Practice Essentials
Primary testicular tumors are the most common solid malignant tumor in men 20 to 35 years of age in the United States. For unknown reasons, the incidence of this cancer—principally, testicular seminomas—increased during the last century. Over the past decade, the incidence of testicular cancer has risen approximately 1.2% per year, although the rate of increase has been slowing. Germ cell cancers account for more than 90% of all testicular cancers. Approximately 9,000 new cases have been diagnosed in United States every year, although only about 400 deaths have occurred annually.
In patients with localized disease, painless swelling or a nodule in one testicle is the most common presenting sign. A dull ache or heavy sensation in the lower abdomen could be the presenting symptom. Patients with disseminated disease can present with manifestations of lymphatic or hematogenous spread. See Presentation.
Ultrasound can distinguish intrinsic from extrinsic testicular lesions and can identify masses within testes. Once the diagnosis of testicular cancer is suspected, a high-resolution CT scan of the abdomen and pelvis and a chest x-ray are ordered as part of the initial staging workup. Radical inguinal orchiectomy is the definitive procedure to permit histologic evaluation of the primary tumor and to provide local tumor control. See Workup.
Initial therapy is selected according to the following features of the cancer:
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Stage group
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Risk stratification (good, intermediate, or poor risk)
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Histology (seminoma versus nonseminoma)
With stage I seminoma, cure can sometimes be achieved by radical inguinal orchiectomy alone. Patients with more advanced disease require adjuvant chemotherapy or radiation therapy. See Treatment and Medication.
Testicular cancers are very sensitive to chemotherapy and are curable even when metastatic. Cure rates for good-risk disease are 90%-95%. However, patients cured of testicular cancer have approximately a 2% cumulative risk of developing a cancer in the opposite testicle during the 15 years after initial diagnosis. The risk of subsequent contralateral testis tumors appears to be higher in men whose primary tumor was a seminoma than in those with nonseminomatous primary tumors. [1]
In the past, metastatic testicular cancer was usually fatal, but advances in treatment, including high-dose chemotherapy and stem cell rescue, have considerably improved the prognosis. Indeed, testicular cancer is a bright spot in the oncologic landscape and is now considered the model for the treatment of solid tumors.
For patient education information, see Testicular Cancer and Testicular Cancer vs. Testicle Infection. For information from the National Cancer Institute, see Testicular Cancer–Patient Version.
See also Testicular Seminoma, Testicular Choriocarcinoma, and Nonseminomatous Testicular Tumors.
Pathophysiology
The cause of testicular cancer is not known. The characteristic genetic change found is an isochromosome of the short arm of chromosome 12 [i(12p)], which is often seen in sporadic cancers. This suggests that genes in this region are important in the development of germ cell tumors. A number of other genes that have a relatively weak effect are also involved in the development of testicular cancer.
That genetic factors have a role in the development of testicular cancer is shown by the fact that the risk for the disease is higher in first-degree relatives of cancer patients than in the general population. About 2% of testicular cancer patients report having an affected relative. Siblings are at particularly increased risk, with a relative risk of 8–10. For sons of affected men, the relative risk is 4–6.
Two models of testicular carcinoma in situ have been proposed. The first posits that fetal gonocytes whose development into spermatogonia is blocked may undergo abnormal cell division and then invasive growth mediated by postnatal and pubertal gonadotropin stimulation.
The second model postulates that the most likely target cell for transformation is the zygotene-pachytene spermatocyte. During this stage of germ cell development, aberrant chromatid exchange events associated with crossing over can occur. Normally, these cells are eliminated by apoptosis. On occasion, this crossing over may lead to increased 12p copy number and overexpression of the cyclin D2 gene (CCND2). The cell carrying this abnormality is relatively protected against apoptotic death because of the oncogenic effect of CCND2, leading to re-initiation of the cell cycle and genomic instability.
Malignant transformation of germ cells is the result of a multistep process of genetic changes. One of the earliest events is the increased copy number of 12p, either as 1 or more copies of i(12p) or as tandem duplications of chromosome arm 12p. This abnormality is found in occult carcinoma in situ lesions as well as more advanced disease. Further studies indicate that CCND2 is present at chromosome band 12p13 and that CCND2 is overexpressed in most germ cell tumors, including carcinoma in situ. Amplification of CCND2 activates cdk4/6, allowing the cell to progress through the G1-S checkpoint.
