Clinical Association Between Pre-Treatment Levels of Plasma Fibrinogen and Bone Metastatic Burden in Newly Diagnosed Prostate Cancer Patients
Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide, with bone metastasis being a common complication that significantly impacts prognosis and treatment strategies. The burden of bone metastasis, particularly in terms of the number and location of lesions, plays a critical role in determining the appropriate therapeutic approach. Recent studies have highlighted the potential role of plasma fibrinogen, a key coagulation factor, as a biomarker in cancer progression and metastasis. This article delves into a comprehensive analysis of the clinical association between pre-treatment plasma fibrinogen levels and the burden of bone metastasis in newly diagnosed PCa patients, as explored in a recent study.
Background and Rationale
The distinction between low-volume metastatic PCa (LVD) and high-volume disease (HVD) is clinically significant, as it influences treatment decisions and patient outcomes. LVD, often referred to as oligo-metastasis, is associated with better prognosis and may benefit from localized therapies combined with androgen deprivation therapy (ADT). Conversely, HVD, characterized by more extensive metastatic spread, often requires more aggressive systemic treatments, including chemotherapy. Given the clinical implications of metastatic burden, identifying reliable biomarkers to assess this burden is of paramount importance.
Fibrinogen, a 340,000 Da glycoprotein synthesized primarily in hepatocytes, plays a central role in the coagulation cascade. Elevated plasma fibrinogen levels have been observed in various malignancies, including PCa, and have been associated with poor prognosis. Previous studies have suggested a link between fibrinogen levels and PCa progression, including higher Gleason scores, advanced tumor stages, and increased incidence of metastasis. However, the specific relationship between pre-treatment fibrinogen levels and bone metastatic burden in PCa patients remains underexplored. This study aimed to address this gap by evaluating the correlation between pre-treatment plasma fibrinogen levels and the extent of bone metastasis in newly diagnosed PCa patients.
Methods
The study was conducted as a single-center retrospective analysis, involving 261 newly diagnosed PCa patients over a four-year period. All patients underwent prostate biopsy, and bone metastasis status was confirmed using single-photon emission computerized tomography-computed tomography (SPECT-CT). The number and location of metastatic lesions were recorded for patients with bone metastasis. Clinical data, including age, prostate-specific antigen (PSA) levels, fibrinogen levels, clinical T stage, and Gleason score, were collected from medical records.
Patients were categorized into three groups based on their bone metastatic status: (1) non-metastatic group (no bone metastasis), (2) HVD group (more than three bone metastases with at least one lesion outside the spine), and (3) LVD group (metastatic patients excluding HVD). Statistical analyses included non-parametric Mann-Whitney tests, Spearman correlation, receiver operating characteristic (ROC) curves, and logistic regression to evaluate the association between fibrinogen levels and bone metastatic burden.
Results
The study revealed several key findings. First, fibrinogen levels were positively correlated with Gleason score (r = 0.180, P = 0.003), PSA levels (r = 0.216, P < 0.001), and the number of metastatic lesions (r = 0.296, P < 0.001). No significant correlation was found between fibrinogen levels and age, clinical T stage, or the number of positive biopsy cores.
Comparative analysis of the three patient groups showed that HVD patients had the highest median PSA levels (104.98 ng/mL) and fibrinogen levels (3.39 g/L), as well as the largest proportion of Gleason scores >7 (86.8%). In contrast, non-metastatic and LVD patients had lower median PSA and fibrinogen levels. Notably, the difference in fibrinogen levels between non-metastatic and LVD patients was not statistically significant (P = 0.076), suggesting that fibrinogen may be more indicative of high-volume disease rather than low-volume metastasis.
Univariate and multivariate logistic regression analyses confirmed that fibrinogen was independently associated with HVD. The odds ratio (OR) for fibrinogen in univariate analysis was 2.16 (95% CI: 1.536–3.038, P < 0.001), and in multivariate analysis, it was 1.726 (95% CI: 1.206–2.472, P = 0.003). The ROC curve analysis further supported the predictive value of fibrinogen for HVD, with an optimal cut-off value of 3.08 g/L, yielding a sensitivity of 0.684 and a specificity of 0.760 (AUC = 0.739, 95% CI: 0.644–0.833, P < 0.001).
Discussion
The findings of this study underscore the potential of pre-treatment plasma fibrinogen as a biomarker for assessing bone metastatic burden in PCa patients. The positive correlation between fibrinogen levels and Gleason score, PSA levels, and the number of metastatic lesions aligns with previous research suggesting that fibrinogen may play a role in cancer progression and metastasis.
Several mechanisms have been proposed to explain the association between fibrinogen and cancer metastasis. Fibrinogen may provide a scaffold for tumor cell proliferation and angiogenesis by supporting growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Additionally, fibrinogen receptors on tumor cells can enhance endothelial adhesion, facilitating the spread of tumor cells to distant sites. Fibrinogen may also promote platelet aggregation around tumor cells, forming a protective layer that shields them from immune surveillance and increases the likelihood of metastasis.
The study’s results highlight the clinical utility of fibrinogen in distinguishing HVD from LVD and non-metastatic PCa. The higher fibrinogen levels observed in HVD patients suggest that fibrinogen could serve as a prognostic marker, guiding treatment decisions and potentially improving patient outcomes. For instance, patients with elevated fibrinogen levels may benefit from more aggressive systemic therapies, while those with lower levels may be candidates for localized treatments.
Limitations and Future Directions
While the study provides valuable insights, several limitations should be acknowledged. First, the retrospective design and single-center nature of the study may introduce selection bias. Second, although SPECT-CT is considered the gold standard for detecting bone metastases, it may still yield false positives or negatives. Third, the study did not account for other conditions that could influence fibrinogen levels, such as varicose veins or atherosclerosis. Finally, the assessment of bone metastasis was limited to the number and location of lesions, without considering the size or volume of metastatic areas.
Future research should aim to address these limitations through multi-center prospective studies with larger sample sizes. Additionally, exploring the role of fibrinogen in conjunction with other biomarkers, such as prostate-specific membrane antigen (PSMA), could enhance the accuracy of metastatic burden assessment. The integration of advanced imaging techniques, such as PSMA-PET/CT, may also improve the detection and characterization of bone metastases.
Conclusion
In conclusion, this study demonstrates a significant association between pre-treatment plasma fibrinogen levels and bone metastatic burden in newly diagnosed PCa patients. Fibrinogen levels were independently associated with high-volume disease, suggesting that fibrinogen could serve as a valuable biomarker for assessing metastatic burden and guiding treatment decisions. The findings contribute to the growing body of evidence supporting the role of fibrinogen in cancer progression and metastasis, highlighting its potential as a prognostic marker in PCa. Further research is warranted to validate these results and explore the underlying mechanisms linking fibrinogen to cancer metastasis.
doi.org/10.1097/CM9.0000000000000506
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