Testicular Cancer

Definition/Description

Testicular cancer is cancer in one or both testicles.[1] It is most often found in young men.[1] This type of cancer can be treated and very often cured.[1]

The testicles[1]

  • The testicles (or testes) are part of the male reproductive system.  In adult men, each one is normally a little smaller than a golf ball.  They are held in a sac of skin called the scrotum.  The scrotum hangs beneath the base of the penis.
  • The testicles make the male hormones testosterone.  They also make sperm.  Sperm cells are carried from the testicles through small tubes (the vas deferens) to the seminal vesicles.  Fluid from the vesicles and from the prostate gland is added.  During ejaculation (orgasm), this fluid, now called semen, travels through a tube (the urethra) in the center of the penis and out of the body.
Testicular.JPG
  • The testicles have several kinds of cells.  The different cells may develop into one or more types of cancer.  It is important to know which kind of cell the cancer started from because these types of cancer are treated differently.  They also differ in the chance of survival for the patient (prognosis).

Main types of testicular tumors[1]

  • Germ cell tumors are the most common type of testicular tumors.  Germ cell tumors grow in the cells that make sperm.
  • Stromal tumors grow in other parts of the testicles like the cells that make hormones.
  • Secondary testicular tumors are from cancer that has spread to the testicles from other parts of the body.

Each of the 3 types is explained in more detail below.

Germ cell tumors[1]

  • More than 9 out of 10 of cancers of the testicles start in the germ cells.  As used here, the term "germ" means seed. These are the cells that make sperm.
  • The 2 main types of germ cell tumors are seminomas and nonseminomas.  These 2 types occur about equally. Seminomas and non-seminomas cells look very different when seen under a microscope.
  • Some cancers contain both non-seminoma and seminoma cells.  These are treated as non-seminomas because they grow and spread like non-seminomas.
  • Seminomas[1]
    • Seminomas start from germ cells of the testicle that make sperm.  The 2 main subtypes of these tumors are classical (or typical) seminomas and spermatocytic seminomas.  Doctors can tell them apart by how they look under the microscope.  
    • Classical seminoma: More than 95% of seminomas are classical.  These usually occur in men when they are between their late 30s and early 50s.
    • Spermatocytic seminoma: This rare type of seminoma tends to occur in older men.  The average age of men diagnosed with spermatocytic seminoma is about 55.  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 detected by 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 for response to therapy.
  • Non-seminomas[1]
    • This type of germ cell tumor usually occurs in men between their late teens and early 40s.  There are 4 main types of non-seminoma tumors:
      • Embryonal carcinoma
      • Yolk sac carcinoma
      • Choriocarcinoma
      • Teratoma
      • Most tumors are mixed with at least 2 different types, but this does not change treatment.  All non-seminoma germ cell cancers are treated the same way.
      • Embryonal carcinomas: This type of non-seminoma is present to some degree 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. T his 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 HCG.
      • Yolk sac carcinomas: These 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.
      • Yolk sac carcinoma is the most common form of testicular cancer in children.  When they occur in children, these tumors usually are treated successfully.  When yolk sac tumors develop in adults, however, they are of more concern, especially if they are "pure" (that is, the tumor does not contain other types of non-seminoma cells).  Yolk sac carcinomas respond very well to chemotherapy, even if they have spread.  This type of tumor almost always increases blood levels of AFP.
      • Choriocarcinomas: This is a very rare and aggressive type of testicular cancer that occurs in adults.  These cancers are likely to spread rapidly to distant organs of the body, including the lungs, bone, and brain.  Pure choriocarcinoma does not often occur in the testicles.  More often, choriocarcinoma cells are present with other types of non-seminoma cells in a mixed germ cell tumor.  This type of tumor increases blood levels of HCG.
      • Teratomas: Teratomas are germ cell tumors with areas that, when seen under the microscope, look like each of the 3 layers of a developing embryo: the endoderm (innermost layer), mesoderm (middle layer), and ectoderm (outer layer).  The 3 main types of these tumors are the mature teratoma, immature teratoma, and teratoma with malignant transformation. Pure teratomas do not increase AFP or HCG levels.
        • Mature teratomas are tumors formed by cells similar to cells of adult tissues.  They are generally benign and rarely spread to nearby tissues and distant parts of the body.  They can usually be cured with surgery.
          • Sometimes deposits of mature teratoma are found after chemotherapy to treat a non-seminomatous mixed germ cell tumor is finished.  These may be the part of a tumor that was left behind after chemotherapy has killed the other components of the tumors.  Some experts believe that chemotherapy can change other types of non-seminoma into teratoma.
        • Immature teratomas are less well-developed cancers with cells that look like those of an early embryo.  Unlike mature teratomas, this type is more likely to grow into (invade) surrounding tissues and to spread (metastasize) outside the testicle.  It can also sometimes recur (come back) years after treatment.
        • Teratoma with malignant transformation is a very rare cancer.  These cancers have some areas that look like mature teratomas but have other areas where the cells have become a type of cancer that develops outside of the testicle, in tissues such as muscles, glands of the lungs or intestines, or the brain.
  • Carcinoma in situ[1]
    • Testicular germ cell cancers may begin as a non-invasive form of the disease called carcinoma in situ (CIS) or intratubular germ cell neoplasia.  Carcinoma in situ may not always progress to invasive cancer.  Researchers have estimated that it can take about 5 years for CIS to progress to the invasive form of germ cell cancer.
    • It is hard to find CIS before it develops into invasive cancer because it generally causes no symptoms and often does not form a lump that you or the doctor can feel.  The only way to diagnose testicular carcinoma in situ is to have a biopsy. Some cases are found incidentally (by accident) in men who have a testicular biopsy for some other reason, such as infertility. 
    • When a testicular tumor like CIS becomes invasive, its cells are no longer just in the seminiferous tubules (where sperm cells are formed) but have 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 that fight infection) through lymphatic channels (fluid-filled vessels that connect the series of lymph nodes), or through the blood circulation to other parts of the body.