Epidemiology
Frequency
United States
Testicular cancers are an uncommon malignancy, representing only 0.5% of all new cancer cases in the United States. [2] The American Cancer Society (ACS) estimates that about 9190 new cases of testicular cancer will be diagnosed during 2023 in the United States. [3] The lifetime chance of developing testicular cancer is about one in 250 and the risk of dying is very low—about one in 5,000. [4] Most cases occur in men aed 20-34 years; the median age at diagnosis is approximately 32 years. [4]
In the United States, the incidence increased by 100% from 1988 to 2001. Diagnoses of seminomas increased 124% during that period and diagnoses of nonseminomas increased by 64%. No significant increase occurred in the incidence of early-stage disease in proportion to all diagnoses in this population, indicating that the increase was not due to more widespread screening or earlier detection. [5] The rate of increase has slowed in recent years. [4]
According to Surveillance, Epidemiology, and End Results (SEER) data from 18 geographic areas, the age-adjusted annual incidence of testicular cancer from 2016–2020 was 6.0 per 100,000 men. [2] However, the incidence varies widely by race/ethnicity (see below).
International
Studies of testicular cancer in selected global populations from 1973-2007 have shown a clear trend toward an increased incidence in most populations evaluated. [6, 7] In recent years, however, rates have plateaued in some areas and even decreased in a few. [6]
A review found that internationally, testicular cancer rates vary in adolescents and young adults (AYA; ages 15-39) and children under 15 years of age. [8] In children, the incidence is highest in Asia (4.2 per million) and South America (5.0 per million) and lowest in Europe (2.1 per million) and North America (2.5 per million). Incidence rates in AYA are as follows:
- Europe - 137.4 per million
- Oceania - 116.9 per million
- North America - 94.9 per million
- South and Central America - 66.5 per million
- Asia - 27.1 per million
Rates are highest in Northern Europe and in men descended from European populations—Northern European populations in particular. The incidence varies even in Northern Europe, however, with rates notably higher in Norway and Denmark than in Sweden and Finland, [7] although rates in Norway and Denmark are currently declining. [35] In recent years, rates in Eastern European countries have risen rapidly, approaching those in Northern European countries. Rates are lowest in Asia and Africa and intermediate in Central and South America. [6]
Epidemiologic observations have suggested that environmental factors are instrumental in determining risk for testicular cancers. However, epidemiologic evidence does not consistently support any specific risk factor. [7, 64]
Race
The incidence of testicular cancer is fivefold higher in whites than in African Americans; however, African Americans tend to present with higher-grade disease and have much worse prognosis than whites. [9] See the Table below. [2]
Table. Incidence of Testicular Cancer by Race (Open Table in a new window)
Race/Ethnicity |
Annual rate per 100,000 men |
All Races |
6.0 |
White |
7.4 |
Black |
1.7 |
Asian/Pacific Islander |
2.3 |
American Indian/Alaska Native |
7.4 |
Hispanic |
5.9 |
A review of SEER data found that in Hispanic Whites ages 15 to 39 years, the annual incidence of testicular germ cell tumors increased 58% between 1992 and 2010, from 7.18 to 11.34 cases per 100,000. By comparison, during that period the incidence in non-Hispanic White young adults increased 7%, from 12.41 to 13.22 cases per 100,000. [10]
Age
Testicular cancer can occur at any age but is most common between the ages of 15 and 35 years; about 50% of cases occur in men 20-34 years old. [2] There is also secondary peak in incidence after age 60. Seminoma is rare in boys younger than 10 years of age but is the most common histologic type in men older than 60.
Prognosis
Testicular cancers are highly curable, even in patients with metastatic disease at diagnosis. According to SEER data from 2013-2019, overall 5-year survival is 95.2%. [2] The prognosis varies somewhat depending on the histologic type of cancer (seminoma versus nonseminoma), stage, and other features such as tumor marker and type of metastatic disease. By stage, 5-year relative survival is 99.2% for patients with localized testicular cancer, 96.0% for patients with cancer that has spread to regional lymph nodes, 73.4% for patients with distant metastatic disease, and 91.3% for unstaged disease. [2]
Testicular cancer survivors are susceptible to a range of late consequences of the biological and psychological stress experienced during cancer therapy. Thoses stresses lead to premature aging and deterioration of immune system, and can result in cardiovascular disease, chronic fatigue, cognitive impairment, and secondary cancers. [11, 12]
Tables
Race/Ethnicity |
Annual rate per 100,000 men |
All Races |
6.0 |
White |
7.4 |
Black |
1.7 |
Asian/Pacific Islander |
2.3 |
American Indian/Alaska Native |
7.4 |
Hispanic |
5.9 |
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|
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Stage |
LDH |
HCG (mIU/mL) |
AFP (ng/mL) |
|
|
|
|
S1 |
< 1.5 times normal |
< 5,000 |
< 1,000 |
S2 |
1.5-10 times normal |
5,000-50,000 |
1,000-10,000 |
S3 |
>10 times normal |
>50,000 |
>10,000 |
LDH=lactate dehydrogenase; HCG=beta human chorionic gonadotropin; AFP=alpha fetoprotein. |
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