Prognostic factors in inpatients with advanced cancer at a palliative care unit

In countries where access to health is poor, most individuals with cancer arrive at health services when it is already at an advanced stage1. Data from a specialized palliative care unit (PCU) in Brazil, indicate that most patients entered the institution with advanced cancer and did not meet the eligibility criteria to receive curative treatment2.

In this context, clinical decisions related to procedures or surgeries, nutrition, artificial hydration, etc., draw on the results of a prognostic assessment3. As a large part of this group of individuals experience reduced survival4, especially in a hospital setting, it is essential for an adequate prognosis to be made to ensure adequate care planning5, with a view to optimizing treatment strategies, minimizing the risk of undertreatment or approaches that are futile and/or disproportionate to the progression of the disease6.

Thus, the use of good discrimination prognostic factors is essential for inpatients, since a shorter survival time and higher mortality rates are observed in the hospital setting. Therefore, this study aims to identify prognostic factors and their discriminatory capacity for advanced cancer patients hospitalized at the PCU of a specialized cancer hospital.

This clinical, observational, prospective cohort study was conducted with patients admitted to the PCU in Brazil. The focus of treatment in the PCU is symptom control and promotion of quality of life and death. It begins when antitumor treatment is interrupted due to ineffective response and/or serious side effects, so none of the patients in the cohort were receiving any curative cancer treatment. The study was approved by the Ethics Committee of INCA (3,550,658) and the participants were included in the research after agreeing and signing the free and informed consent term.

Patients were continuously enrolled from October 2019 to May 2021, evaluated by trained researchers within 72 hours of the first hospital admission, and monitored until the outcome of their hospital stay. Eligibility criteria for the study were: having advanced malignant neoplasm regardless of location, age ≥20 years, Karnofsky Performance Status (KPS) ≥30%, and being able to provide the required information. The KPS is a percentage scale that classifies the individual as to their ability to perform normal daily activities, active work, self-care, and need for regular medical care due to greater evidence of disease (100%: full function; 0%: death)7.

A total of 136 patients were included in the study. Most of them were older (≥60 years: 55.2%), female (68.4%), with gynecological as the primary site of malignancy (23.5%), and had distant metastasis (83.1%). In general, they had low functionality (KPS 30%: 59.6%), nutritional risk (PGSGA SF© ≥9 points: 83.1%), and exacerbated systemic inflammation (albumin <3g/dL: 59.6%, CRP ≥5mg/L: 80.4%, CAR ≥2: 70.9%, mGPS 1+2: 56.4%) (Table 1).

Among the patients evaluated, 77 (56.6%) died within 30 days and the median overall survival was 10 (interquartile range [IQR]: 6-14) days. Death rates were higher in patients with gynecological and GIT tumors (p=0.001), KPS=30% (p=0.030), PG-SGA SF© ≥9 points (p=0.005), albumin <3g/dL (p=0.001), and CAR ≥2 (p=0.051) at admission (Table 1). The survival medians were statistically lower in these same groups (Table 1 and Figure 1).

According to the Cox univariate regression analyses, the primary tumor site, KPS, PG-SGA SF©, serum albumin concentration, CRP, and CAR were candidates for the multiple model. In the multivariate analysis, the primary tumor site located in the GIT (HR: 1.61, 95%CI: 1.11-2.82), KPS=30% (HR: 1.73, 95%CI: 1.09-3.00), PG-SGA SF© ≥9 points (HR: 4.58, 95%CI: 1.62-12.92), and serum albumin concentrations <3g/dL (HR: 1.88, 95%CI: 1.05-3.34) were retained as prognostic factor within 30-day. However, only albumin showed acceptable discrimination, with a C-statistic value of 0.75 (Table 2).

In this study, we identified the prognostic factors and their discriminatory capacity in patients with advanced cancer hospitalized at a specialized PCU at a reference hospital for cancer care. Our results showed that the patients with advanced GIT cancer who presented at the time of hospitalization with impaired functionality, reduced serum albumin, and nutritional risk had a worse prognosis. Among these prognostic factors, serum albumin concentration showed better discriminatory.

Prognostic assessments are challenging for health professionals and researchers, especially for inpatients with advanced cancer. Despite the availability of validated objective tools and prognostic factors, consideration should be given to the method to be applied, since its accuracy may vary according to the population, environment, and forecast period. Death is a prevalent outcome for patients hospitalized with advanced cancer, calling for the use of specific prognostic factors to guide important personal and clinical decisions11. However, there is not a great deal of scientific evidence at the present time that focuses exclusively on cancer inpatients in palliative care.

