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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 33  |  Issue : 2  |  Page : 699-705

The prognostic value of Glasgow prognostic score in epithelial ovarian cancer


1 Department of Clinical Oncology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Meet Ghamr Oncology Center, Ministry of Health, Meet Ghamr, Dakahlia, Egypt

Date of Submission24-Aug-2019
Date of Decision30-Sep-2019
Date of Acceptance12-Oct-2019
Date of Web Publication27-Jun-2020

Correspondence Address:
Salma M El-Menshawy
Zifta, Gharbia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_264_19

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  Abstract 


Objective
In this study, the authors assessed the prognostic value of Glasgow prognostic score (GPS) in overall survival (OS) and progression-free survival.
Background
Inflammation plays an important role in the pathogenesis of ovarian cancer. The GPS is an inflammation-based prognostic score composed of C-reactive protein and albumin.
Patients and methods
A prospective study was conducted in the Department of Clinical Oncology, Menoufia University, between June 2016 and December 2018. The authors analyzed the clinicopathological characteristics and pretreatment C-reactive protein and serum albumin levels of 57 patients with epithelial ovarian cancer. Time to treatment failure and OS were determined using Kaplan–Meier method.
Results
High GPS was significantly associated with age, performance status, elevated Ca125 level, advanced stage, ascites, size of residual tumor after the debulking surgery, and platinum sensitivity (P < 0.001). In addition, patients with higher GPS had shorter progression-free survival (P < 0.001) and OS (P = 0.107). However, multivariate analysis revealed that GPS is not an independent prognostic factor in those group of patients.
Conclusion
High GPS is a poor prognostic factor in patients with epithelial ovarian cancer.

Keywords: High GPS is a poor prognostic factor in patients with epithelial ovarian cancer


How to cite this article:
Hashem TA, Shehata MA, Alhassanin SA, El-Menshawy SM, Gohar SF. The prognostic value of Glasgow prognostic score in epithelial ovarian cancer. Menoufia Med J 2020;33:699-705

How to cite this URL:
Hashem TA, Shehata MA, Alhassanin SA, El-Menshawy SM, Gohar SF. The prognostic value of Glasgow prognostic score in epithelial ovarian cancer. Menoufia Med J [serial online] 2020 [cited 2020 Jul 14];33:699-705. Available from: http://www.mmj.eg.net/text.asp?2020/33/2/699/287768




  Introduction Top


Ovarian cancer represents 2.5% of all malignancies among females but accounts for 5% of female cancer deaths because of low survival rates, largely driven by late-stage diagnoses[1]. Incidence rates are the highest in the USA and Northern Europe and lowest in Africa and Asia. It is associated with the highest mortality rates of all female genital tract malignancies. Approximately 85% of cases occur in those older than 50 years, and 80–85% are epithelial in origin. It is now widely accepted that epithelial ovarian cancer (EOC) is a heterogeneous disease and consists of five main histologic subtypes, that is, high-grade serous, low-grade serous, endometrioid, clear-cell, and mucinous cancers, each associated with a unique origin, pathogenesis, and prognosis[2]. In addition, women previously diagnosed with primary peritoneal cancers would likely be re-classified as having ovarian cancers in view of the new classification, which states that any ovarian/tubal involvement would result in a diagnosis of ovarian cancer[3]. The most common histologic subtype of EOC is serous OC, which usually presents at advanced stages and has the poorest outcomes. High-grade serous cancer which accounts for most of the OC mortality is thought to originate mainly in the fallopian tube and involve the ovaries secondarily[4]. The golden standard of treatment is primary debulking surgery followed by platinum-based chemotherapy. Although most patients initially respond to chemotherapy, cancer cells will eventually develop resistance leading to relapse[5]. EOC is a heterogeneous disease, and associations of inflammatory markers with disease risk may differ between histological subtypes of EOC (serous, mucinous, endometrioid, and clear-cell carcinomas)[6]. It was hypothesized that inflammation may be most strongly associated with tumors of serous histology, which may arise in the fimbriae of the fallopian tube and may be induced by chronic intratubal inflammation[7]. Several inflammation-based prognostic indices have been constructed to predict the clinical outcome. To date, the Glasgow prognostic score (GPS), neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio were reported to display prognostic value in patients with ovarian cancer[8]. Inflammatory markers of the GPS predicted progression-free survival (PFS) and overall survival (OS) in various cancers. Determination of GPS at pretreatment is useful in prognosis of patients with EOC[9].

