Risk factors

Testicular cancer is generally found in young men. The exact cause of testicular cancer is unknown and many men without risk factors develop testicular cancer. Strong connections between certain lifestyles, habits or activities, such as bike riding, have not been made with testicular cancer. Injuries and strains will not increase the risk of developing testicular cancer.

• Age: Young men between the ages of 15-35 are at the highest risk for testicular cancer. However, it can occur in men of any age.
• Race: Testicular cancer is 4.5 times more common in white men verses black men. The risk for Hispanics, American Indians and Asians falls between that of white and black men.
• Non-Descending Testicle (Cryptochidism): Normally, after birth, the testicles descend from inside the abdomen down into the scrotum. In some men one or both testicles fail to descend into the scrotum. Men with a history of a non-descending testicle are 3 to 17 times more likely to develop testicular cancer than men whose testicles descended normally. Surgery to correct the non-descended testicle (orchiopexy) may not reduce the risk of testicular cancer but may allow for better observation of the testicle for abnormalities.
• Gonadal Dysgenesis: Abnormal development of a gonad (testicle) which is usually part of a genetic syndrome increases the risk of testicular cancer.
• Klinefeter Syndrome: A genetic syndrome where males are born with an extra X chromosome increases the risk of testicular cancer.
• Personal or family history of testicular cancer: Having a father, brother or uncle with testicular cancer may slightly increase one’s risk of developing testicular cancer.
• Weaker evidence suggests that infertility, testicular atrophy, twinship or abnormal semen parameters may increase one’s risk for testicular cancer.
• Carcinoma in situ (CIS) also called intratubular germ cell neoplasia: The presence of carcinoma in situ in the testicle increases the risk for testicular cancer.

Causes

The exact cause of most testicular cancers is not known. But scientists have found that the disease is linked with a number of other conditions.

Researchers are learning how certain changes in a cell’s DNA can cause the cell to become cancer. Genes tell our cells how to function. They are packaged in chromosomes, which are long strands of DNA in each cell. Most cells in the body have 2 sets of 23 chromosomes (one set of chromosomes comes from each parent). Cancers can be caused by changes in chromosomes that turn on oncogenes or turn off tumor suppressor genes.

Most testicular cancer cells have extra copies of a part of chromosome 12 (called isochromosome 12p or i12p). Some testicular cancers have changes in other chromosomes as well, or even abnormal numbers of chromosomes (often too many). Scientists are studying these DNA and chromosome changes to learn more about which genes are affected and how this might lead to testicular cancer.

Statistics

Testicular cancer is the most common form of cancer in men 15-35 years old.

Each year, approximately 8,850 men will be diagnosed with testicular cancer and approximately 410 men will die from the disease. That averages out to every hour of every day one man is diagnosed with testicular cancer.

Testicular cancer strikes approximately 6 in 100,000 men per year and 1 in 300,000 men per year will die from the disease. To better understand these numbers, 1 in 250 men will be diagnosed with testicular cancer at some point in their lifetime.

Because testicular cancer usually can be treated successfully, a man’s lifetime risk of dying from this cancer is VERY LOW: about 1 in 5,000

But the key is early detection. When testicular cancer is diagnosed in early stages, meaning the cancer is confined to the testis, the 5-year survival rate is 99%. When the cancer has spread to regional lymph nodes the 5-year survival rate drops to 96%. If the cancer has metastasized (spread) to distant areas the 5-year survival rate is 71%.

Unfortunately, half of all men diagnosed with testicular cancer do not seek medical attention until after the cancer has spread to other areas of the body.

There are currently more than 250,000 men in the U.S. that are testicular cancer survivors.

Testicular cancer accounts for approximately 1% of all cancers in men.

Types

The testicles are made up of many types of cells, each of which can develop into one or more types of cancer. It's important to know the type of cell the cancer started in and what kind of cancer it is because they differ in how they're treated and in their prognosis (outlook).

Doctors can tell what type of testicular cancer by looking at the cells under a microscope.

Germ cell tumors

More than 90% of cancers of the testicle start in cells known as germ cells. These are the cells that make sperm. The main types of germ cell tumors (GCTs) in the testicles are seminomas and non-seminomas.

These types occur about equally. Many testicular cancers contain both seminoma and non-seminoma cells. These mixed germ cell tumors are treated as non-seminomas because they grow and spread like non-seminomas.

• Seminomas. Seminimas tend to grow and spread more slowly than non-seminomas. The 3 sub-types of these tumors are classical (or typical) seminomas, anaplastic, and spermatocytic seminomas.

