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Testicular Cancer Screening (PDQ®)

Description of the Evidence

Background

Incidence and mortality

It is estimated that 8,820 new cases of testicular cancer will be diagnosed in men, and 380 men will die of this disease in the United States in 2014.[1]Testicular cancer is the most common malignancy in men aged 15 to 34 years.[2,3] It accounts for approximately 1% of all cancers in men. Worldwide, testicular cancer has more than doubled in the last 40 years. Incidence varies considerably in different geographical areas, being highest in Scandinavia and Switzerland; intermediate in the United States, Australia, and the United Kingdom; and lowest in Asia and Africa. It also varies according to ethnic groups, with a much higher rate among whites than blacks in the American population.[4] An annual increase of 3% is reported for Caucasian populations.[5] Despite the increase in observed incidence, there has been a dramatic decrease in mortality as a result of effective treatments.

Unlike most other cancers, testicular cancer is generally found in young men.[6] In white men, testicular cancer is the most common cancer from age 20 years to age 34 years, the second most common from age 35 years to age 39 years, and the third most common from age 15 years to age 19 years.

Approximately 69% of testicular cancers are localized, 18% are regional, and 12% are distant stage at diagnosis.[6] Although there has been no appreciable change in the stage distribution at diagnosis, advances in treatment have been associated with a 60% decrease in mortality. The majority of testicular cancers are curable even at advanced stages, and it would be impractical to document a further decrease in mortality associated with screening.

Germ cell tumors (GCTs) of the testis constitute 94% of testicular tumors and include five basic cell types:[7]

  • Seminoma.
  • Embryonal carcinoma.
  • Yolk sac tumor.
  • Teratoma.
  • Choriocarcinoma.

Sixty percent of GCTs are seminomas; the remainder are nonseminomatous GCTs. Almost half of all GCTs contain more than one of the five cell types.[7]

Three subtypes of pure seminomas have been described: classic, anaplastic, and spermatocytic. Classic seminoma accounts for 80% to 85% of all seminomas and occurs most commonly in men aged 30 to 50 years. Anaplastic seminoma accounts for 5% to 10% of all seminomas and has an age distribution similar to that of the typical subtype. A number of features suggest that anaplastic seminoma is a more aggressive and potentially more lethal variant of typical seminoma. These characteristics include greater mitotic activity, higher rate of local invasion, increased rate of metastatic spread, and higher rate of tumor marker (human chorionic gonadotropin [hCG] beta, or beta hCG) production. Spermatocytic seminoma accounts for 2% to 12% of all seminomas, and nearly half occur in men older than 50 years. The cells closely resemble different phases of maturing spermatogonia. The metastatic potential of this tumor is extremely low, and the prognosis is favorable.[8]

Risk Factors

Testicular cancer is more than four times more common among white men than black men,[8,9] with intermediate incidence rates for Hispanics, American Indians, and Asians. High-risk groups exist. Males with cryptorchidism have 3 to 17 times the average risk. Approximately 7% to 10% of patients with testicular tumors have a history of cryptorchidism.[7,8] Although the association is established, the biological mechanism underlying the association remains uncertain; testicular cancer and cryptorchidism may share environmental and/or genetic risk factors; or, it is the ectopic position per se that is a postnatal risk factor for testicular cancer, or it is a combination of the two.[7] Orchiopexy may not prevent cancer in these children but allows clinical surveillance of patients with a previously impalpable gonad.

There is also an increased risk in males with gonadal dysgenesis and Klinefelter syndrome.[10] Men with a family history of testicular cancer may be at a higher risk of this disease.[11] A history of testicular cancer is associated with a higher risk of a contralateral tumor.[7,8] Although not consistently found, infertility, testicular atrophy, twinship, or abnormal semen parameters have been associated with a higher risk of testicular cancer, but the evidence is weak.[7,12-14]

There is a low cumulative risk of metachronous contralateral testicular cancer and a favorable overall survival of patients diagnosed with metachronous contralateral testicular cancer.[15] Future research is necessary to delineate the genetic and environmental risk factors for testicular cancer.[16]

Carcinoma in situ

An additional risk factor for the development of testicular cancer is the presence of carcinoma in situ (CIS), also called intratubular germ cell neoplasia. Testicular CIS appears to develop from fetal gonocytes and is characterized histologically by seminiferous tubules containing only Sertoli cells and malignant-appearing germ cells.[17]

Early reports suggest that CIS is associated with the development of contralateral testicular cancer in 50% of patients at 5 years of follow-up.[18] CIS will be found in approximately 5% of contralateral testes (approximately the same rate as cryptorchid testes).[19]

There is controversy regarding the clinical significance and management of CIS of the testis.[8] Treatment options for CIS include observation, radiation therapy, chemotherapy, and orchiectomy. Although low-dose radiation therapy can preserve Leydig cell function and prevent GCT development, a conservative approach of observation may also be warranted. Individuals at high risk (e.g., cryptorchidism, atrophic testis, and intersex conditions) require close observation.

Evidence of Benefit Associated With Screening

The sensitivity, specificity, and positive predictive value of routine screening of asymptomatic men for testicular cancer are not known.[20,21] In a report of a single-center case series of men being evaluated for infertility, testicular symptoms, or erectile dysfunction, 1,320 men underwent testicular ultrasound.[22] Focal lesions were found in 27 (2%) men, 17 of the lesions were palpable and 10 were nonpalpable. Eighty percent of the lesions were ultimately shown to have benign histologies, for a positive predictive value of about 0.2. It is not clear if early discovery of the cancers resulted in clinical benefit, and the positive predictive value is likely to be lower in the target population of asymptomatic men in the screening setting.

