Why Is Pancreatic Cancer So Hard to Treat?

By Jim Stallard,

Tuesday, November 8, 2016

Illustration of human body with pancreas exploded to side and magnified.
Summary

Pancreatic cancer is relatively uncommon but very deadly. It is hard to detect at an early stage, usually not treatable by surgery, and resistant to drugs that work in many other cancers. But research into new approaches is providing good reason for optimism.

Highlights
  • Pancreatic cancer is not common but is very deadly.
  • Standard cancer therapies are largely ineffective.
  • New treatment approaches give reason for hope.

Pancreatic cancer is relatively rare but notoriously lethal. It is currently the third leading cause of cancer deaths in the United States — and it’s projected to move into the second slot by 2020.

The main reason is that pancreatic cancer has proven very difficult to treat compared with many other, more common types of cancer. Despite decades of research, the prospects remain bleak for those diagnosed, with a survival rate of 20% at one year and 6% at five years for all stages combined. Even patients diagnosed and treated at the earliest stage have a 50% chance that the disease will recur.

Below we discuss why this disease has foiled clinicians and researchers for so long and also explain why they have reason to hope that the outlook will soon be brighter.   

Pancreatic Cancer Is Rarely Caught at an Early Stage

MSK pancreatic cancer expert Steven Leach, director of the David M. Rubenstein Center for Pancreatic Cancer Research, explains that the disease usually does not cause symptoms in its early stages. Those that do occur — such as pain or weight loss — are often mistaken for signs of other illnesses. In addition, the pancreas is located in the back of the abdomen behind many other organs, making it hard for doctors to feel during routine examinations and even to conduct imaging tests to detect tumors.

 “It’s not a frequently occurring cancer, so it becomes hard to generate cost-effective screening strategies for early detection, such as the use of mammography or MRI for breast cancer, or colonoscopy for colorectal cancer,” Dr. Leach says. “We have a long way to go when it comes to early diagnosis.”

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Surgery Is Usually Not an Option

Pancreatic cancer is especially aggressive and its location makes it easy for it to spread into adjacent structures and organs such as the liver or stomach. It is usually diagnosed only after it has moved into surrounding tissue, if not other parts of the body. As a result, only about 15% of patients are good candidates for surgery.

“The pancreas sits in a tricky location, with major blood vessels, the bile duct, and the intestine all in the immediate neighborhood,” Dr. Leach explains. “When the tumor involves these major blood vessels, it generally can’t be removed.”

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Even when surgery is an option, the procedure is very difficult and requires a great degree of expertise. “In high-volume centers like MSK, it’s become routine for the surgeons, who may do between 200 and 300 procedures a year, and we have good outcomes,” Dr. Leach says. “For many hospitals, whose doctors might do just ten a year, it is still a fairly high-risk operation.”

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Pancreatic Cancer Resists Drugs That Work in Other Cancers

Chemotherapies that are effective against other cancers don’t seem to work well against pancreatic cancer. Dr. Leach explains that one reason may be that pancreatic tumors are surrounded by a network of nonmalignant cells, called the stroma, which can act as a protective barrier.

“Sometimes as little as 10% of the whole tumor volume is occupied by the cancer cells, while the rest is made up of nonmalignant cells,” Dr. Leach says. In addition, the tumor usually contains a buildup of certain proteins, called matrix proteins, that cause blood vessels to collapse — which in turn prevents chemotherapy from reaching the cancer cells in sufficient amounts.

Sometimes as little as 10% of the whole tumor volume is occupied by the cancer cells, while the rest is made up of nonmalignant cells.
Steven D. Leach
Steven D. Leach physician-scientist

While some cancers have been successfully treated with targeted therapies, which block the products of specific genetic mutations, these drugs have not been developed for pancreatic cancer. Targeted therapies are effective in cancers that have a fairly large percentage of patients with the same cancer-causing mutation, such as EGFR in lung cancer, or BRAF in melanoma. Pancreatic cancer, by contrast, appears to be spread out over a large number of cancer-driving mutations, each involving a small percentage of patients.

“It’s more challenging to develop a drug that will be effective in only a small subset of patients,” Dr. Leach says. “It’s difficult to enroll enough people for a clinical trial, and there is less financial incentive for pharmaceutical companies.”

Immunotherapy, which has revolutionized treatment for many cancers, has also failed to have much effect against pancreatic cancer. Recent research has found that pancreatic tumors seem to evolve mechanisms that prevent the critical immune cells, called T cells, from infiltrating the tumor.

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Turning the Tide

Despite these many hurdles, Dr. Leach says there is ample reason for optimism.

First, researchers now know more about who is more likely to develop pancreatic cancer. Patients who carry mutations in one of the BRCA genes — which have already been primarily linked to breast and ovarian cancers — are now known to be at higher risk for pancreatic cancer, as well as people who suddenly develop diabetes relatively late in life. These groups could be screened through endoscopic ultrasound, in which a gastroenterologist passes an endoscope into the intestine next to the pancreas to capture high-resolution images.

But something even simpler is needed to make screening more cost-effective, Dr. Leach asserts. MSK researchers are investigating liquid biopsies, which look for circulating tumor cells or tumor DNA in the blood. Analyzing this DNA for mutations could help detect pancreatic cancer at an early stage, and also provide critical information about the specific tumor type.

“There also is a lot of excitement about blood tests that measure large numbers of proteins that indicate pancreatic cancer when they are detected in certain patterns — what we call protein arrays,” he says.

In addition, MSK is making progress in developing new forms of imaging, led by radiochemist Jason Lewis and radiologist Richard Do, both to detect pancreatic cancer at an early stage and also to assess how it may be responding to treatment.