  • Classical seminoma: More than 95% of seminomas are classical. These usually occur in men between 30-50. Classic seminoma rarely, if ever, occurs in adolescents or infants.

  • Anaplastic Seminoma: 5-10% of all seminoma cases are anaplastic seminomas. It occurs at ages similar to classic seminoma. Anaplastic seminomas are more aggressive than the other seminoma types.

  • Spermatocytic seminoma: This rare type of seminoma tends to occur in older men - the average age is about 65. Spermatocytic Seminomas accounts for 2-12% of all seminoma cases. Spermatocytic tumors tend to grow more slowly and are less likely to spread to other parts of the body than classical seminomas.

    Some seminomas can increase blood levels of a protein called human chorionic gonadotropin (HCG). HCG can be checked with a simple blood test and is considered a tumor marker for certain types of testicular cancer. It can be used for diagnosis and to check how the patient is responding to treatment.

• Non-seminomas. These types of germ cell tumors usually occur in men between their late teens and early 30s. The 4 main types of non-seminoma tumors are embryonal carcinoma, yolk sac carcinoma, choriocarcinoma, and teratoma. Most tumors are a mix of different types (sometimes with seminoma cells too), but this doesn’t change the treatment of most non-seminoma cancers.

  • Embryonal carcinoma: These cells are found in about 40% of testicular tumors, but pure embryonal carcinomas occur only 3% to 4% of the time. When seen under a microscope, these tumors can look like tissues of very early embryos. This type of non-seminoma tends to grow rapidly and spread outside the testicle.

    Embryonal carcinoma can increase blood levels of a tumor marker protein called alpha-fetoprotein (AFP), as well as human chorionic gonadotropin (HCG).

  • Yolk sac carcinoma: These tumors are so named because their cells look like the yolk sac of an early human embryo. Other names for this cancer include yolk sac tumor, endodermal sinus tumor, infantile embryonal carcinoma, or orchidoblastoma.

    This is the most common form of testicular cancer in children (especially in infants), but pure yolk sac carcinomas (tumors that do not have other types of non-seminoma cells in them) are rare in adults. When they occur in children, these tumors usually are treated successfully. But they're of more concern when they occur in adults, especially if they are pure. Yolk sac carcinomas respond very well to chemotherapy , even if they have spread.

    This type of tumor almost always increases blood levels of AFP (alpha-fetoprotein).

  • Choriocarcinoma: This is a very rare and fast-growing type of testicular cancer in adults. Pure choriocarcinoma is likely to spread rapidly to other parts of the body, including the lungs, bones, and brain. More often, choriocarcinoma cells are seen with other types of non-seminoma cells in a mixed germ cell tumor. These mixed tumors tend to have a somewhat better outlook than pure choriocarcinomas, although the presence of choriocarcinoma is always a worrisome finding.

    This type of tumor increases blood levels of HCG (human chorionic gonadotropin).

  • Teratoma: Teratomas are germ cell tumors with areas that, under a microscope, look like each of the 3 layers of a developing embryo: the endoderm (innermost layer), mesoderm (middle layer), and ectoderm (outer layer). Pure teratomas of the testicles are rare and do not increase AFP (alpha-fetoprotein) or HCG (human chorionic gonadotropin) levels. Most often, teratomas are seen as parts of mixed germ cell tumors.

    There are 3 main types of teratomas:

    • Mature teratomas are tumors formed by cells a lot like the cells of adult tissues. They rarely spread. They can usually be cured with surgery, but some come back (recur) after treatment.

    • Immature teratomas are less well-developed cancers with cells that look like those of an early embryo. This type is more likely than a mature teratoma to grow into (invade) nearby tissues, spread (metastasize) outside the testicle, and come back (recur) years after treatment.

    • Teratomas with somatic type malignancy are very rare. These cancers have some areas that look like mature teratomas but have other areas where the cells have become a type of cancer that normally develops outside the testicle (such as a sarcoma, adenocarcinoma, or even leukemia).

Carcinoma in situ

Testicular germ cell cancers can start as a non-invasive form of the disease called carcinoma in situ (CIS) or intratubular germ cell neoplasia. In testicular CIS, the cells look abnormal under the microscope, but they have not yet spread outside the walls of the seminiferous tubules (where sperm cells are formed). Carcinoma in situ doesn’t always progress to invasive cancer.