The aim of current study was assessment of prognostic value of GPS in OS and PFS.


  Patients and Methods Top


All procedures were reviewed and approved by the Ethics Committee of the Menoufia University Hospital. This prospective study was conducted in the Clinical Oncology Department of Menoufia University Hospitals from June 2016 to December 2018.

Patients diagnosed with ovarian carcinoma stages (I–IV), with performance status 0–2, in the period from June 2016 to December 2018 were included. Patients with co-morbid major physical illnesses (e.g., renal, hepatic, or heart diseases) or history of other cancer were excluded.

After consent, all patients were initially subjected to through history and clinical examination. Investigation was done in the form of complete blood picture, kidney function tests, liver function tests, pretreatment C-reactive protein (CRP), serum albumin, and CA125, and computed tomography of chest, abdomen, and pelvis.

Baseline information was collected, including date of diagnosis, age, performance status according to Eastern Cooperative Oncology Group performance status scale[10], Pathology, Disease Staging according to the Fédération Internationale de Gynecologic etd'Obstétrique (FIGO) criteria for ovarian carcinoma[11], and type of surgery (optimal, suboptimal) or no surgery.

GPS, which is a cumulative score of CRP and serum albumin, was calculated based on pretreatment CRP and albumin levels. It was estimated that the high GPS group included patients with GPS 2: both high CRP levels greater than 1.0 mg/dl and hypoalbuminemia (<3.5 g/dl). The low GPS group included patients with only one of these abnormal levels (GPS 1) or none of these abnormalities (GPS 0)[12]. We choose this score as it is simple, inexpensive, available, and easily interpreted.

All patients received first-line chemotherapy paclitaxel and carboplatin. Chemotherapy consisted of intravenous paclitaxel (175 mg/m2) and carboplatin (AUC 6) for three to nine 21-day cycles.

Patients were evaluated by clinical examination every cycle, assessment of tumor markers, and computed tomography of chest, abdomen, and pelvis every two to three cycles.

Response evaluation was done according to RECIST criteria (Response Evaluation Criteria in Solid Tumors, version 1.1)[13].

Platinum-sensitive ovarian cancer is defined as if ovarian cancer recurs more than 12 months after completing primary therapy with a platinum-based medication, platinum-intermediate sensitive ovarian cancer is defined when recurrence was more than 6 months and less than 12 months, platinum-resistant ovarian cancer is defined as if ovarian cancer progresses with an interval of less than 6 months, and platinum-refractory ovarian cancer is defined as if ovarian cancer progresses during or within 4 weeks after completion of chemotherapy[14].

The OS was defined as the time between the date of diagnosis and the date of death or last visit. The OS was analyzed in relation to different prognostic factors.

Time to progression (TTP) was defined as the time from diagnosis to the date of response to progression of disease.

Follow-up was completed until December 31, 2018. The primary end point of this study was to determine the relation of GPS with patients and disease feature, and in patients with EOC, the secondary end point was correlation between GPS and TTP and OS.

Results were collected, tabulated, and statistically analyzed by IBM personal computer and statistical package SPSS version 20 (SPSS Technology Inc, Chicago, USA). Statistical analyses were performed using χ2-test for categorical variables to compare between different groups and Monte Carlo correction for correction of χ2 when more than 20% of the cells have expected count less than 5. We performed univariate and multivariate analyses using Cox's proportional hazards model to determine which factors predict PFS after adjusting for effects of known prognostic factors. Kaplan–Meier survival curve was used for the PFS with GPS and OS with GPS.


  Results Top


This is a prospective study that included 57 patients diagnosed in the Clinical Oncology Department, Menoufia University, and Meet Ghamr Oncology Center.

As illustrated in [Table 1], demographic features of patients revealed that mean age of patients is 55 ± 12.69 years. The most common complaint is abdominal distension, and most of them had good performance status. Most patients presented with serous cystadenocarcinoma, with FIGO stage III disease, with elevated CA 125 level. Most of the candidates underwent optimal surgery and were platinum sensitive. Pretreatment GPS in the studied patients was as follows: GPS 0, 15 (26.3%) patients; GPS 1, 16 (28.1%) patients; and GPS 2, 26 (45.6%) patients.
Table 1: Distribution of the studied cases according to demographics table (n=57)

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By the end of the follow-up period, 23 (40.4%) patients experienced disease progression and nine patients representing 15.8% of patients were dead, with median TTP and OS of 10 and 15 months, respectively [Table 1].

