Should serum Ca125 be used in clinical practice as predictive markers of survival in pancreatic ductal adenocarcinoma?
EAES Academy. Napoli N. 07/05/22; 363069; P114
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Abstract
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Introduction
Carbohydrate antigen 125 (CA 125) encoded by mucin 16 (MUC16) and up-regulated by KRAS/ERK axis (Mol cancer Res, 2017) is emerging as a new serum marker of poor prognosis in pancreatic ductal adenocarcinoma (PDAC) (Oncotarget, 2016), probably promoting pancreatic cancer cell motility and development of distant metastasis (Sci Rep, 2013).
Nevertheless, it appears strange that this marker has not yet been extensively introduced into clinical practice to evaluate the survival of patients with PDAC. To further investigate this role, herein we evaluated its ability to predict survival in our patient underwent surgical resection for PDAC, taking into account the stage of neoplasm.
Methods:
Data regarding patients with PDAC underwent pancreatic resection at our institution between 2010 and 2016 were prospectively collect and retrospectively analyzed. Only patients with all preoperative and follow-up data available were considered. Patients operated before 2010 were excluded due to the lack of effective neoadjuvant therapies for locally advanced PDAC. Patients operated after 2016 were excluded due to the short duration of follow-up. Kaplan-Meier curve and Log-rank test were used to evaluate the overall survival (OS) in patient with standard (S-PDAC), borderline (BR-PDAC) and locally advanced (LA-PDAC) PDAC. Cox proportional-hazard regression was used to evaluate the role of CA125 in predicting survival. The last value of CA125 before surgery was considered.
Results:
We considered 188 patients with PDAC underwent to pancreaticoduodenectomy (n=118; 62.8%) and total pancreatectomy (n=70; 37.2%). Seventy-three (38.8%) S-PDAC (localized to the pancreas), 87 (46.2%) BR-PDAC and 28 (14.9%) LA-PDAC were included. The median OS was 22.1 (10.3-61), 19.7 (11.1-44.6) and 16.4 (8.1-50.5) months in the S-PDAC, BR-PDAC and LA-PDAC (p=0.75), respectively (figure 1). Preoperative serum level of CA125 predicted survival in patient with BR-PDAC (RR= 6.17, IQR=1.20-22.4, p=0.01) and LA-PDAC (RR=18.7, IQR=2.42-123.1, p=0.003), but not in S-PDAC (RR= 4.53, IQR=0.57-18.26, p=0.13).
Conclusions:
In our patient cohort serum level of CA125 predicts OS in BR-PDAC and LA-PDAC, but not in S-PDAC. Probably, in the first two groups the up-regulation of CA125/MUC16 favors the onset of distant micro-metastases, which lead to a poor long-term prognosis despite the effective neoadjuvant chemotherapy and the radical surgery. In the latter group, this pattern fails to affect prognosis with the same significance.
Even if these results need to be confirmed in large series, they suggest as the serum level of CA125 should be introduced extensively into clinical practice of PDAC.
Carbohydrate antigen 125 (CA 125) encoded by mucin 16 (MUC16) and up-regulated by KRAS/ERK axis (Mol cancer Res, 2017) is emerging as a new serum marker of poor prognosis in pancreatic ductal adenocarcinoma (PDAC) (Oncotarget, 2016), probably promoting pancreatic cancer cell motility and development of distant metastasis (Sci Rep, 2013).
Nevertheless, it appears strange that this marker has not yet been extensively introduced into clinical practice to evaluate the survival of patients with PDAC. To further investigate this role, herein we evaluated its ability to predict survival in our patient underwent surgical resection for PDAC, taking into account the stage of neoplasm.
Methods:
Data regarding patients with PDAC underwent pancreatic resection at our institution between 2010 and 2016 were prospectively collect and retrospectively analyzed. Only patients with all preoperative and follow-up data available were considered. Patients operated before 2010 were excluded due to the lack of effective neoadjuvant therapies for locally advanced PDAC. Patients operated after 2016 were excluded due to the short duration of follow-up. Kaplan-Meier curve and Log-rank test were used to evaluate the overall survival (OS) in patient with standard (S-PDAC), borderline (BR-PDAC) and locally advanced (LA-PDAC) PDAC. Cox proportional-hazard regression was used to evaluate the role of CA125 in predicting survival. The last value of CA125 before surgery was considered.
Results:
We considered 188 patients with PDAC underwent to pancreaticoduodenectomy (n=118; 62.8%) and total pancreatectomy (n=70; 37.2%). Seventy-three (38.8%) S-PDAC (localized to the pancreas), 87 (46.2%) BR-PDAC and 28 (14.9%) LA-PDAC were included. The median OS was 22.1 (10.3-61), 19.7 (11.1-44.6) and 16.4 (8.1-50.5) months in the S-PDAC, BR-PDAC and LA-PDAC (p=0.75), respectively (figure 1). Preoperative serum level of CA125 predicted survival in patient with BR-PDAC (RR= 6.17, IQR=1.20-22.4, p=0.01) and LA-PDAC (RR=18.7, IQR=2.42-123.1, p=0.003), but not in S-PDAC (RR= 4.53, IQR=0.57-18.26, p=0.13).
Conclusions:
In our patient cohort serum level of CA125 predicts OS in BR-PDAC and LA-PDAC, but not in S-PDAC. Probably, in the first two groups the up-regulation of CA125/MUC16 favors the onset of distant micro-metastases, which lead to a poor long-term prognosis despite the effective neoadjuvant chemotherapy and the radical surgery. In the latter group, this pattern fails to affect prognosis with the same significance.