It's hard to find CIS before it becomes an invasive cancer because it generally doesn't cause symptoms or form a lump that you or the doctor can feel. The only way to diagnose testicular CIS is to have a biopsy. Sometimes CIS is found by accident when a testicular biopsy is done for another reason, such as infertility.

Experts don’t agree about the best treatment for CIS. Since CIS doesn’t always become an invasive cancer, many doctors in the United States consider observation (watchful waiting) to be the best treatment option.

When CIS of the testicle becomes invasive, its cells are no longer just in the seminiferous tubules, they've grown into other structures of the testicle. These cancer cells can then spread either to the lymph nodes (small, bean-shaped collections of white blood cells) through lymphatic vessels (tiny fluid-filled tubes that connect the lymph nodes), or through the blood to other parts of the body.

Stromal tumors

Tumors can also start in the supportive and hormone-producing tissues, or stroma, of the testicles. These tumors are known as gonadal stromal tumors. They make up less than 5% of adult testicular tumors, but up to 20% of childhood testicular tumors. The main types are Leydig cell tumors and Sertoli cell tumors.

• Leydig cell tumors. These tumors start in the Leydig cells in the testicle that normally make male sex hormones (androgens like testosterone). Leydig cell tumors can develop in both adults and children. These tumors often make androgens (male hormones), but sometimes they make estrogens (female sex hormones).

  Most Leydig cell tumors are not cancer (benign). They seldom spread beyond the testicle and can often be cured with surgery. Still, a small number of Leydig cell tumors do spread to other parts of the body. These tend to have a poor outlook because they usually don't respond well to chemo or radiation therapy.

• Sertoli cell tumors. These tumors start in normal Sertoli cells, which support and nourish the sperm-making germ cells. Like the Leydig cell tumors, these tumors are usually benign. But if they spread, they usually don’t respond well to chemo or radiation therapy.

Secondary testicular cancers

Cancers that start in another organ and then spread (metastasize) to the testicle are called secondary testicular cancers. These are not true testicular cancers – they don't start in the testicles. They're named and treated based on where they started.

Lymphoma is the most common secondary testicular cancer. Testicular lymphoma is more common in men older than 50 than primary testicular tumors. The outlook depends on the type and stage of lymphoma. The usual treatment is surgical removal, followed by radiation and/or chemotherapy.

Leukemia cells can also form tumors in the testicle. Other cancers that may form secondary testicular tumors include: prostate cancer, lung cancer, melanoma (skin cancer), kidney cancer and other organ cancers.

Signs & symptoms

Men themselves, not doctors, find most testicular cancers as a painless lump or an enlargement or hardening of the testicle, this is why regular self-exams are so important. If you do notice any lumps or changes it is important to see a doctor immediately. Many men with testicular cancer do not feel ill and many times there is no pain involved.

• Other Signs of Testicular Cancer

  • Any enlargement of a testicle
  • A significant loss of size in one of the testicles
  • A feeling of heaviness in the scrotum
  • A dull ache in the lower abdomen, back or in the groin
  • A sudden collection of fluid in the scrotum
  • Pain or discomfort in a testicle or in the scrotum
  • Enlargement or tenderness of the breasts

• Symptoms of advanced testicular cancer

  Even if testicular cancer has spread to other parts of the body, many men might not have symptoms right away. But some men might have some of the following:

  • Low back pain, from cancer spread to the lymph nodes (bean-sized collections of immune cells) in back of the belly.
  • Shortness of breath, chest pain, or a cough (even coughing up blood) may develop from cancer spread in the lungs.
  • Belly pain, either from enlarged lymph nodes or because the cancer has spread to the liver.
  • Headaches or confusion, from cancer spread in the brain.

Early detection

Monthly self-testicular exams are important to notice changes in one’s testicles. Most testicular cancers are found by men themselves or their partner, very few are found by a physician. Self-testicular exams allow you to become familiar with your testicles thus making it easier to notice any changes. If you do notice any changes then see a doctor immediately.

Most testicular cancers can be found at an early stage, when they're small and haven't spread. In some men, early testicular cancers cause symptoms that lead them to seek medical attention. Most of the time a lump on the testicle is the first symptom, or the testicle might be swollen or larger than normal.

Learn how to do a testicular self-exam.

