Testicular Cancer

Testicular cancer is a disease in which malignant (cancer) cells form in the tissues of one or both testicles (testes), which are located inside the scrotum, a loose bag of skin underneath the penis. The testicles produce male sex hormones and sperm for reproduction. Compared with other types of cancer, testicular cancer is rare, yet testicular cancer is the most common cancer in American males between the ages of 15 and 34. The cause of testicular cancer is unknown. Testicular cancer is highly treatable, even when cancer has spread beyond the testicle. Survival of patients with this cancer has dramatically increased in recent years.

Anatomy and Physiology

Anatomy of the male reproductive and urinary systems. Source: National Cancer Institute

The testicles are comprised of two egg-shaped glands located within the scrotum (a sac of loose skin that lies directly below the penis). The testicles are connected to the rest of the body by the spermatic cords that contain the vas deferens, blood vessels, and nerves that supply the testicles.

The testicles are the male sex glands. They produce testosterone and sperm. Germ cells within the testicles produce immature sperm that travel through a network of tubules (tiny tubes) and larger tubes into the epididymis (a long coiled tube next to the testicles) where the sperm mature and are stored.

Types

Malignant testicular tumors are rare, as white males in the U.S. have only a 0.2% probability of developing this cancer in their lifetime. Approximately 95% of all testicular cancers develop in the germ cells. The two main types of testicular germ cell tumors are seminomas and nonseminomas. These two types grow and spread differently and have different modes of treatment. Nonseminomas tend to grow and spread more quickly than seminomas. Seminomas are more sensitive to radiation.

Many testicular cancers contain more than one type of cell. A testicular tumor that contains both seminomatous and nonseminomatous cells is treated as a nonseminomatous tumor.

Germ cell tumors and subtypes

• Seminoma
  • Anaplastic
  • Spermatocytic
  • Classic

• Non-seminomatous germ cell tumors
  • Embryonal carcinoma
  • Teratoma
  • Yolk sac tumors
  • Choriocarcinomas

Non-germ cell tumors

• Leydig cell tumor
• Lymphoma

Recurrent testicular cancer

Recurrent testicular cancer is cancer that has recurred or returned after it has been treated. The cancer may recur many years after treatment of the initial cancer, and its location may be in the other testicle or in other areas of the body.

Signs and Symptoms

A patient with testicular cancer most commonly presents to the physician with a painless, rapidly enlarging, hard testicle.

These and other symptoms may be caused by testicular cancer. Other conditions may cause similar symptoms. A doctor should be consulted if any of the following problems occur:

• A painless lump or swelling in either testicle
• A dull ache in the lower abdomen or the groin
• A sudden build-up of fluid in the scrotum
• Pain or discomfort in a testicle or in the scrotum
• Enlargement or tenderness of the breasts

Causes

In most cases of testicular cancer, a cause cannot be identified.

Undescended testicles and disorders of sexual differentiation are risk factors for cancer of the testicles.

Diagnosis

Exams and tests

• Physical exam and history: A complete physical exam of the patient is performed. The testicles are examined to check for lumps, swelling, or pain. A history of the patient's symptoms and medical history will be taken.

• Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are directed at the desired internal organs being studied. These waves bounce off different tissues at different intensities making echoes. The echoes are recorded to form a picture of the body tissues called a sonogram.

• Serum tumor marker test: A procedure in which a sample of blood is examined to measure the amounts of certain substances released into the blood by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types of cancer when found in increased levels in the blood. These are called tumor markers. The tumor markers used to detect and follow testicular cancer are:
  • Alpha-fetoprotein (AFP)
  • Beta-human chorionic gonadotropin (Beta-hCG)
  • Lactate dehydrogenase (LDH)

Tumor marker levels are measured before surgery to remove the testicle (radical inguinal orchiectomy) and biopsy to help in the diagnosis of testicular cancer. These tumor markers are also checked after treatment to see whether the tumor has responded to treatment.

• Radical inguinal orchiectomy and biopsy: A procedure to remove the entire testicle through an incision in the groin. A tissue sample from the testicle is then viewed under a microscope to check for cancer cells. (The surgeon does not make an incision through the scrotum to remove the testicle because if there is cancer present, this procedure could cause it to spread into the scrotum and lymph nodes.) If cancer is found, the cell type (seminoma or nonseminoma) is determined in order to help plan treatment.

Determining the cancer stage

After a diagnosis of testicular cancer has been made, further tests are done to find out if cancer cells have spread (metastasized) within the testicles or to other parts of the body.

