Symptoms tell it all: A systematic review of the value of symptom assessment to predict survival in advanced cancer patients

Abstract

Purpose

To determine the prognostic meaning of symptoms in patients with advanced cancer.

Design

Medline, Embase, Cochrane and Cinahl databases were systematically explored. The predicting symptoms were also evaluated in the three stages of palliative care: disease-directed palliation, symptom-oriented palliation and palliation in the terminal stage.

Results

Out of 3167 papers, forty-four papers satisfied all criteria. Confusion, anorexia, fatigue, cachexia, weight loss, cognitive impairment, drowsiness, dyspnea, dysphagia, dry mouth and depressed mood were associated with survival in ≥50% of the studies evaluating these symptoms. Multivariate analysis showed confusion, anorexia, fatigue, cachexia, weight loss, dyspnea and dysphagia as independent prognostic factors in 30–56% of the studies.

In the stage of disease-directed palliation anorexia, cachexia, weight loss, dysphagia and pain and in the stage of symptom-oriented palliation confusion, fatigue, cachexia, weight loss, dyspnea, dysphagia and nausea were shown to be independent predictors of survival in >30% of the studies.

Conclusion

Symptoms with independent predictive value are confusion, anorexia, fatigue, cachexia, weight loss, dyspnea and dysphagia. New insights are added by the variance between the three palliative stages.

Introduction

Predicting the life expectancy of patients with advanced cancer is one of the most difficult challenges in medical care. For patients and their families, being aware of the prognosis makes a difference in decision making and planning the remaining lifetime. Cancer patients tend to choose life-extending therapy if they believe their survival is more than 6 months [1], [2], [3], [4]. This indicates that patients’ autonomy can be supported by providing realistic prognostication.

A systematic review of physicians’ survival predictions in terminally ill cancer patients showed that survival of patients was 30% shorter than predicted [5]. Due to inaccurate prognosis patients may develop unrealistic expectations.

Assessment of prognostic indicators in cancer patients has been performed previously, but the focus was not set on palliative cancer patients [6], [7]. Cognitive failure, weight loss, dysphagia, anorexia and dyspnea appeared to be independent predictors of survival in a systematic review published by Vigano et al. [8] Subsequently, it was demonstrated that the anorexia–cachexia syndrome, dyspnea and pain were associated with shorter survival [9]. These systematic reviews included studies published up to the year 2003. Since then, many new studies on this topic have been published. Moreover, critical appraisal of the literature addressing prognostic symptoms, by using a standardized approach is mostly absent or unsatisfactory.

This systematic review focuses on cancer patients in the palliative phase. The palliative phase starts from the moment that cure is not or no longer possible and lasts until the moment of death.

In palliative care three stages are distinguished. In the first stage palliation is disease-directed with the aim of prolonging life and improving or maintaining the quality of life by means of treating the underlying malignancy.

The second stage (symptom-oriented palliation) starts when anti-tumor treatment is discontinued because of lack of effect and/or severe side-effects. The focus in this stage is quality of life and stabilization and prevention of symptoms.

The terminal stage refers to the point at which it becomes clear that the patient is in a progressive state of decline and that death is imminent. In this stage the emphasis is set on improving the quality of dying by constraining symptoms to minimize suffering with acceptance of a potential loss of cognitive, emotional and social functioning. Little is known about the prognostic meaning of symptoms in relation to these three stages although symptom burden becomes the most hampering issue in quality of life during the progression of the disease [10], [11], [12].

In light of the aforementioned, the first aim of this review is to analyze the available evidence in literature about symptoms that predict the life expectancy in people with advanced cancer. The second aim is to relate the prognostic value of these symptoms to the three stages of palliative care. The third and last aim is to evaluate the quality of reporting of observational studies according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.

We suggest a set of prognostic symptoms for further research in daily practice of palliative care.