Diagnosis & testing

In order to diagnose testicular cancer a physician will need a full medical history and a physical examination. If a lump or abnormality is detected the doctor will order an ultrasound of the scrotum. If the ultrasound indicates that there is a solid tumor within the testicle then surgery will be required to remove the testicle and test the tumor to see if it is cancerous. Unfortunately, biopsies are not recommended for testicular cancer as the biopsy itself can increase the chances of the cancer spreading to other areas of the body. If the tumor is determined to be cancerous then other tests will be ordered such as a chest x-ray, CT scan and blood work in order to determine how advanced the cancer is and if it has spread.

• Physical Exam: Your physician will examine your testicles by gently rolling them between two fingers and thumb to identify any abnormal lumps. Your physician may also check your groin area, abdomen, armpits and neck to look for swollen lymph nodes. The doctor may also exam you for breast tenderness or enlargement and listen to your lungs.
• Scrotal Ultrasound: The scrotal ultrasound is a painless non-invasive procedure in which high frequency sound waves are used to produce images of inside the scrotum and testicles. It is the same technology that is used in pregnant women when they get a sonogram. The images will show if there are any solid masses, swelling or fluid collections within the scrotum.
• Radical Orchiectomy: Orchiectomy means removal of one or both of the testicles. Radical means that the removal is done by making an incision high up in the groin area. The incision is not made on the scrotum itself. The reason the testicle is removed from higher up is so that there are no changes made to the lymph drainage system. The reason is similar to why the transscrotal biopsy is condemned. Contrary to rumors the removal of a testicle does not affect the ability to achieve an erection and seldom interferes with the ability to father children. Once the testicle is removed a biopsy or a small sample of the tumor is sent to the laboratory to determine if the cells are cancerous (malignant) or non-cancerous (benign).
• Chest X-ray: A front and side chest x-ray are done to see if the cancer has spread to the lungs or chest cavity.
• CT Scan: CT-Scans create three-dimensional pictures of the inside of the body with an x-ray machine. They usually require you to drink a dye and also have a contrast dye injected into you veins in order to see the internal structures better. CT-scans are the most common imaging tests used for testicular cancer. A CT-scan of the abdomen/pelvis is done to see if any lymph nodes in the retroperitoneal area (stomach area) or pelvis have been affected by the cancer. The CT-scan is the most effective imaging test to determine if the cancer has spread and scans may also be done of the chest and/or brain.
• MRI, Bone Scan, PET Scans. CT-scans are the preferred imaging test for testicular cancer patients. However, other tests such as a MRI, Bone Scan or PET scan may be needed in certain situations. If your doctor orders one of the tests you should discuss with him why the test is needed.

• Blood Tests or Tumor Markers: Testicular cancer or germ cell tumors can secrete proteins or hormones into the bloodstream. The levels of these proteins/hormones in the blood can be measured in the laboratory and are often called tumor markers. The levels of the tumor markers can help verify that a diagnosis is correct and/or that a patient is responding to certain treatments. These tumor markers include: AFP (alpha-Fetoprotein), beta-hCG (beta-Human Chorionic Gonadotropin) and LDH (Lactic Acid Dehydrogenase). Not all forms of testicular cancer produce tumor markers or elevate their levels and you can have testicular cancer even if your tumor markers are normal.

  • AFP (alpha-Fetoprotein): AFP may be produced by pure embryonal carcinoma, yolk sac tumor or combined tumors. It is not secreted by pure seminoma or choriocarcinoma. If a diagnosis of seminoma is made but the APF is elevated then the pathology specimen should be reviewed again.
  • Beta-hCG (beta-Human Chorionic Gonadotropin): Beta-hCG is the same substance that helps identify if women are pregnant. However, some testicular cancers can also secrete the substance. These tumors include embryonal carcinoma and choriocarcinoma. Only 5-10% of seminomas secrete beta-hCG and if secreted it is usually done so at lower levels.
  • LDH (Lactic Acid Dehydrogenase): LDH is the least specific tumor marker for testicular cancer. The levels may be elevated for reasons other than testicular cancer. However, monitoring the LDH levels can give your physician more information about your cancer and treatment.
• Transscrotal Biopsy: The procedure of taking a biopsy from outside the scrotum and into the testicle.

Transscrotal Biopsy is to be condemned and SHOULD NOT BE PERFORMED. The lymph system of the testicles drain into the abdomen while the lymph system of the scrotum drains into the lower legs. By doing a biopsy through the scrotum, cancerous cells can be left in the scrotum and the lymph drainage can be altered. This means that any cancer can spread in a way that is not as predictable as normal testicular cancer spread.

