In Pancreatic Cancer, If CA 19-9 Is Up, Then Chemo First

Veronica Hackethal, MD

November 09, 2015

Changing the standard sequence of treatment for operable pancreatic cancer could improve survival for some patients, say researchers.

Some patients with operable disease and elevated levels of the CA 19-9 biomarker should receive chemotherapy first, rather than undergo the usual approach ― surgery followed by chemotherapy.

That is because patients with elevated CA 19-9 levels, which are associated with worse outcomes in general, benefit from the hit of chemotherapy before surgery.

The study is the largest so far to look at this issue, and it is the first to use a national database applicable to the general population. The findings were presented November 9 at the Western Surgical Association annual meeting, in Napa, California.

"Patients with any elevation [of CA 19-9] above normal did significantly worse, stage for stage," commented senior author Mark Truty, MD, a gastrointestinal surgical oncologist at Mayo Clinic, in Rochester, Minnesota.

"When we looked at a proportion of patients who had chemo before their operation, we found that the detriment to survival [of an elevation in CA 19-9 level] was no longer present," he continued.

The biggest differences were for patients with stage I cancer and elevated CA 19-9 levels, in whom survival was basically cut in half if they received surgery before chemotherapy, Dr Truty said.

"Any patient with pancreatic cancer should have a tumor marker checked, particularly those patients who have seemingly early-stage disease," he advised. "If the tumor marker is elevated, our recommendation based on these data is that you should have chemo first, regardless of whether or not your tumor can be removed."

The key point, according to Dr Truty, is that any degree of elevation in CA 19-9 level, rather than a threshold, should be used to guide therapy sequence.

Recent advances in chemotherapy for pancreatic cancer may have enabled this shift, he pointed out.

At diagnosis, about 50% of people with pancreatic cancer have metastatic disease and are treated with chemotherapy. About 15% to 20% of the other half, in whom there is no evidence of metastasis, are candidates for surgery, which is potentially curative, Dr Truty explained. For several decades, the standard approach — which has been shown to improve survival ― has been to perform surgery in those who are eligible, and to then administer chemotherapy.

The problem is that a significant portion of patients develop metastatic cancer soon after the operation and have significantly limited survival, he continued. Being able to predict who should have surgery first or whether some patients would do better with chemotherapy followed by surgery could optimize pancreatic cancer treatment.

The CA 19-9 test dates from the 1980s; it is widely available and is inexpensive. Patients with elevated CA 19-9 levels at diagnosis usually do worse than those with normal levels. But physicians have been reluctant to use CA 19-9 to guide therapy because no one has been able to pinpoint the ideal threshold.

"In a tumor that's otherwise removable, everyone's always afraid of missing some opportunity [that the tumor will metastasize before surgery]. That's not how things work. If the tumor metastasized, it metastasized long before the diagnosis," Dr Truty said.

 
If the tumor metastasized, it metastasized long before the diagnosis. Dr Mark Truty
 

In the study, researchers used the National Cancer Data Base to identify about 90,000 patients diagnosed with pancreatic cancer from 2004 to 2011. For about 20% of these patients (n = 71024), CA 19-9 levels were measured. Compared with patients for whom CA 19-9 levels were not available, those with any amount of CA 19-9 elevation had lower survival for all cancer stages, especially stage I.

Patients with elevations in CA 19-9 levels, when compared with patients without eleavations, also had worse overall survival at 1, 2, and 3 years (36% vs 50%; 16% vs 31%; 9% vs 21%; all P < .001).

Adjusted survival modeling showed that elevated CA 19-9 levels independently increased the risk for death (hazard ration, 1.41; P < .0001), but that receiving chemotherapy basically eliminates this risk (P = .46).

The Mayo Clinic has been using this new approach for several years, Dr Truty said, noting that he would like to get the word out to other institutions.

"I definitely think this is something that needs to be incorporated. It's cheap, widely available, and it's a quick way to determine how best to treat these patients," he emphasized.

"The current study is hypothesis-generating and may help guide discussions with patients, but we should await the published, peer-reviewed results," commented Ryan D. Nipp, MD, an oncologist at the Harvard Cancer Center, in Boston, Massachusetts.

"These are preliminary data, in abstract form, with many details still lacking that clinicians will need before they use the results to change their practice," he pointed out. He mentioned that the findings will need to be confirmed, ideally in a randomized controlled trial (RCT).

Nevertheless, current guidelines from the National Comprehensive Cancer Network recommend testing for CA 19-9 before surgery, Dr Nipp mentioned. Guidelines also recommend that doctors consider chemotherapy for patients with resectable pancreatic cancer and poor prognostic features, including high CA 19-9 levels.

In commending the authors on their study, Dr Nipp concluded: "In the absence of these data [from RCTs], clinicians may consider using CA 19-9 to help guide discussions with their patients about treatment decisions."

Because CA 19-9 levels can also be elevated in association with biliary disorders, clinicians should take into account each patient's clinical scenario, he mentioned.

The authors and Dr Nipp have disclosed no relevant financial relationships.

Western Surgical Association 2015 Annual Scientific Session: Presented November 9, 2015.

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