Perhaps the most promising development is a new initiative called Precision Promise, a large-scale clinical trial that will investigate multiple treatment options under one clinical trial design. Sponsored by the Pancreatic Cancer Action Network, Precision Promise is a collaboration among MSK and other leading institutions to use each patient’s unique molecular profile to determine the best treatment for that person. The trial will be conducted at 12 sites, including MSK. (Precision Promise will be discussed in more detail in an upcoming OnCancer story.)

“This is a really innovative initiative because we’re getting a wonderful partnership of leading academic centers with pharmaceutical companies that recognize its vast potential, and something they want to be part of,” Dr. Leach says. “It’s going to allow us to try things that simply weren’t possible before, and we’re excited to be able to participate in something that’s this important.”

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Comments

Have pancreatic cancer....had Whipple 1 yr ago..Had chemo and radiation. ..first CTs were good. ..last set 2 weeks ago show it came back. .my oncologist wants to try another chemo drug. ..only palliative. .say I may have 11 to 18 month
..i.want to fight this. ..can you help me !!

Dear Miriam, we are sorry to hear about your diagnosis. If you would like to make an appointment with one of our specialists to discuss possible next steps in your care, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

My husband had stage 4 pancreatic cancer and passed away about ayear after his diagnosis. The problem was he also had portal vein thrombosis and varicose veins in his neck which erupted twice. The 2nd time he passed away. So sad. He was only 50.

Dear Jean, we are so sorry for your loss. Thank you for sharing your thoughts and experience on our blog.

My wife passed away from this at the age of 39 and her father at the age of 36. She has a brother and sister and 2 sons. What should we do to be tested ??

Dear Eric, we are sorry for your loss. If your wife's family is interested in learning more about genetic counseling and possibly being tested for genetic mutations that may predispose them to certain cancers, please visit our Clinical Genetics page: https://www.mskcc.org/cancer-care/risk-assessment-screening/hereditary-…. They can make an appointment for a consultation by calling 646-888-4050.

They may also be interested in learning more about MSK’s Familial Pancreatic Tumor Registry, which is investigating the causes of pancreatic cancer in people with family members who also have the disease: https://www.mskcc.org/cancer-care/types/pancreatic/about/risk-factors

We hope this information is useful. Thank you for reaching out to us.

I am curious, out of how many studies has patients survived with a full whipple surgery (pancreas removed) past 10 years? Or has actually gone through the procedure?

Laura, thank you for reaching out. The five year survival after Whipple procedure for pancreatic cancer is ~20%; at ten years it is approximately 10%

Hi
I live in Scotland. My father died of pancreatic cancer 9 years ago. My gran died of breast cancer. My sister and mum have both has breast cancer. My mum doesn't have the gene tho and they won't text me for it. Is there anyway to get tested as I'm very interested now that pancreatic cancer has been linked to the gene.
Thank you

Dear Juliet, we are sorry for your loss. We would recommend that you ask your physician for a referral to a genetic counselor who specializes in cancer. Meeting with a genetic counselor will help give you a reliable assessment of your cancer risk and what steps you can take to reduce your risk. Thank you for reaching out to us.

My husband died a little over a year ago of pancreatic cancer. He survived 14 months after diagnosis. He was only 45. He was perfectly healthy otherwise. He had a Whipple and chemo. Then it went away for a about a month and came back with a vengeance. His mother that had breast cancer testes positive for a gene mutation PALB 2 gene. Which now we think may have caused his. I'm worried now about whether my 2 smalls kids have that bad gene. They are 7 and 4. I've been told I can't find out till they are 18 because they have to consent to it. Now I have to worry . Can you guys offer me any advice. I'm so devastated to think my babies could have to go through what he did. Thanks

Dear Kristie, we are very sorry for your loss. Do speak with your children's physician to make sure he or she knows about your family history of cancer. It may be helpful to reach out to a grief counselor to discuss ways to manage and cope with the fears you are experiencing with regard to your children's risk for developing cancer. It also helps to find distractions to help relieve your anxiety - such as meditation, yoga, or enjoying your hobbies and fun activities with your children. Focusing on living a healthy lifestyle by eating healthy and exercising is always recommended and a good way to reduce your family's overall cancer risk.

Thank you for reaching out to us.

I was diagnosed with pancreatic cancer in 2/16. Had Whippel in April 16. Started Gemzar in may, radiation and 5FU in June and Gemzar for 5 more months. 29 lymph nodes were negative, all organs removed were negative, all borders were clear.
Stage 2A. Will have restaging cat scan on Dec 1. Being this cancer is so aggressive is there anything I can do to stay proactive. I would be willing to come to Sloan. I think my oncologist at Moffitt was part of your team at one time. Hope to hear from you soon. thank you

Dear Carol, we are sorry to hear about your diagnosis. Your oncologist will continue to monitor you for signs of recurrence, and it's always encouraged for people (whether or not they have been treated for cancer) to make healthy lifestyle choices such as eating a health diet, staying active, and choosing not to smoke.

If you do develop a recurrence, and you would like to make an appointment with one of our specialists to discuss possible next steps in your care, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

It is really sad to hear about the victim-ins who are suffering from cancer. Hope so they will soon get rid from it.

My husband has pancreatic cancer. 2nd round of chemo is breaking him down. Dr. Asked to look BRCA gene....but our oncologist didn't think it was a good idea bc can't go in and take biopsy. Any suggestions?

Dear Fay, we are sorry to hear about your husband's diagnosis. We can't suggest a course of action without knowing more about your husband and his disease. If you would like to make an appointment with one of our specialists to discuss possible next steps in his care, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.

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