Note: A separate PDQ summary on Testicular Cancer Screening is also available.

Note: Estimated new cases and deaths from testicular cancer in the United States in 2008:[1]

• New cases: 8,090.
• Deaths: 380.

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Testicular cancer is a highly treatable, often curable, cancer that usually develops in young and middle-aged men. Testicular cancer is broadly divided into seminoma and nonseminoma types for treatment planning because seminomas are more sensitive to radiation therapy. For patients with seminoma (all stages combined), the cure rate exceeds 90%. For patients with low-stage disease, the cure rate approaches 100%.[2]

Tumors that have a mixture of seminoma and nonseminoma components should be managed as nonseminomas. Nonseminomas include embryonal carcinomas, teratomas, yolk sac carcinomas, choriocarcinomas, and various combinations of these cell types. Tumors that appear to have a seminoma histology but that have elevated serum levels of alpha-fetoprotein (AFP) should be treated as nonseminomas. Elevation of the beta subunit of human chorionic gonadotropin (hCG) alone is found in approximately 10% of the patients with pure seminoma.

Risk of metastases is lowest for teratoma and highest for choriocarcinoma, with the other cell types having intermediate risk.

A number of prognostic classification schema are in use for metastatic nonseminomatous testicular cancer and for primary extragonadal nonseminomatous germ cell cancers treated with chemotherapy.[3-5] Most incorporate some or all of the following factors, which may independently predict worse prognosis:

• Presence of liver, bone, or brain metastases.
• Very high serum markers.
• Primary mediastinal nonseminoma.
• Large number of lung metastases.

Even patients with widespread metastases at presentation, including those with brain metastases, may be curable and should be treated with this intent.[6]

Radical inguinal orchiectomy with initial high ligation of the spermatic cord is the procedure of choice in treating a malignant testicular mass.[7] Transscrotal biopsy is not considered appropriate because of the risk of local dissemination of tumor into the scrotum or its spread to inguinal lymph nodes. A retrospective analysis of reported series in which transscrotal approaches had been used showed a small but statistically significant increase in local recurrence rates compared with the recurrence rates when the inguinal approach was used (2.9% vs. 0.4%).[8][Level of evidence: 3iiiDii] Distant recurrence and survival rates, however, were indistinguishable in the two approaches. Local recurrence was similar in patients who did not have scrotal violation, regardless of whether or not additional treatments, such as hemiscrotal radiation therapy, hemiscrotal resection, or inguinal lymph node dissection, were used.

An important aspect of the diagnosis and follow-up of testicular cancer is the use of serum markers. Serum markers include AFP, hCG (measurement of the beta subunit reduces luteinizing hormone cross-reactivity), and lactate dehydrogenase. The serum markers may detect a tumor that is too small to be discovered on physical examination or x-rays. In patients younger than 15 years, approximately 90% of testicular germ cell cancers are yolk sac tumors. In these types of patients, the AFP is elevated at diagnosis and is an excellent indicator of response to therapy and disease status.[9] Serum markers plus chest x-rays are important parts of the monthly checkups for patients after definitive therapy of testicular cancer as well as periodic abdominal computed tomographic (CT) scans for 2 to 3 years. The absence of markers does not mean the absence of tumor. After diagnosis and treatment, patients typically receive follow-up monthly for the first year and every other month for the second year. While the majority of tumor recurrences appear within 2 years, late relapse has been reported, and lifelong marker, radiologic, and physical examination is recommended.[10]

Evaluation of the retroperitoneal lymph nodes, usually by CT scanning, is an important aspect of treatment planning in adults with testicular cancer.[11,12] Patients with a negative result however, have a 25% to 30% chance of having microscopic involvement of the lymph nodes. For seminoma, some physicians think that knowing the results of both the lymphangiogram and the CT scan is important for treatment planning. For nonseminoma, the inaccuracy of both is a problem, and frequently surgical staging is required. About 25% of patients with clinical stage I nonseminomatous testicular cancer will be upstaged to pathologic stage II with retroperitoneal lymph node dissection (RPLND), and about 25% of clinical stage II patients will be downstaged to pathologic stage I with RPLND.[13] In children, the use of serial measurements of AFP has proven sufficient for monitoring response after initial orchiectomy. Lymphangiography and para-aortic lymph node dissection do not appear to be useful or necessary in the proper staging and management of these patients.[9]

Patients who have been cured of testicular cancer have approximately a 2% to 5% cumulative risk of developing a cancer in the opposite testicle during the 25 years after initial diagnosis.[14-16] Within this range, men with nonseminomatous primary tumors appear to have a lower risk of subsequent contralateral testis tumors than men with seminomas.[16,17]

HIV-infected men are reported to be at increased risk for developing testicular germ cell cancer.[18] Depending on comorbid conditions such as active infection, these men are generally managed similarly to non-HIV-infected patients.