Exams and tests

The process used to determine if and how extensively the cancer has spread throughout the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

• Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto a film, making a picture of that area inside the body.

• CT scan (CAT scan): A procedure that makes a series of detailed pictures of the body that is usually ordered by the physician to view certain areas at a time. A more detailed view is obtained due to multiple beams delivered from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

• Lymphangiography: A procedure used to x-ray the lymph system. A dye is injected into the lymph vessels in the feet. The dye travels upward through the lymph nodes and lymph vessels, and x-rays are taken to see if there are any blockages. This test helps determine whether cancer has spread to the lymph nodes.

• Abdominal lymph node dissection: A procedure to examine lymph nodes in the abdomen. Lymph nodes are removed and a pathologist checks them for cancer cells. For patients with a nonseminoma, removing the lymph nodes may help stop the spread of disease. Cancer cells in the lymph nodes of patients with a seminomatous cancer can be treated with radiation therapy.

• Radical inguinal orchiectomy and biopsy: A procedure to remove the entire testicle through an incision in the groin. A tissue sample from the testicle is then viewed under a microscope to check for cancer cells. (The surgeon does not cut through the scrotum into the testicle to remove a sample of tissue for biopsy, because if cancer is present, this procedure could cause it to spread into the scrotum and lymph nodes.)

• Serum tumor marker test: A procedure in which a sample of blood is examined to measure the amounts of certain substances released into the blood by organs, tissues, or tumor cells in the body. Certain substances are linked to specific types or cancer when found in increased levels in the blood. These are called tumor markers. The following three tumor markers are used in staging testicular cancer:
  • Alpha-fetoprotein (AFP)
  • Beta-human chorionic gonadotropin (β-hCG)
  • Lactate dehydrogenase (LDH)

Tumor marker levels are measured again, after radical inguinal orchiectomy and biopsy, in order to determine the stage of the cancer. This helps in determining if all of the cancer has been removed or if more treatment is needed. Tumor marker levels are also measured during follow-up as a way of checking if the cancer has come back.

Stages of testicular cancer

The following stages are used for testicular cancer:

Stage 0 (carcinoma in situ)

In stage 0, abnormal cells are found in the tiny tubules where the sperm cells begin to develop. These abnormal cells may become cancer and spread into nearby normal tissue. All tumor marker levels are normal. Stage 0 is also called carcinoma in situ.

Stage I

In stage I, cancer has formed. Stage I is divided into stage IA, stage IB, and stage IS and is determined after a radical inguinal orchiectomy is done.

Stage IA

• In stage IA, cancer is in the testicle and epididymis and may have spread to the inner layer of the membrane surrounding the testicle. All tumor marker levels are normal.

Stage IB

In stage IB, cancer:

• is in the testicle and the epididymis and has spread to the blood or lymph vessels in the testicle; or
• has spread to the outer layer of the membrane surrounding the testicle; or
• is in the spermatic cord or the scrotum and may be in the blood or lymph vessels of the testicle. All tumor marker levels are normal.

Stage IS

In stage IS, cancer is found anywhere within the testicle, spermatic cord, or the scrotum and either:

• all tumor marker levels are slightly above normal; or
• one or more tumor marker levels are moderately above normal or high.

Stage II

Stage II is divided into stage IIA, stage IIB, and stage IIC and is determined after a radical inguinal orchiectomy is done.

Stage IIA

In stage IIA, cancer:

• is anywhere within the testicle, spermatic cord, or scrotum; and
• has spread to up to five lymph nodes in the abdomen, none larger than two centimeters. All tumor marker levels are normal or slightly above normal.

Stage IIB

In stage IIB, cancer is anywhere within the testicle, spermatic cord, or scrotum; and either:

• has spread to up to five lymph nodes in the abdomen; at least one of the lymph nodes is larger than two centimeters, but none are larger than five centimeters; or
• has spread to more than five lymph nodes; the lymph nodes are not larger than five centimeters. All tumor markers levels are normal or slightly above normal.

Stage IIC

In stage IIC, cancer:

• is anywhere within the testicle, spermatic cord, or scrotum; and
• has spread to a lymph node in the abdomen that is larger than five centimeters. All tumor marker levels are normal or slightly above normal.

Stage III

Stage III is divided into stage IIIA, stage IIIB, and stage IIIC and is determined after a radical inguinal orchiectomy is done.

