The dread and fear that can come with a cancer diagnosis have their roots in its killer nature: Cancer is the second most common cause of death in Americans after heart disease, according to the Centers for Disease Control and Prevention. Even when diagnosed early and attacked with the latest treatments, cancer still has the power to kill.
Worldwide, the three cancers that killed the most people in 2020 were lung cancer (1.80 million deaths), colorectal cancer (935,000 deaths) and liver cancer (830,000 deaths). But those aren't the deadliest cancers, according to Rebecca Siegel, senior scientific director of surveillance research at the American Cancer Society (ACS).
The number of people a cancer kills each year depends on two factors: how many people have it (cancer incidence) and what percentage of people diagnosed with the cancer survive it (survival), Siegel explained. The deadliest cancers are those with the lowest survival.
Cancer researchers determine survival with a measure called the 5-year relative survival. This is the percentage of people who are expected to survive the effects of a given cancer, excluding risks from other possible causes of death, for five years past a diagnosis, according to the Surveillance, Epidemiology, and End Results Program (SEER), a National Cancer Institute (NCI) initiative that collects, compiles, analyzes and reports data and statistics on cancer cases nationwide.
Here's a look at the 10 deadliest cancers in the United States based on SEER 5-year relative survival data for cases diagnosed between 2011 and 2017.
Related: 10 tips for avoiding cancer
1. Pancreatic cancer, 5-year relative survival: 10.8%
Pancreatic cancer begins in the tissues of the pancreas, which aids digestion. Digestive system cancers in general are quite deadly, with fewer than half of patients surviving five years, according to SEER data, and pancreatic cancer is the deadliest of the bunch. Most pancreatic cancers are exocrine cancers, which means the cancer arises in the cells that make digestive enzymes. Less commonly, cancers arise in the pancreas's endocrine cells, which make hormones such as insulin; these are called pancreatic neuroendocrine tumors (NETs), or islet cell tumors, according to the ACS. NETs make up 2% of pancreatic cancers and have a much better prognosis, according to the ACS.
Depending on how far it has spread, doctors may treat pancreatic cancers with surgery, radiation or chemotherapy. Other treatments might include immunotherapy (which ramps up the immune system to attack the cancer) or targeted therapies (drugs that target molecules specific to cancer cells), according to the ACS. The NCI predicts pancreatic cancer to claim 48,220 U.S. lives in 2021.
2. Mesothelioma, 5-year relative survival: 11.5%
The mesothelium is a layer of cells that line certain cavities of the body and surround the internal organs, according to the ACS. Mesothelioma is a cancer of these cells. Three out of four mesotheliomas develop in the mesothelium that surrounds the lungs, which is called the pleura. This type of cancer is called pleural mesothelioma.
The next most common type of mesothelioma forms in the peritoneum, the tissue that lines the abdomen and surrounds many abdominal organs, such as the stomach and the liver; this cancer type is called peritoneal mesothelioma.
Rarely, mesothelioma occurs in the tissues that surround the heart and testicles, according to the ACS. Exposure to asbestos, a mineral fiber once commonly used in insulation, is the primary cause of malignant pleural mesotheliomas and can contribute to development of peritoneal mesothelioma, according to the ACS.
Treatment for mesothelioma depends on how far it has progressed but may include surgery, chemotherapy, radiotherapy, targeted therapies and immunotherapies.
3. Gallbladder cancer, 5-year relative survival: 19.4%
This digestive system cancer begins in the gallbladder. The gallbladder, located underneath the liver, concentrates and stores bile, which is a substance made by the liver that aids in digestion, according to the ACS. Gallstones, which are small, hard deposits of cholesterol and other materials in the gallbladder, significantly increase the risk of developing gallbladder cancer, according to the ACS.
Treatments, which depend on how far the cancer has progressed when it is diagnosed, include surgery, chemotherapy and radiation. Patients can also consider participating in clinical trials of immunotherapies and targeted therapies for gallbladder cancer, according to the ACS.
4. Esophageal cancer, 5-year relative survival: 19.9%
The esophagus is the muscular tube that transports food from the throat into the stomach. Risk factors for esophageal cancer include older age, being male, smoking, drinking alcohol and having acid reflux, in which stomach acid comes up into the lower esophagus, according to the ACS.
Treatments, which depend on how far the cancer has progressed, may include surgery, chemotherapy, radiation, immunotherapy or targeted therapies. The NCI estimates esophageal cancer to kill around 15,530 Americans in 2021.
5. Liver and intrahepatic bile duct cancer, 5-year relative survival: 20.3%
Liver cancer is one of the most common forms of cancer worldwide. Though liver cancer is uncommon in the United States, it has been on the rise, with liver cancer incidence in the U.S. more than tripling since the 1980s, according to the ACS.
The most significant risk factor for liver cancer is chronic hepatitis B or hepatitis C infections, according to the ACS. Both of these infections are transmitted through bodily fluids, including blood and semen. The CDC recommendations that all children be vaccinated against hepatitis B virus, but there is no vaccine for hepatitis C, according to the ACS.
A closely related cancer is intrahepatic bile duct cancer, which occurs in the ducts that carry bile from the liver and gallbladder to the small intestine, where the bile helps digest fats from food, according to the ACS. The NCI estimates that in 2021, approximately 30,230 Americans will die from liver and intrahepatic bile duct cancer.
6. Lung and bronchial cancer, 5-year survival: 21.7%
Lung and bronchial cancer kill the most people worldwide and in the U.S. every year. Smoking and use of tobacco products are the major causes of it, according to the NCI. There are two major types: non-small cell lung cancer, which is the most common, and small cell lung cancer, which spreads more quickly, according to the ACS. The best thing patients who smoke can do to prepare for treatment is to quit smoking, according to the ACS.
