C-reactive Protein Is A Potential Prognostic Factor For Metastatic ...

Discussion

The present study revealed that CRP is an independent prognostic factor for patients with MGC.

In order to remove bias by treatment, only patients who received S-1 plus CDDP for MGC as first-line chemotherapy were included in this study. MST and median PFS were 394 and 171 days, respectively, which were consistent with the data in a previous Phase III trial (MST: 390 days, median PFS: 180 days) (4), suggesting that the present data were reliable.

Although no significant differences were found for response rate in this study, the CRP≥1.0 group showed significantly shorter PFS and poorer overall survival than the CRP<1.0 group. These results suggested that chemosensitivity declines quickly even if anticancer agents are effective temporarily in the CRP≥1.0 group. CRP is produced as a response to some inflammatory cytokines and has been widely accepted as a representative marker for inflammation. Inflammatory cells have powerful effects on tumor development by releasing growth and survival factors, promoting angiogenesis and lymphangiogenesis, stimulating DNA damage, and remodeling the extracellular matrix invasion (5). Hence, higher levels of inflammatory cytokines and chemokines were hypothesized to result in poor survival for patients with MGC in the CRP≥1.0 group. In fact, some previous reports have shown positive correlation between levels of serum CRP and interleukin-6 (IL-6), one of the inflammatory cytokines in gastric cancer (10, 11).

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Adverse events ≥Grade 3.

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Univariate and multivariate analyses for survival.

Although there were significantly more patients with PS≥1 in the CRP≥1.0 group versus the CRP<1.0 group in this study, CRP was the strongest prognostic factor in the multivariate analysis that included PS. PS≥2 has been previously identified as a poor prognostic factor in a study of patients with advanced gastric cancer treated with capecitabine plus cisplatin (26) and a large study of patients with advanced and metastatic esophagogastric cancer (27). However, no study investigated CRP. Due to the small number of patients with PS≥2, this population could not be included in the present analysis. However, considering that the CRP≥1.0 group included more patients with PS≥1, the CRP level may positively correlate with PS.

Being female was the only other independent prognostic factor in the present study, but the significance is unclear. Although it is well known that the incidence of gastric cancer is higher for men than for women, previous studies reported that women with gastric cancer showed better prognosis than men (28, 29). However, as these previous studies rarely included patients with MGC, there may be some differences between localized gastric cancer and MGC.

The frequency of leukopenia and neutropenia was comparatively reduced, whereas anemia was comparatively increased in the CRP≥1.0 group. The white blood cell and neutrophil counts may have increased prior to chemotherapy due to inflammation in the CRP≥1.0 group. Similarly, some anemia may have already occurred due to inflammation in the CRP≥1.0 group. These adverse events can be speculated to be due to baseline differences between the two groups.

The current study had potential limitations due to its retrospective nature and small sample size. However, we believe the results are reliable because the population was restricted to the same first-line chemotherapy and prominent differences for survival were observed between the two groups in the multivariate analysis. Therefore, the results provide important information on the management of MGC. CRP is considered to be a very good and useful prognostic factor because measurement of CRP levels is easy, cost effective and familiar to most physicians.

In conclusion, serum CRP levels before treatment might be a potential prognostic factor for patients with MGC. As early progression of MGC is predicted for patients with high CRP levels, more stringent follow-up should be expected for this group.