Stromal tumors[1]

  • Tumors can also develop 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 2 main types are Leydig cell tumors and Sertoli cell tumors.
    • Leydig cell tumors: These generally benign tumors develop from the Leydig cells in the testicle that normally produce male sex hormones (androgens like testosterone).  Leydig cell tumors can develop in both adults (75% of cases) and children (25% of cases).  They often produce androgens but sometimes produce estrogens (female sex hormones).
      • Most Leydig cell tumors do not spread beyond the testicle and are cured with surgery.  Sometimes, however, these tumors do spread to other parts of the body.  If they do metastasize, Leydig cell tumors have a poor prognosis because they usually do not respond well to chemotherapy or radiation therapy.
    • Sertoli cell tumors: These tumors develop from normal Sertoli cells, which support and nourish the sperm-producing germ cells.  Like the Leydig cell tumors, they are usually benign.  However, if they spread, they tend to be resistant to chemotherapy and radiation therapy.

Secondary testicular tumors[1]

  • Secondary testicular tumors are those that start in another organ and then spread to the testicle.  Lymphoma is the most common secondary testicular cancer.  Testicular lymphoma is more common than primary testicular tumors in men older than 50.  Their prognosis depends on the type and stage of lymphoma.  The usual treatment is surgical removal, followed by radiation and/or chemotherapy.  In boys with acute leukemia, the leukemia cells can sometimes form a tumor in the testicle.
  • Cancers of the prostate, lung, skin (melanoma), kidney, and other organs also can spread to the testicles.  The prognosis for these cancers is usually poor because these cancers generally spread widely to other organs as well.  Treatment depends on the specific type of cancer.

The TNM staging system[1]

  • A staging system is a standardized way for your cancer care team to summarize and describe the extent of your cancer. Testicular cancer is staged using the TNM system created by the American Joint Committee on Cancer (AJCC).
  • The staging system of testicular cancer contains 4 key pieces of information:
    • T refers to how much the primary tumor has spread to tissues next to the testicle.
    • N describes how much the cancer has spread to regional (nearby) lymph nodes.
    • M indicates whether the cancer has metastasized (spread to distant lymph nodes or other organs of the body).
    • S indicates the serum levels of certain proteins (tumor markers) that are produced by some testicular cancers.
  • Primary tumor (T)[1]
    • TX: The primary tumor cannot be assessed
    • T0: There is no evidence of primary tumor
    • Tis: Carcinoma in situ (noninvasive cancer cells)
    • T1: The tumor has not spread beyond the testicle and the narrow tubules next to the testicles where sperm undergo final maturation (epididymis). Cancer cells are not found inside blood vessels or lymph vessels next to the tumor. The cancer may have grown through the inner layer surrounding the testicle (tunica albuginea) but not the outer layer covering the testicle (tunica vaginalis).
    • T2: Similar to T1 except that the cancer has spread to blood or lymph vessels near the tumor, or the tunica vaginalis
    • T3: The tumor invades the spermatic cord (which contains blood vessels, lymph vessels, nerves, and the vas deferens)
    • T4: The tumor invades the skin surrounding the testicles (scrotum)
  • Regional lymph nodes (N)[1]
    • NX: Regional (nearby) lymph nodes cannot be assessed
    • N0: No spread to regional lymph nodes is seen on x-rays
    • N1: There is spread to at least one lymph node, but no lymph node is larger than 2 cm (about 3/4 inch) in any dimension
    • N2: There is spread to at least one lymph node that is larger than 2 cm but is not bigger than 5 cm (2 inches) in any dimension
    • N3: There is spread at least one lymph node that is larger than 5 cm in any dimension
  • Distant metastasis (M)[1]
    • MX: Distant metastasis cannot be assessed
    • M0: There is no distant metastasis (no spread to lymph nodes outside the area of the tumor or other organs, such as the lungs)
    • M1: Distant metastasis is present
      • M1a: The tumor has metastasized to distant lymph nodes or to the lung
      • M1b: The tumor has metastasized to other organs, such as the liver, brain, or bone
  • Serum tumor markers (S)[1]

    Serum tumor markers and stages.jpg


Prevalence

-The American Cancer Society's most recent estimates for the United States:[1] 

  • about 8,400 new cases of testicular cancer will be diagnosed during 2009.
  • about 380 men will die of testicular cancer

-The rate of testicular cancer has been increasing in many countries, including the United States.[1] 

  • The increase is mostly in seminomas. 
  • Experts have not been able to find reasons for this increase.
  • Lately, the rate of increase has slowed.