Treatments for lung cancer include surgery, chemotherapy, radiation, immunotherapies and, in the case of non-small cell lung cancer, targeted therapies. The NCI estimates lung and bronchial cancer to claim around 131,880 lives in 2021.
7. Pleural cancer, 5-year survival: 22%
Pleural cancer occurs in the pleural cavity, the space within the chest cavity but outside the lungs, or in the layer of cells that surrounds the lungs. The NCI includes pleural mesothelioma in the mesothelioma category for purposes of monitoring survival, so cases of pleural mesothelioma aren't included in pleural cancer statistics, according to Kathy Cronin, a scientist with the Surveillance Research Program at the NCI.
But not all pleural cancers are mesotheliomas. Many of these non-mesothelioma pleural cancers are "tissues of unknown histology," meaning that doctors are unsure what tissue or cell type they are, Cronin said. Treatments for pleural cancer may include surgery, chemotherapy or radiation, according to The University of Texas Southwestern Medical Center.
8. Acute monocytic leukemia, 5-year relative survival: 24.8%
Acute monocytic leukemia is a subtype of a type of leukemia called acute myeloid leukemia (AML). It develops in blood precursor cells that are on their way to becoming immune-system cells called monocytes, explained Laura Romundstad, a registered nurse who helps patients find clinical trials as a clinical trial nurse navigator with the Leukemia & Lymphoma Society (LLS). Monocytes are a major part of the innate immune system (the branch of the immune system that doesn't involve the development of antibodies but instead recognizes common features of pathogens and immediately attacks), she said.
Treatments for acute monocytic leukemia may include chemotherapy, stem cell transplantation, or targeted therapies.
9. Brain cancer, 5-year relative survival: 29.4%
In adults, brain tumors rarely begin in the brain. More often, they spread there from other cancers, according to the ACS. But brain cancers that are caused by cancers that originated somewhere else in the body aren't included in brain cancer survival statistics because cancers are categorized according to their site of origin. If a person dies of cancer that originated in the lung and metastasized to the brain, for example, that person's case would affect lung cancer survival statistics, not survival statistics for brain cancer, according to Cronin.
In children, most brain tumors begin in the brain, according to the Mayo Clinic. The only risk factors for brain tumors are family history and exposure of the head to radiation. Radiation exposure usually occurs during treatment for some other cancer, according to the ACS.
Treatment for brain tumors depends on the tumor type and how much the cancer has grown by the time it's diagnosed and might include surgery, radiation, chemotherapy, immunotherapies or targeted therapies, according to the ACS. Brain and other nervous system cancers are predicted to cause the deaths of around 18,600 Americans in 2021, according to the NCI.
10. Acute myeloid leukemia, 5-year relative survival: 29.5%
Leukemias develop from stem cells in the bone marrow, which differentiate into different blood-cell precursors and eventually blood cells. Leukemia occurs when blood cell development is halted and the cells become cancerous, explained Romundstad. Leukemias are classified according to the stage at which blood cells and precursors halt their development and become cancerous, Romundstad said. Acute myeloid leukemia refers to any cancer that develops in myeloid cells (as opposed to in lymphoid cells), which are blood precursor cells that have the potential to develop into red blood cells, some types of white blood cells, and platelets, according to the ACS.
In AML, rather than developing into these blood cell types, stem cells get stuck at an immature stage and are called "blast cells," according to LLS. There are no or very few blast cells in healthy blood. Having too many blast cells and too few healthy blood cells causes many symptoms of AML, including frequent infections, bruising, and bleeding easily, according to LLS.
AML is more common in adults than in children, though it can occur at any age. For the most part, doctors don't know what causes it, though smoking, previous chemotherapy or radiation treatments for other cancers, and exposure to the chemical benzene increase the risk of getting it, according to the ACS. Treatment approaches may include chemotherapy, a stem cell transplant or targeted therapies. AML is predicted to claim the lives of some 11,400 Americans in 2021, according to the NCI.
Why is there no cure?
During most of the 20th century, the number of people killed by cancer every year relative to population size, or — the cancer death rate — rose steadily to its peak in 1991, according to the ACS's most recent summary of the state of cancer in the U.S. Since 1991, the cancer death rate has fallen by 31%, which is equivalent to 3.2 million fewer cancer deaths compared with the death rate in 1991.
The study authors attribute the decrease in cancer death rates to reductions in smoking, earlier detection and better treatments for some cancers. "We have made a lot of progress in the fight against cancer," Siegel said.
Yet despite all that progress, a wholesale "cure for cancer" remains elusive for many reasons. The first issue is that cancer is not just one disease that could be eradicated with one cure. Instead, it's hundreds of diseases, Siegel explained. "We would need hundreds of different types of cures to cure all cancer," she said.
Another reason it's hard to cure cancer is that the bar for cancer being cured is incredibly high. Cancer is cured if there are no traces of it in the body and it will never come back, according to the NCI, or is not expected to come back, according to the ACS. But even when all traces of a cancer have disappeared, there's no way of knowing with certainty that it won't return.
"There is never a guarantee that cancer will not recur because cancer cells can hide in the body undetected by a person's immune system," Siegel said. That said, the longer a person is in remission, meaning that their signs and symptoms of cancer are reduced or absent, the less likely it is that the cancer will come back, according to the ACS.
Finally, just because there are effective treatments for a particular cancer doesn't mean that the treatment will work for everyone. "Each person's cancer has a unique molecular signature and responds differently to treatment compared to someone else with the same type of cancer," Siegel said.