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Papillary Vs. Medullary Thyroid Cancer
Papillary thyroid cancer is more common than medullary thyroid cancer and tends to be easier to treat. However, both types of thyroid cancer have a good prognosis in the early stages.
If the cancer has spread far from the original site, medullary cancer has a less favorable prognosis than papillary cancer. Papillary thyroid cancer is rarely fatal with treatment.
This article explores the differences between papillary versus medullary thyroid cancer, including differences in prognosis, causes, and treatment. It also examines how they compare to other types of thyroid cancer.
Papillary and medullary thyroid cancers affect the thyroid gland, but they start in different types of cells.
Papillary thyroid cancer is a type of differentiated thyroid cancer, which means it starts in cells that make and release thyroid hormones. It typically forms in only one lobe of the thyroid gland, and about 80% of people with thyroid cancer have this type. While it grows slowly, it often spreads to lymph nodes in the neck.
Medullary thyroid cancer is less differentiated and forms in C cells, which produce calcitonin. Calcitonin is a hormone that helps regulate calcium levels in the blood.
Sometimes, medullary thyroid cancer can spread to the lymph nodes, the liver, or lungs even before the discovery of a thyroid nodule or lump. It is much less common than papillary thyroid cancer, accounting for only 4% of people with thyroid cancer.
Medullary is more aggressive than papillary thyroid cancer. Doctors categorize the latter as a nonaggressive type of cancer.
Papillary cancer is rarely fatal, even if it has spread to nearby lymph nodes. Treatment usually works to stop the spread and cause remission.
However, some less common subtypes can grow faster. In the early stages, these types of papillary thyroid cancer have the same favorable outlook as the most common subtype, but if they are more advanced, this may affect the prognosis.
Medullary cancer is more difficult to detect and treat than papillary thyroid cancer. However, the prognosis does not differ significantly from the papillary type until the later stages, after the cancer has spread to distant body parts.
The outlook depends on the stage of the thyroid cancer at diagnosis. It may be:
The chart below compares the 5-year relative survival rates of the two types of cancer. This statistic shows how likely it is that people with a specific type and stage of cancer will live at least 5 years after their diagnosis compared to the general population.
The exact cause of most thyroid cancers is unknown. Changes in a person's DNA can cause cells to become cancerous, but it is not always clear why this happens to some people and not others.
Sometimes, people inherit genetic differences that predispose them to cancer. This can occur in papillary and medullary thyroid cancer, but it is more common in medullary thyroid cancer.
Statistics indicate that around 5% of people with papillary and follicular thyroid cancer develop it because others in the family have had the same condition. For medullary, there is familial occurrence in 15–30% of people.
Other risk factors for thyroid cancer include:
For localized or regional papillary thyroid cancer, treatment may involve:
If the cancer has spread to other parts of the body and it responds to RAI, treatment may include RAI and suppression therapy. If it does not, doctors may recommend the following:
For localized medullary thyroid cancer, treatment typically involves surgery to remove the thyroid and EBRT. If it has spread further afield, treatment may involve targeted therapy. If the cancer has advanced, a person may require palliative care to relieve symptoms and improve quality of life as much as possible.
Follicular thyroid cancer is another type of differentiated thyroid cancer. Approximately 10% of people with thyroid cancer have follicular thyroid cancer. However, unlike papillary and medullary cancer, it typically does not spread to the lymph nodes.
Follicular thyroid cancer can spread to other parts of the body, such as the bones or lungs. Typically, follicular cancer has a favorable outlook but less favorable than the outlook for papillary cancer. The survival rates are similar to papillary cancer.
Anaplastic thyroid cancer is an undifferentiated type of thyroid cancer, which means the cancer cells do not resemble typical thyroid gland cells. Anaplastic thyroid cancer is rare, accounting for about 2% of people with thyroid cancer.
Unlike papillary thyroid cancer, which spreads slowly, anaplastic thyroid cancer spreads rapidly to the neck and other parts of the body. It is challenging for doctors to treat.
There are several key differences between papillary and medullary thyroid cancer. Papillary is much more common than medullary, and it usually has a favorable outlook when a person receives prompt treatment.
Medullary thyroid cancer has lower survival rates once it becomes advanced. Its prognosis is similar to papillary thyroid cancer in its early stages. However, it can spread to distant body parts before detection, making it harder for doctors to treat.
Although the causes of most thyroid cancers are unknown, heredity plays a role. Familial occurrence is more common in medullary thyroid cancer than papillary thyroid cancer.
Retevmo Is 'Very Exciting' For Some With Advanced Thyroid Cancer
Retevmo as a treatment for patients with advanced RET-mutant medullary thyroid cancer "is very exciting," as treatment options were previously limited, an expert told CURE®.
The study authors determined that the 12-month PFS was 86.8% in the Retevmo group and 65.7% in the control group.
Treatment with Retevmo (selpercatinib) demonstrated better outcomes in patients with advanced RET-mutant medullary thyroid cancer, compared with treatment with Cabometyx (cabozantinib) or Caprelsa (vandetanib), two other types of tyrosine kinase inhibitors (TKIs), according to a recent study.
