All About Testicular Cancer

Author: OncoLink Team
Last Reviewed: February 22, 2019

What are the testicles?

Testicles (also called testes or gonads) are male sex glands found behind the penis in a sack of skin called the scrotum. These glands are responsible for producing and storing sperm, as well as producing male hormones.

What is testicular cancer?

Testicular cancer begins when cells within the testicle become cancerous and begin to grow out of control. Ninety-five percent of testicular tumors are a type called germ cell tumors. The term "germ cell" refers to cells that make sperm. It is not related to the more common definition of the word "germ," an organism that can cause infections. Other types of tumors found in the testicle are uncommon. 

Testicular cancer is classified as one of two types: seminoma, which accounts for 40% of all testicular cancers, and nonseminoma.  

  • Seminomas: Includes classic or anaplastic seminoma. They generally occur between the ages of 25 and 45 years. Spermatocytic seminoma occurs later in life, with an average age at diagnosis of 65 years. 
  • Nonseminomas: Typically occur between the ages 20 and 30. Four subtypes:
    • Choriocarcinoma.
    • Embryonal carcinoma.
    • Teratoma.
    • Yolk sac tumors. 

The two types behave differently and have different prognoses and treatments, so distinguishing between seminoma and nonseminoma is critical to appropriate treatment. Most testicular tumors contain a mixture of both cell types and are called mixed germ-cell tumors. If a tumor contains any proportion of non seminomatous tissue, it is classified as a nonseminoma. If the tumor contains only seminoma cells, it is called a pure seminoma.

What causes testicular cancer and am I at risk? 

The American Cancer Society estimates that 9,560 new cases of testicular cancer are diagnosed annually. It is not a common cancer diagnosis but the incidence rate has been increasing over the past several decades. The average age of diagnosis is 33.  Testicular cancer occurs more frequently in Caucasians than other races.

The cause of testicular cancer is still unknown, but a few factors have been linked to a higher risk of developing the disease. Not all risk factors have been clearly identified. Rates have been steadily increasing over the past 40 years. Some experts attribute this to environmental factors and estrogen exposure, either in utero or after birth. 

An undescended testicle (also called cryptorchidism) is a condition where the testicle did not move into the scrotum before birth. Surgery can be performed to correct the problem and this may lower the risk of developing testicular cancer, particularly when performed before 6 years of age. While the risk is higher with this history, it is important to remember that only 1-5% of boys born with an undescended testicle will go on to develop testicular cancer, and 90% of cases are in men without this history. Men whose testicles did not develop normally are also at higher risk. 

Men with a first degree relative (father, brother, son) with the disease are at an increased risk of developing the disease.

Klinefelter's Syndrome is a genetic disorder characterized by low levels of male hormones, sterility, breast enlargement, and small testes. This syndrome carries an increased risk of testicular cancer.

Other risk factors include HIV infection and a personal history of testicular cancer.

How can I prevent testicular cancer? 

Unfortunately, the risk factors listed above that increase risk cannot be prevented. The best outcomes for patients with testicular cancer occur when the disease is found early, so early detection is important. This is best done by testicular self-exam. Also, correcting cryptorchidism during boyhood may help decrease risk of developing testicular cancer in adulthood.

What screening tests are available? 

There are no routine screening blood tests for germ cell tumors. Most testicular cancers are found by men themselves, or during a routine exam by a healthcare provider. The best method of examination is known as testicular self-exam or TSE. TSE includes regular inspection and palpation of the testicles. Men (and boys) should be familiar with the normal weight, texture and consistency of their testicles. Examination should be done once a month after a bath or shower, when the scrotal sac is relaxed. Each testicle should be rolled between the thumb and forefinger to examine for any lumps. Any lumps or abnormalities should be reported to a healthcare provider immediately. 

What are the signs of testicular cancer? 

Some men find a lump in their testicle before any other symptoms are present. However, others experience symptoms including: 

  • Swelling in either testicle, or a change in the way it feels. 
  • A feeling of heaviness in the scrotum.
  • A sudden collection of fluid in the scrotum.
  • Pain or discomfort in the scrotum.
  • Breast growth or tenderness: Some germ cell tumors cause an increase in the hormone human chorionic gonadotropin (HCG) which can cause the breasts to grow or become painful.

Remember, these symptoms can be a sign of conditions other than cancer. If any of these symptoms are experienced, a healthcare provider should evaluate them. Early detection of a lump, swelling or other testicular changes is key.

Testicular cancer can be quite aggressive and spread to other parts of the body. Symptoms associated with more advanced testicular cancer include pain in the low back, cough, difficulty catching your breath chest pain, belly pain and confusion or headaches. These symptoms are related to the area of the body where the cancer has spread.

