Testicular cancer, although an uncommon malignancy, is the most frequently occurring cancer in young men. In the year 2009, an estimated 8,400 cases of testicular cancer will be diagnosed in the United States, and approximately 380 men will succumb to the disease. For unknown reasons, the incidence of this cancer has increased since the turn of the century, from 2 cases per 100,000 population in the 1930s, to 3.7 cases per 100,000 population from 1969 to 1971, to 5.4 cases per 100,000 population from 1995 to 1999. The greatest rise has been observed in Puerto Rico (1973 to 1997: 220%). This trend seems greatest for the development of seminoma.
Most testicular tumors are of germ-cell origin. These cancers are uniquely sensitive to chemotherapy and are considered the model for the treatment of solid tumors. Perhaps the most controversial area in the management of germ-cell tumors is the proper approach to early-stage disease (ie, surveillance vs primary retroperitoneal lymphadenectomy for nonseminomatous germ-cell tumors [NSGCTs] or radiation therapy for seminomas). In advanced disease, chemotherapy plays an essential role, but novel treatment regimens are currently being evaluated through multi-institution clinical trials.
Epidemiology
Age
Testicular cancer can occur at any age, but it is most common between the ages of 15 and 35 years. There is a secondary peak in incidence after age 60. Seminoma is the most common histology in the older population, but it is rare in those younger than age 10. There is a slightly increased prevalence of testicular cancer among fathers and brothers of testicular cancer patients.
Race
Testicular cancer is rare among blacks (1.6/100,000 population), yet black men present with higher grade disease and have significantly worse survival at 5 and 10 years. The incidence of this cancer has increased in whites during the 20th century but has remained flat in blacks. Non-Hispanic white patients typically present with disease at early stages when compared with black, Native-American, Hawaiian, and Hispanic patients.
Geography
Denmark has the highest incidence of testicular cancer; the Far East has the lowest incidence of this disease.
Primary site
Germ-cell tumors present most commonly in the testes (90%) and only infrequently in extragonadal sites (10%). The most common extragonadal sites (in decreasing order of frequency) are the retroperitoneum, mediastinum, and pineal gland. Many patients presumed to have a primary retroperitoneal germ-cell tumor may have an occult germ-cell tumor of the testicle. This possibility should be evaluated with testicular ultrasonography, especially when the retroperitoneal tumor is predominantly one-sided.
Survival
The 5-year survival rate for all patients with testicular cancer is ~95%. Cure rates are highest for early-stage disease, which is treated primarily with surgery or radiation therapy (early seminoma), and lower for advanced disease, for which chemotherapy is the primary therapy (Table 1).
Etiology and risk factors
The specific cause of germ-cell tumors is unknown, but various factors have been associated with an increased risk of this malignancy.
Prior testicular cancer
Perhaps the strongest risk factor for germ-cell tumors is a history of testicular cancer. Approximately 1% to 2% of patients with testicular cancer will develop a second primary in the contralateral testis over time. This represents a 500-fold increase in incidence over that noted among the normal male population.
The risk of contralateral testicular cancer was studied in a large population-based cohort of men diagnosed with testicular cancer before the age of 55. For 29,515 cases reported from 1973 through 2001 to the NCI’s SEER Program, the 15-year cumulative risk of developing metachronous contralateral testicular cancer was 1.9%, reaffirming the practice of not performing a biopsy on the contralateral testis at initial presentation.
Cryptorchidism
Patients with cryptorchidism have a four- to eight-fold increased risk of developing germ-cell tumors when compared with their normal counterparts. Orchiopexy, even at an early age, appears to reduce the incidence of germ-cell tumor only slightly (if at all). For an undescended testis, the most common malignant histology is seminoma. For those undergoing early orchiopexy, the most common malignancy is non-seminoma. Of note, in ~10% of patients with cryptorchidism who develop germ-cell tumors, the cancer is found in the normally descended testis. Biopsies of nonenlarged cryptorchid testes demonstrate an increased incidence of intratubal germ-cell neoplasm, a presumed precursor lesion.
