Testicular cancer

INTRODUCTION — Testicular cancer occurs when cancer cells develop in one or both of the testicles. Testicles are the male reproductive glands located within the scrotum (show figure 1). The scrotum is a sack of loose skin that contains the testicles and hangs directly below the penis.

Testicular cancer is the most common cancer arising in young men. Fortunately, it has become one of the most curable of all cancers, largely due to advances in medical treatment. More than 95 percent of all men diagnosed with testicular cancer survive their disease.

TYPES OF TESTICULAR CANCER — Approximately 95 percent of testicular cancers develop from a type of cell in the testicle called a germ cell. Thus, they are called testicular germ cell tumors.

Seminoma vs Nonseminomatous germ cell tumor (NSGCT) — There are two major types of testicular germ cell tumors: seminoma and nonseminomatous germ cell tumors (NSGCTs). Approximately one-third of all testicular germ cell tumors are seminomas; the remainder are NSGCGTs. Both seminoma and NSGCT primarily affect men between the ages of 15 and 35 years of age, although seminomas occur in a slightly older group of men (show table 1).

SYMPTOMS — For most men, the first symptom of testicular cancer is a painless lump or swelling in the scrotum. Some men may also experience a dull ache or heavy sensation in the lower abdomen, area around the anus, or scrotum. Pain is the first symptom in about 10 percent of men.

DIAGNOSIS — Men who detect a lump in their testicle should see a healthcare provider as soon as possible. The provider will perform a general examination, with special attention to the breasts (which can become enlarged in some men with testicular cancer), the abdomen (to evaluate the lymph nodes and abdominal organs) and the scrotum. Both testicles will be examined and compared. (See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors").

If testicular cancer is suspected, several tests may be ordered to support the diagnosis. However, the only way to be certain that the diagnosis is testicular cancer is to remove the testicle. Testicular ultrasound — Testicular ultrasound uses sound waves to measure the size and characteristics of the testicle and mass (lump), and can determine whether the mass is inside or outside of the testicle and whether it contains fluid or is a solid mass. Testicular cancers are solid and develop inside the testicle. Often, the ultrasound will strongly suggest the diagnosis of testicular cancer. Orchiectomy — The only way to confirm the diagnosis of testicular cancer is by surgically removing the testicle. This procedure is called a radical inguinal orchiectomy (see "Radical inguinal orchiectomy" below).

STAGING AND PROGNOSTIC CLASSIFICATION — Staging is used to determine if there is spread (metastasis) of the cancer beyond the testicle. Stage I testicular cancer is defined as cancer that is limited to the testis only. Stage II testicular cancer has spread (metastasized) to the retroperitoneal lymph nodes (located in the abdomen). Stage III testicular cancer has spread to other organs (show table 2 and show table 3).

Blood tests and imaging (eg, CT scan) are used in the process of staging.

Blood tests — Substances produced by a testicular cancer (called tumor markers) can be measured in the blood. The three most important markers are: Alpha fetoprotein (AFP) Beta human chorionic gonadotropin (beta-hCG) Lactate dehydrogenase (LDH)

High levels of these tumor markers are suggestive of testicular cancer, and can help determine the specific type of testicular cancer that is present. These markers are also used during and after treatment to monitor a patient's response.

CT scans — Most men with a suspected testicular cancer will undergo a CT scan (sometimes called a CAT scan) of the abdomen and pelvis. A chest x-ray or CT scan of the chest is also commonly done.

These tests are done to determine if the suspected cancer has spread beyond the testicle (metastasized). The most common site of metastasis in testicular cancer is the lymph nodes in the abdomen; metastasis to the lung, liver, bones, and brain is also possible.

Prognostic classification — Men with stage II or III testicular cancer (both seminomas and NSGCTs) can be classified as having a good, intermediate, or poor prognosis (chance of survival and recovery) based upon the stage of disease and particular type of testicular tumor. Men with stage I testicular cancer have an excellent prognosis, and are not included in this classification system.