Because the majority of testis cancer patients who receive chemotherapy are curable, it is necessary to be aware of possible long-term effects of platinum-based treatment, such as the following:

1. Fertility: Many patients have oligospermia or sperm abnormalities prior to therapy. Virtually all become oligospermic during chemotherapy. Many recover sperm production, however, and can father children, often without the use of cryopreserved semen. In a population-based study, 70% of patients actually fathered children.[19] The likelihood of recovering fertility is related to the type of treatment received. The children do not appear to have an increased risk of congenital malformations.[20-23]



2. Secondary leukemias: Several reports of elevated risk of secondary acute leukemia, primarily nonlymphocytic, have appeared.[24] In some cases, the risks were associated with the prolonged use of alkylating agents or with the use of radiation.[25,26] Etoposide-containing regimens are also associated with a risk of secondary acute leukemias, usually in the myeloid lineage, and with a characteristic 11q23 translocation.[24,27-29] Etoposide-associated leukemias typically occur sooner after therapy than alkylating agent-associated leukemias and often show balanced chromosomal translocations on the long arm of chromosome 11.[24] Standard etoposide dosages (<2 g/m² cumulative dose) are associated with a relative risk of 15 to 25, but this translates into a cumulative incidence of leukemia of less than 0.5% at 5 years. Preliminary data suggest that cumulative doses of more than 2 g/m² of etoposide may confer higher risk.



3. Renal function: Minor decreases in creatinine clearance occur (about a 15% decrease, on average) during platinum-based therapy, but these appear to remain stable in the long term and without significant deterioration.[30]



4. Hearing: Bilateral hearing deficits occur with cisplatin-based chemotherapy, but the deficits generally occur at sound frequencies of 4 kHz to 8 kHz, which is outside the range of conversational tones;[30] therefore, hearing aids are rarely required if standard doses of cisplatin are administered.

Although bleomycin pulmonary toxic effects may occur, it is rarely fatal at total cumulative doses of less than 400U. Because life-threatening pulmonary toxic effects can occur, the drug should be discontinued if early signs of pulmonary toxic effects develop. Although decreases in pulmonary function are frequent, they are rarely symptomatic and are reversible after the completion of chemotherapy. Reportedly, men treated curatively for germ cell tumors with cisplatin-based regimens have had elevations in total serum cholesterol.[31] This could not be confirmed, however, in another study.[32]

Radiation therapy, often used in the management of pure seminomatous germ cell cancers, has been linked to the development of secondary cancers, especially solid tumors in the radiation portal, usually after a latency period of a decade or more.[24,33] These include melanoma and cancers of the stomach, bladder, colon, rectum, pancreas, lung, pleura, prostate, kidney, connective tissue, and thyroid. Chemotherapy has also been associated with an elevated risk of secondary cancers.[24]

Oligospermia or sperm abnormalities prior to therapy are common. Radiation therapy, used to treat pure seminomatous testicular cancers, can cause fertility problems because of radiation scatter to the remaining testicle during radiation therapy to retroperitoneal lymph nodes as evidenced in the SWOG-8711 trial, for example.[34] (For more information on fertility, refer to the Sexuality and Reproductive Issues summary.) Depending on scatter dose, sperm counts fall after radiation therapy but may recover over the course of 1 to 2 years. Shielding techniques can be used to decrease the radiation scatter to the remaining normal testicle. As with treatment with chemotherapy, some men have been reported to father children after radiation treatment of seminoma, and the children do not appear to have a high risk of congenital malformations.[19,34][Level of evidence: 3iiiDiv]

