Screening for Pancreatic Cancer Is Effective, Has Value— at Least in High-Risk Individuals

Caroline Helwick

August 2011, Vol 2, No 5 - Cancer Care

Ongoing efforts to screen asymptomatic persons for pancreatic cancer have been unsuccessful, but targeting persons at high risk for the disease appears to be clinically effective as well as cost-effective.

Researchers have combined the use of a serum biomarker, CA 19-9, and endoscopic ultrasonography to create a screening protocol for persons at risk for the malignancy on the basis of family history and age and reported their results in the July issue of Gastro – intestinal Endoscopy (Zubarik R, et al. Gastrointest Endosc. 2011;74:87-95).

High-Risk Characteristics

Serum CA 19-9 has performed poorly in several previous studies, but in those studies participants were often younger than age 50 years (an age associated with low risk for pancreatic cancer) or have been tested with insensitive imaging modalities.

“Our hypothesis was that a highrisk population identified by age and at least 1 first-degree relative with pancreatic cancer can be success – fully screened,” said lead investigator Richard Zubarik, MD, Associate Professor of Medicine and Chief of Endoscopy, University of Vermont, Burlington.

“Our objective was to determine whether early pancreatic neoplasia can be detected in a high-risk population by using tumor marker CA 19-9 followed by targeted endoscopic ultrasonography. We also sought to determine whether this protocol was more likely to detect early-stage pancreatic cancer than standard means of detection.”

This study enrolled 546 patients aged ≥50 years with at least 1 firstdegree relative with pancreatic cancer. Enrollment was initiated at age 45 if an individual had 2 affected first-degree relatives and at age 40 if the person had a BRCA2 mutation or Peutz- Jeghers syndrome.

The BRCA2 mutation raises the risk of pancreatic cancer by 3.5- to 10-fold, whereas Peutz-Jeghers syndrome is associated with a 132-fold increased risk, according to Marcia Canto, MD, Associate Professor of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, an expert in the field who did not participate in this study.

Johns Hopkins Hospital conducts high-risk screening using multiple imaging modalities that include not only endoscopic ultrasonography but also magnetic resonance imaging, magnetic resonance cholangiopancreatographic imaging, and endoscopic retrograde cholangiopancreatography in select cases.

Elevated Biomarkers Raised Suspicion

In the current study, all patients underwent serum CA 19-9 level testing, and those with an elevated level (>37 U/mL) were referred for endoscopic ultrasonography. For comparison, the study included patients who were diagnosed with pancreatic cancer at the University of Vermont during the same period but were not enrolled in this study.

Serum CA 19-9 was elevated in 27 patients (4.9%). Neoplastic (potentially premalignant or malignant) findings were detected in 5 patients (0.9%); 1 (0.2%) of those lesions was identified as stage I adenocarcinoma of the pancreas. No additional cases of pancreatic cancer were identified at 1-year follow-up.

In the comparison group, pancreatic cancer was diagnosed in 124 patients during the study period, and the tumors in 114 of these patients were staged, revealing that:

  • 1 patient (0.9%) had stage I disease
  • 52 patients (45.6%) had stage II disease
  • 20 patients (17.5%) had stage III disease
  • 41 (36%) had stage IV disease.

“The one patient detected in the CA 19-9/endoscopic ultrasonography study had stage I disease, whereas detection of stage I cancer in the comparison group was rare (1 of 114 patients),” according to Dr Zubarik.

Among the 122 patients in the comparison group for whom survival data were available, median overall survival was only 7 months, and the 2- year survival rate was 10%.

“The one patient found to have adenocarcinoma of the pancreas by our screening protocol is still alive, without evidence of recurrence, 3 years after surgical resection, and is the longest survivor of pancreatic cancer detected in a published screening protocol,” Dr Zubarik noted.

Cost Implications

Potentially curable pancreatic cancer can be identified with CA 19-9 testing and targeted endoscopic ultrasonography, and stage I disease is more likely to be found using this screening protocol than through standard means of detection, the investigators maintain.

The cost to detect pancreatic neoplasia was determined from Medicare reimbursement data from 2010. The reimbursement for CA 19-9, physician, and facility fees for endoscopic ultrasonography S, and cytopathology were considered, but subsequent therapy after detection of the neoplastic process and secondary costs were not.

The cost of detecting 1 pancreatic neoplasm as part of the protocol was approximately $8430, whereas the cost of identifying 1 pancreatic tumor was $41,133.

For detecting neoplasia and adenocarcinoma, the respective breakdown of costs was $3249 and $16,276 for the CA 19-9 test; $3028 and $15,748 for the endoscopic ultrasonography facility fee; $993 and $4469 for the endoscopic ultrasonography professional fee; $795 and $3182 for endoscopic ultrasonography/ biopsy professional fee; and $364 and $1458 for cytopathology professional fees.

This screening approach offers “acceptable rates of disease diagnosis and exclusion as well as acceptable costs,” Dr Zubarik suggested. “Early pancreatic adenocarcinoma, associated with prolonged disease-free survival, can be detected as part of this pancreatic screening protocol.”