Retevmo is a type of TKI that blocks certain proteins, including the proteins produced by the RET-fusion gene or the RET-mutant gene. When the drug blocks the proteins, it helps prevent cancer cells from growing, the National Cancer Institute defines.
The Food and Drug Administration approved Retevmo for three cancer types with RET alterations, including advanced RET-mutant medullary thyroid cancer, in 2020.
Advanced RET-mutant medullary thyroid cancer is "one of the most rare types of thyroid cancer," according to Dr. Kaitlyn Frazier, an otolaryngology-head and neck surgery resident at John Hopkins Hospital. However, she noted that it can be difficult to control the source of the tumor once the cancer spreads.
"Once (the tumor has) metastasized, and gone in the bloodstream, it's very hard. You're kind of just treating these things as they arise kind of like Whac-A-Mole," Frazier explained. "You can't systematically take (tumors) all out with surgery, and some of these places that they can go to, it's not possible to do surgery, or it will be extremely debilitating and leave patients with a very poor quality of life, depending on where the metastases are."
A study from The New England Journal of Medicine reported on findings from the phase 3 LIBRETTO-531 randomized trial, which included 291 patients. Two groups were evaluated: 193 patients in the Retevmo group and the control group of Cabometyx (73 patients) or Caprelsa group (25 patients).
According to the study authors, the trial's primary endpoint (the main result measured at the end of a study to see if treatment worked) was progression-free survival (PFS; the length of time during and after treatment when a patient lives with cancer but does not worsen).
The study authors determined that the 12-month PFS was 86.8% in the Retevmo group and 65.7% in the control group. The 24-month PFS was 76.4% and 37.2%, respectively.
"That's astronomically different, that is twice as many patients," Frazier said, regarding the trial's PFS rates, in an interview with CURE®. "And I want to put all that in context: without treatment, these patients with stage 4 medullary, thyroid cancer probably have a 21% 10-year overall survival."
READ MORE: Firstline Retevmo Improves Survival Rates Without Disease Progression in Select Patients With Thyroid Cancer
The most common side effects in the control group, the study authors reported, included diarrhea in 60.8% of patients, hand-foot syndrome in 42.3% and high blood pressure in 41.2%. In the Retevmo group, the most common side effects were high blood pressure in 42.5% of patients, dry mouth in 31.6% of patients, diarrhea in 26.4% and increased levels of alanine aminotransferase enzymes in the liver in 26.4%.
There were higher levels of side effects of any severity in the control group compared with the Retevmo group, according to the study authors. These side effects included — but were not limited to — diarrhea, increased levels of alanine aminotransferase enzymes in the liver, nausea, decreased appetite, hand-foot syndrome, physical weakness, low calcium levels in the blood, vomiting and weight decrease.
As researchers continue to establish more beneficial outcomes for patients regarding Retevmo, Frazier recognized the unmet needs that have been addressed with the drug.
"Ideally, we would be finding this disease earlier and not have to have advanced cases, but it's good to have options across the board," Frazier noted. "And this is very exciting for those patients where we previously didn't have very much to offer."
While Retevmo demonstrated significant benefits in terms of PFS versus the control, there are still unmet needs that persist.
"It's valuable to notice that this drug can effectively get (patients) two more years and have good odds of that with (their families). But I think we should dream bigger: we want five years, we want 10 years, we want to be cured. I think that data is still too early to see. It just takes time," said Frazier.
"(An) exciting thing is, even if the drug can't shrink all these distant metastases, there are options where it can then make something resectable (removable) by surgery that wasn't (possible) before," Frazier added. "So, it can shrink it to a point where we can take it out without causing some of the harm."
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Thyroid Hormone Treatment Hastens Recovery After Cardiac Surgery
Thyroid hormone treatment after surgery requiring heart bypass speeds recovery in children undergoing correction of congenital heart defects, according to a clinical trial published in The Lancet.The effects were greatest in the patients who underwent long and difficult surgeries. Following trauma or surgery or during a critical illness, thyroid hormone concentrations plummet. Many experts thought this was an adaptive response by the body to minimize metabolic demands during a time of crisis and that the best response was to do nothing. But there was never any proof of this, and researchers have suggested in recent years that transient hypothyroidism can be dangerous in some cases. Children and adults with highly depressed thyroid function fare worse following cardiac surgery than patients with mildly lowered thyroid function.
The Heidelberg group conducted a randomized, double-blind, placebo-controlled trial of 40 children, ages 2 days to 10.4 years, who were scheduled for surgery to repair congenital heart defects. Patients were treated intravenously with either saline solution or tri-iodothyronine each day after surgery until dopamine treatment was stopped or after 12 days, whichever came first. The treated children had an increase in cardiac index by than 20% (p<0.004) in the first 24 hours after the operation when compared to placebo-treated kids.
The results were especially dramatic in patients who had undergone operations that lasted four or more hours.
The results suggest that low levels of thyroid hormone may be potentially harmful for patients who have serious cardiac dysfunction, and this form of treatment may be useful.
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