Surgeon-scientist Vinod Balachandran says pancreatic cancer is difficult to detect early and often has spread to nearby organs when it is diagnosed.
Many people have questions about pancreatic cancer and its prognosis. MSK surgeon-scientist and pancreatic cancer expert Vinod Balachandran, MD, discusses why the disease is so hard to detect, what the latest treatment options are, and how promising research may improve survival rates.
1. What is the outlook for someone diagnosed with pancreatic cancer?
Pancreatic cancer has a worse prognosis compared with many other cancers. The five-year survival rate for people with all types of pancreatic cancer is approximately 13%. Pancreatic cancer is the third leading cause of cancer-related death in the U.S. and is expected to climb to the second leading cause in the coming years. There could be a national pancreatic cancer crisis unless we find better treatments.
Overall, pancreatic cancer remains one of the most difficult cancers to treat. Other cancers — such as breast, prostate, and colorectal — are far more common, but we have more effective therapies for them.
Stage 4 (Metastatic) Pancreatic Cancer Prognosis
Pancreatic cancer is often diagnosed at a late stage, with many patients diagnosed with stage 4 disease. This means the cancer has spread from the pancreas to other organs, usually the liver or lung. For someone diagnosed with stage 4 pancreatic cancer, the median survival time is less than one year.
2. Why is pancreatic cancer hard to diagnose early?
Pancreatic cancer usually does not cause symptoms in its early stages. Some that do occur — such as pain or weight loss — can often be mistaken for signs of other illnesses. There’s no self-examination someone can do to check for early signs, and pancreatic cancer does not show up in blood tests because we don’t have good biomarkers to detect it. The biomarkers that exist are used to monitor disease progression and response to treatment.
3. What are pancreatic cancer causes or risk factors?
There is no single, direct cause of pancreatic cancer, just as there is no assured way to prevent pancreatic cancer. Risk for pancreatic cancer depends on a mix of things you can control, like having a healthy lifestyle, and some you can’t. Some of the risk factors for the disease are:
- Smoking
- Obesity
- Type 2 diabetes
- Older age (55 and above)
- Family history (defined as two or more first-degree relatives — parents, siblings, or children — with pancreatic cancer)
- Chronic pancreatitis (long-term inflammation of the pancreas)
- Heavy alcohol consumption
- Being African American
Genetic Risk Factors for Pancreatic Cancer
About 10% of pancreatic cancers are hereditary, meaning that an inherited genetic mutation likely increases risk for developing the disease. You are nine times more likely to get pancreatic cancer if you have a family history of the disease.
Specific genetic mutations that increase pancreatic cancer risk include:
- BRCA1 and BRCA2 — the most common genes associated with familial pancreatic cancer
- CDKN2A
- TK11
- TP53
However, most pancreatic cancers (90%) are thought to be caused by mutations that occur during a person’s lifetime, rather than those that are inherited.
4. How is pancreatic cancer usually treated, and how have therapies improved in recent years?
The mainstays of pancreatic cancer treatment are surgery, chemotherapy, and radiation. Patients have much better outcomes if we can remove the tumor with surgery. Most people, however, can’t have surgery because when they are diagnosed the disease has already spread outside of the pancreas into other organs, such as the liver.
Nonetheless, there has been great progress in pancreatic cancer research and treatment over the last decade, including:
Chemotherapy
Studies have shown that giving a combination of four chemotherapy drugs after surgery can extend overall pancreatic cancer survival rates to nearly five years. This applies only to a particular group of patients, but the goal is to replicate this success for other groups. In people whose cancer has already spread (metastatic), a three-drug chemotherapy combination called NALIRIFOX was approved by the U.S. Food and Drug Administration (FDA) in 2024 as a first-line treatment. This was the first approval in more than a decade of a new first-line treatment for metastatic pancreatic cancer.
Targeted Therapies
We are also learning that therapies that target specific molecules unique to cancer cells (targeted therapies) may be helpful in some patients. A class of drugs known as PARP inhibitors has shown promise in treating certain pancreatic tumors in people with inherited mutations in the BRCA genes. These are the same genes that have been linked to hereditary breast and ovarian cancer. Studies have shown that PARP inhibitors can be effective against these cancers.
In addition, as more than 90% of pancreatic cancers have KRAS gene mutations, researchers are testing several targeted therapies that block altered KRAS proteins. The FDA has already approved KRAS inhibitors to treat other cancers driven by KRAS mutations. These new drugs are currently in testing either alone or in combination with other pancreatic cancer therapies.
Immunotherapy
Pancreatic cancers are almost completely insensitive to currently available immunotherapies. However, people with pancreatic cancer whose tumors have mutations that affect certain DNA repair genes may respond to immunotherapy drugs called checkpoint inhibitors. In 2017, the FDA approved a checkpoint inhibitor drug, pembrolizumab (Keytruda®), for patients with these mutations. Even though pembrolizumab helps only a small fraction of people with pancreatic cancer, it proves that immunotherapy can work for this disease. As we continue to learn about the molecular makeup of pancreatic cancers, it will help us develop better immunotherapy approaches.
5. How are researchers studying therapeutic vaccines to treat pancreatic cancer?
We are studying whether therapeutic vaccines can train the immune system to prevent or delay pancreatic cancer from coming back. To accelerate this work, MSK established a cancer vaccine research hub, The Olayan Center for Cancer Vaccines (OCCV) — and early results are promising.
We recently published results from a phase 1 clinical trial testing a therapeutic cancer vaccine that is custom-made for each patient’s unique cancer. We found that these vaccines activated immune cells that recognize and target pancreatic cancer cells. Importantly, these immune cells stayed in the body up to nearly four years after treatment in some patients. In addition, patients whose immune system responded to the vaccine were less likely to have their cancer return, compared with patients whose immune systems did not respond. The vaccine is being tested in a larger group of patients in a phase 2 clinical trial at MSK and other institutions.
Another approach uses a general “off-the-shelf” vaccine to treat patients whose tumors harbor KRAS mutations. Medical oncologist Eileen O’Reilly, MD, is helping lead clinical trials testing this vaccine in certain patients with pancreatic or colorectal cancers. In 2024, early results from a phase 1 trial demonstrated this vaccine is safe and appears to stimulate the patient’s immune system to create cancer-fighting cells. The vaccine is now being tested in a phase 2 research study at MSK and other institutions.
Overall, people today have many more treatment options and clinical trials available than they did 10 years ago. Furthermore, there is more hope than ever — a real belief and determination in the pancreatic cancer community that we can effectively treat this disease. But continued progress requires continued research.
This story was originally published in March of 2019 and has been updated.
