Are You Sure You Have Cancer? Ask for a second opinion.
WSJ opens an urgent clinical problem this week.
Are You Sure You Have Cancer?
Ask for a second opinion. Misdiagnoses are all too common, especially for rare forms of the disease.
The patient who came to me for a consultation was frightened. He was in his 60s and had gone to the emergency room a couple of weeks earlier because he was fatigued and had been losing weight. His blood counts there weren’t normal: He had profound anemia and a struggling immune system. This prompted a hospital admission for blood transfusions to correct the anemia and a bone-marrow biopsy to determine the cause of his deficiencies. The biopsy report indicated he had cancer, either myelodysplastic syndrome or acute leukemia, and the hospital physician told him he needed to see a specialist—me—and to get his affairs in order.
Cancer is characterized by excessive growth of abnormal cells that ignore the body’s signals to stop growing. Cancer encroaches on normal tissue and compromises its function. When this happens in the lungs, a mass forms, causing difficulty breathing or coughing. Leukemia arises in the bone marrow, the tissue that makes blood cells. When cancer cells grow there, the factory breaks down and blood counts suffer.
I reviewed my patient’s bone-marrow biopsy report from the other hospital, and it indicated that a quarter of his bone marrow was infested with leukemia.
But something didn’t feel right about the diagnosis. My patient’s blood counts weren’t quite as devastated as I usually see in such a case. He also seemed healthier than my other patients with leukemia. I repeated his bone-marrow biopsy, just to be sure, and ordered some additional blood tests.
Making a cancer diagnosis can be tricky, particularly for uncommon cancers. Acute myeloid leukemia, which represents 1% of all new cancer diagnoses, affects about 4 in 100,000 people in the U.S. a year. Breast cancer, by comparison, accounts for 15% of new cancer diagnoses and occurs in about 130 in 100,000 women in the U.S. a year. A general oncologist practicing in a community setting sees many more women with breast cancer than people with leukemia—as does a pathologist analyzing the tumor biopsy. Both have more experience in identifying common cancers and may miss subtleties that could suggest—or rule out—rarer conditions.
How often do mistakes in diagnoses happen? I lead a study conducted through the National Heart, Lung and Blood Institute and the National Cancer Institute, in which we are collecting clinical information and bone-marrow samples from 2,000 people who had abnormal blood counts and a suspected diagnosis of myelodysplastic syndrome. They were enrolled from over 140 cancer centers around the U.S. We compared the diagnoses at local cancer centers with those of pathologists who have expertise in myelodysplastic syndrome and leukemia and reviewed the same bone-marrow specimens.
The results were surprising. Expert pathologists agreed with the diagnoses of local doctors only 80% of the time. That means 1 in 5 patients may have been told that they had cancer when they didn’t, that they had a different cancer from the one growing in their bone marrow, or that they were cancer-free when they weren’t.
Expert analyses of the specimens occurred months after the biopsies, so this information couldn’t be fed back to patients in real time. Three of us who specialize in myelodysplastic syndrome and leukemia reviewed the treatments given to patients at their local cancer center and discovered something even more disturbing: About 7% of patients who received the wrong diagnosis also received the wrong therapy. Some were undertreated, while others were given chemotherapy without a verified cancer diagnosis.
Similar rates of misdiagnosis have been reported in breast cancer, melanoma, lung cancer and other tumors. Some of these are subtle differences in pathologic classifications that only eggheads like me would debate and don’t affect a patient’s prognosis or treatment. Others are more serious.
The accuracy of a cancer diagnosis can affect confidence in the efficacy of newly approved cancer drugs too. I recently participated in a meeting of the Food and Drug Administration’s Oncologic Drugs Advisory Committee in which our panel offered its opinion about a clinical trial of a drug to treat patients with aggressive lymphomas. Lymphomas are another cancer for which diagnoses can be challenging. In a 2012 study from Memorial Sloan Kettering Cancer Center of over 700 patients with lymphoma referred for a second opinion, some 17% received a major revision in their diagnosis, which altered the recommended treatment.
At the FDA meeting, we learned that for one subtype of aggressive lymphoma, the new drug worked well, even extending patient survival compared with the standard therapy. For another subtype, the drug didn’t appear to make much difference. And for patients with a third lymphoma subtype, the drug may have caused harm. Almost 900 patients from over 200 sites worldwide were enrolled in the trial. None had their diagnoses confirmed by pathologists with expertise in lymphoma.
Despite this, the FDA approved the drug earlier this year based on results of this trial. It’s hard to know how much faith to place in the new treatment over the previous standard therapy, though, given its wide range of efficacy in uncorroborated lymphoma diagnoses. Studies have shown that drugs don’t tend to work as well in a general population after FDA approval, compared with their performance in the trial that led to their approval. Failing to confirm cancer diagnoses may play a role in that.
The government should require that cancer diagnoses be confirmed by experts to ensure that a new drug is effective in the cancer for which it is approved. We should also make getting a second opinion on diagnoses and what treatments to pursue standard practice—for patients and doctors. The consequences of getting it wrong, for a condition as serious as cancer, can be devastating.
Dr. Sekeres is chief of hematology at the University of Miami’s Sylvester Comprehensive Cancer Center and author of “When Blood Breaks Down: Life Lessons from Leukemia” and “Drugs and the FDA: Safety, Efficacy, and the Public’s Trust.”
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