-Testicular cancer is not common; a man's lifetime chance of developing testicular cancer is about 1 in 300.[1]

-Because treatment is so successful, the risk of dying from this cancer is very low: about 1 in 5,000.[1]

-Testicular cancer is one of the most curable forms of cancer.[1] 

-According to the National Cancer Institute, the 5-year relative survival rate for all men with this cancer is 95%.[1]

  • If the cancer hasn't spread outside the testicle, the 5-year relative survival rate is 99%.  
  • Even if the cancer has spread to nearby lymph nodes, the 5-year relative survival rate is 96%. 
  • If the cancer has spread beyond the lymph nodes, the 5-year survival rate is around 71%. 
  • More than 170,000 men in the United States have survived testicular cancer.

-Testicular cancer is relatively rare and occurs most often in young men between the ages of 15 and 35 years old, although any male can be affected at any time (including infants).[2]
-Testicular cancer in the most common solid organ tumor in young men.[3]
-Testicular cancer is the second most common malignancy from age 35 to 39 years with a white-to-black incidence ratio of 5 to 1.[3]
-According to the National Cancer Institute’s Surveillance, about 8,000 men are diagnosed with testicular cancer each year (390 deaths annually).[3]
-The incidence of testicular cancer around the world has doubled in the past 30 to 40 years.[3]
-There are considerable geographic and ethnic variations in the global incidence of  testicular cancer.[3]
-The disease mainly affects Western populations, with an increasing incidence since the middle of the twentieth century.[3]
-Average rates in developed areas of the world are six times higher than those in developing areas.[3]
-Approximately 79,200 new cases of testicular cancer were estimated to occur in the United States in 2007.[3]

Characteristics/Clinical Presentation

-The most common initial sign of testicular cancer is enlargement of the testis with diffuse testicular pain, swelling, hardness, or some combination of these findings.[3]

  • The condition may go undetected if no pain is experienced and the male is not periodically performing testicular self-examination.[3]

Clinical Signs and Symptoms

  • A lump in either testicle[2]
  • Any enlargement, swelling, or hardness of a testicle[2]
    • The enlargement may be accompanied by an ache in the abdomen or scrotum or a sensation of heaviness in the scrotum.[3]
  • Significant loss of size in one of the testicles[2]
  • Feeling of heaviness in the scrotum and/or lower abdomen[2]
  • Dull ache in the lower abdomen or in the groin[2]
  • Sudden collection of fluid in the scrotum[2]
  • Pain or discomfort in a testicle or in the scrotum[2]
    • Pain may be the sole presenting symptom in metastasis to the retroperitoneal, cervical, and supraclavicular lymphatic chains.[3]
      • Approximately 20% of all cases have involved lymph nodes.[3]
  • Enlargement or tenderness of the breasts[2]
    • This symptom occurs because certain types of germ cell tumors secrete high levels of a hormone called human chorionic gonadotropin (HCG), which stimulates breast development.[1]
  • Unexpected fatigue or malaise[2]
  • Infertility[2]
  • Metastasis, with little or no local change, is noted in the scrotum.[3]
  • Low back pain (metastases to retroperitoneal lymph nodes) in later stage testicular cancer[2]
    • Up to 21% of men with testicular germ cell cancer have back pain as the primary presenting symptoms.[1]
    • Retroperitoneal primary tumors may present with back pain and/or groin or pelvic pain (psoas muscle invasion).[3]
    • Metastatic testicular cancer can present as back pain (may be the primary presenting complaint), abdominal mass, hemoptysis, or neck or supraclavicular adenopathy.[3]
  • Bone metastasis is a late event, often combined with metastasis to the retroperitoneal lymph nodes, lung, and liver.[3]
    • Even when testicular cancer has spread to other organs, only about 1 man in 4 may have symptoms.[1]
    • If the cancer has spread to the lungs, persistent cough, chest pain, and/or shortness of breath can occur.[2]
      • Hemoptysis (sputum with blood) may also develop.[2]
    • In rare cases, testicular cancer spreads to the brain and can cause headaches.[1]

Symptoms similar to those of testicular cancer[1]

  • A number of non-cancerous conditions, such as testicle injury or inflammation, can produce symptoms similar to those of testicular cancer.
    • Inflammation of the testicle, known as orchitis, can cause painful swelling.
      • The mumps virus causes orchitis in about 1 man in 5 who contracts mumps as an adult.
    • Epididymitis (inflammation of the epididymis) can also cause swelling and pain.
    • Both of these can be caused by viral or bacterial infections.