Diagnosis & testing

After someone is diagnosed with testicular cancer, doctors will try to figure out if it has spread, and if so, how far. This process is called staging. The stage of a cancer describes how much cancer is in the body (how big the tumor is, how much it has grown and whether it has spread to other areas of the body such as the lymph nodes or other organs). It helps determine how serious the cancer is and how best to treat it.

The earliest stage of testicular cancer is stage 0 (also called germ cell neoplasia in situ, or GCNIS). The other stage groupings range from I (1) through III (3). There is no stage IV (4) testicular cancer. Some stages are split further to cover more details, using capital letters (A, B, etc.).

As a rule, the lower the number, the less the cancer has spread. A higher number, such as stage III, means cancer has spread more. And within a stage, an earlier letter means a lower stage -for example stage IIa is somewhat less severe that stage IIb..

The staging of testicular cancer follows guidelines set up by the American Joint Committee on Cancer (AJC) and the International Union Against Cancer. Staging follows a TNM system (Tumor, Nodes, Metastasis, Serum Tumor Markers) which is based on 4 key pieces of information:

• T (Tumor) – The size and extent of the main tumor (How large is the tumor? Has it grown into nearby structures or organs?)
• N (Nodes) – The spread to nearby lymph nodes (Has the cancer spread to nearby lymph nodes ? How many, and how big are they?)
• M (Metastsis) – The spread (metastasis) to distant sites (Has the cancer spread to distant parts of the body? (The most common sites of spread are distant lymph nodes, the bones, the liver, and the lungs.)
• S (Serum) – serum (blood) levels of tumor markers (Are any tumor marker levels higher than normal?)

Once a person’s T, N, M, and S categories have been determined, this information is combined in a process called stage grouping to assign an overall stage.

Most common treatment options

• Active Surveillance: If a patient has early stage testicular cancer and their tumor markers are normal or return to normal after surgery then an active surveillance program may be a treatment option. This option involves regular doctor visits with CT-scans, x-rays and blood work to closely monitor for the cancer returning. This option requires great dedication by the patient and the doctor to follow the surveillance schedule so that any recurrence can be detected early. Many men (70-80%) may be able to avoid additional chemotherapy/radiation after the orchiectomy and active surveillance allows for this option but the follow up schedule does require a lot of dedication and needs to be discussed with your doctor. Some schedules may require check-ups every 1-2 months.

• Radiation Therapy: Radiation therapy uses high-energy beams of radiation to help destroy any cancer cells that were left behind after the orchiectomy. These left over cancerous cells can spread through the lymph system to other areas of the body. The external radiation is aimed at the lymph nodes in the abdominal and/or groin area to kill any cancer cells. Radiation therapy is usually done daily for five days a week for 3-4 weeks. Normal cells are also killed by the radiation and can lead to side effects.

  Side effects of radiation therapy include: fatigue, skin changes/burns, loss of appetite, nausea, diarrhea, stiff joints/muscles. These side effects are usually only temporary and should improve once treatments are over. Radiation therapy can also interfere with sperm production despite the use of shields to reduce the amount of radiation that the remaining testicle receives.

• Chemotherapy: Chemotherapy are drugs that are given intravenously to kill any remaining cancer cells and to keep the cancer from returning. Chemotherapy is usually used more for non-seminomas that seminomas. Chemotherapy is usually given in cycles meaning that it is given daily for 5 days and then none is given for the next two weeks and then the cycle is repeated.

  Chemotherapy also kills healthy cells and can lead to side effects. Side effects of chemotherapy include: nausea, vomiting, hair loss, loss of appetite, fatigue, mouth sores, fever, chills, numbness. Chemotherapy can also interfere with sperm production which can be permanent.

• Retroperitoneal Lymph Node Dissection (RPLND): This is a surgery to remove the retroperitoneal lymph nodes that are located at the back of the abdomen. The surgery involves an incision down the middle of the abdomen to remove the lymph nodes. A RPLND is a complex operation that requires substantial experience and technical skill in order to remove the lymph nodes and reduce the likelihood of side effects. A RPLND should only be done by a surgeon who is highly experienced with this operation.

Complementary and alternative methods

Complementary methods refer to treatments that are used along with your regular medical care. Alternative treatments are used instead of a doctor’s medical treatment. These methods can include vitamins, herbs, and special diets, or other methods such as acupuncture or massage, to name a few.

Only the cancer care team can advise if a complementary or alternative method might be helpful. They can give more information about what is known (or not known) about the method, which can help patients make an informed decision.