Pancreatic cancer treatment in Germany

Pancreatic cancer is one of the most severe forms of cancer: statistically, the 5-year survival rate after diagnosis is among the lowest of all cancers. Treatment is further complicated by the fact that the malignant tumour is rarely detected at an early stage.

The clinical features of the disease are weight loss, abdominal pain and jaundice. The diagnosis is established by CT. Treatment involves surgery (resection) together with adjuvant chemotherapy and radiotherapy. The prognosis is poor, because the disease is usually recognised at a late stage.

Most pancreatic cancers are tumours of the exocrine pancreas arising from ductal and acinar cells. Endocrine tumours of the pancreas are discussed below.

Adenocarcinomas of the exocrine pancreas arising from the ductal epithelium are 9 times more common than those arising from acinar cells; in 80% of cases the tumour is located in the head of the gland. The mean age at onset is 55 years, and men are affected 1.5–2 times more often than women. Risk factors are smoking, a history of chronic pancreatitis, obesity and possibly long-standing diabetes mellitus (predominantly in women). Heredity plays a certain role. Alcohol and caffeine consumption is, in all probability, not a risk factor.

Clinical signs and symptoms of pancreatic cancer

Clinical features appear at late stages. At the time of diagnosis, 90% of patients have a locally advanced tumour that invades retroperitoneal structures, spreads to the regional lymph nodes, or metastasises to the liver and lungs.

Most patients experience pain in the upper abdomen, usually radiating to the back. The pain is relieved by leaning forward and by the “fetal position”. Weight loss is common. Adenocarcinomas of the head of the pancreas are accompanied by obstructive jaundice (often with pruritus) in 80–90% of patients.

Cancer of the body and tail of the pancreas may impair blood flow through the splenic vein, leading to splenomegaly, oesophageal and gastric varices, and gastrointestinal bleeding. The cancer causes diabetes mellitus in 25–50% of patients, with symptoms of hyperglycaemia (polyuria, polydipsia). In some patients pancreatic cancer may also impair the production of digestive enzymes in the pancreas and disrupt the breakdown of food and the absorption of nutrients. This causes bloating, flatulence and watery, oily and/or foul-smelling diarrhoea, leading to weight loss and vitamin deficiency.

Diagnosis of pancreatic cancer

• spiral CT or magnetic resonance cholangiopancreatography (MRCP);
• measurement of the CA 19-9 antigen for follow-up monitoring (not as a screening test).

If CT or MRCP reveals an unresectable mass or metastatic disease, percutaneous needle aspiration biopsy of an accessible part of the tumour may be considered in order to obtain a tissue sample. If CT reveals a potentially resectable tumour, or no tumour at all, it is advisable to perform MRCP or endoscopic ultrasound to determine the stage of the disease or to detect small tumours not visible on CT. In patients with obstructive jaundice, ERCP may be performed as the first diagnostic procedure.

Standard laboratory tests should be performed. Elevated alkaline phosphatase and bilirubin indicate bile duct obstruction or liver metastases. The CA 19-9 antigen, which is produced in the pancreas, may be used to monitor the course of the disease once pancreatic cancer has been diagnosed, and as a screening test in patients at high risk of the disease. However, this marker lacks sufficient sensitivity and specificity for use in cancer screening. An initially elevated CA 19-9 level should fall with effective treatment; a subsequent rise indicates disease progression. Amylase and lipase levels usually remain within the normal range. Prognosis in pancreatic cancer

The prognosis depends on the stage of the disease, but is generally poor (5-year survival is < 2%), because in many patients the disease is already at an advanced stage at the time of diagnosis.

Treatment of pancreatic cancer

• the Whipple procedure;
• adjuvant chemotherapy and radiotherapy;
• symptomatic treatment.

In 80–90% of cases the tumour is inoperable at the time of diagnosis because of metastases or invasion of major vessels. Depending on the location of the tumour, the treatment of choice in most cases is the Whipple procedure (pancreaticoduodenectomy). Adjuvant therapy with 5-fluorouracil (5-FU) and external beam radiotherapy is usually given, which raises 2-year survival to 40% and 5-year survival to 25%. The same combination is also used for locally advanced but inoperable tumours and provides a mean survival of about 1 year. Newer drugs (for example gemcitabine, irinotecan, paclitaxel, oxaliplatin, carboplatin) may be more effective than 5-FU-based chemotherapy, yet no single agent, either as monotherapy or in combination with others, offers a clear advantage in prolonging survival. Patients with liver metastases or distant metastases at other sites may be offered chemotherapy within clinical trials, although the prognosis is generally poor both with and without treatment, and some patients may prefer not to take part in trials.

If an inoperable tumour is found during surgery and there is, or is expected to be, obstruction of the stomach, duodenum or bile duct, a double gastric and biliary bypass anastomosis is performed to relieve the obstruction. In patients with inoperable tumours and jaundice, endoscopic placement of a biliary stent can relieve the jaundice. Because of the risk of stent-related complications, surgery is more appropriate when a patient with an inoperable tumour has a life expectancy of > 6–7 months.