Associated Co-morbidities/Complications

  • No associated co-morbidities found.
  • The most serious long-term complications of chemotherapy or radiotherapy are cardiovascular toxicity and second malignancies; each has a 25-year risk of approximately 16%.[3]
    • There is an increased incidence of metabolic syndrome in long-term survivors that is most likely caused by the lower testosterone levels.[3]
  • Possible side effects of radiation therapy 
    • Radiation therapy can affect nearby healthy tissue along with the cancer cells.[1]
    • Although uncommon, some men experience a skin reaction like sunburn.[1]
      • This slowly fades away.[1]
    • Other possible side effects include fatigue, nausea, or diarrhea.[1]
    • To reduce the risk of side effects, doctors carefully figure out the exact dose you need and aim the beam as accurately as they can to hit the target.[1]
    • Generally, treatment of testicular cancer uses lower radiation doses than those needed for other types of cancer.[1]
      • Special protective devices are placed over the remaining testicle to help preserve fertility.[1]
  • Possible side effects of chemotherapy
    • Chemotherapy drugs work by attacking cells that are dividing quickly, which is why they work against cancer cells.[1]
    • But other cells in the body, such as those in the bone marrow, the lining of the mouth and intestines, and the hair follicles, also divide quickly.[1]
      • These cells are also likely to be affected by chemotherapy, which can lead to side effects.[1]
    • The side effects of chemotherapy depend on the type and dose of drugs you are given and for how long.[1]
    • These side effects can include:
      • Hair loss[1]
      • Mouth sores[1]
      • Loss of appetite[1]
      • Nausea and vomiting[1]
      • Increased chance of infections (due to low white blood cell counts)[1]
      • Easy bruising or bleeding (due to low blood platelet counts)[1]
      • Fatigue (due to low red blood cell counts)[1]
      • These side effects are usually short-term and go away after treatment is finished.[1]
    • Some of the drugs used to treat testicular cancer can cause long-term side effects.[1]
      • Cisplatin can cause kidney damage.[1]
        • It can also damage nerves, causing hearing loss, numbness or tingling sensations in the hands or feet, and sensitivity to cold or heat.[1]
          • This is called peripheral neuropathy.[1]
            • In most cases this goes away once treatment is stopped, but it may last a long time in some people.[1]
        • Long-term sequelae of cisplatin use may include leukemia, cardiovascular events, and reports that circulating cisplatin can be detected in the plasma as long as 20 years after treatment.[3]
          • Chemotherapy-related cardiovascular toxicity may be the result of both direct endothelial damage induced by cisplatin and indirect hormonal and metabolic changes.[3]
            • People who have had chemotherapy for testicular cancer seem to have a higher risk of heart problems later in life.[1]
            • Several studies have also suggested that this chemotherapy treatment can sometimes cause high blood cholesterol to develop over time, which may later require treatment.[1]
        • Cisplatin-based chemotherapy results in 30% to 50% infertility rates in men with testicular cancer who are treated with chemotherapy.[3]
      • Bleomycin can damage lungs, causing shortness of breath and trouble with physical activity.[1]
    • Other chemotherapy-induced complications include chronic neurotoxicity (50%), permanent ototoxicity and renal function impairment (30%), pulmonary fibrosis (5% to 10% when treated with bleomycin); and late relapse.[3]
    • Development of a second cancer (usually leukemia, related to etoposide) is a very serious but fortunately, a rare side effect.[1]
      • It occurs in less than 1% of testicular cancer patients treated with chemotherapy.[1]
    • In some cases, the doses of the chemotherapy drugs may need to be reduced or treatment may need to be delayed or stopped to prevent the effects from getting worse.[1]

Medications

Chemotherapy

  • Chemotherapy is the use of drugs for treating cancer.[1]
  • The drugs can be swallowed in pill form, or they can be injected by needle into a vein or muscle.[1]
    • To treat testicular cancer, the drugs are usually given into a vein.[1]
  • Doctors give chemotherapy in cycles, with each period of treatment followed by a rest period to allow the body time to recover.[1]
    • Chemotherapy cycles generally last about 3 to 4 weeks.[1]
  • Using 2 or more chemotherapy drugs is often more effective than using any single drug.[1]
  • The main drugs used to treat testicular cancer are:[1]
    • Cisplatin
    • Vinblastine
    • Bleomycin
    • Cyclophosphamide
    • Etoposide
    • Paclitaxel
    • Ifosfamide
    • These drugs are used in various combinations.[1]
    • The chemotherapy regimens most commonly used as the initial treatment for testicular cancer are bleomycin, etoposide, and cisplatin (called BEP), or etoposide and cisplatin (also known as EP).[1]
    • New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, may also be used.[3]

Diagnostic Tests/Lab Tests/Lab Values

Medical history and physical exam

  • If you have signs or symptoms that may suggest testicular cancer, your doctor will want to take a complete medical history to check for risk factors and symptoms.[1]
  • During a physical exam, the doctor will feel the testicles for swelling or tenderness and for the size and location of any lumps.[1]
  • The doctor will also examine your abdomen, lymph nodes, and other parts of your body carefully, looking for any signs the tumor has spread.[1]
  • Often the results of the exam are normal aside from the testicular abnormalities.[1]

Ultrasound of the testicles

  • An ultrasound can help doctors tell if a lump is solid or filled with fluid.[1]
    • Testicular ultrasound is used to differentiate a variety of scrotal disorders besides cancer (e.g., epididymitis, orchitis, hydrocele, or hematocele).[3]
  • This test uses sound waves to produce images of internal organs.[1]
  • A transducer (wand-like instrument) emits the sound waves and picks up the echoes as they bounce off the organs.[1]
  • A computer processes the pattern of echoes to produce an image on a monitor.[1]
    • The echoes from most tumors differ from those of normal tissues.[1]
    • These patterns of echoes also can help distinguish some types of benign and malignant tumors from one another.[1]