Following radical inguinal orchiectomy, a physician treats testicular cancer according to the type of tumor (seminoma or nonseminomatous germ cell tumor), the stage of the disease, and the patient's prognosis.

All men with seminoma are classified as having a good or intermediate prognosis. Men with NSGCT may have a good, intermediate, or poor prognosis, depending upon the stage of their disease. Good prognosis — Men with seminoma have a good prognosis if the tumor has not metastasized to organs other than the lungs and if they have a normal AFP serum level.

Patients with NSGCTs have a good prognosis if the tumor is located only in the testicle or area outside or behind the abdominal wall, if the tumor has not metastasized to organs other than the lungs, and if their serum tumor markers are only slightly elevated. Intermediate prognosis — Patients with seminoma have an intermediate prognosis if the tumor has metastasized to organs other than the lungs and their AFP test is normal.

Patients with NSGCTs have an intermediate prognosis if the tumor is found in only one testicle or in the area outside or behind the abdominal wall, if the tumor has not spread to organs other than the lungs, and if serum tumor markers are not significantly elevated. Poor prognosis — Men with NSGCTs are classified as having a poor prognosis if the tumor develops in the center of the chest between the lungs (called the mediastinum), if it has spread to organs other than the lungs, or if any of the serum tumor markers are significantly elevated.

Even for patients with a poor prognosis, approximately one-half are cured with aggressive treatment.

TREATMENT — Treatment of both seminoma and NSGCT generally includes surgery to remove the affected testicle; this surgery is called radical inguinal orchiectomy (see "Radical inguinal orchiectomy" below). The need for further treatment is determined by the type of cancer, the stage of the cancer, and the prognosis. Advances in chemotherapy and radiation therapy, often used in combination with surgery, have improved the outcome for patients with testicular cancer, and approximately 95 percent of patients can be cured.

Radical inguinal orchiectomy — Radical inguinal orchiectomy is not only required for diagnosis, but is also the initial step in treatment for most patients.

Orchiectomy is usually done in an operating room after the patient receives general or epidural anesthesia. A small incision (cut) is made in the groin and the testicle is removed. The standard treatment is to remove the entire affected testicle to avoid the risk of spreading the tumor within the scrotum. Tissue from the testicle is then examined using a microscope.

Chemotherapy

What is chemotherapy? — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. Chemotherapy works by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply. Because most of an adult's normal cells are not actively dividing or multiplying, they are not affected by chemotherapy. However, the bone marrow (where the blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. The side effects of chemotherapy drugs are related to effects on these and other normal tissues (see "Chemotherapy side effects" below).

Most drugs are given intravenously (IV) rather than by mouth. They are not usually taken daily, but periodically, in cycles. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover. For example, a typical chemotherapy regimen could include a one hour IV infusion of two different chemotherapy medications given once every three weeks. This three week period is one cycle of therapy. If this regimen were repeated for a total of three months, four cycles of chemotherapy would be administered.

Adjuvant chemotherapy — The term adjuvant therapy refers to additional anticancer treatment that is given after surgery to eliminate any remaining tumor cells in the body (often termed micrometastases). Adjuvant therapy significantly decreases the chance that the cancer will return (or recur), and also improves the likelihood of surviving cancer. As a result, adjuvant therapy has become an important component of treatment. Modern adjuvant chemotherapy typically involves a combination of two or more drugs; these combinations are referred to as regimens.

Chemotherapy for testicular cancer — Chemotherapy is sometimes used as an adjuvant treatment for men with early stage testicular cancer, as well as for men with more advanced disease. Patients with more advanced stages of cancer and those who have a disease relapse after radiation therapy usually undergo multiple cycles of combination chemotherapy. A cycle of chemotherapy refers to the time it takes to give the drugs and the time required for the body to recover. Combination chemotherapy involves giving more than one drug, which improves the chance of a cure and reduces the chance that the tumor will develop resistance to one chemotherapy drug.

