D-Dimer Levels and Disease Progression in Refractory Prostate Cancer
D-Dimer Levels and Disease Progression in Refractory Prostate Cancer
Changes in quantitative D-dimer levels, circulating tumor cell (CTC) counts, and prostate-specific antigen (PSA) levels were measured in 28 patients with refractory castration-resistant prostate cancer to assess their concordance during the course of therapy and their relationship with risk of progressive disease. A significant correlation was identified between changes in PSA and both CTC counts and D-dimer levels (r = 0.67 and 0.58, respectively; P < .001). In addition, there was a significant correlation between changes in CTC count and D-dimer level (r = 0.62; P < .001). A significantly stronger concordance between these biomarkers was noted for increasing values (sensitivity, 72%–77.8%) compared with decreasing values (specificity, 43.8%–71.4%). Notably, increases in PSA and D-dimer levels, not CTC counts, were associated with increased risks for progressive disease (P < .024). Increases in quantitative D-dimer levels correlate with progressive disease better than CTC counts in patients with refractory prostate cancer.
Prostate cancer (PCa) is the most common epithelial malignancy in men and the second leading cause of cancer-related deaths in the United States. A subset of PCa is characterized by de novo or progressive resistance to hormonal therapy, commonly referred to as castration-resistant PCa. Although measurements based on quantification of serum prostate-specific antigen (PSA) levels remain widely used to assess disease progression in patients with PCa, their role appears limited in castration-resistant cases. The usefulness of radiographic tools to assess clinical end points in PCa is also generally limited. Accordingly, there remains a clinical need for biomarkers that can complement or surpass PSA in assessing disease status, especially in patients with PCa who fail first-line therapy and are castration-resistant.
Circulating tumor cell (CTC) enumeration has recently emerged as a useful prognostic tool in patients with prostate, breast, or colon cancer. Notably, several studies have demonstrated that CTC enumeration is an accurate and independent predictor of overall survival in castration-resistant PCa. Patients with unfavorable pretherapy or posttherapy CTC counts (>5 CTCs/7.5 mL of whole blood) were found to have a significantly shorter median overall survival in comparison with patients with favorable counts (≤5 CTCs/7.5 mL of whole blood). In addition, relative to PSA monitoring, determination of CTC counts may allow earlier clinical decisions regarding response to therapeutic interventions in patients with PCa.
Hypercoagulability with venous thromboembolism is frequent in a variety of cancers. As by-products of fibrin degradation, plasma D-dimer levels are generally elevated in association with hypercoagulable conditions. Because hypercoagulability associated with cancer increases in severity with disease progression, quantitative assessment of plasma D-dimer levels has been suggested as a measure of disease status in patients with malignant neoplasms. Indeed, D-dimer levels have been found to rise proportionally to the extent and severity of disease in patients with PCa. However, D-dimer levels may be elevated in a variety of other conditions such as trauma, surgery, and inflammatory processes, thereby limiting assay specificity. The use of quantitative D-dimer determinations in conjunction with PSA and CTC count (hypothetically to enhance specificity) has not been evaluated in patients with refractory PCa.
In this study, we assessed the relationship between quantitative D-dimer levels, CTC counts, and PSA levels in patients with refractory, castration-resistant PCa and asked whether changes in these parameters are concordant when measured in longitudinal studies during the course of therapy. In addition, we asked whether quantitative D-dimer levels and CTC enumeration, alone or in combination, enhance the usefulness of the PSA level in assessing disease status in this category of patients with PCa.
Abstract and Introduction
Abstract
Changes in quantitative D-dimer levels, circulating tumor cell (CTC) counts, and prostate-specific antigen (PSA) levels were measured in 28 patients with refractory castration-resistant prostate cancer to assess their concordance during the course of therapy and their relationship with risk of progressive disease. A significant correlation was identified between changes in PSA and both CTC counts and D-dimer levels (r = 0.67 and 0.58, respectively; P < .001). In addition, there was a significant correlation between changes in CTC count and D-dimer level (r = 0.62; P < .001). A significantly stronger concordance between these biomarkers was noted for increasing values (sensitivity, 72%–77.8%) compared with decreasing values (specificity, 43.8%–71.4%). Notably, increases in PSA and D-dimer levels, not CTC counts, were associated with increased risks for progressive disease (P < .024). Increases in quantitative D-dimer levels correlate with progressive disease better than CTC counts in patients with refractory prostate cancer.
Introduction
Prostate cancer (PCa) is the most common epithelial malignancy in men and the second leading cause of cancer-related deaths in the United States. A subset of PCa is characterized by de novo or progressive resistance to hormonal therapy, commonly referred to as castration-resistant PCa. Although measurements based on quantification of serum prostate-specific antigen (PSA) levels remain widely used to assess disease progression in patients with PCa, their role appears limited in castration-resistant cases. The usefulness of radiographic tools to assess clinical end points in PCa is also generally limited. Accordingly, there remains a clinical need for biomarkers that can complement or surpass PSA in assessing disease status, especially in patients with PCa who fail first-line therapy and are castration-resistant.
Circulating tumor cell (CTC) enumeration has recently emerged as a useful prognostic tool in patients with prostate, breast, or colon cancer. Notably, several studies have demonstrated that CTC enumeration is an accurate and independent predictor of overall survival in castration-resistant PCa. Patients with unfavorable pretherapy or posttherapy CTC counts (>5 CTCs/7.5 mL of whole blood) were found to have a significantly shorter median overall survival in comparison with patients with favorable counts (≤5 CTCs/7.5 mL of whole blood). In addition, relative to PSA monitoring, determination of CTC counts may allow earlier clinical decisions regarding response to therapeutic interventions in patients with PCa.
Hypercoagulability with venous thromboembolism is frequent in a variety of cancers. As by-products of fibrin degradation, plasma D-dimer levels are generally elevated in association with hypercoagulable conditions. Because hypercoagulability associated with cancer increases in severity with disease progression, quantitative assessment of plasma D-dimer levels has been suggested as a measure of disease status in patients with malignant neoplasms. Indeed, D-dimer levels have been found to rise proportionally to the extent and severity of disease in patients with PCa. However, D-dimer levels may be elevated in a variety of other conditions such as trauma, surgery, and inflammatory processes, thereby limiting assay specificity. The use of quantitative D-dimer determinations in conjunction with PSA and CTC count (hypothetically to enhance specificity) has not been evaluated in patients with refractory PCa.
In this study, we assessed the relationship between quantitative D-dimer levels, CTC counts, and PSA levels in patients with refractory, castration-resistant PCa and asked whether changes in these parameters are concordant when measured in longitudinal studies during the course of therapy. In addition, we asked whether quantitative D-dimer levels and CTC enumeration, alone or in combination, enhance the usefulness of the PSA level in assessing disease status in this category of patients with PCa.
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