and the main outcomes of interest (QoL, OS, healthcare resource utilisation and patient and family satisfaction). Additional variables such as funding sources and declared conflicts of interest were recorded when available.

Risk of bias assessment

To reduce selection bias, two reviewers independently and blindly assessed eligibility, following the PRISMA Guidelines. In addition to selection bias, common sources of bias included deviations from intended interventions due to limited blinding, incomplete outcome data related to patient deterioration and selective reporting of results.

Results

Search process

A total of 522 records were identified through database searches. After removing duplicates, titles and abstracts were screened independently by two reviewers to assess eligibility. Studies deemed potentially relevant were retrieved for full-text review. This second phase was also conducted independently. Ultimately, 19 studies met the eligibility criteria and were included in the final synthesis [16–34]. The full selection process is illustrated in the PRISMA flow diagram (Figure 1).

Characteristics of included articles

A total of 19 studies published between 2014 and 2025 met the eligibility criteria and were included in the final synthesis. The evidence base comprised a heterogeneous set of designs, including randomised clinical trials, multicentre parallel-group trials, prospective observational cohorts, retrospective cohort analyses and systematic reviews with or without meta-analysis. The principal characteristics of the included studies are presented in Table 1.

Definitions of EPC differed considerably across studies in terms of timing, structure and clinical intensity. Several trials implemented EPC as structured, multidisciplinary outpatient integration within oncology services, requiring scheduled consultations within weeks of enrolment and regular follow-up (typically at least monthly) until death [17, 20, 22, 23, 25, 26, 30, 33]. These models commonly involved PC physicians and nurses and incorporated systematic symptom management, goals-of-care discussions and psychosocial support.

In other studies, EPC consisted primarily of hospital-based consultations with a predefined number of visits [18, 24, 29, 31], while some interventions emphasised broader multidisciplinary assessment including psychologists, nutrition specialists and social care services, with additional elements such as home-based support and coordination with community services [19, 21]. Other approaches incorporated structured educational programs combined with telephone coaching and periodic assessments by an integrated team [16].

For studies that were systematic reviews and meta- analyses [27, 28, 32, 34], detailed information regarding the exact structure, frequency and composition of EPC interventions was not consistently available.

Outcome measures predominantly relied on validated patient-reported instruments, with QoL and OS representing the most frequently assessed primary endpoints. Secondary outcomes, when reported, included healthcare utilisation, prognostic understanding, treatment intensity at the EoL and indicators of alignment between care delivery and patient preferences.

Despite methodological heterogeneity, the included studies collectively provide a comprehensive overview of contemporary approaches to EPC integration across diverse healthcare systems and cancer populations.

Quality of life

Regarding QoL, of the 15 studies reporting outcomes, 10 demonstrated a statistically significant improvement among patients receiving EPC, with p-values ranging from < 0.001 to 0.05 across multiple validated instruments. In contrast, 5 studies found no significant differences between intervention and control groups. Results are presented in Table 2.

Overall survival

An overview of OS results is provided in Table 3. Across the 9 studies reporting results, 3 demonstra- ted a statistically significant advantage associated with EPC, while the other 6 found no meaningful difference between EPC and standard care.

Healthcare resource utilisation

Table 4 presents the findings related to healthcare resource utilisation, including chemotherapy use near the EoL, hospital admission and emergency room visits. For chemotherapy near the EoL, 4 studies showed significantly lower use in the EPC group, whereas the remaining studies reported no significant differences. Hospital admissions were significantly reduced in 1 study, with others showing mixed or non-significant results. A similar pattern was observed for emergency room visits, where only 1 study demonstrated a significant reduction with EPC.

