What is Posttransplantation Cancer?
Organ transplant is sometimes the only way to extend the lives of patients with severe organ failure. However, this procedure comes with its own risks. One of the main causes of death after an organ transplant is cancer. The other two major causes of death, cardiovascular disease and infection, are becoming less common due to improved screening, preventive measures, and treatments.
Understanding cancer after an organ transplant is tricky. There’s a lack of established guidelines and difficulties in early detection. The risk of cancer becomes complex due to altered body responses and unique clinical presentations due to the transplant.
Research has shown that people who have had an organ transplant have double to quadruple the risk of developing cancer. There are several reasons for this. One factor is long-term use of drugs to suppress the immune system which can make it easier for cancerous cells to grow. Also, after a transplant, patients are more likely to get infections, especially from certain viruses (Epstein-Barr virus, Varicella, Cytomegalovirus, and Human herpesvirus), which can increase the risk of cancer.
Doctors and patients face a difficult situation as cancer in transplant patients tends to be more aggressive while the cancer treatment options may be limited due to other health conditions and the fear that treatment may cause organ rejection. This article will explore the various aspects related to cancer after an organ transplant including its patterns, causes, symptoms and diagnosis, as well as strategies for screening and treatment.
What Causes Posttransplantation Cancer?
The chances of developing cancer after an organ transplant can be influenced by three main factors: patient characteristics, aspects of the transplant itself, and the types of medications taken after the transplant.
Patient-related Risk Factors
Older age is a well-known risk factor for cancer, especially skin cancer, after an organ transplant. Spending a lot of time in the sun or having a history of cancer before the transplant can also increase the risk. Research has found that people who have had cancer before their transplant are more likely to die from cancer or develop new cancers after their transplant than those without a history of cancer before transplant.
Smoking and drinking alcohol can also increase the risk of developing cancer after a transplant. Certain viruses including the Epstein-Barr virus (EBV), human herpesvirus 8 (HHV-8), human papillomavirus (HPV), the Merkel cell polyomavirus, and hepatitis B and C can lead to the development of certain kinds of cancer, including lymphomas and nasopharyngeal cancers (cancers of the upper part of the throat).
Transplant-related Risk Factors
The type of organ transplant can influence cancer risk. For example, kidney transplant recipients who receive an organ from a living donor have a lower chance of developing genitourinary cancer and lymphomas following the transplant. Though rare, a donor can pass on certain types of cancer, including melanoma, lung, breast, colon, kidney, and others to the recipient.
Medication-related Risk Factors
Certain drugs taken after the transplant can have an effect on cancer risk. Immunosuppressive drugs, which are necessary to prevent the body from rejecting the transplanted organ, can make it harder for the immune system to recognize and destroy cancer cells and can increase the likelihood of virally induced cancers. The specific type of drug, the strength of the drug, and the length of time taking the drug can all influence the chances of developing cancer. Drugs that have been linked to this increased risk include anti-thymocyte globulin, basiliximab, corticosteroids, azathioprine, mycophenolate mofetil, cyclosporine, tacrolimus, and mTOR inhibitors such as rapamycin and everolimus.
Risk Factors and Frequency for Posttransplantation Cancer
The Israel Penn International Transplant Tumor Registry is the largest and most detailed registry in the world that records non-melanoma skin cancers as the most common cancer in patients after an organ transplant. There are several other cancers that are associated with organ transplants. Additionally, there are other common cancers that have seen a significant increase in organ transplant patients.
- Kaposi sarcoma
- Skin (nonmelanoma, nonepithelial)
- Non-Hodgkin lymphoma
- Liver
- Anus
- Vulva
- Lip
Other common cancers with a significant increase include:
- Lung
- Kidney
- Colon and rectum
- Pancreas
- Hodgkin’s lymphoma
- Melanoma
Signs and Symptoms of Posttransplantation Cancer
Early diagnosis of cancer can often improve the outcomes for patients. However, organ transplant recipients often have a shortened life expectancy and multiple health conditions, making regular check-ups and medical history tracking very important. Typically, cancer develops approximately 3 to 5 years after a transplant and is usually diagnosed at around the age of 40. However, these circumstances can change based on the type of cancer, with lymphoma and Kaposi sarcoma developing sooner and cancers of the epithelial cells occurring later after transplantation.
It’s vital to ask specific questions during history taking. For example, prolonged sun exposure, skin health issues, and the appearance of irregular skin lesions could all suggest possible skin cancer. It’s also been found that continuous smoking and alcohol consumption can lead to aggressive types of cancer like squamous cell malignancy and urinary bladder cancer. If a patient reports fever, weight loss or any neurological disturbance, further checking such as radiological investigations should be performed to rule out Post-transplant lymphoproliferative disorders (PTLD).
If there’s a concern about lower digestive tract bleeding, it is crucial to check the colon to eliminate any chance of cancer. Patients who have received organ transplants usually need more thorough and more frequent medical checks than the general population. During these regular check-ups, probing for potential secondary cancers should be a priority – this includes skin checks, breast checks, a digital rectal examination to check for prostate cancer, and a neurological examination to check for lymphoma in the brain and to rule out PTLD.
Treatment Options for Posttransplantation Cancer
Screening for early signs of cancer can lead to more successful treatments. Here are some specific recommendations for various types of cancer:
1. Breast cancer: Women aged 50 to 69 should have a mammogram each year, which may include a clinical breast exam. Between ages 40 to 49, the benefits of screening aren’t as clear, so it’s up to the patient and their doctor to decide. Women over 70 should get yearly screenings as long as their life expectancy is at least 8 years.