Even if these results need to be confirmed in large series, they suggest as the serum level of CA125 should be introduced extensively into clinical practice of PDAC.
Introduction
Carbohydrate antigen 125 (CA 125) encoded by mucin 16 (MUC16) and up-regulated by KRAS/ERK axis (Mol cancer Res, 2017) is emerging as a new serum marker of poor prognosis in pancreatic ductal adenocarcinoma (PDAC) (Oncotarget, 2016), probably promoting pancreatic cancer cell motility and development of distant metastasis (Sci Rep, 2013).
Nevertheless, it appears strange that this marker has not yet been extensively introduced into clinical practice to evaluate the survival of patients with PDAC. To further investigate this role, herein we evaluated its ability to predict survival in our patient underwent surgical resection for PDAC, taking into account the stage of neoplasm.
Methods:
Data regarding patients with PDAC underwent pancreatic resection at our institution between 2010 and 2016 were prospectively collect and retrospectively analyzed. Only patients with all preoperative and follow-up data available were considered. Patients operated before 2010 were excluded due to the lack of effective neoadjuvant therapies for locally advanced PDAC. Patients operated after 2016 were excluded due to the short duration of follow-up. Kaplan-Meier curve and Log-rank test were used to evaluate the overall survival (OS) in patient with standard (S-PDAC), borderline (BR-PDAC) and locally advanced (LA-PDAC) PDAC. Cox proportional-hazard regression was used to evaluate the role of CA125 in predicting survival. The last value of CA125 before surgery was considered.
Results:
We considered 188 patients with PDAC underwent to pancreaticoduodenectomy (n=118; 62.8%) and total pancreatectomy (n=70; 37.2%). Seventy-three (38.8%) S-PDAC (localized to the pancreas), 87 (46.2%) BR-PDAC and 28 (14.9%) LA-PDAC were included. The median OS was 22.1 (10.3-61), 19.7 (11.1-44.6) and 16.4 (8.1-50.5) months in the S-PDAC, BR-PDAC and LA-PDAC (p=0.75), respectively (figure 1). Preoperative serum level of CA125 predicted survival in patient with BR-PDAC (RR= 6.17, IQR=1.20-22.4, p=0.01) and LA-PDAC (RR=18.7, IQR=2.42-123.1, p=0.003), but not in S-PDAC (RR= 4.53, IQR=0.57-18.26, p=0.13).
Conclusions:
In our patient cohort serum level of CA125 predicts OS in BR-PDAC and LA-PDAC, but not in S-PDAC. Probably, in the first two groups the up-regulation of CA125/MUC16 favors the onset of distant micro-metastases, which lead to a poor long-term prognosis despite the effective neoadjuvant chemotherapy and the radical surgery. In the latter group, this pattern fails to affect prognosis with the same significance.
Even if these results need to be confirmed in large series, they suggest as the serum level of CA125 should be introduced extensively into clinical practice of PDAC.
Carbohydrate antigen 125 (CA 125) encoded by mucin 16 (MUC16) and up-regulated by KRAS/ERK axis (Mol cancer Res, 2017) is emerging as a new serum marker of poor prognosis in pancreatic ductal adenocarcinoma (PDAC) (Oncotarget, 2016), probably promoting pancreatic cancer cell motility and development of distant metastasis (Sci Rep, 2013).
Nevertheless, it appears strange that this marker has not yet been extensively introduced into clinical practice to evaluate the survival of patients with PDAC. To further investigate this role, herein we evaluated its ability to predict survival in our patient underwent surgical resection for PDAC, taking into account the stage of neoplasm.
Methods:
Data regarding patients with PDAC underwent pancreatic resection at our institution between 2010 and 2016 were prospectively collect and retrospectively analyzed. Only patients with all preoperative and follow-up data available were considered. Patients operated before 2010 were excluded due to the lack of effective neoadjuvant therapies for locally advanced PDAC. Patients operated after 2016 were excluded due to the short duration of follow-up. Kaplan-Meier curve and Log-rank test were used to evaluate the overall survival (OS) in patient with standard (S-PDAC), borderline (BR-PDAC) and locally advanced (LA-PDAC) PDAC. Cox proportional-hazard regression was used to evaluate the role of CA125 in predicting survival. The last value of CA125 before surgery was considered.
Results:
We considered 188 patients with PDAC underwent to pancreaticoduodenectomy (n=118; 62.8%) and total pancreatectomy (n=70; 37.2%). Seventy-three (38.8%) S-PDAC (localized to the pancreas), 87 (46.2%) BR-PDAC and 28 (14.9%) LA-PDAC were included. The median OS was 22.1 (10.3-61), 19.7 (11.1-44.6) and 16.4 (8.1-50.5) months in the S-PDAC, BR-PDAC and LA-PDAC (p=0.75), respectively (figure 1). Preoperative serum level of CA125 predicted survival in patient with BR-PDAC (RR= 6.17, IQR=1.20-22.4, p=0.01) and LA-PDAC (RR=18.7, IQR=2.42-123.1, p=0.003), but not in S-PDAC (RR= 4.53, IQR=0.57-18.26, p=0.13).
Conclusions:
In our patient cohort serum level of CA125 predicts OS in BR-PDAC and LA-PDAC, but not in S-PDAC. Probably, in the first two groups the up-regulation of CA125/MUC16 favors the onset of distant micro-metastases, which lead to a poor long-term prognosis despite the effective neoadjuvant chemotherapy and the radical surgery. In the latter group, this pattern fails to affect prognosis with the same significance.
Even if these results need to be confirmed in large series, they suggest as the serum level of CA125 should be introduced extensively into clinical practice of PDAC.
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