Discussion

Across the 19 included studies, there was no consistent or standardised definition of EPC. Although most studies aimed to introduce PC early in the disease trajectory, the criteria used to define “early” differed substantially. Some trials used time-based thresholds, such as initiating EPC within 2, 4, 8 or up to 12 weeks of diagnosis of advanced cancer. Others linked EPC initiation to study enrolment or randomisation, regardless of when the diagnosis was made. Several studies defined EPC in relation to clinical criteria, such as the start of palliative systemic therapy or confirmation of metastatic disease, while others embedded EPC into routine oncology visits without specifying any temporal criteria. In addition to timing, the structure and intensity of EPC varied markedly. Some programs delivered regularly scheduled multidisciplinary visits, whereas others involved less standardised, flexible or symptom- triggered approaches, including consultative models or educational and telephone-based interventions. Furthermore, differences in team composition, frequency of follow-up, and degree of integration within oncology services suggest that EPC represented a spectrum of care models rather than a uniform intervention. Taken together, although all studies aimed to involve PC earlier than usual practice, the lack of a unified definition limits comparability across trials and likely contributes to the heterogeneity observed in patient outcomes.

The majority of included studies reported improvements in QoL among patients receiving EPC, supporting its role as a patient-centred intervention. Although some trials failed to demonstrate statistically significant differences, this variability likely reflects methodological heterogeneity, including differences in intervention timing, intensity, delivery models and the QoL instruments employed. Quality of life is a multidimensional construct encompassing physical, emotional, and social domains, and variations in measurement tools may differentially capture these dimensions.

The overall direction of effect, however, consistently favours EPC. These findings reinforce the conceptual foundation of EPC, which emphasises proactive symptom management, psychosocial support and structured communication, factors known to contribute to improved well-being in advanced illness.

In contrast to QoL, evidence regarding OS was less consistent. Only a minority of studies demonstrated a statistically significant survival benefit. Survival outcomes are influenced by multiple variables, including tumour biology, treatment regimens, disease stage and follow-up duration. The absence of a consistent survival advantage should therefore not be interpreted as a lack of clinical value. Instead, these findings suggest that EPC neither compromises survival nor uniformly prolongs it, while still providing meaningful improvements in patient-centred outcomes. Future research with stratified analyses may help clarify whether specific patient subgroups derive survival benefit.

Findings related to healthcare utilisation indicate a tendency toward reduced aggressive care at the EoL among patients receiving EPC, particularly regarding chemotherapy administration near death. Reductions in hospital admissions and emergency department visits were less consistently observed. Early integration of PC may facilitate earlier goals- of-care discussions, better prognostic awareness and improved symptom control. These factors can promote care that is more closely aligned with patient preferences, potentially reducing non-beneficial high-intensity interventions. The variability observed across studies may reflect differences in healthcare systems, access to outpatient palliative services and cultural approaches to EoL decision-making.

Patient satisfaction was evaluated in two studies, McDonald et al. [30] and Zimmermann et al. [33], both of which reported significantly higher satisfaction among patients receiving EPC. Xie et al. [31] assessed family satisfaction, finding a significant improvement in the EPC group. This likely reflects improvements in communication, emotional support and continuity of care, aspects that are central to the PC model but often underemphasised in standard oncological care.

Limitations of the study

This review may be subject to publication bias, as studies with positive findings are more likely to be published. Additionally, language and date restrictions (limited to English and Spanish publications from 2010 onwards) may result in the exclusion of relevant studies published in other languages or before the selected timeframe.

There may also be heterogeneity in study designs, populations, definitions of early vs. late PC and outcome measures, which could limit comparability.

Another potential limitation is the variability in the quality of the included studies, particularly observational ones, which may carry a higher risk of bias. Moreover, some studies may lack detailed reporting of key variables, such as the advance care planning or satisfaction.

Finally, as a secondary analysis of published data, the review depends entirely on the accuracy and completeness of the original reports, without the possibility of accessing raw data.

Conclusions

Early palliative care has demonstrated meaningful benefits for patients with advanced cancer, most consistently in improving quality of life. Findings for other outcomes, including OS, healthcare resources utilisation and satisfaction were variable. This variability largely reflects the lack of standardised EPC definitions and intervention structures across studies. Standardisation of EPC models and outcome measures is essential to strengthen future evidence and enable more reliable comparison across trials.

Disclosures

1. Institutional review board statement: Not applicable.

2. Assistance with the article: None.

3. Financial support and sponsorship: None.

4. Conflicts of interest: None.

References