Most testicular cancers are first detected by the patient, either unintentionally or by self-examination. Some are discovered by routine physical examination. However, no studies have been done to determine the effectiveness of testicular self-examination or clinical testicular examination in reducing mortality from testicular cancer. An updated systematic review performed on behalf of the U.S. Preventive Services Task Force, published in 2010, found no randomized trials, cohort studies, or case-control studies that examined benefits of testicular cancer screening (whether by physical examination, self-examination, or other screening tests) in an asymptomatic population.[21] Likewise, a systematic Cochrane Collaboration review found no randomized or quasi-randomized controlled trials that evaluated the effectiveness of screening by a health professional or patient self-examination.[23]

Screening would be very unlikely to decrease mortality substantially because therapy is so effective at virtually all stages of disease.[24](Refer to the PDQ summary on Testicular Cancer Treatment for more information.) However, early detection may affect therapy. There is an increase in both the number of courses of chemotherapy and the extent of surgery required for treatment of advanced disease that results in higher morbidity. Patients diagnosed with localized disease require less treatment and have lower morbidity.[25]

Evidence of Harm Associated With Screening

Harms of screening for testicular cancer are poorly quantified. They may include false positive tests [22] and resulting anxiety as well as subsequent unwarranted invasive diagnostic procedures. Two systematic reviews found no studies that provided a quantitative assessment of the harms of screening. [21,23]

References

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed November 24, 2014.
  2. McGlynn KA, Devesa SS, Sigurdson AJ, et al.: Trends in the incidence of testicular germ cell tumors in the United States. Cancer 97 (1): 63-70, 2003. [PUBMED Abstract]
  3. Garner MJ, Turner MC, Ghadirian P, et al.: Epidemiology of testicular cancer: an overview. Int J Cancer 116 (3): 331-9, 2005. [PUBMED Abstract]
  4. Huyghe E, Matsuda T, Thonneau P: Increasing incidence of testicular cancer worldwide: a review. J Urol 170 (1): 5-11, 2003. [PUBMED Abstract]
  5. Horwich A, Shipley J, Huddart R: Testicular germ-cell cancer. Lancet 367 (9512): 754-65, 2006. [PUBMED Abstract]
  6. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2009 (Vintage 2009 Populations). Bethesda, Md: National Cancer Institute, 2012. Also available online. Last accessed December 15, 2014.
  7. Dieckmann KP, Pichlmeier U: Clinical epidemiology of testicular germ cell tumors. World J Urol 22 (1): 2-14, 2004. [PUBMED Abstract]
  8. Richie JP, Steele GS: Neoplasms of the testis. In: Campbell MF, Wein AJ, Kavoussi LR: Campbell-Walsh Urology. 9th ed. Philadelphia, Pa: Saunders Elsevier, 2007, pp 893-935.
  9. Moul JW, Schanne FJ, Thompson IM, et al.: Testicular cancer in blacks. A multicenter experience. Cancer 73 (2): 388-93, 1994. [PUBMED Abstract]
  10. Henderson BE, Benton B, Jing J, et al.: Risk factors for cancer of the testis in young men. Int J Cancer 23 (5): 598-602, 1979. [PUBMED Abstract]
  11. Dieckmann KP, Pichlmeier U: The prevalence of familial testicular cancer: an analysis of two patient populations and a review of the literature. Cancer 80 (10): 1954-60, 1997. [PUBMED Abstract]
  12. Jacobsen R, Bostofte E, Engholm G, et al.: Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 321 (7264): 789-92, 2000. [PUBMED Abstract]
  13. Walsh TJ, Croughan MS, Schembri M, et al.: Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 169 (4): 351-6, 2009. [PUBMED Abstract]
  14. Hotaling JM, Walsh TJ: Male infertility: a risk factor for testicular cancer. Nat Rev Urol 6 (10): 550-6, 2009. [PUBMED Abstract]
  15. 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]
  16. Richiardi L, Pettersson A, Akre O: Genetic and environmental risk factors for testicular cancer. Int J Androl 30 (4): 230-40; discussion 240-1, 2007. [PUBMED Abstract]
  17. Olesen IA, Hoei-Hansen CE, Skakkebaek NE, et al.: Testicular carcinoma in situ in subfertile Danish men. Int J Androl 30 (4): 406-11; discussion 412, 2007. [PUBMED Abstract]
  18. Jørgensen N, Müller J, Giwercman A, et al.: Clinical and biological significance of carcinoma in situ of the testis. Cancer Surv 9 (2): 287-302, 1990. [PUBMED Abstract]
  19. Dieckmann KP, Loy V: Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms. J Clin Oncol 14 (12): 3126-32, 1996. [PUBMED Abstract]
  20. U.S. Preventive Services Task Force: Screening for testicular cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med 154 (7): 483-6, 2011. [PUBMED Abstract]
  21. Lin K, Sharangpani R: Screening for testicular cancer: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med 153 (6): 396-9, 2010. [PUBMED Abstract]
  22. Carmignani L, Gadda F, Gazzano G, et al.: High incidence of benign testicular neoplasms diagnosed by ultrasound. J Urol 170 (5): 1783-6, 2003. [PUBMED Abstract]
  23. Ilic D, Misso ML: Screening for testicular cancer. Cochrane Database Syst Rev (2): CD007853, 2011. [PUBMED Abstract]
  24. Feldman DR, Bosl GJ, Sheinfeld J, et al.: Medical treatment of advanced testicular cancer. JAMA 299 (6): 672-84, 2008. [PUBMED Abstract]
  25. Sagalowsky AI: Expectant management of stage A nonseminomatous testicular tumors. In: Ratiff TL, Catalona WJ, eds.: Genitourinary Cancer. Boston: Martinus Nijhoff, 1987, pp 225-237.
  • Updated: February 27, 2014