NORD gratefully acknowledges Liang Cheng, MD, Virgil H. Moon Professor of Pathology and Urology, Director of Molecular Diagnostics and Molecular Pathology Laboratory, Chief of Genitourinary Pathology Division, Director, Fellowship in Urologic Pathology, Indiana University School of Medicine, for assistance in the preparation of this report.
Testicular cancer is an uncommon form of cancer and accounts for only 1% of all cancers in men. However, it is the most common form of cancer in men between the ages of 15 and 35. In the United States, approximately 8,850 men are diagnosed annually. About 95% of testicular cancers are germ cell tumors. Symptoms can be similar to a variety of conditions. It is one of the most treatable forms of cancer and is usually curable with surgery and sometimes radiation therapy or chemotherapy.
Testicular cancer is an uncommon form of cancer that arises in the testicles (testes). The testicles are the two small, egg-shaped glands that are located within the scrotum, which is the loose sack of skin found below the penis. The testicles produce sperm and male sex hormones. Germ cells are the cells that develop into the embryo and later on become the cells that make up the reproductive system of men and women.
Approximately 95% of testicular cancers are germ cell tumors. Germ cells make up the reproductive system of men and women. Most germ cell tumors occur in the testes or ovaries (gonads) or the lower back. When these tumors occur outside of the gonads, they are known as extragonadal tumors. Testicular germ cell tumors are generally split into two main subtypes: seminomas and nonseminomatous germ cell tumors (NSGCTs). NSGCTs are sometimes referred to as nonseminomas. Each type accounts for about 50% of testicular germ cell tumors. There are several different types of nonseminomas including choriocarcinoma, yolk sac tumor, embryonal carcinoma, and teratoma. The 5% of people who develop a non-germ cell tumor may develop lymphoma affecting the testicles or a sex cord-stromal tumor, which is a tumor that arises from the supportive tissues of the testicles.
The initial sign of a testicular tumor is often a firm, painless bump (nodule) or swelling of one testicle. Some individuals have initially developed a dull ache in the abdomen or groin region, or a feeling of heaviness in the scrotum. Sometimes, there may be a collection of fluid in testicles. Discomfort or pain in the testicles may also be present upon touch. Less often, rapid, severe pain may develop in the affected testicle. In rare instances, tenderness or enlargement of the breasts or lower back pain may occur.
In about 10% of affected individuals, the initial signs or symptoms of testicular cancer will develop because the cancer has spread (metastasized) away from the testicles. This can vary depending upon the specific area of the body to which the cancer has spread. This can include a mass in the neck; a cough or difficulty breathing if affecting the lungs; bone pain if affecting the skeleton; nausea and vomiting; unintended weight loss; and gastrointestinal bleeding if affecting the area behind the duodenum, which is the first part of the small intestine (retroduodenal area).
The exact, underlying cause of testicular cancer is not fully understood, and researchers speculate that multiple factors are involved in its development. These factors can include genetic, environmental, infectious, and immunologic factors.
In most people, testicular cancer develops randomly without a family history (sporadically). Cancer is characterized by abnormal, uncontrolled cellular growth that forms a tumor in the testicles and can invade surrounding tissues, possibly spreading (metastasizing) to distant bodily tissues or organs via the bloodstream, the lymphatic system, or other means. In most people with testicular cancer, the cancer arises in germ cells.
Although the causes and genetic aspects of testicular cancer are not fully understood, several risk factors have been identified. Risk factors are anything that increases a person’s risk of developing a condition. Having a risk factor does not mean a person will develop that condition, and people who do not have any risk factors can still develop a condition. Risk factors for testicular cancer include age; race; failure of the testicles to descend into the scrotum, a condition called cryptorchidism; a rare chromosomal disorder called Klinefelter syndrome; defective development of the testicles or ovaries (gonadal dysgenesis); and a family history of testicular cancer. Testicular cancer is more common in men between 15-35 years of age. It occurs more often in Caucasian individuals then in African or Asian Americans. Doctors do not know why cryptorchidism increases the risk of testicular cancer, but this risk remains even after the testicles are surgically lowered into the scrotum, although the risk is lower after surgery. Klinefelter syndrome is a rare chromosome abnormality that affects the development of the testicles.