Lymph node removal — The most common sites of spread for testicular cancer are the lymph nodes in the back of the abdomen, called the retroperitoneal lymph nodes. Surgical removal (called retroperitoneal lymph node dissection or RPLND) of these nodes may be needed in the following situations: If the CT scan of the abdomen shows enlarged nodes, raising suspicion that the cancer has spread to this area. For men who have no evidence of enlargement of the retroperitoneal lymph nodes, RPLND may still be performed because a CT cannot determine lymph node involvement in as many as one-third of cases.

There are alternatives to RPLND, including periodic physical examination and CT scans (called surveillance or watchful waiting), the administration of a short course of chemotherapy, or, in the case of seminomas, low-dose radiation therapy directed at the retroperitoneal lymph nodes.

Men with stage II or III testicular cancer may not undergo RPLND at all, or may only have it if there is still cancer present after chemotherapy.

RPLND requires specialized knowledge and training; patients who require this procedure should seek care in a facility where the surgeon is experienced with RPLND. Risks of the procedure depend upon the amount of surgery needed to remove the lymph nodes and whether the patient has undergone chemotherapy; patients are more likely to have complications if they have received chemotherapy.

Radiation therapy — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cancer cells from growing further and causes them to eventually die.

RT for testicular cancer is given as external beam radiation therapy, meaning that the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath or in front of the machine. The high energy beams are directed at the paraaortic lymph nodes, not the scrotum (show figure 2).

Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects.

Radiation therapy (RT) is often recommended after orchiectomy for men with seminoma. RT effectively prevents relapse in over 95 percent of patients with clinical stage I seminoma. RT may also be used after orchiectomy for men with non-bulky stage II seminoma. However, there are potential risks of RT, including impaired fertility, second malignancy, or late cardiac disease (see "Radiation therapy side effects" below). For these reasons, RT is usually reserved for older men, men who could not tolerate chemotherapy, and men who are not good candidates for surveillance.

Surveillance — In some cases, men with small stage I testicular cancers do not require additional treatment after orchiectomy. However, these men do need to follow up regularly with a healthcare provider to monitor for signs or symptoms of relapse. This approach is called surveillance.

Surveillance is only appropriate for men who are motivated to participate in their care and willing to have follow up over a period of years. Men who are not able or willing to undergo this active surveillance may require additional treatment with either radiation therapy or chemotherapy (see "Seminoma" below). During surveillance, men are usually seen every few months for a physical examination, blood tests, and imaging studies (eg, CT scan of the abdomen and pelvis, chest x-ray). This schedule is recommended for the first three to four years, and then visits may become less frequent (eg, twice per year for several years, and then once per year until at least 10 years after diagnosis).

Recommendations

Seminoma — In general, seminomas grow slowly and do not spread rapidly to other areas of the body. About 80 percent of men have an early stage of cancer that is only in the testicle, and about 15 percent have cancer that metastasizes to the retroperitoneal lymph nodes.

Surgery (radical inguinal orchiectomy) is recommended for all men with early stage seminoma. Following surgery, three treatment options are possible, all of which have a cure rate of approximately 98 percent. Treatment options include surveillance (watchful waiting), radiation therapy, and chemotherapy. Retroperitoneal lymph node dissection is used in some situations after chemotherapy, but is not usually performed initially (see "Lymph node removal" above). A short course of chemotherapy or radiation therapy is sometimes used to treat patients with stage I seminoma who are not candidates for active surveillance.

Not all treatments are suitable for all patients; a physician will work with the patient to determine the most appropriate option based upon the individual's situation.

Nonseminomatous germ cell tumors — Surgery (radical inguinal orchiectomy) is recommended for all men with NSGCT. NSGCTs are not as sensitive to radiation therapy as seminomas. NSGCTs are also more likely to spread through the bloodstream to other areas of the body, such as the liver, lungs, and brain. Treatment with one or two cycles of adjuvant chemotherapy, usually with cisplatin and another chemotherapy agent, has a lower initial relapse rate than RPLND. Overall cure rates are similar to that seen with either careful surveillance or RPLND. Although enthusiasm for chemotherapy has been tempered by concerns about its long-term efficacy and adverse effects, one or two cycles of adjuvant chemotherapy is a reasonable option and is not as toxic as longer course of chemotherapy.

