What are the clinical features, diagnosis, and management of pancreatic carcinoma?

Clinical Features, Diagnosis and Management of Carcinoma Pancreas

Pancreatic ductal adenocarcinoma is a highly lethal cancer with over 95% mortality rate, requiring prompt diagnosis and management through a comprehensive approach of imaging, pathological confirmation, and surgical evaluation to identify the minority of patients who may benefit from potentially curative resection.

Clinical Features

• Persistent back pain, marked and rapid weight loss, abdominal mass, ascites, and supraclavicular lymphadenopathy usually indicate an incurable situation 1
• Obstructive jaundice is a common presenting symptom, particularly in pancreatic head tumors 2
• Adult-onset diabetes without predisposing features or family history may be an early indicator of pancreatic cancer 1
• Unexplained episodes of acute pancreatitis should prompt investigation for underlying pancreatic cancer 1
• Epigastric pain, anorexia, early satiety, and sleep problems are common presenting symptoms in advanced disease 3
• Approximately 25% of patients may have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis 3

Diagnosis

Initial Evaluation

• Ultrasound of the liver, bile duct, and pancreas should be performed without delay when clinical presentation suggests pancreatic cancer 1
• Serum tumor marker CA 19-9 has approximately 83% sensitivity and can be used for diagnosis and monitoring disease status 4, 5
• Blood counts and liver enzymes should be included in the initial workup 1

Advanced Imaging

• Pancreatic protocol CT scan or MRI are the preferred imaging studies for diagnosis and staging 6, 1
• When malignancy is suspected from clinical symptoms and/or ultrasound findings, selective use of CT, ERCP, and/or MR (including MRCP and occasionally MRA) will accurately delineate tumor size, infiltration, and metastatic disease 1
• Endosonography (EUS) may be appropriate in selected cases for better visualization of the pancreas and to obtain tissue samples 1

Pathological Diagnosis

• Pathological diagnosis should be made according to the World Health Organization classification from a biopsy or fine needle aspiration 1
• Ductal adenocarcinomas constitute 95% of pancreatic epithelial tumors 1
• Attempts should be made to obtain tissue diagnosis during investigative endoscopic procedures 1
• Fine-needle biopsy allows diagnosis with a sensitivity of 83% and specificity of 99% 4
• Failure to obtain histological confirmation does not exclude the presence of a tumor when clinical suspicion is high 1

Staging and Risk Assessment

• Staging includes complete history and physical examination, blood counts, liver enzymes, chest X-ray, abdominal imaging, and possibly endosonography 1
• TNM staging system is used, though it does not well reflect tumor resectability 1
• Evaluation of resectability often requires surgery, preferably staging laparoscopy to exclude clinically occult intra-abdominal and lymph node metastases 1
• Resectable tumors must show no evidence of extra-pancreatic disease, direct tumor extension to the celiac axis and superior mesenteric artery, or non-obstructive invasion of the superior mesenteric-portal vein confluence 1
• Less than 20% of patients have resectable disease at diagnosis 1, 7

Management

Resectable Disease (10-15% of patients)

• Complete surgical resection is the only potentially curative treatment available 1, 5
• Five-year overall survival after resection is only 10-20% 1
• Long-term survival in lymph node positive (N+) tumors is rare 1
• Adjuvant chemotherapy with FOLFIRINOX (fluorouracil, irinotecan, leucovorin, oxaliplatin) represents a standard approach with median overall survival of 54.4 months compared to 35 months for single-agent gemcitabine 5
• Neoadjuvant systemic therapy with or without radiation followed by evaluation for surgery is an accepted treatment approach 5

Locally Advanced Unresectable Disease

• Systemic therapy followed by radiation is an option for definitive locoregional disease control 5
• Optimal symptomatic treatment has a prime role in management 1
• Stenting or bypass surgery may be required for obstructive jaundice or gastric outlet obstruction 1

Metastatic Disease

• Gemcitabine is FDA-approved as first-line treatment for locally advanced or metastatic adenocarcinoma of the pancreas 8
• Gemcitabine has been associated with a small survival benefit compared with bolus 5-fluorouracil 1
• Multiagent chemotherapy regimens including FOLFIRINOX, gemcitabine/nab-paclitaxel, and nanoliposomal irinotecan/fluorouracil all have a survival benefit of 2-6 months compared with single-agent gemcitabine 5
• For the 5-7% of patients with BRCA pathogenic germline variants and metastatic disease, olaparib maintenance therapy following initial platinum-based therapy improves progression-free survival 5

Follow-up

• Due to the limited effectiveness of treatments, follow-up after complete resection should be restricted to history and physical examination 1
• Response evaluation should be symptom-driven rather than based on radiographic tests alone 1

Special Considerations

• Patients at increased inherited risk of pancreatic cancer should be referred to specialist centers offering genetic counseling and appropriate testing 1
• Secondary screening for pancreatic cancer in high-risk cases should be carried out as part of an investigational program coordinated through specialist centers 1
• Examination and biopsy of the periampullary region is important in patients with longstanding familial adenomatous polyposis 1
• Continued health education to reduce tobacco consumption should lower the risk of developing pancreatic carcinoma 1