Testicular Cancer

Updated: Jun 03, 2016
  • Author: Kush Sachdeva, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
  • Print
Overview

Background

Primary testicular tumors are the most common solid malignant tumor in men between the ages of 20 and 35 years 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. However, the absolute mortality rate has been stable or decreasing; approximately 9,000 new cases have been diagnosed in United States every year, and only about 350 to 400 deaths have occurred annually.

The American Cancer Society (ACS) estimates that about 8720 new cases of testicular cancer will be diagnosed during 2016 in the United States. [1] The ACS estimates that 380 men will die of testicular cancer in 2016. The lifetime chance of developing testicular cancer is about one in 263 and the risk of dying is very low—about one in 5,000. [2]

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 oncological landscape and is now considered the model for the treatment of solid tumors.

Testicular cancers are very sensitive to chemotherapy and are curable even when metastatic. Cure rates for good-risk disease cure rates 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. [3]

Next:

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.

Previous
Next:

Epidemiology

Frequency

United States

Testicular cancers are not a common malignancy. The American Cancer Society (ACS) estimates that about 8720 new cases of testicular cancer will be diagnosed during 2016 in the United States. [1] Most cases occur in young and middle-aged men; the median age at diagnosis is approximately 33 years. [2]

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. [4] The rate of increase has slowed in recent years. [2]

According to Surveillance, Epidemiology, and End Results (SEER) data from 17 geographic areas, the age-adjusted annual incidence of testicular cancer from 2009–2013 was 5.7 per 100,000 men. [5] 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 towards 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]

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] 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]

Mortality/Morbidity

Testicular cancers are highly curable, even in patients with metastatic disease at diagnosis. The prognosis depends upon the histologic type of cancer (seminoma versus nonseminoma), stage, and other features such as tumor marker and type of metastatic disease.

Patients with seminomas that confer a good prognosis, which constiute about 90% of seminomas, have a 5-year survival of 86%; patients with good-prognosis nonseminomas (56% of nonseminomas) have a 5-year survival of 92%. With intermediate-prognosis cancers (28% of nonseminomas), 5-year survival is 72% with seminomas and 80% with nonseminomas. With poor-prognosis nonseminomas (about 16% of nonseminomas) 5-year survival is 48%.

Those survival data are based on patients treated between 1975 and 1990; more recent studies has shown much better survival with nonseminomatous germ cell tumors (NSGCT). Pooled 5-year survival estimates for NSGCT were 94% for good-prognosis, 83% for intermediate-prognosis, and 71% for poor-prognosis tumors.

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. [8] See the Table below. [5]

Table. Incidence of Testicular Cancer by Race (Open Table in a new window)

Incidence of Testicular Cancer by Race
Race/Ethnicity Annual rate per 100,000 men
All Races 5.7
White 6.7
Black 1.5
Asian/Pacific Islander 2.1
American Indian/Alaska Native 4.9
Hispanic 5.0

A review of data from the Surveillance, Epidemiology, and End Results Program 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. [9]

Age

Testicular cancer can occur at any age but is most common between the ages of 15 and 35 years; 50% of cases occur in men 20-34 years old. [5] 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.

Previous