2. Liver cancer: Patients with chronic hepatitis B or C and cirrhosis should have a blood test (AFP) and liver ultrasound every 6 to 12 months.
3. PTLD, a type of disease that can happen after an organ transplant: Patients should have a complete check-up every three months, especially in the first year after the transplant.
Examining the anogenital area (the region comprising the anus and the genitals) early on, including a women’s pelvic exam and cytology studies, can be beneficial. But there isn’t sufficient evidence to recommend anoscopy (inspection of the anus) or biopsies of the anal lining. Additionally, all women over 18 and sexually active girls under 18 should have an annual pelvic exam and Pap smear.
Monitoring skin health is important too, especially for those at higher risk due to their ethnicity, where they live, or if they have HHV, a type of virus. These patients may benefit from more frequent screenings.
Ideally, both the donor and recipient should be thoroughly checked for any signs of pre-existing cancer before the transplant. This can help avoid complications down the line.
Following a transplant, reducing or stopping the use of immunosuppressants (drugs that lower the body’s ability to reject a transplanted organ) can sometimes lead to the regression of certain cancers. This is particularly beneficial for kidney transplant recipients as losing the transplanted kidney is not life-threatening for these patients.
Cancers in the anogenital area that are identified early can be treated with laser therapy, electrocautery (using electric current to destroy the tissue), or a topical drug called fluorouracil. Invasive tumors need more extensive surgical removal.
Visceral cancers (those in organs within the body cavities) are treated with traditional methods such as surgery, radiation therapy, or chemotherapy.
The management of PTLD, which can develop post-transplant, has evolved over time. This might involve reducing immunosuppression, immunotherapy (treatment that uses the immune system to fight cancer), chemotherapy, radiation therapy, or a combination of these. The choice of treatment often depends on the specific type of PTLD. For example, early lesions often only require a reduction in immunosuppression. Some types of PTLD can be treated with a combination of the reduction of immunosuppression and a drug called rituximab. If the treatment doesn’t work, surgical intervention can be considered.
What else can Posttransplantation Cancer be?
When diagnosing certain medical conditions, doctors often have to consider other disorders that might present similar signs and symptoms. This process is known as differential diagnosis:
- PTLD (post-transplant lymphoproliferative disorder): This condition could be mistaken for a throat infection caused by streptococcal bacteria or the “kissing disease” known as mononucleosis, especially in people with weakened immune systems. Another common mimic is lung infection with the fungus Aspergillus which shows up on lung scans just like PTLD.
- Melanoma: Certain types of fungal infections in the mouth can look very much like mucosal melanoma. Doctors often have to track the progression of the lesions and examine their cellular structure to distinguish between the two.
- Skin cancers: Some benign skin conditions, such as keratoacanthoma (a rapid-growing bump that looks like a horn) and solar keratosis (also known as actinic keratosis) caused by sun exposure, can look similar to squamous cell skin cancer. A tissue sample collected during a biopsy helps the doctor tell them apart.
- CNS Lymphoma: Certain viral (like CMV) and parasitic (like Toxoplasma) infections often seen in people with weakened immune systems can cause changes in the brain that are mistaken for CNS (central nervous system) lymphoma. Also, benign conditions in transplanted kidneys, livers, and lungs can mimic post-transplant cancer like conditions. For example, fibrosis (thickening or scarring), kidney infection, and subcapsular hematoma (collection of blood under the outer kidney capsule) can mimic cancer on ultrasound and CT scans. Similarly, liver transplant complications like biliary necrosis and hepatic infarcts can mimic recurrent HCCs, a type of liver cancer, on imaging studies.
What to expect with Posttransplantation Cancer
People who have undergone organ transplants have a higher risk of developing certain types of cancer that can lead to a higher chance of death. The Israel Penn International Transplant Tumor Registry found that, after a solid organ transplant, patients had lower survival rates for certain cancers (such as colon, lung, breast, prostate, and bladder) compared to those who hadn’t had a transplant.
According to this registry, the 1-year survival rate for patients with colorectal, prostate and non-small-cell lung cancer after a transplant were 10%, 40%, and 20%, respectively. In comparison, these survival rates in the general population were 40%, 80%, and 30%, respectively. A separate study by Farrugia et al. showed that the overall risk of death from cancer after a transplant was ten times higher than in individuals of the same age and gender who hadn’t had a transplant.
Possible Complications When Diagnosed with Posttransplantation Cancer
Transplant patients may face challenges, including a reduced quality of life, death, and an increase in healthcare costs due to cancer that develops after transplant.
Main Complications:
- Reduced quality of life
- Potential death
- Increase in healthcare costs
Preventing Posttransplantation Cancer
People who have received organ transplants need to be aware of possible issues that can arise after the procedure, one of them being the increased risk of developing cancer. According to a survey carried out by the National Kidney Foundation, only a third of transplant patients could remember being told about this risk by a health care professional before their transplant. Even fewer (23%) only found out about the potential for developing cancer after they had had the surgery.
This points to a clear need for improved communication with patients about the risks before they have the transplant and during their follow-up visits. It’s especially important to talk to patients about the risks they can control or change. For example, they could be given different medications to stop their body from rejecting the transplant (these are called immunosuppressive drugs), or they could be treated for any viral infections they have. There’s a real chance to prevent cancer developing after a transplant by making sure patients know what to watch out for.
This is why ongoing patient education is so essential. One way to do this is to provide education and tools for patients after the operation. This gives patients the opportunity to take the information on board in their own time, helping to extend the doctor’s knowledge into the patients’ hands.