Men with stage II and III NSGCT are generally treated with combination chemotherapy following orchiectomy. Men who have a mass remaining after chemotherapy may require surgery to remove it. Patients who require this type of surgical treatment are best treated at a cancer center that treats a high volume of testicular cancer patients.

TREATMENT SIDE EFFECTS AND COMPLICATIONS — Side effects and complications related to treatment depend upon the type of treatment used and the severity of the disease.

Fertility issues — Testicular cancer frequently occurs in younger men who have not begun or completed having children. Treatment with surgery, radiation, or chemotherapy can reduce or eliminate sperm production, causing infertility. For reasons that are not well understood, up to 50 percent of men with testicular cancer have a low number of sperm, even before treatment.

For these reasons, men preparing to have treatment for testicular cancer should consider storing their sperm for future use. The storage process is called semen cryopreservation, and involves storing semen at very low temperatures. Cryopreservation requires that a man give several samples of semen. Ideally, a semen sample should be collected in a clinician's office after masturbation; if this is not possible, the man may be allowed to collect a sample at home in a sterile laboratory container or chemical-free condom. (See "Patient information: Evaluation of the infertile couple"). If possible, collection should be started before surgical removal of the testicle and before chemotherapy or radiation therapy; this allows the greatest number and healthiest sperm to be stored.

Even men with very low sperm counts (before cancer treatment) should be encouraged to store their sperm. Intracytoplasmic sperm injection (ICSI) is a type of in vitro fertilization (IVF) that requires a very small number of sperm. Approximately 30 percent of ICSI procedures result in a viable pregnancy and delivery of an infant.

Men who are unable to store sperm before treatment may still be able to father a child after treatment, depending upon the type and amount of treatment used. Advances in infertility treatment allow 30 and 60 percent of all men who undergo testicular cancer treatment to father a child. (See "Patient information: Treatment of infertility in men").

Chemotherapy side effects — There are a number of side effects and complications that can develop as a result of chemotherapy. These can be divided into acute side effects (that occur during and shortly after treatment) and long-term risks.

Short-term side effects — Men who undergo chemotherapy can have side effects such as fatigue, hair loss, and nausea or vomiting. Nausea can be prevented or treated with oral or intravenous medications, and hair regrows after treatment is completed. Low blood cell counts can occur in the first few weeks of chemotherapy, which can increase the risk of infection. This generally does not require that the dose or schedule of treatment be changed.

Long-term complications — Chemotherapy can cause serious problems in a number of organ systems within the body, especially when given in combination and if multiple cycles of chemotherapy are required. The type and severity of these problems depends upon the type and dose of chemotherapy. A few of the most common include: Impaired kidney function Damage to nerves, causing pain in the arms and feet or hearing loss Damage to blood vessels in the heart, potentially increasing the risk of cardiovascular disease. This typically occurs many years after treatment is completed. Lung inflammation and scarring

Another serious long-term risk of testicular cancer treatment is the development of a second cancer. This is not a metastasis of the testicular cancer, but is a new cancer that develops in the blood or blood forming organs (leukemia), lung, colon, pancreas, bladder, stomach, or other organ system.

Retroperitoneal lymph node dissection — The most common side effect of RPLND is decreased or absent semen with ejaculation. Advances in surgical techniques with nerve-sparing retroperitoneal lymph node dissection have reduced the incidence of this problem. For those men who do have decreased or absent ejaculatory volume, infertility treatments are available.

Radiation therapy side effects — During radiation therapy, fatigue is common but usually not debilitating. Gastrointestinal effects, including nausea, vomiting, increased stool frequency, and rapid gastric emptying, have been described, but are not typical. Anti-nausea medications may be used for control of nausea and vomiting. Suppression of the bone marrow can occur (potentially causing anemia), but is usually mild. Mild tanning of the treated skin occurs in the weeks after radiation.