Blood tests for tumor markers

  • Some blood tests can help diagnose testicular tumors.[1]
  • Serum tumor markers are increased in 40% to 60% of all cases and may be used to guide treatment and follow-up.[3]
  • Many testicular cancers secrete high levels of certain proteins, such as alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG).[1]
    • When these proteins (called tumor markers) are in the blood, it suggests that there is a testicular tumor.[1]
  • A tumor may also increase the levels of an enzyme called lactate dehydrogenase (LDH).[1]
    • However, LDH levels can also be increased in conditions other than cancer.[1]
  • Non-seminomas often raise AFP and/or HCG levels.[1]
  • Pure seminomas occasionally raise HCG levels but never AFP levels, so any increase in AFP means that the tumor has a non-seminoma component.[1]
  • (Tumors can be mixed and have areas of seminoma and non-seminoma.)[1]
  • A high LDH often (but not always) indicates widespread disease.[1]
  • Sertoli and Leydig cell tumors do not produce these substances.[1]
  • The levels of these proteins may not be elevated if the tumor is small.[1]
  • For more information on the values of the serum tumor markers, please refer to the table in Defintion/Description.

Imaging Tests

  • Chest x-ray
    • This test is done to see if your cancer has spread to your lungs or the lymph nodes in the middle area of the chest known as the mediastinum.[1]
    • If the x-ray result is normal, you probably don't have cancer in your lungs.[1]
    • But most doctors feel a computed tomography (CT) scan can better judge whether the cancer has spread to the chest.[1]
  • Computed tomography (CT) scan
    • The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body.[1]
    • Instead of taking one picture, like a conventional x-ray, a CT scanner takes many pictures of the part of your body being studied as it rotates around you.[1]
    • A computer then combines these pictures into an image of a slice of your body.[1]
    • CT scans are helpful in staging the cancer.[1]
      • They can help tell if your cancer has spread into your lymph nodes, lungs, liver, or other organs.[1]
    • Before the scan, you may be asked to drink a contrast solution and/or get an intravenous (IV) injection of a contrast dye that helps better outline abnormal areas in the body.[1]
    • CT scans are sometimes used to guide a biopsy needle precisely into a suspected metastasis.[1]
      • For this procedure, called a CT-guided needle biopsy, you remain on the CT scanning table while a radiologist advances a biopsy needle through the skin toward the location of the mass.[1]
    • CT scans are repeated until the doctors are confident that the needle is within the mass.[1]
      • A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue) is removed and examined under a microscope.[1]
  • Magnetic resonance imaging (MRI) scan
    • Like CT scans, MRI scans provide detailed images of soft tissues in the body.[1]
      • But MRI scans use radio waves and strong magnets instead of x-rays.[1]
    • The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases.[1]
    • A computer translates the pattern of radio waves given off by the tissues into a very detailed image of parts of the body.[1]
    • A contrast material might be injected just as with CT scans but is used less often.[1]
    • MRI scans are particularly helpful in examining the brain and spinal cord.[1]
  • Lymphangiogram
    • Because of improvements in other imaging tests, lymphangiograms are rarely done today.[1]
    • Most doctors prefer CT scans instead.[1]
    • For a lymphangiogram, a special dye is injected into a lymph vessel in the foot or leg.[1]
      • The dye travels to the lymph nodes.[1]
    • A special monitor displays x-ray images of the lymph system, which doctors can study to detect signs that cancer has spread to the lymph nodes.[1]
    • CT scans are used to examine lymph nodes more frequently than lymphangiograms.[1]
      • However, the technique is sometimes used for patients with early-stage non-seminomas who are being watched for signs of progression before getting more chemotherapy or radiation.[1]
  • Positron emission tomography (PET) scan
    • For a PET scan, radioactive glucose (sugar) is injected into the patient's vein.[1]
      • The amount of radioactivity is very low.[1]
    • Because cancers use sugar much faster than normal tissues, the cancer cells in the body absorb large amounts of the radioactive substance.[1]
    • A special camera can then be used to create a picture of areas of radioactivity in the body.[1]
    • The picture is not finely detailed like a CT or MRI scan, but it can provide helpful information about your whole body.[1]
    • This test can be helpful for spotting small collections of cancer cells.[1]
    • It is sometimes useful for looking at enlarged lymph nodes that remain after chemotherapy.[1]
    • A PET scan may help the doctor decide if they contain scar tissue or active tumor.[1]
    • Often the PET scan is combined with a CT scan.[1]
      • This helps decide if abnormalities seen on the CT scan are cancer or something else.[1]
  • MR lymphography may replace the currently used tomography scanning or MRI used to noninvasively stage retroperitoneal lymph nodes.[3]
  • The American Cancer Society recommends monthly self-exam of the testicles for adolescents and men, starting at age 15.[3]
    • Testicular self-examination is an effective way of getting to know this area of the body and thus detecting testicular cancer at a very early, curable stage.[3]
    • The self-exam is best performed once each month or after a warm bath or shower when the heat has relaxed the scrotum.[3]