There is a significant correlation between high GPS score and elevated CA125, presence of ascites (P < 0.001), elevated CRP (P < 0.001), type of surgery (P < 0.001), advanced stage (P < 0.001), disease progression (P = 0.020), platinum nonsensitive disease (P < 0.001), and serous pathology (P = 0.59), as shown in [Table 2].
Table 2: Relation between Glasgow prognostic score and all patient features (n=57)

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The median PFS is 18 months. However, median OS was not reached.

PFS for patients with high pretreatment GPS (GPS 2) was shorter than for patients with lower GPS (GPS 0, 1) (PFS: P < 0.001) [Figure 1].
Figure 1: Kaplan–Meier curve for progression free survival with Glasgow prognostic score.

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OS for patients with high pretreatment GPS (GPS 2) were shorter than for patients with lower GPS (GPS 0, 1) (OS: P < 0.107) [Figure 2].
Figure 2: Kaplan–Meier curve for overall survival with Glasgow prognostic score.

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In our study, univariate analysis of PFS showed tan there is significant association between, age (P = 0.047), GPS (P = 0.001) were significantly associated with PFS, pathology is (P = 0.078) and stage (P = 0.021), optimal surgery (P = 0.001), response to treatment (P = 0.018), platinum sensitivity (P < 0.001) were significantly associated with PFS in the all patients. In multivariate analysis, age, CRP, albumin, GPS, stage, optimal surgery, and platinum response were not significantly associated with PFS.

Especially, the multivariate analysis showed GPS to be not an independent predictor of PFS.

In multivariate analysis of PFS, the results showed platinum sensitivity (P < 0.001) was significantly associated with PFS [Table 3].
Table 3: Univariate and multivariate Cox regression analyses for the parameters affecting progression free survival (n=57)

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  Discussion Top


Known prognostic factors for ovarian cancer include residual tumor and chemotherapy response, but these parameters are not sufficient to predict accurate ovarian cancer prognoses. Therefore, a new approach for pretreatment assessment of ovarian cancer is needed.

Several inflammation-based prognostic indices have been constructed to predict the clinical outcome of patients with ovarian cancer[8].

CRP is an acute-phase protein and is one of the important markers of inflammation[15]. Albumin reflects nutritional status of patients, which is also a negative acute-phase protein. A negative correlation has been found between the levels of albumin and CRP[16]. GPS is a prognostic scoring system based on CRP and albumin levels and is significantly related to poor survival in patients with various malignancy, including liver, colorectal, and renal cell cancers[17].

In this prospective study, we investigated pretreatment serum albumin and CRP in the form of GPS, a combination of CRP and albumin levels forming the inflammatory prognostic score, and its correlation with prognosis of patients with ovarian epithelial carcinoma.

A total of 57 newly diagnosed patients with malignant EOC, who presented to Clinical Oncology Department, Menoufia University and Meet Ghamr Oncology Center, were included in this study. Mean age at diagnosis was 55 years (ranging from 23 to 80 years).

In our study, we found that 64.9% of patients were older than 50 years, with a median age of 57 years, as EOC is an age-related disease and is considered mainly a postmenopausal disease. This has been supported by Zohre et al.[18] who reported that incidence of this ovarian cancer is more in old women than younger ones and median age at diagnosis is 50–79 years.

We found that patients have high GPS (1, 2) were 42 cases. which matched with elevation of CRP and depressed level of serum albumin in most of them.

Patients presented with ascites in 33 cases, which correlated with most of the cases were high-staged disease (III and IV). This correlates with Katarina et al.[19], who reported that ascites are found in most patients (89%) with advanced disease (FIGO stages III and IV).

We found that epithelial ovarian tumor with serous histology were the most the most common in 33 (57%) of patients, which was supported by Conklin and Gills[20], who reported serous type of ovarian carcinoma accounts to be the most common around the world.

We found that the vast majority of our patient with advanced-stage are serous histology subtype, as detailed by Torre et al.[21], who reported that most common type is serous carcinoma.

In our study, GPS was significantly associated with age of patients. High GPS was in older patients. Nakamura et al.[22] found significant correlation between pretreatment GPS with age in endometrial carcinoma.