How is testicular cancer diagnosed? 

If your healthcare provider suspects testicular cancer, they may perform several tests to confirm the diagnosis. These tests often include:

  • An ultrasound of the affected testicle and scrotum, to identify and better classify a mass in the testicle. 
  • Blood tests for tumor markers of testicular cancer are measured. These include: alpha-fetoprotein (AFP), Beta human chorionic gonadotropin (Beta-HCG) and lactate dehydrogenase (LDH). While these levels are not elevated in all types of testicular cancer and alone they cannot diagnose the disease, very high levels are rare without the disease and they can help differentiate between types. 

The next step is to discuss fertility preservation with your healthcare provider. Testicular cancer itself can impact the function of both testicles, even if both are not cancerous. Certain treatments for testicular cancer can also impact your fertility. If you are thinking about wanting to father a child in the future, discuss options like a semen analysis (looks at sperm count, sperm activity and shape) and sperm banking. This must be completed before surgery.

Surgery to remove the effected testicle is called an orchiectomy. All patients will require removal of the affected testicle (orchiectomy). An incision is made within the groin, not the scrotum. After the testicle is removed, it is sent to the lab to be review by a pathologist. The pathologist will describe the way the tumor looks under a microscope and can also tell what kind of testicular tumor it is.

Your healthcare provider may also order imaging tests like a chest x-ray, CT scan, MRI, bone scan and/or PET scan to evaluate if the tumor has spread to other parts of the body.

How is testicular cancer staged? 

With these tests, a stage is determined to help decide the treatment plan. The stage of cancer, or extent of disease, is based on information gathered through the various tests done as the diagnosis and work-up of the cancer is being performed. 

Testicular cancer is most commonly staged using the “TN(S)M system.” The TN(S)M system is used to describe many types of cancers. It has four components: T-describing the extent of the "primary" tumor (the tumor itself); N-describing if there is cancer in the lymph nodes; S-describing the level of serum tumor markers and M-describing the spread to other organs (metastases). The staging system is very complex and is provided at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for a patient's cancer. 

How is testicular cancer treated?

The treatment of testicular cancer is determined by the type and stage of the tumor. Nonseminomas tend to be treated more aggressively due to the nature of the tumor.

For many stage I seminomas, surgery alone is typically curative. Some healthcare providers may suggest further treatment with chemotherapy or radiation in stage I seminoma patients. There is no perfect way to know exactly which stage I seminoma patients will benefit from further therapy after surgery and which patients will do just fine without it. The goal of any further therapy is to prevent disease recurrence in abdominal lymph nodes (specifically the para-aortic nodes). Different patients have different baseline risks of this disease recurrence after surgery, and so decisions for therapy vs. observation are incredibly complicated. These complex therapy decisions make it important to be treated by a provider who is familiar with this relatively rare disease.

Surgery

Surgery to remove the effected testicle is called an orchiectomy. All patients will require removal of the affected testicle (orchiectomy). An incision is made within the groin, not the scrotum. For individuals with nonseminomas, a second surgery, called nerve sparing retroperitoneal lymph node dissection (RPLND) may be performed. RPLND removes the lymph nodes where the tumor typically spreads.

In men with nonseminomas who have residual tumor after completion of chemotherapy, surgical resection (removal) is recommended. This is partly due to the fact that many nonseminomas contain some teratoma tissue that is resistant to chemotherapy, but is removable by a skilled surgeon.

Radiation Therapy

The choice of whether to treat with adjuvant (after surgery) radiation depends on the tumor type. Seminomas are very sensitive to radiation. Therefore, para-aortic and/or pelvic lymph nodes can be treated with radiation to prevent disease recurrence (in stage I) or to treat known disease (in stage II). Nonseminomas are not very sensitive to radiation, and therefore are not typically treated with radiation.

The remaining testicle can be shielded during treatment to reduce the amount of scattered radiation during nodal treatment, thereby reducing the risk of losing sperm-producing ability. Sperm counts may fall after radiation, but typically return to normal within one to two years after treatment.

Chemotherapy

Chemotherapy is the use of medications to kill cancer cells and it can be given in either by pill or intravenously. In some cases, chemotherapy is given to patients after surgery to kill any remaining tumor cells in the body. This is often referred to as adjuvant chemotherapy.

The regimen of chemotherapy is decided upon by your healthcare provider and is based on the tumor type and stage, your general health, and your ability to tolerate expected side effects. The most commonly used chemotherapy medications include: cisplatinbleomycinifosfamidepaclitaxelvinblastine, and etoposide, and mesna. In some tumors, an immunotherapy called pembrolizumab may be an option for metastatic testicular cancer. As with surgery, sexuality and fertility issues should be discussed before treatment is started.

