Laboratory-Clinic InterfaceThe systemic inflammation-based Glasgow Prognostic Score: A decade of experience in patients with cancer
Introduction
Cancer remains the leading cause of death worldwide in individuals aged 35–64 years and globally accounts for at least 500,000 deaths each year. In the UK approximately one in three develops cancer and one in four dies of cancer. Despite this relatively poor outcome for most common cancers, much high profile research is carried out with a view to cure whereas the reality for most patients with cancer is disease progression and death.
Therefore, against this background, predicting the likely outcome of the patient with cancer is of considerable importance since even without improvements in treatment, if patients are given the appropriate treatment, then outcomes will improve for all patients. Unfortunately, without objective measures of likely outcome, the allocation of treatment will continue to be suboptimal. For example, Temel and coworkers1 recently reported that, in patients with metastatic lung cancer randomised to palliative care vs standard care, palliative care was associated with better quality of life and increased survival.
Currently, the cornerstone of cancer prognosis is accurate staging of the tumour and establishing whether there has been tumour spread. However, there is increasing recognition that patient related factors, in particular nutritional and functional decline, are associated with poorer outcome independent of tumour stage. The most commonly used measures of this decline, weight loss and performance status, are recognised to be subjective and therefore their reliability in predicting outcome is compromised. Moreover, they do not provide objective therapeutic targets.
There is now good consistent evidence that the presence of a systemic inflammatory response is a major factor underlying such patient decline.[2], [3], [4], [5] Since the initial studies of using C-reactive protein, as a sensitive measure of the systemic inflammatory response, reported independent prognostic value in operable colorectal cancer[6], [7] there have been a plethora of studies reporting the prognostic value of C-reactive protein and other markers of the systemic inflammatory response in a wide variety of operable8 and inoperable9 cancers.
In this early work it was noted as circulating C-reactive protein concentrations increased albumin concentrations fell and this relationship was similar across different tumour types.10 Also, given that albumin concentrations reflected both systemic inflammation and the amount of lean tissue,11 it was of interest to examine the prognostic value of the combination of an elevated C-reactive protein concentration (>10 mg/l) and hypoalbuminaemia (<35 g/l). In the first report by Forrest and coworkers in Glasgow, this objective combination compared favourably with the clinical standard combination of stage and performance status.12 The resultant prognostic score (0, 1, 2) was defined as follows; patients with both an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia (<35 g/l) were allocated a score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a score of 1. Patients in whom neither of these abnormalities was present were allocated a score of 0. However, the score of 1 was most commonly due to an elevated C-reactive protein emphasising the inflammatory basis of the GPS (Table 1,12).
This systemic inflammation based prognostic score was subsequently termed the Glasgow Prognostic Score (GPS,13). On further investigation the GPS was modified, termed the mGPS, to reflect the observation that hypoalbuminaemia without an elevated C-reactive protein concentration was rare and that hypoalbuminaemia on its own was not associated with poor survival (Table 1,14). The GPS/mGPS being simple to measure, routinely available and well standardised world-wide has subsequently been the subject of prognostic studies in wide variety of operable and inoperable cancers. Since the initial work, a decade ago, there have been more than 60 studies (>30,000 cancer patients) that have examined and validated the use of the GPS/mGPS in a variety of clinical scenarios. The present review provides a concise overview of these studies and comments on the current and future clinical utility of this simple objective systemic inflammation-based score.
Section snippets
Methods
This systematic review of published literature was undertaken according to a pre-defined protocol. The primary outcome of interest was the relationship between the GPS/mGPS and cancer outcome (overall survival, cancer specific survival, disease recurrence or response to treatment). The secondary outcomes of interest were the associations between the GPS/mGPS and other clinical, pathological or inflammatory characteristics.
A literature search, using appropriate free text and medical subject
Studies of the prognostic value of the GPS/mGPS, in an unselected cohort of patients with cancer
Four studies, comprising data on 19,481 patients, reported prognostic value of the GPS/mGPS in unselected cohorts of patients with cancer (Table 2,[15], [16], [17], [18]). All studies used the mGPS and reported prognostic value independent of tumour site (breast, bladder, gynaecological, prostate, gastro-oesophageal, haematological, renal, colorectal, head and neck, hepatopancreaticobiliary and pulmonary) and were from the Glasgow group. Two studies compared the prognostic value of the GPS/mGPS
Studies of the prognostic value of the GPS/mGPS in patients with operable cancer
Twenty-eight studies, comprising data on 8,333 patients, reported prognostic value of the GPS/mGPS in patients with operable cancer (Table 3,[14], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46]). Fourteen studies were in colorectal (including liver metastases) cancer and the GPS/mGPS was reported to have prognostic value independent of tumour stage and pathological features,
Studies of the prognostic value of the GPS/mGPS, in cancer patients receiving chemo/radiotherapy
Eleven studies, comprising data on 1,504 patients, reported prognostic value of the GPS/mGPS in cancer patients receiving chemo/radiotherapy (Table 4,[13], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56]). Four studies were in gastro-oesophageal cancer and the GPS/mGPS was reported to have prognostic value independent of tumour stage and performance status. These studies were from groups in the UK (1 study), Japan (1 study), Taiwan (1 study) and South Korea (1 study). Over these four
Studies of the prognostic value of the GPS/mGPS, in patients with inoperable cancer
Eleven studies, comprising data on 2,119 patients, reported prognostic value of the GPS/mGPS in patients with inoperable cancer (Table 5,[57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67]). Three studies were in lung cancer and the GPS/mGPS was reported to have prognostic value independent of tumour stage, performance status and treatment and other measures of the systemic inflammatory response. These 3 studies were from groups in the UK. Over these three studies the weighted
Studies of the associations with the GPS/mGPS in patients with cancer
Fifteen studies, comprising data on 2,215 patients, reported associations between the GPS/mGPS and weight and muscle loss, nutritional status, performance status, biochemical and cytokine disturbances (Table 6,[68], [69], [70], [71], [72], [73], [74], [75], [76], [77], [78], [79], [80], [81], [82]). This was particularly evident in gastro-oesophageal (5 studies), colorectal (5 studies) and lung (2 studies) cancer. There were also single studies in hepatocellular cancer, pancreas and ear nose
Discussion
From the present review and given that the HR was similar across different tumours, countries and clinical scenarios it can be concluded that GPS/mGPS is a reliable independent prognostic factor in patients with cancer. Its use has been reported in (a) unselected cohorts (4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies, >1500 patients) (d) inoperable disease 11 studies, >2,000 patients). Also, association studies (15 studies,
Acknowledgements
The author gratefully acknowledges the support and advice of clinical and scientific colleagues at Glasgow Royal Infirmary, in particular Professors of Surgery Clem Imrie and Paul Horgan, and funding from Glasgow Royal Infirmary Endowment Funds, the Chief Scientist Office and Cancer Research UK.
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