Stage IIIA

In stage IIIA, cancer:

• is anywhere within the testicle, spermatic cord, or scrotum; and
• may have spread to one or more lymph nodes in the abdomen; and
• has spread to distant lymph nodes or to the lungs. The level of one or more tumor markers may range from normal to slightly above normal.

Stage IIIB

In stage IIIB, cancer:

• is anywhere within the testicle, spermatic cord, or scrotum; and
• may have spread to one or more nearby or distant lymph nodes or to the lungs. The level of one or more tumor markers may range from normal to high.

Stage IIIC

In stage IIIC, cancer:

• is anywhere within the testicle, spermatic cord, or scrotum; and
• may have spread to one or more nearby or distant lymph nodes or to the lungs or anywhere else in the body. The level of one or more tumor markers may range from normal to very high.

Treatment

Different types of treatments are available for patients with testicular cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. Before starting treatment, patients may want to think about taking part in a clinical trial.

Three types of standard treatment are used:

Surgery

Surgery to remove the testicle (radical inguinal orchiectomy) and some of the lymph nodes may be done at diagnosis and staging. Tumors that have spread to other places in the body may be partly or entirely removed by surgery.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to increase the chances of a cure, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Lifelong follow-up

Lifelong follow-up exams are very important for men who have had testicular cancer.

Men who have had testicular cancer have an increased risk of developing cancer in the other testicle. A patient is advised to regularly check the other testicle and report any unusual symptoms to a doctor right away.

Lifelong clinical exams are very important. The patient will probably have checkups once per month during the first year after surgery, every other month during the next year, and less often after that.

Experimental therapies

New types of treatment are being tested in clinical trials. These include the following:

High-dose chemotherapy with stem cell transplant

High-dose chemotherapy with stem cell transplant is a method of giving high doses of chemotherapy and replacing blood-forming cells destroyed by the cancer treatment. Stem cells (immature blood cells) are removed from the blood or bone marrow of the patient or a donor and are frozen and stored. After the chemotherapy is completed, the stored stem cells are thawed and given back to the patient through an infusion. These re-infused stem cells grow into (and restore) the body's blood cells.

Treatment options by stage

Stage I testicular cancer

Treatment of stage I testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.

Treatment of a seminoma is usually surgery to remove the testicle, with or without radiation therapy to lymph nodes in the abdomen after the surgery, with lifelong follow-up.

Treatment of a nonseminoma may include the following:

• Surgery to remove the testicle and the associated lymph nodes in the abdomen, with lifelong follow-up.
• Surgery to remove the testicle, followed by chemotherapy and lifelong follow-up.
• Surgery to remove the testicle, with lifelong follow-up.

Stage II testicular cancer

Treatment of stage II testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.

Treatment of seminoma may include the following:

• When the tumor is five centimeters or smaller, treatment is usually surgery to remove the testicle followed by radiation therapy to lymph nodes in the abdomen and pelvis, with lifelong follow-up.
• When the tumor is larger than five centimeters, treatment is usually surgery to remove the testicle followed by combination chemotherapy or radiation therapy to lymph nodes in the abdomen and pelvis with lifelong follow-up.

Treatment of nonseminoma may include the following:

• Surgery to remove the testicle and lymph nodes, with lifelong follow-up.
• Surgery to remove the testicle and lymph nodes, followed by combination chemotherapy and lifelong follow-up.
• Surgery to remove the testicle followed by combination chemotherapy and a second surgery if cancer remains, with lifelong follow-up.
• Combination chemotherapy before surgery to remove the testicle, for cancer that has spread and is thought to be life-threatening.
• A clinical trial of combination chemotherapy instead of removing the lymph nodes.

Stage III testicular cancer

Treatment of stage III testicular cancer depends on whether the cancer is a seminoma or a nonseminoma.

Treatment of seminoma may include the following:

• Surgery to remove the testicle followed by combination chemotherapy. Any tumor remaining after treatment will need lifelong follow-up.
• A clinical trial of a new therapy.
• A clinical trial of high-dose chemotherapy with bone marrow transplant.

Treatment of nonseminoma may include the following:

• Surgery to remove the testicle, followed by combination chemotherapy.
• Combination chemotherapy followed by surgery to remove any remaining tumor. Additional chemotherapy may be given if the tumor tissue removed contains cancer cells that are growing.
• Combination chemotherapy combined with radiation therapy to the brain for cancer that has spread to the brain.
• Combination chemotherapy before surgery to remove the testicle, for cancer that has spread and is thought to be life-threatening.
• A clinical trial of a new therapy.
• A clinical trial of high-dose chemotherapy with bone marrow transplant.