In rare cases when testicular cancer is not able to be cured or controlled, high dose chemotherapy is given followed by an autologous stem cell transplant. High dose chemotherapy typically uses combinations of carboplatin, etoposide, paclitaxel, ifosfamide, gemcitabine and oxaliplatin. Cells are then collected from the patient and then reinfused intravenously after the chemotherapy has been given. This therapy is reserved for patients with poor prognostic features and is still being studied in clinical trials. 

Clinical Trials 

There are clinical research trials for most types of cancer, and every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow up Care and Survivorship 

Follow-up testing is an important part of the treatment plan, due to the risk of recurrence or the development of a second tumor. Although most recurrences occur within two years for seminomas, and five years for nonseminomas, some patients experience a recurrence many years later. Thus, ongoing, regular follow-up is very important. This should include: a physical exam by a healthcare provider and abdominal and pelvic CT scans. Your provider may also perform a testicular ultrasound should your physical exam be concerning for recurrence. Your provider may also recommend a chest x-ray or chest CT if symptoms are concerning. The frequency of your follow up visits is dependent on the stage of your disease as well as if you received chemotherapy after surgery. Typically, the later the stage of disease at diagnosis the more frequent your follow up visits will be.

Fear of recurrence, sexuality and reproductive issues, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by testicular cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer. 

Cancer survivorship is a relatively new focus of oncology care. With some 15 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink

Resources for More Information 

The Testicular Cancer Resource Center 

The first website devoted to helping people understand testicular and extra-gonadal germ cell tumors. Provides education, support, treatment information and links to research studies. 

http://tcrc.acor.org/ 

TC Cancer.com 

Provides education, discussion board and personal stories. 

http://www.tc-cancer.com/ 

Testicular Cancer Society 

Dedicated to increasing awareness and education about the disease and providing support for fighters, survivors and caregivers. 

http://www.testicularcancersociety.org/index.html 

Testicular Cancer Awareness Foundation 

Dedicated to improving the lives of those affected by testicular cancer; educating others about the importance of awareness and early detection, and continuing to save lives. 

http://www.testicularcancerawarenessfoundation.org/ 

Appendix: AJCC TNM Staging Classification for Testis Cancer, 8thEd., 2017

Primary Tumor(T)

Clinical(c)/Patholgical(p)

Description

cTX, pTX

Primary tumor cannot be assessed.

cT0, PT0

No evidence of primary tumor

cT1s, pT1s

Germ cell neoplasia in situ

pT1*

Tumor limited to testis (including rete testis invasion) without lymphocascular invasion

pT1a

Tumor small than 3 cm in size

pT1b

Tumor 3 cm or larger in size

pT2

Tumor limited to testis (including rete testis invasion) with lymphovascular invasion

OR
Tumor invading hilar soft tissue or epididymis or penetrating visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion 

pT3

Tumor directly invades spermatic cord soft tissue with our without lymphovascular invasion

cT4, pT4

Tumor invades scrotum with or without lymphovascular invasion

 *pT1 applies only to per seminoma

Regional Lymph Nodes (N)-Clinical(c)/Pathological(p)

Description

cNx, pNx

Regional lymph nodes cannot be assessed

cN0, pN0

No regional lymph node metastasis

cN1

Metastasis with a lymph node mass 2 cm or smaller in greatest dimension
OR
Multiple lymph nodes, none larger than 2 cm in greatest dimension 

pN1

Metastasis with a lymph node mass 2 cm or smaller in greatest dimension and less than or equal to five nodes positive, none larger than 2 cm in greatest dimension 

cN2

Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension
OR
Multiple lymph nodes, any one mass larger than 2 cm but not larger than 5 cm in greatest dimension 

pN2

Metastasis with a lymph node mass larger than 2 cm but not larger than 5 cm in greatest dimension; or more than five nodes positive, none larger than 5 cm; or evidence of extranodal extension of tumor 

cN3, pN3

Metastasis with a lymph node mass larger than 5 cm in greatest dimension 

 

Distant Metastasis(M)

Description

M0

No distant metastasis

M1

Distant metastasis

M1a

Non-retroperitoneal nodal or pulmonary metastases

M1b

Non-pulmonary visceral metastases

 

Serum Markers (S)