The hospitalized patients in palliative cancer care from our study had low survival (10 days [IQR: 6-14]), which is consistent with the findings of other studies5 12. In an Argentine cohort, hospitalized cancer patients in palliative care were found to have a higher risk of death than those receiving outpatient follow-up (HR: 1.87, 95%CI: 1.24-2.84, p-value: 0.003)13.

The cutoff points selected for biomarkers analysis (albumin<3.05, CAR≥2.014, CRP≥515, and scores GPS 1+216 were based on previous studies, which observed lower survival when using them. Considering a context of lower survival, we used more severe cutoff points to better support the care plan for these patients.

Turning to tumor location, other cohort studies carried out at the same referral center found a high prevalence of GIT and gynecological cancer4 17 18. The multivariate Cox regression used in our study found that patients with GIT cancer had a worse prognosis (HR: 1.61, 95%CI: 1.11-2.82, p-value: 0.049), which is similar to the findings of Martin et al. (2010)19 (HR: 1.69, 95%CI: 1.30-2.19, p-value<0.001). This could be attributed to the fact that this type of cancer is associated with a greater nutritional impact, and consequently with repercussions on overall survival.20 In a Brazilian multicentric study, upper digestive cancer had a strong association with malnutrition [odds ratio (OR): 4.51, 95%CI: 3.31-6.1, p-value<0.001].21

Functional capacity is recognized as a relevant prognostic factor in different health contexts, including in cancer patients, where it is considered a strong independent predictor of survival.22 In their multivariate analysis, Fiorin de Vasconcellos et al. (2019)23 found that patients with solid tumors at an advanced stage and with worse functionality had a higher risk of death within 30 days (HR: 2.01, 95%CI: 1.14-3.53, p-value: 0.016).

Furthermore, the median KPS at admission was significantly lower in those who progressed to death than in those whose outcome was discharge.24 These data corroborate our findings, as our multivariate analysis revealed that the presence of KPS=30% was a prognostic factor within 30 days (HR: 1.73, 95%CI: 1.09-3.00, p-value: 0.042). Consistent with this, some specific prognostic tools for patients in palliative care – such as the palliative performance scale, the palliative prognostic score, and the palliative prognostic index – include functionality as a crucial variable in their composition.25

As expected, most of our inpatients (83.1%) had an overall PG-SGA SF© score ≥9 points (HR: 4.58, 95%CI: 1.62-12.92, p-value: 0.004), which indicates nutritional risk, considered an important prognostic factor. A previous publication, based on research developed at the same PCU, demonstrated that PG-SGA SF© was associated with lower survival and a higher risk of 90-day mortality, making it an indicator of a worse prognosis16. This cutoff point, despite not being validated for the Brazilian cancer population, is widely used to classify patients at nutritional risk.26

As for albumin, in addition to its good prognostic power, it is also a marker of nutritional status and a simple parameter capable of reflecting inflammatory status.27 In a study of patients with inoperable advanced esophageal cancer, survival was significantly shorter in those with a serum concentration of this acute-phase protein was lower than 3.5g/dL.28 In a cohort study developed at the same PCU, the presence of hypoalbuminemia was also an independent prognostic factor within 90-day (HR: 2.04, 95%CI: 1.16-3.58, p-value: 0.013).16 Furthermore, in a systematic review and meta-analysis, Dolan et al. (2017)29 found studies in which patients with serum albumin levels <3.0g/dL had lower survival (HR: 1.57, 95%CI: 1.26-1.95, p-value<0.0001), corroborating our findings (HR: 1.88, 95%CI: 1.05-3.34, p-value<0.033).29

There are some limitations of our study that deserve to be highlighted. First, the study was undertaken at a single site and had a small sample size, which could interfere with the power of the statistical tests used. Larger studies would be needed to overcome this limitation. Meanwhile, the study's strength is that it analyzes simple and objective elements for prognostic assessment that could be used by any member of the multidisciplinary team, making it more easily applied in the clinical setting.

Inpatients with advanced cancer in the GIT (primary site), impaired functionality, reduced serum albumin, and nutritional risk at admission have a worse prognosis. Serum albumin concentration has better discriminatory ability than the other factors identified. Although this relationship is well explored in the literature, the use of these variables and, some of them, with more severe cutoff points, specifically for hospitalized patients, is an issue that has not yet been explored, which can better support the care plan in this specific group.