Treatment of pancreatic cancer begins with one question: can the tumour be removed completely? Complete surgical removal is the only treatment that can cure ductal adenocarcinoma, but only about 20% of patients present with disease that is amenable to resection. For everyone else, treatment aims to control the cancer and its symptoms rather than to eliminate it. Because the disease is uncommon and the operations are complex, management is usually coordinated by a multidisciplinary team and carried out in a high-volume centre.
Assessing resectability
The first step is to judge whether the tumour can be separated from the major blood vessels that run beside the pancreas, and whether it has already spread. CT does this job, and it places patients into one of the following groups:
- Resectable — the tumour has not grown into the major vessels, so it can be removed.
- Borderline resectable — the tumour touches or partly involves a major vessel, so it may be removable, but often only after chemotherapy or chemoradiation.
- Locally advanced — the tumour involves the local vessels in a way that usually prevents removal.
- Metastatic — the cancer has spread beyond the pancreas, so surgery cannot cure it.
This distinction, rather than the numbered stage, is what guides treatment, because it maps directly onto what can be done.
Surgery
When a tumour in the head of the pancreas is resectable, the usual operation is the Whipple procedure, or pancreaticoduodenectomy, which removes the head of the pancreas together with the gallbladder, part of the bile duct, part of the small intestine and part of the stomach. Tumours of the body and tail are removed by distal pancreatectomy, often together with the spleen. Occasionally the whole pancreas must be removed. Enough pancreas is usually left to make digestive enzymes and insulin, but enzyme supplements are sometimes needed with meals afterwards. Even after a complete resection, the tumour often returns, most often elsewhere in the body, so surgery is combined with systemic treatment.
Chemotherapy around surgery
Chemotherapy given after resection, called adjuvant treatment, improves survival compared with surgery alone and is standard for patients who are well enough. The choice depends on fitness: modified FOLFIRINOX, a four-drug combination, is used for patients with a good performance status, while a gemcitabine-based regimen is used for those who cannot tolerate intensive treatment.
For borderline resectable tumours, chemotherapy, sometimes with radiation, is given before surgery (neoadjuvant treatment). Shrinking the tumour first can make complete removal more likely and can reveal cancers that progress despite treatment, sparing a patient an operation that would not have helped.
Locally advanced and metastatic disease
When the tumour cannot be removed, chemotherapy is the mainstay. The common regimens are FOLFIRINOX and the combination of gemcitabine with nab-paclitaxel; for metastatic disease, chemotherapy is usually given as a combination over about six months. Radiation is sometimes added to chemotherapy for locally advanced disease, although its effect on survival is still debated.
A minority of tumours carry molecular features that make a targeted or immune drug worth adding. These include BRCA1 or BRCA2 mutations, which may respond to a PARP inhibitor such as olaparib; fusions involving NTRK or RET; and mismatch repair deficiency, high microsatellite instability or a high tumour mutational burden, which may respond to an immune checkpoint inhibitor such as pembrolizumab. Because these drugs are chosen by marker, tumour molecular testing is part of the assessment for advanced disease. Clinical trials are offered at every stage, since conventional treatment still achieves only limited control.
Relieving symptoms
Much of the day-to-day care of advanced pancreatic cancer is palliative, and it can begin at any stage alongside cancer-directed treatment. When the tumour obstructs the bile duct, an endoscopic stent can be placed to relieve jaundice; if the duodenum is blocked, a stent or a bypass operation can restore the passage of food. Pain from invasion of the coeliac plexus can be controlled with a nerve block. Exocrine insufficiency and the weight loss it causes are treated with pancreatic enzyme replacement. Because the disease is rarely curable, controlling symptoms is an important part of treatment at every stage, not only at the end.