Precision medicine is redefining what makes cancer rare

Having cancer is difficult enough, but the diagnosis of rare cancer is often accompanied by additional difficulties. Many rare cancers are difficult to identify, which can lead to a delayed diagnosis or loss of diagnosis. It is also difficult to find doctors with experience in treating these diseases, and little information is generally available about them. Because they affect far fewer patients, by definition, relatively few clinical trials spend time and resources developing new treatments for rare cancers, which often means fewer options are available to treat them.

But in an increasing number of cases, the era of precision medicine has changed perceptions about rare and common cancers. Research has shown that some cancers that have long been considered common are just a group of rare subtypes that share the same origin. Advances in immunotherapy have also led to new treatments for some rare types of cancer that were once difficult to treat. Advanced genomic testing has revealed molecular features in some rare cancers that can be treated with previously developed drugs for more common forms of the disease. “The definition of rare cancers has changed over time, both because of the role of genetic testing and because of the evidence that different subtypes provide clinically useful information that influence treatment and outcomes,” says Murray Markman, MD, chief of medicine and science from the Cancer Treatment Centers of ^America® (CTCA).

Rare facts about cancer

• Rare cancers account for about 20 percent of all cancer diagnoses in adults.
• In Europe, rare cancer is defined as a condition in which 6 or fewer cases are diagnosed per 100,000 people per year, less than half the number (15) used in the United States.
• Most rare cancers are diagnosed in children, teens, and young adults. Rare cancers account for 71 percent of diagnoses in patients younger than 20 years and 39 percent in patients 20 to 39 years old.

From adenoma (a rare form of bone cancer) to Waldenstrom’s megaglobulin (a type of non-Hodgkin’s lymphoma), more than 500 types of rare cancers have been documented, according to the National Cancer Institute (NCI). Rare cancers are not just those that cannot be pronounced and that are found in certain cells or in darker parts of the body. They also include cancer of the stomach, esophagus, bone, vagina, penis, and gallbladder.

Because these cancers are so rare, it is often difficult to find information on how to identify them, stage them, or treat them. “In places where there is limited experience in treating cancers, managing rare cancers is a particular challenge,” says Dr. Markman. “A doctor can only see one case every few years, or even less. The lack of clinical trials for rare cancers makes the situation even more difficult.”

By deepening their understanding of the specific cancer model, scientists and oncologists have discovered that some of the so-called common cancers may not be common at all. The author of a 2016 paper on rare cancers wrote in Lancet Oncology , adding that “rare is the new commonplace in the post-genomics era.” For example, skin cancer is the fifth most common cancer diagnosed in the United States, with more than 90,000 new cases annually. But scientists have divided skin cancer into multiple subtypes, each with unique mutations in their DNA. Melanoma “is a group of rare cancers, each with a unique biology that has different implications for treatment, and is an increasingly common pattern in oncology,” the researchers wrote. Each of these subtypes are considered rare cancers, according to National Cancer Institute guidelines.

Genetic testing for rare cancers can also detect common mutations found in a variety of cancers, which could lead to new treatments. “We may be looking for rare cancer treatments based on genetic analysis that was initially performed on many common cancers or where mutations appear more frequently,” says Dr. Markman. “For example, an HER-2 mutation is closely related to breast cancer, but the presence of this abnormality may help determine an effective treatment approach for cancer where anti-HER-2 therapy is not naturally available. Consider a standard treatment.” Researchers are studying a targeted therapy drug. ^Trastuzumab (Herceptin® ), which is often prescribed for the treatment of HER2-positive breast cancer, is a potential treatment for salivary duct and serous uterine carcinomas, rare and aggressive cancers that may contain HER2-positive mutations.

These new discoveries that marked the era of precision medicine helped lead to new treatments and potential treatments for rare cancers. In 2017, immunotherapy drugs known as checkpoint inhibitors were approved to treat Merkel cell carcinoma, an extremely rare form of skin cancer, and Hodgkin’s lymphoma, a rare blood cancer. Immunotherapy is also being investigated as a potential treatment for other rare types of cancer, such as thymic carcinoma and mesothelioma.

Rare Cancer Challenge

However, cancers that are considered rare still pose challenges to clinicians and patients. According to a 2017 study from the American Cancer Society:

• Fifty-nine percent of rare cancers are diagnosed at an advanced stage, compared to 45 percent of common cancers.
• The five-year survival rate for men with rare cancers is 55 percent, compared to 75 percent for common cancers.
• The five-year survival rate for women with rare cancers is 60 percent, compared to 74 percent for common cancers.

“The most important finding was the knowledge that collectively rare cancers are still more likely to be diagnosed at later stages and that the overall survival rate is low,” said study author Carol DeSantis, MPH. Medicine Journal. Encountering such massive proportions can be devastating for patients. But Stephen Lynch, MD, an insertion and primary care physician at Phoenix Hospital, encourages patients to take control of their diagnoses and learn all they can about cancer. “Often, whether it’s a common cancer or really rare, a lot of patients don’t really understand it,” says Dr. Lynch. They have been told they have breast cancer. Well, breast cancer has many different diseases. They were told they had lung cancer. There are many different diseases. So the first and most important thing is to help the patient understand the causes of his illness.”

As scientists and researchers delve into the genomics of each cancer, they are discovering that every cancer, like every patient, has unique characteristics that often require individual treatments. Dr. Lynch says it’s important to educate patients about what makes their particular cancer work, despite it being categorized as common or rare. “Depling into this diagnosis and helping patients learn about the unique molecular aspects of their tumor will help them better understand what they are dealing with and what questions to ask,” he says.