Pancreatic cancer

Dr Nirasha Chiranjan explains why pancreatic cancer is renowned for being one of the most lethal cancers.

Pancreatic cancer has been in the spotlight due to the passing of celebrities, like Patrick Swayze, Steve Jobs, Alan Rickman and Luciano Pavarotti, who all succumbed to this illness.

Renowned for being one of the most lethal cancers, it is a leading cause of cancer mortality worldwide. Despite improvements in the survival rates of most other cancers, pancreatic cancer survival rates remain relatively unchanged.

Risk factors

The lifetime risk of developing pancreatic cancer is 1 in 67¹. It can occur at all ages but peaks between 60 to 70 years of age. Most pancreatic cancers are sporadic, however, there is a family history of pancreatic cancer in 5-10% of cases.

Risk factors are smoking, obesity and physical inactivity, diabetes, history of chronic pancreatitis and familial genetic mutations^2,3.

Screening for pancreatic cancer should be undertaken for those individuals with two first-degree relatives with pancreatic cancer, or known genetic syndromes associated with an increased risk of pancreatic cancer⁴.

What is the pancreas?

The pancreas is a fish-shaped organ lying across the central abdomen. It is made up of a head, body and tail. Most of the pancreas contains exocrine tissue that produces enzymes for digestion. The remaining tissue consists of endocrine tissue that produces hormones that regulate blood sugar levels.

What causes pancreatic cancer?

Pancreatic cancer can arise from the exocrine and endocrine components. The most common type of pancreatic cancer arising from the exocrine pancreas is a ductal adenocarcinoma. It represents about 85% of all pancreatic neoplasms.

About 60% of pancreatic cancers occur in the head of the pancreas and the remaining in the body and tail.

Symptoms

• Abdominal pain that is typically in the stomach and radiates to the back.

• Weight loss with decrease in appetite.

• Diarrhoea, with change in stools to a greasy appearance, that is difficult to flush.

• Jaundice – yellowing of the skin and eyeballs – usually due to a blockage in the ducts draining bile from the liver.

Due to the aggressive nature of this disease, many patients will present with advanced disease and symptoms related to their metastases.

Clinical examination

The signs of pancreatic cancer on clinical examination are jaundice, an enlarged liver, right-sided upper abdominal mass, evidence of severe weight loss (cachexia)⁵.

Tests

Specific tests used in the initial evaluation for suspected pancreatic cancer are transabdominal ultrasound, abdominal CT scan, endoscopic retrograde cholangiopancreatography (ERCP) and tumour markers.

Diagnosis

A tissue biopsy is required to make   the diagnosis. This can be done preoperatively via ultrasound-guided biopsy, or at the time of surgery.

Patients are then staged according to the TNM staging system. This is based on the evaluation of the primary tumour, lymph node status and presence of metastatic disease.

The aim of staging is to determine the extent of loco-regional disease and presence of metastases. These factors  will all help to determine what is the  best treatment for the individual patient.

Evaluation of a patient with pancreatic cancer within the domains of a multi-disciplinary team – including surgeons, radiologists, pathologists, radiation oncologists, medical oncologists and allied health professionals – is preferred   to improve patient outcomes.

Treatment

The treatment algorithm for a pancreatic cancer patient depends on the resectability of the tumour⁷. A pancreatic cancer is deemed unresectable, if distant metastases are present, or if there is extensive local invasion of surrounding blood vessels. Operability is also dependent on a patient’s physical and mental performance status.

Whipple procedure

For patients with early stage disease that is resectable, surgery remains the best option for cure. The operation is called a Whipple procedure; the head of the pancreas, duodenum (first part of the bowel), the bile duct, gallbladder and part of the stomach are removed. Only about 20% of patients will have resectable disease at diagnosis.

Adjuvant therapy

For patients undergoing surgery, further treatment, called adjuvant therapy, is often recommended. Trials have demonstrated a significant survival benefit for adjuvant chemotherapy. The use of adjuvant radiation therapy or chemo-radiation therapy is often recommended in the US.

Neoadjuvant therapy

Borderline resectable patients are offered neoadjuvant therapy, before surgery, to increase the likelihood of removing the cancer completely at the time of surgery.

Unresectable disease

Patients with unresectable disease and distant metastases are offered a combination of chemotherapy, radiotherapy, chemo-radiation, novel therapies and palliative care to improve their quality of life. The optimal management of these patients is controversial and there are no global standard approaches.

Forecast

In conclusion, we hope future focused efforts will lead to individualised oncological pharmacotherapy enabling the transformation of pancreatic cancer from a fatal disease to a treatable one⁹.

MEET OUR EXPERT  – DR NIRASHA CHIRANJAN

Dr Nirasha Chiranjan is a radiation oncologist. Her special areas of interests are breast, gynaecological, head and neck, and central nervous system cancers. She is based at Life Flora Hospital, Sandton Oncology and Ahmed Kathrada Cancer Institute.

References:

1. Becker AE, , Hernandez YG, , Frucht H, , Lucas AL. Pancreatic ductal adenocarcinoma: risk factors, screening, and early detection. World J. Gastroenterol.20(32), 11182–11198 (2014).
2. Nitsche C, , Simon P, , Weiss FU, et al.Environmental risk factors for chronic pancreatitis and pancreatic cancer.
3. 3. Bracci PM. Obesity and pancreatic cancer: overview of epidemiologic evidence and biologic mechanisms.  Carcinog.51(1), 53–63 (2012)
4. Canto MI, , Harinck F, , Hruban RH, et al.International Cancer of the Pancreas Screening (CAPS) Consortium summit on the management of patients with increased risk for familial pancreatic cancer. Gut62(3), 339–347 (2013).
5. Porta M, Fabregat X, Malats N, et al. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage. Clin Transl Oncol 2005; 7:189.
6. Kamarajah SK, Burns WR, Frankel TL, et al. Validation of the American Joint Commission on Cancer (AJCC) 8th Edition Staging System for Patients with Pancreatic Adenocarcinoma: A Surveillance, Epidemiology and End Results (SEER) Analysis. Ann Surg Oncol 2017; 24:2023.
7. Evans DB, George B, Tsai S. Non-metastatic Pancreatic Cancer: Resectable, Borderline Resectable, and Locally Advanced-Definitions of Increasing Importance for the Optimal Delivery of Multimodality Therapy. Ann Surg Oncol 2015; 22:3409
8. Khorana AA, Mangu PB, Berlin J, et al. Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016; 34:2541.
9. Mohammed A, , Janakiram NB, , Pant S, , Rao CV. Molecular targeted intervention for pancreatic cancer. Cancers (Basel) 7(3), 1499–1542 (2015)