Genetic factors can play a role in the development of cancer. When a genetic change (variation) in a certain gene or genes occurs in greater frequency in individuals with a specific type of cancer, this may be known as a genetic predisposition. A genetic predisposition means that a person has gene(s) for a disease, but the disease will not develop unless additional genetic or environmental factors are also present.
Many germ cell tumors are characterized by extra copies of chromosome 12p. Chromosomes, which are present in the nucleus of human cells, carry the genetic information. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q” and a narrowed region at which the two arms are joined (centromere). An isochromosome is an abnormal chromosome with identical arms on each side of the centromere. More specifically, in certain cases of testicular cancer, there is duplication of the short arm of chromosome 12. Some researchers suggest that this may lead to abnormal activities on genes that cause germ cells to remain as immature cells called gonocytes. This can lead to overexpression of embryonic transcription factors, which are proteins that promote tumor cell growth, cell survival, and motility.
Variations in single genes is not common in testicular cancer but has been reported. The genes that are most commonly altered in germ cell tumors are KIT, TP53, KRAS/NRAS, and BRAF. KIT, KRAS/NRAS, and BRAF are oncogenes, which control and promote cell growth. TP53 is a tumor suppressor gene, which controls cell division and ensures that cells die at the proper time.
The underlying genetic factors associated with testicular cancer are very complex and more research is necessary for doctors to figure out all the genetic interactions that contribute to the development of these tumors.
Testicular cancer is an uncommon form of cancer and accounts for only 1% of all cancers in men. However, it is the most common form of cancer in men between the ages of 15 and 35. Approximately 8,850 men are diagnosed with testicular cancer each year in the United States.
A diagnosis of testicular cancer is based on identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation, and a variety of specialized tests. It may first be suspect because of a small bump or swelling in or on the one of the testicles. Prompt diagnosis and early treatment is essential in treating testicular cancer.
Clinical Testing and Workup
If testicular cancer is suspected, the affected individual will undergo a scrotal ultrasound. An ultrasound uses reflected sound waves to create pictures of internal organs and other structures and are effective at detecting small areas of cancer that are near the surface of the body (superficially located). An ultrasound of the scrotum can detect a small bump or mass. It can also detect microlithiasis, a common condition in which tiny calcium deposits build up in the testicles. Some studies have shown a strong association between microlithiasis and testicular cancer, but no causative link has been demonstrated.
Routine blood tests will be performed to look for serum tumor makers. A tumor marker is a chemical substance that is elevated in the blood, urine, or body tissues when a specific type of cancer is present. Tumor markers for testicular cancer include alpha-fetoprotein, the beta subunit of human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase. Positive blood tests can help to diagnosis testicular cancer but are not definitive.
A diagnosis can be confirmed with the surgical removal of the affected testicle. This is called a radical orchiectomy. It also serves as the first step of treatment for testicular cancer. In some individuals, doctors may be able to perform surgery that spares the testicle such as a partial orchiectomy.
Routine x-rays (radiographs) and specialized imaging techniques may be performed to determine the extent of the cancer and whether it has spread to other areas of the body. X-rays of the lungs may be recommended. Computerized tomography (CT) scanning is a specialized imaging technique that uses a computer and x-rays to create cross-sectional images of certain tissue structures. A CT scan of the abdomen and pelvic areas can reveal cancer in these areas.
When an individual is diagnosed with testicular cancer, assessment is also required to determine the extent or “stage” of the disease. Staging is important to help characterize the potential disease course and determine appropriate treatment approaches. A variety of diagnostic tests may be used in staging testicular cancer (e.g., blood tests, CT scanning). Testicular cancer can be staged by the American Joint Committee on Cancer (AJCC)/the Union for International Cancer Control (UICC) system, which is based on the tumor, node, and metastasis (TNM) classification system.
