Pancreatic cancer diagnosis

Tracking down a clinically silent killer

From a diagnostic perspective, pancreatic cancer is an elusive disease.1 No screening protocols exist,2 and it is usually not diagnosed until the disease has advanced.3

Patients diagnosed later with unresectable disease face a bleak outlook.3 Yet currently, relatively few patients (approximately 15%) are diagnosed when they have a small, potentially resectable tumor.4 

According to the National Comprehensive Cancer Network (NCCN), no definitive early-warning signs are established for pancreatic cancer.5 Research has shown that presenting symptoms are nonspecific,2 can mimic those of other unrelated conditions,5 and typically occur only after the disease has spread to local tissue or metastasized to distant sites.1

By the time they are diagnosed, researchers estimate that approximately 85% of patients have locally advanced or metastatic disease.6

Presenting Symptoms of Advanced Pancreatic Cancer7
Symptom Percentage of patients
Nausea and weight loss 50-86
Weight loss 66-84
Abdominal pain 78-82
Jaundice 56-80
Diabetes or impaired glucose tolerance 80
Anorexia 64
Early satiety 62
Sleep disorders 54
Back pain 48

 

Challenges in diagnosis

NCCN guidelines recommend imaging evaluations as the first step toward determining the presence of pancreatic cancer.5

However, certain conditions can confound a diagnosis. For example, autoimmune pancreatitis can present with clinical and radiologic characteristics that are similar to those of pancreatic cancer.5

Some of these clinical characteristics include

  • Jaundice
  • Weight loss
  • Elevated CA 19-9 levels

Examples of radiologic characteristics include5

  • Diffuse pancreatic enlargement
  • Ductal stricture
  • Focal pancreatic masses

 

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Assessing patient health

As noted in NCCN guidelines, locally advanced and metastatic patient’s performance status (PS) plays a significant role in clinical decision-making.5 In pancreatic cancer, many of these patients are elderly and have multiple comorbidities. Treatment options may add significant toxicities and unwelcome side effects.5

The 2 most commonly used performance status measurements are the Karnofsky Performance Status (KPS) and the Eastern Cooperative Oncology Group (ECOG) scale,8 both shown below.

ECOG Performance Status9
Grade ECOG
0 Fully active, able to carry on all predisease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light house work, office work
2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours
3 Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 Dead

 

Karnofsky Performance Status10
100% Normal, no complaints, no signs of disease
90% Capable of normal activity, few symptoms or signs of disease
80% Normal activity with some difficulty, some symptoms or signs
70% Caring for self, not capable of normal activity or work
60% Requiring some help, can take care of most personal requirements
50% Requires help often, requires frequent medical care
40% Disabled, requires special care and help
30% Severely disabled, hospital admission indicated but no risk of death
20% Very ill, urgently requiring admission, requires supportive measures or treatment
10% Moribund, rapidly progressive fatal disease processes
0% Death

 

Current diagnostic techniques

Numerous potential genetic and epigenetic markers, DNA methylation alterations, and bioactive substances are being studied as markers of early pancreatic cancer. Certain biomarkers can be collected and analyzed from fine-needle aspirates, or from pancreatic juice collected during routine upper GI endoscopies.4

Clinical investigators agree, however, that the ideal biomarker for detecting and diagnosing pancreatic cancer remains to be found.1,2,4,7

 

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Diagnostic tools currently in use or being evaluated

CA 19-9 biomarker: Currently, CA 19-9 is the most commonly used serum marker in clinical practice. It has demonstrated sensitivity levels of 79% to 81% and specificity levels of 82% to 90% for the diagnosis of pancreatic cancer in symptomatic patients.11 CA 19-9 use in diagnostics is very limited, however, because elevated levels are not specific to pancreatic cancer.4 It also lacks utility as a screening marker because of low positive predictive value (0.5%-0.9%).11

Still, CA 19-9 measurements are often taken as a baseline to monitor progression and guide ongoing treatment.11 NCCN Guidelines, for example, recommend measuring CA 19-9 levels in patients prior to surgery (if bilirubin levels are normal), prior to adjuvant therapy, and for surveillance.5

MIC-1 biomarker: MIC-1 may be a more sensitive marker than CA 19-9, with one study showing 90% of patients with resectable pancreatic cancer had elevated MIC-1 levels, while 62% had elevated CA 19-9. However, MIC-1 faces the same challenges as CA 19-9 in terms of distinguishing pancreatitis from pancreatic cancer.4

Computed tomography (CT): CT is the most widely available and best-validated imaging modality for diagnosing and staging pancreatic cancer.12,13

Vascular involvement is key to determining resectability. Because CT scans can visualize the extent of vascular invasion of a tumor, it is the primary means by which the disease is staged.5 Tri-phasic pancreatic protocol CT provides about 80% accuracy of prediction of resectability.1 CT use is recommended in clinical practice guidelines from the NCCN, while European Society of Medical Oncology (ESMO) guidelines cite contrast-enhanced multi-detector CT as an appropriate option.5,14

Computed tomography images depicting spectrum of localized pancreatic cancer

Computed tomography images depicting spectrum of localized pancreatic cancer. Black arrows point to low-density tumors; white arrows point to superior mesenteric vein and show the relationship of tumor to vessel.2

Used with permission from Lippencott Williams & Wilkins. Cancer: Principles and Practice of Oncology. 9th edition.