Radiation therapy and/or chemotherapy for patients with testicular cancer may be associated with an increase in cardiovascular morbidity. In a retrospective series of 992 patients treated for testicular cancer at the Royal Marsden Hospital between 1982 and 1992, cardiac events were increased approximately 2.5-fold in patients treated with radiation therapy and/or chemotherapy compared with those who underwent surveillance after a median of 10.2 years. The actuarial risks of cardiac events were 7.2% for patients who received radiation therapy (92% of whom did not receive mediastinal radiation therapy), 3.4% for patients who received chemotherapy (primarily platinum-based), 4.1% for patients who received combined therapy, and 1.4% for patients who underwent surveillance management after 10 years of follow-up.[35] A population-based retrospective study of 2,339 testicular cancer survivors in the Netherlands, treated between 1965 and 1995 and followed for a median of 18.4 years, found that the overall incidence of coronary heart disease (i.e., myocardial infarction and/or angina pectoris) was increased 1.17 times (95% confidence interval [CI], 1.04–1.31) compared with the general population.[36] Patients who received radiation therapy to the mediastinum had a 2.5-fold (95% CI, 1.8–3.4) increased risk of coronary heart disease, and those who also received chemotherapy had an almost 3-fold (95% CI, 1.7–4.8) increased risk. Patients who were treated with infradiaphragmatic radiation therapy alone had no significantly increased risk of coronary heart disease. In multivariate Cox regression analyses, the older chemotherapy regimen of cisplatin, vinblastine, and bleomycin (PVB), used until the mid 1980s, was associated with a significant 1.9-fold (95% CI, 1.2–2.9) increased risk of cardiovascular disease (i.e., myocardial infarction, angina pectoris, and heart failure combined). The newer regimen of bleomycin, etoposide, and cisplatin (BEP) was associated with a borderline significant 1.5-fold (95% CI, 1.0–2.2) increased risk of cardiovascular disease.[24,36][Level of evidence: 3iiiDii]

Although testicular cancer is highly curable, all newly diagnosed patients are appropriately considered candidates for clinical trials designed to decrease morbidity of treatment while further improving cure rates.

References

1. American Cancer Society.: Cancer Facts and Figures 2008. Atlanta, Ga: American Cancer Society, 2008. Also available online. Last accessed October 1, 2008. 
   
   
2. Bosl GJ, Bajorin DF, Sheinfeld J, et al.: Cancer of the testis. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1269-90. 
   
   
3. Bajorin DF, Bosl GJ: The use of serum tumor markers in the prognosis and treatment of germ cell tumors. Cancer: Principles and Practice of Oncology Updates 6(1): 1-11, 1992. 
   
   
4. Mead GM, Stenning SP, Parkinson MC, et al.: The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party. J Clin Oncol 10 (1): 85-94, 1992.  [PUBMED Abstract]
   
   
5. International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol 15 (2): 594-603, 1997.  [PUBMED Abstract]
   
   
6. Spears WT, Morphis JG 2nd, Lester SG, et al.: Brain metastases and testicular tumors: long-term survival. Int J Radiat Oncol Biol Phys 22 (1): 17-22, 1992.  [PUBMED Abstract]
   
   
7. Leibovitch I, Baniel J, Foster RS, et al.: The clinical implications of procedural deviations during orchiectomy for nonseminomatous testis cancer. J Urol 154 (3): 935-9, 1995.  [PUBMED Abstract]
   
   
8. Capelouto CC, Clark PE, Ransil BJ, et al.: A review of scrotal violation in testicular cancer: is adjuvant local therapy necessary? J Urol 153 (3 Pt 2): 981-5, 1995.  [PUBMED Abstract]
   
   
9. Huddart SN, Mann JR, Gornall P, et al.: The UK Children's Cancer Study Group: testicular malignant germ cell tumours 1979-1988. J Pediatr Surg 25 (4): 406-10, 1990.  [PUBMED Abstract]
   
   
10. Gerl A, Clemm C, Schmeller N, et al.: Late relapse of germ cell tumors after cisplatin-based chemotherapy. Ann Oncol 8 (1): 41-7, 1997.  [PUBMED Abstract]
    
    
11. Socinski MA, Stomper PC: Radiologic evaluation of nonseminomatous germ cell tumor of the testis. Semin Urol 6 (3): 203-15, 1988.  [PUBMED Abstract]
    
    
12. Consensus conference. Magnetic resonance imaging. JAMA 259 (14): 2132-8, 1988.  [PUBMED Abstract]
    
    
13. Donohue JP, Thornhill JA, Foster RS, et al.: The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol 153 (1): 85-9, 1995.  [PUBMED Abstract]
    
    
14. Osterlind A, Berthelsen JG, Abildgaard N, et al.: Risk of bilateral testicular germ cell cancer in Denmark: 1960-1984. J Natl Cancer Inst 83 (19): 1391-5, 1991.  [PUBMED Abstract]
    
    
15. Colls BM, Harvey VJ, Skelton L, et al.: Bilateral germ cell testicular tumors in New Zealand: experience in Auckland and Christchurch 1978-1994. J Clin Oncol 14 (7): 2061-5, 1996.  [PUBMED Abstract]
    
    
16. Fosså SD, Chen J, Schonfeld SJ, et al.: Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 97 (14): 1056-66, 2005.  [PUBMED Abstract]
    