A simple staging system for testicular cancer is:
Stage 1: Cancer affects only one testicle
Stage 2: Cancer has spread beyond the testicle to the lymph nodes of the pelvis and abdomen (retroperitoneal area)
Stage 3: Cancer has spread to other organs
The therapeutic management of individuals with testicular cancer may require the coordinated efforts of a team of medical professionals such as physicians who specialize in the diagnosis and treatment of diseases of the urinary system (urologists), physicians who specialize in the diagnosis and treatment of cancer (medical oncologists), physicians who specialize in the diagnosis and treatment of cancer with surgery (surgical oncologists), physicians who specialize in the use of radiation therapy for treatment of cancer (radiation oncologists), oncology nurses, psychiatrists, nutritionists, and other healthcare specialists. Psychosocial support for the entire family is essential as well.
Specific therapeutic procedures and interventions may vary, depending on numerous factors such as disease stage, tumor size, specific testicular cancer subtype (e.g., seminoma versus nonseminomatous germ cell tumor), degree of elevation of tumor serum markers, whether the cancer has spread to other areas of the body, an individual’s age and general health, or other elements. Decisions concerning the use of drug regimens or other treatments should be made by physicians and other members of the healthcare team in careful consultation with the patient based on the specifics of his case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors.
Whenever possible, a baseline sperm count and sperm banking should be offered. A baseline is a starting point used for comparison. This means, prior to diagnosis and therapy, an affected individual’s sperm levels are measured, and this baseline value is used to compare sperm levels during and after treatment. Sperm banking, also known as cryopreservation, is when the sperm is collected, frozen, and stored in case affected individuals want to use the sperm in the future.
Seminomas are generally slow-growing tumors. If testicular cancer is only found in one testicle (localized) and has not spread, then surgery to remove the affected testicular is usually curative. Following surgery, doctors may recommend watchful waiting, radiation therapy, or chemotherapy. Watchful waiting means that a person will be periodically monitored by physicians to detect if the cancer returns or if symptoms develop. Because of the low chance for the cancer to return, many affected individuals decide on watchful waiting.
Surgical removal of one testicle usually does not affect a man’s ability to have a child, sex drive, or ability to have an erection. The risk of infertility is associated with other treatments, specifically radiation therapy or chemotherapy.
Radiation therapy uses x-rays or similar forms of radiation to directly destroy cancer cells. Chemotherapy is the use of certain medications to slow down or stop the growth of cancer cells. Cancer cells grow and divide rapidly, which makes them susceptible to chemotherapy medications. Different combinations of medications may be used; this is called a chemotherapy regimen. When radiation therapy or chemotherapy is used following surgery, this is referred to as adjuvant therapies. This is to make sure that all of the cancer cells in the body are destroyed following the surgical removal of the tumor. Chemotherapy drugs that are approved for testicular cancer include bleomycin, cisplatin, dactinomycin, vinblastine sulfate, and etoposide.
Nonseminomas grow faster and are more likely to spread to other areas of the body then seminomas. They are also less responsive to radiation therapy. All individuals with nonseminomas are recommended to undergo surgical removal of the affected testicle, followed by chemotherapy.
The lymph nodes in pelvic area and the abdomen (retroperitoneal area) is where testicular cancer usually spreads to first. If the cancer has not spread (metastasized) further, then the affected lymph nodes are typically treated by surgical removal (and/or radiation treatment). The surgical removal of lymph nodes may be referred to as a lymph node dissection or lymphadenectomy. This surgery is necessary for individuals with stage 2 testicular cancer and sometimes recommended for all individuals with nonseminomas.
If testicular cancer returns, individuals who have not been treated with chemotherapy will undergo treatment with a chemotherapeutic regimen. If the person has already undergone chemotherapy, they will most likely be treated with a different chemotherapy regimen.
The drug ifosfamide (Ifex) has been approved by the U.S. Food and Drug Administration (FDA) for use, with other drugs, to treat testicular germ cell cancer in individuals who have undergone treatment with two other types of chemotherapy.
Individuals who undergo surgical removal of a testicle are offered the option of an artificial (prosthetic) testicle.