POST-TREATMENT MONITORING — Relapses of testicular germ cell tumors usually occur within two years of the end of treatment, although they can occur later. As a result, all patients who have been successfully treated for testicular cancer should be monitored for cancer recurrence with blood tests, x-rays, computed tomography (CT) scans, and other imaging tests. Monitoring is generally more frequent in the first few years after treatment is completed.

Blood tests such as the beta-hCG and the AFP are used to monitor for early signs of a relapse. In 30 to 50 percent of patients who relapse, increases in serum tumor markers are the first sign of cancer relapse. A patient who relapses may have no changes in their tumor markers, and for this reason, the combination of blood testing, CT, and x-ray is recommended.

Stage I follow up — The optimal schedule for posttreatment surveillance is controversial. Most experts recommend frequent monitoring with blood tests and imaging studies (eg, x-ray, CT scan) every few months for the first few years, decreasing to twice per year for several years then once per year for the man's lifetime.

After RPLND — For men who undergo retroperitoneal lymph node dissection (RPLND) for limited stage disease, most experts recommend blood testing for tumor markers and a chest x-ray every few months initially, decreasing to once per year after several years. CT scan of the abdomen and pelvis may be done less frequently because of the decreased risk of retroperitoneal relapse.

Advanced disease follow up — Follow up of men with advanced disease is similar to that of men with stage 1 disease. Follow up does not begin until after the man has a complete response to chemotherapy. More intensive surveillance may be recommended for men who undergo chemotherapy for advanced disease followed by an RPLND.

PROGNOSIS — Patients with stage I, good prognosis disease have an excellent chance for cure when treated appropriately (see "Staging and prognostic classification" above). Patients who have an intermediate or poor prognosis also generally respond well to treatment, and require a more aggressive treatment regimen. Even for those with a poor prognosis, approximately one-half can be cured.

CLINICAL TRIALS — Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

www.cancer.gov/clinical_trials/learning/
www.cancer.gov/clinical_trials/
http://clinicaltrials.gov/


SUMMARY Testicular cancer occurs when cancer cells develop in one or both of the testicles. Testicles are the male reproductive glands located within the scrotum (show figure 1). The scrotum is a sack of loose skin that hangs below the penis. There are two types of testicular cancer: seminoma and nonseminomatous germ cell tumors (NSGCTs). More than 95 percent of all men diagnosed with testicular cancer can be cured with treatment. Several tests are needed to diagnose testicular cancer. Testing is also needed to determine if cancer has spread to areas outside the testicle. The only way to know for sure if a man has testicular cancer is to remove the testicle. The tests used to diagnose cancer are also used to choose the best treatment. Treatment always requires surgery to remove the testicle that contains cancer. Some men also have lymph nodes (glands) removed at the same time. Some men require treatment with radiation (similar to an x-ray) or chemotherapy (medicine given into a vein) after surgery, depending upon the type of testicular cancer and whether the cancer has spread to other areas. Treatment for testicular cancer often has side effects, including difficulty with sex and infertility (being unable to father a child). Men should discuss these side effects with their doctor before treatment begins. After cancer treatment, men should see their doctor or nurse regularly. These visits are used to monitor for signs that the cancer has returned.

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. American Cancer Society

(www.cancer.org)
Lance Armstrong Foundation

(www.laf.org)
National Cancer Institute

(www.cancer.gov)
National Institutes of Health: Clinical Trials

(www.clinicaltrials.gov)
National Library of Medicine

(www.nlm.nih.gov/medlineplus/healthtopics.html)
OncoLink

(www.oncolink.com/index.cfm)
Testicular Cancer Resource Center

(http://tcrc.acor.org)
Clinical Trials Links

(www.cancer.gov/clinicaltrials/ or http://clinicaltrials.gov/)
People Living With Cancer: The official patient information

website of the American Society of Clinical Oncology
(www.plwc.org/portal/site/PLWC)


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