We found that that patients with high GPS had poor performance status, which suggests the aggressiveness of disease causing increasing of GPS.

In our study, we found Eastern Cooperative Oncology Group PS was better, and mucinous adenocarcinoma was more frequent in patients with low GPS than in other patients.

This correlates with Zhu et al.[23], who reported PS was better, and nonserous ovarian carcinoma was more frequent in patients with GPS = 0 than in other patients in advanced EOC.

In this study, we have found that high GPS was significantly associated with CA125, ascites, higher staging, serous histology, and surgery at presentation.

This significant association matches with other study conducted by Omichi et al.[9], who found a significant correlation between high GPS and stage, histology, ascites, neoadjuvant treatment, no residual tumor, and ovarian carcinoma, and with Nakamura et al.[22], who found significant correlation between pretreatment GPS and disease staging and histology in endometrial carcinoma.

Furthermore, we found higher GPS was related to poor responses to neoadjuvant chemotherapy, as reported by Zhu et al.[23], where patients with EOC who had high GPS were less responsive to neoadjuvant chemotherapy.

In our study, there were significant relations between GPS and pretreatment CRP and albumin levels, as CRP level and albumin level form this score.

This matching with Liu et al.[8], who reported that CRP/albumin ratio has significant correlation with GPS in ovarian cancer.

We have found that high CRP was significantly associated with disease progression and OS, and this matches with Hefler et al.[24], who reported that elevated CRP was associated with OS in univariate analysis.

In this study, we found that the PFS for patients with high pretreatment GPS (GPS 2) was shorter than patients with low GPS (GPS 0, 1).

This matches with Zhu et al.[23], who found patients with GPS = 0 had significantly better PFS than those with GPS = 1 or 2 in advanced EOC.

Survival analysis in patients showed that OS for patients with high pretreatment GPS (GPS 2) was shorter than for patients with lower GPS (GPS 0, 1). However, this difference in OS between the two subgroups was statistically nonsignificant (P < 0.107).

Zhu et al.[23] reported in a multicenter retrospective study that OS for patients with high pretreatment GPS (GPS 2) was shorter than for patients with lower GPS (GPS 0, 1), but this was statistically significant (P < 0.001).

In our study, in univariate analysis, we found that age, CRP, albumin, GPS, stage, optimal surgery, and platinum sensitivity have significant association with PFS.

This matches with Omichi et al.[9] who reported that in the univariate Cox regression analysis that patient age, CRP, albumin, GPS, disease staging and surgery, and platinum sensitivity were significantly associated with PFS.

Moreover, Zhang et al.[25] found in univariate Cox regression analysis for PFS of patients with ovarian clear-cell carcinoma according to various clinicopathologic factors that serum albumin, disease staging, and surgery were associated with PFS.

In our study, the multivariate analysis showed GPS to be not significantly associated with PFS, so GPS is not an independent prognostic factor for PFS.

Liang et al.[26] reported that no association was identified between GPS of 2 and PFS.

However, Omichi et al.[9] reported in multivariate analysis that GPS has a significant correlation with PFS, so in particular, the multivariate analysis showed GPS to be an independent predictor for PFS in patients with ovarian cancer.

In multivariate analysis of PFS results, platinum sensitivity was significantly associated with PFS, so platinum sensitivity is a significant independent predictors of PFS.

This matches with Zhu et al.[23], who reported that chemosensitivity was significantly associated with PFS in multivariate analysis of PFS and concluded that chemosensitivity was independent prognostic factor for PFS in a multicenter retrospective study.

This incompatibility between our results and the previous reports might be explained by a relatively short duration of follow-up (median duration of follow-up was 18 months) and the small number of the patients with ovarian epithelial carcinoma included in the study.

Our study has some drawbacks. Relatively short-period of follow-up of the study group constitutes the most important one. This might have affected the correlation between the prognostic significance of the marker and the patients' outcome (whether therapeutic or survival outcome). A further limitation of this study is the small number of patients included in the study (57 patients).


  Conclusion Top


High GPS was associated with factors suggestive of poor prognosis in patients with EOC like pathology, disease staging, surgery, and platinum sensitivity. However, the correlation between elevated GPS and the outcome was not reached. We suggest that assessment of serum albumin and CRP levels in combination with GPS before treatment initiation, as an inexpensive, widely available, and easy interpreted method in OS and PFS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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