Description

SX

Marker studies not available or performed

S0

Marker study levels within normal limits

S1

LDH <1.5 x N* and hCG (mIU/mL) <5,000 and AFP (ng/mL) <1,000 

S2

LDH 1.5–10 x N* or hCG (mIU/mL) 5,000-50,000 or AFP (ng/mL) 1,000–10,000 

S3

LDH >10 x N* or hCG (mIU/mL) >50,000 or AFP (ng/mL) > 10,000 

 

Stage Grouping

N

M

S

Stage 0

pT1s

N0

M0

S0

Stage I

pT1-T4

N0

M0

S0

Stage IA

pT1

N0

M0

S0

Stage IB

pT2

pT3

pT4

N0

N0

N0

M0

M0

M0

S0

S0

S0

Stage IS

Any pT/TX

N0

M0

S1-3

Stage II

Any pT/TX

N1-3

M0

SX

Stage IIA

Any pT/TX

Any pT-TX

N1

N1

M0

M0

S0

S1

Stage IIB

Any pT-TX

Any pT-TX

N2

N2

M0

M0

S0

S1

Stage IIC

Any pT-TX

Any pT-TX

N3

N3

M0

M0

S0

S1

Stage III

Any pT-TX

Any N

M1

SX

Stage IIIA

Any pT-TX

Any pT-TX

Any N

Any N

M1a

M1a

S0

S1

Stage IIIB

Any pT-TX

Any pT-TX

N1-3

Any N

M0

M1a

S2

S2

Stage IIIC

Any pT-TX

Any pT-TX

Any pT-TX

N1-3

Any N

Any N

M0

M1a

M1b

S3

S3

Any S

References

American Cancer Society (2018). Testicular cancer. Retrieved from: https://www.cancer.org/cancer/testicular-cancer/about/what-is-testicular-cancer.html, 21 February 2019.

Abeloff, M., Armitage, J., Niederhuber, J., Kastan, M. & McKenna, G. (Eds.): Abeloff’s Clinical Oncology, 5th ed. (2014). Elsevier, Philadelphia, PA. 

Batool, A., Karimi, N., Wu, X. N., Chen, S. R., & Liu, Y. X. (2019). Testicular germ cell tumor: a comprehensive review. Cellular and Molecular Life Sciences, 1-15.

Cheng, L., Albers, P., Berney, D. M., Feldman, D. R., Daugaard, G., Gilligan, T., & Looijenga, L. H. (2018). Testicular cancer. Nature Reviews Disease Primers4(1), 29.

Fung C, Fossa SD, Beard CJ, Travis LB. (2012). Second malignant neoplasms in testicular cancer survivors. Journal of the National Comprehensive Cancer Network : JNCCN, 10(4):545-56. 

Gilligan TD, Seidenfeld J, Basch EM, et al.(2010). American Society of Clinical Oncology Clinical Practice Guideline on uses of serum tumor markers in adult males with germ cell tumors. Journal of Clinical Oncology, 10;28(20):3388-404. 

Haugnes HS, Bosl GJ, Boer H, Gietema JA, Brydoy M, Oldenburg J, et al. (2012). Long-term and late effects of germ cell testicular cancer treatment and implications for follow-up. Journal of Clinical Oncology, 30(30):3752-63. 

Heidenreich, A., & Pfister, D. (2018). Postchemotherapy Retroperitoneal Lymph Node Dissection in Advanced Germ Cell Tumors of the Testis. Urologic Oncology, 1-15.

Ilic, Dragan, and Marie L. Misso. Screening for testicular cancer. Cochrane Database Syst Rev 2 (2011). 

National Comprehensive Cancer Network (2018). Testicular cancer. Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf(log-in required), 21 Feb 2019.

Nichols CR, Roth B, Albers P, Einhorn LH, Foster R, Daneshmand S, et al. Active surveillance is the preferred approach to clinical stage I testicular cancer. Journal of Clinical Oncology. 2013. 31(28):3490-3. 

Paoli, D., Pallotti, F., Lenzi, A., & Lombardo, F. (2018). Fatherhood and Sperm DNA Damage in Testicular Cancer Patients. Frontiers in endocrinology9, 506.

Rossen P, Pedersen AF, Zachariae R, von der Maase H. (2012). Sexuality and body image in long-term survivors of testicular cancer. European journal of cancer, 48(4):571-8. 

Semaan, A., Haddad, F. G., Eid, R., Kourie, H. R., & Nemr, E. (2019). Immunotherapy: last bullet in platinum refractory germ cell testicular cancer. Future Oncology15(5), 533-541.

Sheth KR, Sharma V, Helfand BT, Cashy J, Smith K, Hedges JC, et al. (2012). Improved fertility preservation care for male patients with cancer after establishment of formalized oncofertility program. The Journal of urology, 187(3):979-86. 


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