Treatment options for recurrent testicular cancer

Treatment of recurrent testicular cancer may include the following:

• Combination chemotherapy.
• High-dose chemotherapy with bone marrow transplant.
• Surgery to remove cancer that has either:
  • come back more than two years after complete remission; or
  • come back in only one place and does not respond to chemotherapy.
• A clinical trial of a new therapy.

Prevention

Studies suggest that a child with an undescended testicle who has the testicle surgically placed into the scrotum at an earlier age may have a lower risk of testicular cancer. ^[1] The surgery does make detection of testicular cancer easier.

Early Detection

Although detecting testicular cancer early does not prevent it, it does increase the chances of successful treatment. Testicular self-examination is recommended for all men beginning in adolescence, and especially for boys who have previously had surgery for undescended testicles or who have other risk factors.

Testicular self-examination

Some recommend monthly testicular self-examination. Any new or concerning lumps in the scrotum should be evaluated by a practitioner who treats problems of the male genitalia.

The Testicular Cancer Resource Center provides detailed instructions on how to do a testicular self-examination. ^[2]

Chances of Developing Testicular cancer

Testicular cancer is the most common cancer in men 15 to 35 years old.

According to the National Cancer Institute's SEER Database ^[3], it is estimated that 7,920 men will be diagnosed with and 380 men will die of cancer of the testis in 2007. The overall incidence is 5.3 per 100,000 men. One in 277 men will be diagnosed with testicular cancer during their lifetime.

Risk factors

Anything that increases the chance of getting a disease is called a risk factor. Risk factors for testicular cancer include:

• Having had an undescended testicle.
• Having had abnormal development of the testicles.
• Having a personal or family history of testicular cancer.
• Having Klinefelter syndrome or a disorder of sexual differentiation.
• Race, seen more in whites.
• Socioeconomic status.
• exposure to DES, a synthetic form of estrogen, prescribed for some pregnant women before the 1980s^[4]

Related Problems

Complications

Infertility

Certain treatments for testicular cancer can cause infertility that may be permanent. Patients who may wish to have children should consider sperm banking before having treatment. Sperm banking is the process of freezing sperm and storing it for later use.

Secondary malignancy

Patients who are treated with radiation therapy may go on several years later to develop a secondary malignancy, or a new cancer that occurs as a result of treatment of the original tumor.

Comorbidity

Infertility

Men who undergo evaluation for infertility are found to have a higher incidence of testicular cancer than the general population. One study reported an incidence of 0.7% and encouraged the routine use of scrotal ultrasound in men who are requesting evaluation for infertility.^[5]

Undescended testicle

Studies of testicular cancer in men with undescended testicles show that there is an increased risk of cancer in testicles that did not descend normally. One study reports this risk as 5.9 times higher than that in men whose testicles did descend normally.^[6]

There is debate about whether early surgery to bring an undescended testicle into the scrotum actually lowers the chance of developing testicular cancer or simply makes it easier to detect. A recent meta-analysis suggests that surgery before puberty decreases the chance of cancer.^[1]

Clinical Trials

A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment.

Clinical trials are taking place in many parts of the country. Information about ongoing clinical trials is available at:

• Clinical Trials.gov

Or for clinical trials by stage, the NCI web site:

• stage I malignant testicular germ cell tumor
• stage II malignant testicular germ cell tumor
• stage III malignant testicular germ cell tumor
• recurrent malignant testicular germ cell tumor

Expected Outcome

Overall survival rates

According to the American Cancer Society,^[7] the risk of a man who is diagnosed with testicular cancer dying from it is 1 in 5000.

The five-year survival rate for testicular cancer of all types is 96%.

Specific prognoses

Testicular cancer is often curable. The prognosis (chance of recovery) and treatment options depend on the following:

• Stage of the cancer (whether it is in or near the testicle or has spread to other places in the body, and blood levels of AFP, β-hCG, and LDH)
• Type of cancer
• Size of the tumor
• Number and size of retroperitoneal lymph nodes

Testicular tumors are divided into three groups, based on how well the tumors are expected to respond to treatment.

Good prognosis

For nonseminoma, all of the following must be true:

• The tumor is found only in the testicle or in the retroperitoneum (area outside or behind the abdominal wall); and
• The tumor has not spread to organs other than the lungs; and
• The levels of all the tumor markers are slightly above normal.