Causes/Risks

Causes

  • The etiology of testicular cancer is not well understood.[3]
  • Although the cause is unknown, hormonal balance at various life stages appear to be related.[3]
  • Congenital and acquired factors have been associated with the development of testicular cancer; familial clustering has been observed particularly among siblings.[3]
  • The first susceptibility gene for testicular cancer has been located and named TGCT1 on the long arm of chromosome X, inherited from the mother; its presence increases a man’s risk of testicular cancer by up to 50 times.[3]
  • There is some evidence that cancer stem cells are derived from normal stem cells that have gradually accumulated various genetic defects; a group of tumor-specific antigens known as cancer/testis antigens (CTAs) may be expressed at early stages during embryogenesis in germ cell precursors eventually leading to testicular cancer.[3]
  • A great deal of research is being done to learn more about the causes.[1]
    • During the past few years, researchers have learned a lot about certain changes in chromosomes and DNA that may cause normal testicular germ cells to develop into germ cell tumors.[1]
      • Meiosis is the process by which germ cells with 46 chromosomes develop into sperm or egg cells with 23 chromosomes.[1]
        • Testicular germ cell tumors may form when something abnormal happens during meiosis.
        • Instead of forming normal sperm cells with 23 chromosomes, all 46 chromosomes remain.
        • Usually, these chromosomes become unstable and progressively more abnormal in their shape and number (often between 69 and 82) as the cells continue to divide.
        • Testicular cancer cells often have extra copies of a part of chromosome 12 (this is called isochromosome 12p).
        • Scientists are studying DNA from this chromosome to learn more about exactly what goes wrong during meiosis and how this might be prevented or reversed.
      • Several other abnormal chromosomes and changes in the factors that regulate cell division and the cell cycle have been associated with testicular cancer, both in animals and in humans.
      • All of these changes are being studied to find the true causes of testicular cancer.

Risk Factors

  • The most significant factor in testicular cancer is the association of cryptorchidism (the testes not descending into the scrotum).[3]
    • Although most cancers develop in the undescended testicle, about 1 out of 4 cases occur in the normally descended testicle.[1]
    • The incidence of testicular cancer is 35 times higher in males with a cryptoid testis.[3]
    • Risk is higher than average for boys born with an undescended testicle (cryptorchidism).[2]  The cancer risk for boys with this condition is increased even if surgery is done to move the testicle to the scrotum.[2]
    • In the case of unilateral cryptorchidism, the risk of testicular cancer is increased in the normal testicle as well.[2]  This fact suggests testicular cancer is due to whatever caused the undescended testicle.[2]
  • Having a brother or father with testicular cancer also increases an individual’s risk.[2]
    • If a man has the disease, there is an increased risk that one or more of his brothers or sons will also develop it.[1]
    • However, only about 3% of testicular cancer cases are actually found to occur in families.[1]
    • Most men with testicular cancer do not have a family history of the disease.[1]
  • A previous history of testicular cancer and history of infertility and poor semen quality or infection have been associated with an increased risk of developing testicular cancer.[3]
    • A causal relationship has not been established between infertility and infection and testicular cancer.[3]
    • About 3% or 4% of men who have been cured of cancer in one testicle will eventually develop cancer in the other testicle.[1]
  • Age
    • About 9 out of 10 testicular cancers occur in men between the ages of 20 and 54.[1]
    • But this cancer can affect males of any age, including infants and elderly men.[1]
  • There is now strong evidence that prenatal or postnatal environmental estrogen exposures (e.g., endocrine-mimicking environmental pollutants, pesticides, industrial chemicals, or chemical contaminants in drinking water) contributes to testicular cancer; this remains under further investigation.[3]
  • Other risk factors still under investigation may include mothers who took exogenous estrogen during pregnancy (diethylstilbestrol), scrotal trauma, exposure to high levels of radiofrequency/microwave radiation in radar technicians, first-born sons, and nonidentical twins.[3]
  • Other risk factors may include occupation (e.g., miners, oil and gas workers, leather workers, food and beverage processing workers, janitors, firefighters, utility workers) and HIV infection.[2]
    • Some evidence has shown that men infected with the human immunodeficiency virus (HIV), particularly those with AIDS, are at increased risk.[1]
    • No other infections have been shown to increase testicular cancer risk.[1]
  • Men with Kleinfelter’s syndrome (a sex chromosome disorder characterized by low levels of male hormones, sterility, breast enlargement, and small testes) are also at greater risk of developing testicular cancer.[3]
  • Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, but they are not likely involved in the initiation of the cancer development.[3]
  • Race and ethnicity
    • The risk of testicular cancer among white men is about 5 times that of black men and more than 3 times that of Asian-American and American Indian men.[1]
    • The risk for Hispanics is between that of Asians and non-Hispanic whites.[2]  The reason for this difference is unknown.[2]
    • The testicular cancer rate has more than doubled among white Americans in the past 40 years but has not changed for African Americans.[2]
    • Worldwide, the risk of developing this disease is highest among men living in the United States and Europe and lowest among African and Asian men.[2]