 
 
 

Magnetic resonance imaging (MRI): Although not as widely used as CT,2 pancreas protocol MRI is emerging as an equivalent alternative to CT, and was added to the 2012 NCCN guidelines as an option for the initial workup of patients for whom pancreatic cancer is suspected.5 Because CT often requires an intravenous contrast medium, MRI may be a viable alternative for patients who cannot tolerate use of these agents.1

Positron emission tomography (PET): Until recently, PET has seen limited use in pancreatic cancer. One new technique that is changing diagnostic methodology is called fluorine-labeled 18fluorodeoxyglucose PET scanning (FDG-PET). FDG-PET is able to distinguish between cancerous and benign masses, such as those associated with pancreatitis. Accuracy has been reported at approximately 90%. However, use of FDG-PET is limited by the expensive, specialized equipment involved and the expertise needed to operate it.15 PET has also been combined with CT to enhance precise anatomic and functional localization of tumors.16

PET-CT detection of a lesion on the left lobe of the liver (right) that was not identified by CT alone (left)

PET-CT detection of a lesion on the left lobe of the liver (right) that was not identified by CT alone (left). Subsequent biopsy confirmed lesion as metastic pancreatic adenocarcinoma.15

With kind permission from Springer Science+Business Media: Annals of Surgical Oncology, 15, 2008, 2470, Jeffrey M Farma, et al.

 
 
 

Endoscopic ultrasound (EUS): EUS involves use of an endoscope with an ultrasound transducer on the tip. The endoscope is passed into the stomach and duodenum, where it collects high-resolution images of the pancreas and surrounding vessels. This technique can also be used to direct fine-needle biopsies.17  EUS has been shown to be superior to CT in diagnosing and staging small tumors,18 demonstrating accuracy of up to 91% in the detection of tumors smaller than 2 cm.15

Laparoscopy: There is growing evidence to support the selective use of staging laparoscopy:

  • In all tumors of the neck, body, or tail of the pancreas
  • Where large primary tumors (>3 cm) are suspected
  • Where imaging suggests the presence of distant metastases12

Other clinical factors of advanced disease, such as elevated CA 19-9 levels may also warrant laparoscopy.5,12 Opinions regarding the value of laparoscopic staging vary.12

Laparoscopy is an invasive procedure that may compromise comfort and quality of life in patients with advanced disease who are not likely to benefit from surgical resection.12

 

Last information update: September, 2013

 

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References
  1. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378:607-620.
  2. Royal RE, Wolff RA, Crane CH. Cancer of the pancreas. In: DeVita Jr VT, Lawrence TS, Rosenberg SA, eds. Cancer Principles & Practice of Oncology. 9th ed. Philadelphia, PA: Lippencott Williams & Wilkins. 2011:961-989.
  3. SEER Stat Fact Sheets. Cancer of the pancreas. http://seer.cancer.gov/statfacts/html/pancreas.html#incidence-mortality. Accessed June 6, 2013.
  4. Goggins M. Molecular markers of early pancreatic cancer. J Clin Oncol. 2011;23(20):4524-4531.
  5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma. V.1.2013.
  6. Benson III AB, Moore M. Accomplishments in 2007 in the management of localized pancreatic cancer. Gastrointest Cancer Res. 2008;2(3 suppl 1):S32-S36.
  7. Sharma C, Eltawil KM, Renfrew PD, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol. 2011;17(7)867-897.
  8. Ma C, Bandukwala S, Burman D, et al. Interconversion of three measures of performance status: an empirical analysis. Euro J Cancer. 2010;46:3175-3183
  9. Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the eastern cooperative oncology group. Am J Clin Oncol. 1982;5(6):649–55.
  10. Karnofsky DA, Burchenal JH. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod CM, editor. Evaluation of chemotherapeutic agents in cancer. New York: Columbia University Press; 1949. pp191–205.
  11. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: an evidence based appraisal. J Gastrointest Oncol. 2012;3(2):105-119.
  12. Callery MP, Chang KJ, Fishman EK, Talamonti MS, Traverso LW, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16(17):1727-1733.
  13. Wong JC and Lu DSK. Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastro and Hep. 2008;6:1301-1308.
  14. Seufferlein T, Bachet JB, VanCutsem E, Rougier P; for the ESMO Guidelines Working Group. Pancreatic adenocarcinoma: ESMO–ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Clin Oncol. 2012;23(suppl7):vi33-vi40.
  15. Balci NC, Semelka RC. Radiologic diagnosis and staging of pancreatic ductal adenocarcinoma. Eur J Radiol. 2001;38(2):105-112.
  16. Farma JM, Santillan AA, Melis M, et al. PET/CT fusion scan enhances CT staging in patients with pancreatic neoplasms. Ann Surg Oncol. 2008;15(9):2465-2471.
  17. Willet CG, Czito BG, Bendell JC, Ryan DP. Locally advanced pancreatic cancer. J Clin Oncol. 2005;23(20):4538-4544.
  18. Cascinu S, Falconi M, Valentini  V,  Jelic S; for ESMO Guidelines Working Group. Pancreatic cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(suppl 5):v55-v58.