br Conclusions CA elevation could
Conclusions: CA19-9 elevation could preceded recurrence confirmed by radiographic examinations in most patients. Tumor marker-guided salvage treatment can significantly prolong disease-free survival and overall survival in patients under surveillance after pancreatic cancer resection.
© 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.
In 2018, it 158021-47-7 is estimated that there will be 458, 918 new cases of pancreatic cancer worldwide and almost all are expected to die from this high-risk disease [1,2]. Even in patients who have un-dergone curative pancreatic resection followed by adjuvant ther-apy, unfortunately, the median disease-free survival (DFS) is only 1 year, and high rates of recurrence make it difficult to improve the outcomes of patients receiving surgery [3e7].
Carbohydrate antigen 19-9 (CA19-9) is the most commonly used tumor marker in management of pancreatic cancer because it has
* Corresponding author.
** Corresponding author.
utility in diagnosis, prognosis and surveillance [8e14]. When pa-tients receive cytotoxic chemotherapy postoperatively, CA19-9 levels can reflect the clinical disease progression and its increasing value is often associated with a worse prognosis [14e17]. Regular radiographic examinations such as enhanced computed tomography (CT) have limited sensitivity in detecting small-volume recurrence, and postoperative CA19-9 elevation can pre-cede radiographic evidence of recurrence by more than 6 months [18e21]. Therefore, elevating CA19-9 may become an indication to start salvage treatment. However, there is no evidence that “tumor marker-guided” salvage treatment can benefit patients with resectable pancreatic cancer.
Because postoperative CA19-9 elevation might precede the radiographic evidence of recurrence, the purpose of this study was to explore the impact of such an aggressive strategy on patients' survival and to determine whether salvage treatment should be established based only on CA19-9 elevation without radiographi-cally proven recurrence.
Materials and methods
The study cohort consisted of 80 pancreatic cancer patients who underwent R0 surgical resection and received adjuvant chemo-therapy at Peking Union Medical College Hospital (PUMCH) be-tween January 2014 and July 2017. All patients had comprehensive and detailed follow-up data with a rising postoperative CA19-9 level and recurrence diagnosed by radiological examinations in this study. Patients who were followed up at other institutions and did not have available recurrence data were excluded. Because CA19-9 is undetectable in Lewis antigen-negative individuals, pa-tients whose CA19-9 levels were < 5 U/mL persistently were considered as Lewis antigen negative and were not analyzed . Pancreatic endocrine tumors were not included in the current research.
When CA19-9 appeared to rise but the suspicion of recurrence was not confirmed by radiographic evaluations, patients who started salvage treatment immediately were included in group A as well as the intervention group. Patients who did not alter their existing schemes until there was radiographic evidence of recur-rence were in group B. Patients with increasing tumor marker CA19-9 found at the time of radiological confirmation or after the confirmation were in group C. Both group B and C were defined as the control group because microsporangia did not consider CA 19-9 as an indication. The study protocol was approved by the ethics com-mittee at PUMCH.
A professional team in the department of general surgery per-formed all pancreatic resections and optimal adjuvant chemo-therapy schemes were determined by doctors in the department of medical oncology. Tumor characteristics were assessed by experi-enced pathologists. TNM stages classification was based on the 7th edition of the American Joint Committee on Cancer (AJCC) classi-fication system .
All patients followed up every three months. At each post-operative follow-up visit, CA19-9 tumor marker panel, necessary radiological examination (such as enhanced CT/MRI or occasional PET-CT), physical examination and routine laboratory examinations were performed. CA19-9 measurements were carried out by the laboratory department in PUMCH. In this study, we defined CA19-9 elevation as a value greater than the normally used upper limit (37 U/mL) with an increase over 30%. Furthermore, the CA19-9 level may be artificially elevated because of biliary infection or obstruction, which does not indicate progressed disease, so the CA19-9 value was not adopted when patients had abnormal bili-rubin levels .
The follow-up data were updated until October 2018. Disease-free survival (DFS) was defined as the time from pancreatectomy to the first recurrence identified by radiological examinations or death. The time from CA19-9 elevation to radiographic recurrence was defined as interval. Overall survival (OS) was the time from the surgical resection to the latest follow-up date or death.