Systemic Involvement

-Men can experience back pain (as well as hip, groin, SI, and sacral pain) caused by referred pain from the male reproductive system.[3]
-Back pain, changes in bladder function, and sexual dysfunction are the most common symptoms associated with male reproductive disorders.[3]
-Metastases occur via the blood or lymph system.[2]
-The most common place for the disease to spread is to the lymph nodes in the posterior part of the abdomen.[2]  Therefore, lower back pain is a frequent symptom of later stage testicular cancer.[3]
-If cancer has spread to the lungs, persistent cough, chest pain, and/or shortness of breath can occur.[2]  Hemoptysis (sputum with blood) may also develop.[2]
-Back pain associated with cancer is usually constant, intense, and worse at night or with weight-bearing activities, although vague, diffuse back pain can be an early sign of non-Hodgkins lymphoma and multiple myeloma.[2]
-Pain with metastasis to the spine may become quite severe before any radiologic manifestations appear.[2]
-Back pain associated with malignant retroperitoneal lymphadenopathy or testicular cancers is characterized as persistent, poorly localized low back pain present at night but relieved by forward flexion.[2]
-Pain may be so excruciating while lying down that the patient can sleep only while sitting in a chair hunched forward over a table.[2]
-Typically systemic back pain is not relieved by recumbency.[2]
-In fact the bone pain of metastasis or myeloma tends to be more continuous, progressive, and prominent when the client is recumbent.[2]
-Beware of the client with acute backache who is unable to lie still.[2]
-Almost all clients with regional or nonspecific backache seek the most comfortable position (usually recumbency) and stay in that position.[2]
-In contrast, individuals with systemic backache tend to keep moving trying to find a comfortable position.[2]
-Back pain that is unrelieved by rest or change in position, or pain that does not fit the expected mechanical or neuromusculoskeletal pattern, should raise a red flag.[2]
-When the symptoms cannot be reproduced, aggravated, or altered in any way during the examination, additional questions to screen for medical disease is indicated.[2]
-Pain at night can signal a serious problem such as tumor, infection, or inflammation.[2]
-Long-standing night pain unaltered by positional change suggests a space-occupying lesion, such as a tumor.[2]
-Systemic back pain may get worse at night, especially when caused by vertebral osteomyelitis, septic discitis, Cushing’s disease, osteomalacia, primary and metastatic cancer, Paget’s disease, ankylosing spondylitis, or tuberculosis (of the spine).[2]

Medical Management (current best evidence)

-The 3 main methods of treatment for testicular cancer are:[1]

  • Surgery
  • Radiation therapy
  • Chemotherapy

Surgery is typically the first treatment for all testicular cancers.[1]

  • Radical inguinal orchiectomy
    • This type of surgery removes the testicle (or testicles) containing the cancer.[1]
    • An incision is made in the groin, and the testicle is taken from the scrotum through the opening.[1]
    • A cut is made through the spermatic cord that attaches the testicle to the abdomen.[1]
    • The surgeon takes special precautions to avoid spreading cancer cells into the surgical wound or dislodging them from the tumor into the bloodstream.[1]
    • All stages of testicular cancer are typically treated with this type surgery.[1]
  • Retroperitoneal lymph node dissection
    • Depending on the type and stage of your cancer, some lymph nodes behind the abdomen may also be removed at the same time or during a second operation.[1]
    • Retroperitoneal lymph node dissection can be a major operation.[1]
      • A large incision is often made to remove these lymph nodes.[1]
      • About 5% to 10% of patients have temporary complications after surgery, such as bowel obstruction or wound infections.[1]
      • This is a difficult and long operation.[1]
    • In some cases, the surgeon can remove lymph nodes through very small skin incisions in the abdomen by using a laparoscope (a narrow, lighted tube, which lets doctors operate on the abdomen without making a large incision and scar).[1]
      • Although laparoscopic surgery seems to be a lot easier for the patient, doctors are unsure if it is as safe and efficient as the open surgery in removing all of the potentially cancerous lymph nodes.[1]
    • Surgery to remove retroperitoneal lymph nodes may damage nearby nerves that control ejaculation.[1]
      • If these nerves are damaged, when a male ejaculates, the semen is not deposited outside the body but rather goes into the bladder.[1]
        • This is known as retrograde ejaculation.[1]
    • This type of surgery does not cause impotence--a man can still have erections and sexual intercourse--but retrograde ejaculation can make it harder to father children.[1]
    • To save the normal ejaculation function, surgeons have developed a type of retroperitoneal lymph node surgery called nerve-sparing surgery that has a very high rate of success in experienced hands.[1] 
      • Nerve-sparing retroperitoneal lymph node dissection is an integral part of testis cancer management strategies for both early and advanced-stage disease.[3]
      • Testicular-sparing management of testicular cancer is an alternative to radial orchiectomy and allows for preservation of sperm and hormonal function without endangering survival rates.[3]
        • Sperm collection and cryopreservation before the initiation of therapy is an available reproductive technology.[3]
          • Men with testicular cancer often have lower than normal sperm counts, which may make it difficult to collect a good sperm sample.[1]
            • Only a few sperm are needed for successful in vitro fertilization.[3]
  • Testicular prosthesis
    • Men with testicular cancer are usually young and may be concerned that their appearance has changed.[1]
    • They may be single and dating and worry about a partner's reaction, or they may be athletic and feel embarrassed by the missing testicle when in locker rooms.[1]
    • Since the operation also removes the cord above the testicle, that side of the scrotum can look and feel empty to them.[1]
    • To restore a more natural look, a man can have a testicular prosthesis surgically implanted in his scrotum.[1]
      • The prosthesis approved for use in the United States is filled with saline (salt water), and it comes in different sizes to match the remaining testicle.[1]
      • When in place, it can look like a normal testicle.[1]
      • There can be a scar after the operation, but it is often partly hidden by pubic hair.[1]