Side Effects and Late Effects
The major side effect of chemotherapy or radiation therapy is the risk of infertility. The surgical removal of one testicle will not affect a person’s ability to have a child. Chemotherapy and radiation therapy both carry the risk of temporarily or permanently lowering sperm counts and causing infertility. Other common side effects include including hair loss, fatigue, and nausea and vomiting.
Because many individuals are young adults when they undergo therapy, there is risk of late effects from cancer therapy. Late effects from cancer therapy refer to various issues that may develop later in life because of the chemotherapy or radiation therapy they received during childhood. These risks can include chronic fatigue; cardiovascular disease; high blood pressure (hypertension); lung disease including scarring of the lungs; reduced production of hormones by the testicles (hypogonadism), which can cause infertility and sexual dysfunction; damage to the nerves including tingling, numbness, or a burning sensation in the feet (peripheral neuropathy); reduced kidney function; hearing loss or a ringing in the ears (tinnitus); or the development of a second, different cancer later in life.
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Cheng L, Ablers P, Berney DM, et al. Testicular cancer. Nat Rev Dis Primers. 2018;4:29. https://www.ncbi.nlm.nih.gov/pubmed/30291251
Leao R, Ahmad AE, Hamilton RJ. Testicular cancer biomarkers: a role for precision medicine in testicular cancer. Clin Genitourin Cancer. 2018;S1558-7674. https://www.ncbi.nlm.nih.gov/pubmed/30497810
Magers MJ, Idrees MT. Updates in staging and reporting of testicular cancer. Surg Pathol Cancer. 2018;11:813-824. https://www.ncbi.nlm.nih.gov/pubmed/30447843
Cheng L, Albers P, Berney DM. Testicular cancer. Nat Rev Dis Primers. 2018;4:29. https://www.ncbi.nlm.nih.gov/pubmed/30291251
Michalski W, Jonas-Gmyrek J, Poniatowska G, et al. Testicular teratomas: a growing problem? Med Oncol. 2018;35:153. https://www.ncbi.nlm.nih.gov/pubmed/30367327
Moirano G, Zugna D, Grasso C, et al. Postnatal risk factors for testicular cancer: the EPSAM case-control study. Int J Cancer. 2017;141:1803-1810. https://www.ncbi.nlm.nih.gov/pubmed/28699204
Mark JR. Testicular Cancer. Merck Manual Online Consumer Version website. January 2018. Available at: https://www.merckmanuals.com/home/kidney-and-urinary-tract-disorders/cancers-of-the-kidney-and-genitourinary-tract/testicular-cancer Accessed December 19, 2018.
Mayo Clinic for Medical Education and Research. Testicular Cancer. April 26, 2018. Available at: https://www.mayoclinic.org/diseases-conditions/testicular-cancer-care/symptoms-causes/syc-20352986 Accessed December 19, 2018.
Canadian Cancer Society. What is Testicular Cancer? Available at: http://www.cancer.ca/en/cancer-information/cancer-type/testicular/testicular-cancer/?region=on Accessed December 19, 2018.
Steele GS, Richie JP, Oh WK, Michaelson MP. Clinical manifestations and staging of testicular germ cell tumors. UpToDate, Inc. 2018 Oct 23. Available at: https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-staging-of-testicular-germ-cell-tumors Accessed December 2018.
Oh WK. Overview of the treatment of testicular germ cell tumors. UpToDate, Inc. 2018 Jan 15. Available at: https://www.uptodate.com/contents/overview-of-the-treatment-of-testicular-germ-cell-tumors Accessed December 2018.
Beard CJ, Vaughn DJ. Approach to the care of long-term testicular cancer survivors. UpToDate, Inc. 2018 Apr 30. Available at: https://www.uptodate.com/contents/approach-to-the-care-of-long-term-testicular-cancer-survivors Accessed December 2018.
Oh WK. Patient education: Testicular cancer (Beyond the Basics). UpToDate, Inc. 2017 Jan 17. Available at: https://www.uptodate.com/contents/testicular-cancer-beyond-the-basics Accessed December 2018.
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