For seminoma, all of the following must be true:

• The tumor has not spread to organs other than the lungs; and
• The level of alpha-fetoprotein (AFP) is normal. Beta-human chorionic gonadotropin (β-hCG) and lactate dehydrogenase (LDH) may be at any level.

Intermediate prognosis

For nonseminoma, all of the following must be true:

• The tumor is found in one testicle only or in the retroperitoneum (area outside or behind the abdominal wall); and
• The tumor has not spread to organs other than the lungs; and
• The level of any one of the tumor markers is more than slightly above normal.

For seminoma, all of the following must be true:

• The tumor has spread to organs other than the lungs; and
• The level of AFP is normal. β-hCG and LDH may be at any level.

Poor prognosis

For nonseminoma, at least one of the following must be true:

• The tumor is in the center of the chest between the lungs; or
• The tumor has spread to organs other than the lungs; or
• The level of any one of the tumor markers is high.

There is no poor prognosis grouping for seminoma testicular tumors.

History

Statistics

A recent study in the Netherlands found a marked improvement in testicular cancer survival rates. They compared survival in 1970-1979 to 2000-2002. Ten-year relative survival for seminoma TC patients improved from 81% to 95%; for non-seminoma these rates were 54% to 92%. Five-year relative survival for patients with seminoma and non-seminoma five years after diagnosis was 99% and 96%, respectively.^[8]

These advances are mainly due to improvements in cancer chemotherapy over the years. ^[9]

Interesting Facts

Famous people

Professional cyclist Lance Armstrong was diagnosed with testicular cancer at age 25. When he was diagnosed, the cancer had spread to his abdomen, lungs, and brain. Following his treatment with surgery and chemotherapy, he went on to win six consecutive Tours de France. While undergoing treatment, Lance Armstrong founded Livestrong ^[10], the Lance Armstrong Foundation.

Comedian Tom Green also had testicular cancer. He filmed The Tom Green Cancer Special while at MTV.

Notable Experts

Organizations

• National Cancer Institute: Testicular Cancer
• American Urological Association: UrologyHealth.org: Testicular Cancer

Social Issues

Cultural issues

If a man is concerned about his physical appearance, a testicular prosthesis is an option. This is a silicone device that is implanted in the scrotum. The prosthesis is selected to match the size of the other testicle. Risks of this procedure include poor cosmetic result, infection, and pain or discomfort.

References

1. ↑ ^{1.0 1.1} Richie JP. Prepubertal orchiopexy for cryptorchidism may be associated with lower risk of testicular cancer. Urol Oncol. 2008 Mar-Apr;26(2):219-20. Abstract
2. ↑ Testicular Cancer Resource Center How to Do a Testicular Self Examination.
3. ↑ National Cancer Institute: Cancer of the Testis.
4. ↑ Strohsnitter WC, Noller KL, Hoover RN, Robboy SJ, Palmer JR, Titus-Ernstoff L, Kaufman RH, Adam E, Herbst AL, Hatch EE. Cancer risk in men exposed in utero to diethylstilbestrol. J Natl Cancer Inst. 2001 Apr 4;93(7):545-51. Full Text
5. ↑ Phillips N, Jequier AM. Early testicular cancer: a problem in an infertility clinic. Reprod Biomed Online. 2007 Nov;15(5):520-5. Abstract
6. ↑ Strader CH, Weiss NS, Daling JR, Karagas MR, McKnight B. Cryptorchism, orchiopexy, and the risk of testicular cancer. Am J Epidemiol. 1988 May;127(5):1013-8. Abstract
7. ↑ American Cancer Society: What Are the Key Statistics About Testicular Cancer?
8. ↑ Verhoeven RH, Coebergh JW, Kiemeney LA, Koldewijn EL, Houterman S. Testicular cancer: trends in mortality are well explained by changes in treatment and survival in the southern Netherlands since 1970. Eur J Cancer. 2007 Nov;43(17):2553-8. Epub 2007 Oct 18. Abstract
9. ↑ William P. Didusch Society: Racing to Win: Knocking Out Cancer with Chemotherapy.
10. ↑ Lance Armstrong Foundation: Livestrong.

External Links

National Cancer Institute: Testicular Cancer

American Urological Association: UrologyHealth.org: Testicular Cancer

The Testicular Cancer Resource Center: Home Page

American Cancer Society: All About Testicular Cancer

NCI SEER Stat Fact Sheet: Cancer of the Testis

Jason A. Struble Memorial Cancer Fund: Home Page: distributes a video, brochure and card about testicular self-examination.