    
17. van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW, et al.: Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol 11 (3): 415-24, 1993.  [PUBMED Abstract]
    
    
18. Foster RS, Donohue JP: Surgical treatment of clinical stage A nonseminomatous testis cancer. Semin Oncol 19 (2): 166-70, 1992.  [PUBMED Abstract]
    
    
19. Brydøy M, Fosså SD, Klepp O, et al.: Paternity following treatment for testicular cancer. J Natl Cancer Inst 97 (21): 1580-8, 2005.  [PUBMED Abstract]
    
    
20. Drasga RE, Einhorn LH, Williams SD, et al.: Fertility after chemotherapy for testicular cancer. J Clin Oncol 1 (3): 179-83, 1983.  [PUBMED Abstract]
    
    
21. Nijman JM, Schraffordt Koops H, Kremer J, et al.: Gonadal function after surgery and chemotherapy in men with stage II and III nonseminomatous testicular tumors. J Clin Oncol 5 (4): 651-6, 1987.  [PUBMED Abstract]
    
    
22. Hansen PV, Trykker H, Helkjoer PE, et al.: Testicular function in patients with testicular cancer treated with orchiectomy alone or orchiectomy plus cisplatin-based chemotherapy. J Natl Cancer Inst 81 (16): 1246-50, 1989.  [PUBMED Abstract]
    
    
23. Stephenson WT, Poirier SM, Rubin L, et al.: Evaluation of reproductive capacity in germ cell tumor patients following treatment with cisplatin, etoposide, and bleomycin. J Clin Oncol 13 (9): 2278-80, 1995.  [PUBMED Abstract]
    
    
24. van den Belt-Dusebout AW, de Wit R, Gietema JA, et al.: Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 25 (28): 4370-8, 2007.  [PUBMED Abstract]
    
    
25. Redman JR, Vugrin D, Arlin ZA, et al.: Leukemia following treatment of germ cell tumors in men. J Clin Oncol 2 (10): 1080-7, 1984.  [PUBMED Abstract]
    
    
26. Travis LB, Andersson M, Gospodarowicz M, et al.: Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst 92 (14): 1165-71, 2000.  [PUBMED Abstract]
    
    
27. Pedersen-Bjergaard J, Daugaard G, Hansen SW, et al.: Increased risk of myelodysplasia and leukaemia after etoposide, cisplatin, and bleomycin for germ-cell tumours. Lancet 338 (8763): 359-63, 1991.  [PUBMED Abstract]
    
    
28. Nichols CR, Breeden ES, Loehrer PJ, et al.: Secondary leukemia associated with a conventional dose of etoposide: review of serial germ cell tumor protocols. J Natl Cancer Inst 85 (1): 36-40, 1993.  [PUBMED Abstract]
    
    
29. Bajorin DF, Motzer RJ, Rodriguez E, et al.: Acute nonlymphocytic leukemia in germ cell tumor patients treated with etoposide-containing chemotherapy. J Natl Cancer Inst 85 (1): 60-2, 1993.  [PUBMED Abstract]
    
    
30. Osanto S, Bukman A, Van Hoek F, et al.: Long-term effects of chemotherapy in patients with testicular cancer. J Clin Oncol 10 (4): 574-9, 1992.  [PUBMED Abstract]
    
    
31. Raghavan D, Cox K, Childs A, et al.: Hypercholesterolemia after chemotherapy for testis cancer. J Clin Oncol 10 (9): 1386-9, 1992.  [PUBMED Abstract]
    
    
32. Ellis PA, Fitzharris BM, George PM, et al.: Fasting plasma lipid measurements following cisplatin chemotherapy in patients with germ cell tumors. J Clin Oncol 10 (10): 1609-14, 1992.  [PUBMED Abstract]
    
    
33. Travis LB, Fosså SD, Schonfeld SJ, et al.: Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 97 (18): 1354-65, 2005.  [PUBMED Abstract]
    
    
34. Gordon W Jr, Siegmund K, Stanisic TH, et al.: A study of reproductive function in patients with seminoma treated with radiotherapy and orchidectomy: (SWOG-8711). Southwest Oncology Group. Int J Radiat Oncol Biol Phys 38 (1): 83-94, 1997.  [PUBMED Abstract]
    
    
35. Huddart RA, Norman A, Shahidi M, et al.: Cardiovascular disease as a long-term complication of treatment for testicular cancer. J Clin Oncol 21 (8): 1513-23, 2003.  [PUBMED Abstract]
    
    
36. van den Belt-Dusebout AW, Nuver J, de Wit R, et al.: Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol 24 (3): 467-75, 2006.  [PUBMED Abstract]
    
    

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