Pancreatic cancer - New treatments, better outcomes

From the Mayo Clinic Health Letter, January 2021.

Pancreatic cancer
New treatments, better outcomes

Pancreatic cancer begins in the tissues of your pancreas — an organ in your abdomen that lies behind the lower part of your stomach.
Pancreatic cancer often doesn't cause symptoms in its early stages when it's most curable. Thus, in many people with pancreatic cancer, the cancer has spread to other organs at the time of diagnosis. In this group, treatment is limited to chemotherapy only and does not cure the cancer.
For people in whom the cancer has not spread to other organs, treatment options may include surgery, chemotherapy, radiation therapy or a combination of these — with the only known curative treatment being surgery. And, historically speaking, only a small percentage of people with confined cancer would have been considered candidates for surgery.
However, in 2019, Mayo Clinic doctors published research advances related to a specific subset of people with pancreatic cancer that would have been previously considered inoperable. This subset is the roughly one-third of people in whom the cancer has not spread to other organs, but the tumor has grown outside of the pancreas to involve critical blood vessels adjoining the pancreas. The research showed a dramatic survival benefit of surgery for those who underwent a specific treatment plan of chemotherapy and chemoradiation before surgery.

Here, Mark Truty, M.D., a Mayo Clinic surgeon and lead author of the study, answers our questions about the findings.

Q: You found that people who meet three criteria before surgery tend to have the best outcomes. Could you briefly explain each criterion?

A: The first is extended chemotherapy before surgery. We found that the more cycles of effective chemotherapy people receive before surgery, the
longer they live. Many cancer doctors (oncologists) have feared that giving too much chemotherapy may somehow weaken a person or cause toxicities that would preclude an operation later on. But this is not the case. Also, some oncologists worried that if we don't intervene surgically soon, then we would lose our "window of surgical opportunity" and the tumor may spread in this chemotherapy interim, but this is a false premise.

The second criterion is a CA 19-9 tumor marker that falls to a normal level after chemotherapy. CA 19-9 is a tumor marker that is often used in pancreatic cancer. We have come to realize that the higher the tumor marker is at diagnosis, the worse the survival. If elevated, we want to see the CA 19-9 drop with chemotherapy. Most medical centers typically want to see the CA 19-9 just go down in general, but we found that those people whose CA 19-9 went down to normal levels with chemotherapy treatment did significantly better in terms of survival than did those whose CA 19-9 dropped but was still elevated.

Third, we look for a tumor that, when surgically removed, was found to be all or mostly dead due to chemotherapy. If the preoperative treatment has led to complete or near complete death of the primary cancer, then it is very likely that the chemotherapy also killed any hidden (occult) cancer cells elsewhere in the body, which we know most people have. Thus, these patients have the longest survival. If the primary cancer is still alive after all this treatment, then the opposite is true. In the past, we typically didn't know this factor until after surgery, when it's too late.
We have incorporated positron emission tomography (PET) scans heavily into our practice to judge effectiveness of chemotherapy. If the tumor is dead on a PET scan after chemotherapy, we have a much better predictor of that person's survival before considering surgery. This has been game-changing for people with pancreatic cancer.

Mark Truty, M.D., Hepatobiliary and
Pancreas Surgery

Q: How long does it typically take for a person undergoing chemotherapy to achieve the desired results? Is there a risk in continuing chemotherapy too long before having surgery?

A: This has continued to evolve. What started as only a couple of months has increased to a period of six months to a year prior to surgery. Many thought that if a person didn't respond to initial chemotherapy then he or she wouldn't respond to any chemotherapy. This was false. A significant portion of our patients undergo a switch in chemotherapy. This has also been practice-changing.

Q: What demographic groups benefit the most from this approach? Who, if anyone, doesn't qualify?

A: Up to half of all patients with pancreatic cancer - those in whom the cancer hasn't spread to other organs yet — are eligible for this approach. People who are older and sicker are more challenging to treat.
However, we've successfully treated people age 80 and older. We are specifically using this approach in the third of patients whose tumors involve critical vascular structures and are considered inoperable elsewhere. We are now able to offer curative intent surgery for many of these patients here at Mayo Clinic that was otherwise not possible anywhere else.

January 2021
Mayo Clinic Health Letter