Radiation therapy

  • Radiation therapy uses a beam of high-energy rays (such as gamma rays or x-rays) or particles (such as electrons, protons, or neutrons) to destroy cancer cells or slow their rate of growth.[1]
  • In treating testicular cancer, radiation is used mainly to kill cancer cells that have spread to lymph nodes.[1]
  • Radiation therapy for testicular cancer is delivered by a carefully focused beam of radiation from a machine outside the body.[1]
    • This is known as external beam radiation.[1]
  • The treatment is much like getting an x-ray, but the radiation is more intense.[1]
    • The procedure itself is painless.[1]
  • Before your treatments start, the medical team will take careful measurements to determine the correct angles for aiming the radiation beams and the proper dose of radiation.[1]
  • Each treatment lasts only a few minutes, although the setup time -- getting you into place for treatment -- usually takes longer.[1]
  • In general, radiotherapy is mainly used for patients with seminoma, which is very sensitive to radiation.[1]
  • It does not seem to work well for non-seminomas.[1]
  • Sometimes it is used after orchiectomy (the operation to remove the testicle) and is directed at the lymph nodes at the back of the abdomen (the retroperitoneal lymph nodes).[1]
    • This is to kill any tiny bits of cancer in those lymph nodes that can't be seen.[1]
  • Radiotherapy can also be used to treat small amounts of seminoma that are known to have spread to the nodes (based on changes seen on CT and PET scans).[1]

Chemotherapy

  • Management of testicular cancer has changed substantially in the last 20 years, primarily because of the ability of cisplatin-containing combination chemotherapy to cure advanced disease.[3]
  • Chemotherapy is considered systemic therapy.[1]
    • This means that the drug enters the bloodstream and circulates throughout the body to reach and destroy the cancer cells.[1]
  • Chemotherapy is an effective way to destroy any cancer cells that break off from the main tumor and travel in the bloodstream to lymph nodes or distant organs.[1]
  • Chemotherapy is often used to cure testicular cancer when it has spread outside the testicle or to decrease the risk of cancer coming back after the testicle is removed.[1]
    • It is not used to treat the cancer that is only in the testicle.[1]

High-dose chemotherapy and stem cell transplantation

  • In general, testicular cancers respond well to chemotherapy, but not all cancers are cured.[1]
  • Even though higher doses of chemotherapy might be more effective, they are not given because they could severely damage the bone marrow, which is where new blood cells are formed.[1]
    • This could lead to life-threatening infections, bleeding, and other problems because of low blood cell counts.[1]
  • A stem cell transplant allows doctors to use higher doses of chemotherapy.[1]
  • Blood-forming stem cells are collected from the bloodstream in the weeks before treatment using a special machine.[1]
    • In the past the stem cells were taken from the bone marrow, but this is done less often now.[1]
      • These stem cells are frozen, while the patient receives high-dose chemotherapy.[1]
  • After treatment is finished, the patient gets a transplant of blood-forming stem cells.[1]
  • This type of transplant does not involve surgery--it is actually much like a blood transfusion.[1]
  • The stem cells settle in the bone marrow and start making new blood cells over the next few weeks.[1]

Physical Therapy Management (current best evidence)

-No known physical therapy management exists for testicular cancer.

-Additional resources that patients can find are in the Resources section. 

Differential Diagnosis

-Men can experience back pain (as well as hip, groin, SI, and sacral pain) caused by referred pain from the male reproductive system.[3]
-Back pain, changes in bladder function, and sexual dysfunction are the most common symptoms associated with male reproductive disorders.[3]

Symptoms similar to those of testicular cancer[1]

  • A number of non-cancerous conditions, such as testicle injury or inflammation, can produce symptoms similar to those of testicular cancer.
  • Inflammation of the testicle, known as orchitis, can cause painful swelling.
  • The mumps virus causes orchitis in about 1 man in 5 who contracts mumps as an adult.
  • Epididymitis (inflammation of the epididymis) can also cause swelling and pain.
    • Both of these can be caused by viral or bacterial infections.

Resources

http://www.cancer.org/docroot/HOME/pff/PFF_5.asp

http://www.cancer.org/docroot/ETO/eto_1_3_Bone_Marrow.asp

http://www.cancer.org/docroot/PED/content/PED_2_3X_Do_I_Have_Testicular_Cancer.asp?sitearea=PED

http://www.cancer.org/docroot/MIT/MIT_7_1x_SexualityforMenandTheirPartners.asp

http://www.cancer.org/docroot/ETO/ETO_1_5x_Guide_for_Patients_and_Families.asp

http://www.cancer.org/docroot/ETO/ETO_1_5x_radiation_therapy_guide_for_patients_and_families.asp

www.cancer.gov

www.cancer.org

http://tcrc.acor.org

http://www.mayoclinic.com/health/testicular-cancer/DS00046

Recent Related Research (from Pubmed)

References

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