Testicular Cancer

Introduction

Testicular cancer is relatively uncommon in the United States, with approximately 5500 cases per year. The overall incidence of testicular tumors worldwide ranges from 0.2-10.3 cases per 100,000 persons. Such tumors may arise in males of nearly any age and may be of germ cell or non–germ cell origin. Tumor histology (see Histologic Findings) and tumor stage (see Staging) are of primary importance in determining the prognosis of testicular tumors. This article addresses the demographics, histology, prognosis, and treatment of nonseminomatous germ cell tumors (NSGCTs).

History of the Procedure

The treatment of testicular cancer has developed in earnest over the past half century. Before 1970, testicular tumors carried a mortality rate that approached 50%, whereas recent studies have reported that the cure rate using multimodal therapy exceeds 90%. Improved understanding of the histology, mechanisms of tumor spread, and tumor markers, combined with the improved quality of radiographic imaging for accurate staging, have greatly contributed to the management of testicular cancer. The combination of refinements in surgical intervention and the application of effective combination chemotherapy has emerged as a paradigm for the successful use of multimodal therapy for solid tumors.

Problem

Testicular cancer has 3 main types—(1) germ cell tumors, (2) non–germ cell tumors, and (3) extragonadal tumors. Germ cell tumors, which are the most common, are classified as either seminoma or nonseminoma, based on histology. Of the 3 main types of testicular cancer, NSGCTs are behind only seminoma in terms of frequency. This discussion explores the incidence, risk factors, diagnosis, treatment options, and prognosis of NSGCTs.

Frequency US incidence

Testicular cancer is relatively uncommon, with approximately 5500 new cases per year in the United States. The peak incidence is in men aged 20-34 years. Testicular cancer is the most common solid tumor in this otherwise young, healthy, and productive age group. Furthermore, despite improvements in survival rates since the introduction of platinum-based chemotherapy in the United States in the 1970s and 1980s, from 1975-2001, the incidence of testicular cancer among white males in the United States rose by 46%. Currently, the incidence is approximately 5.44 cases per 100,000 persons. The rate of NSGCTs specifically also appears to have increased. In addition, the incidence of NSGCTs among active servicemen in the military almost doubled from 1988-1996.NSGCTs are less common in African American males than in white males.

International incidence

Worldwide, testicular cancer has the highest incidence in Norway, Denmark, Germany, and Switzerland. The incidence in Switzerland in 1997 was 10.3 cases per 100,000 persons, with NSGCTs accounting for 45%-50% of cases. The incidence in this population has increased alarmingly (>300%) since 1955. The risk for the disease has increased in all birth cohorts except for those born during World War II.

Etiology

Factors that alter the differentiation of the primordial germ cell, resulting in the presence of an embryonal stem cell, can increase the risk of NSGCT. Risk factors include a history of testicular cancer in the contralateral testis, cryptorchidism (undescended testis), gonadal dysgenesis, prenatal exposure to high estradiol levels, exposure to chemical carcinogens, trauma, and orchitis. Other risk factors may include childhood inguinal hernias and any cause of testicular atrophy. In 2005, a 25-year follow-up study of 44,864 Swedish men suggested that elevated serum cholesterol levels may increase the risk of testicular cancer.Further validation studies are required to evaluate these findings in other populations.

One of the most significant risk factors for testicular cancer is cryptorchidism. In addition, the age at which orchidopexy (an operation to bring the testicle down into the scrotum) is performed appears to play a significant role. A 2007 study reported a 2.23 relative risk (in comparison with the general Swedish population) of testicular cancer in patients who underwent orchidopexy before age 13 years, while the relative risk among those who underwent orchidopexy at age 13 years or older was 5.40.Therefore, among boys with cryptorchidism, orchidopexy performed before puberty appears to reduce the likelihood of testicular cancer later in life.

Pathophysiology

NSGCTs refer to the germ cell tumors that contain embryonal stem cells. These may be differentiated into extraembryonic tissues or somatic elements. Most tumors are composed of a mixture of these elements.

The 4 histologic classifications of NSGCTs include (1) embryonal carcinoma, (2) teratoma, (3) choriocarcinoma, and (4) yolk sac tumor.

Mixed tumors are those with a mixture of these histologies. Tumors with both seminomatous and nonseminomatous elements are considered NSGCTs because the NSGCT component most accurately reflects the response to treatment and overall prognosis.


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Presentation

The classic presentation of a testicular tumor is a painless, swollen, hard testis in an otherwise healthy man in the third or fourth decade of life. The presentation can vary depending on the amount of disease, clinical stage, and the presence of metastases at the time of referral. Some patients present with a swollen painful mass in the scrotum that may be dismissed as infectious or inflammatory in nature, potentially resulting in a detrimental delay in starting treatment for NSGCT. Whenever the physical examination reveals any deviation from a palpably normal testicle, scrotal ultrasonography should be performed.

In all patients in whom testicular tumors are suspected, obtain a complete history and perform a complete physical examination. The history should include specific questions regarding possible risk factors for testicular cancer. Questions about cryptorchidism, trauma, and mumps orchitis are useful. Likewise, the occupational, chemical exposure, and smoking history of the patient should be obtained.

During the general physical examination, special attention should be given to the presence of gynecomastia, which is a finding in 5% of testicular cancer cases. Supraclavicular adenopathy may be a finding in advanced disease. Lung examination in patients with widespread lung metastases may reveal areas of decreased breath sounds. Abdominal examination should be performed to assess for visceral or bulky lymphatic involvement. The contralateral testis must be examined for possible abnormalities. Finally, a neurologic examination is also important to evaluate for possible brain metastasis. The testicles should be readily palpable in the scrotum. The contour of each testicle should be smooth and the consistency uniform. Any size discrepancy between the 2 testicles should be assessed and noted.

Differentiation of the scrotal contents should be found with careful palpation. The epididymis, attached to the posterior aspect of the testicle, is frequently the site of induration or cysts. Patients may discover such abnormalities during self-examination, prompting them to seek medical attention. These conditions should be identifiable during the physical examination. If the inability to perform an adequate evaluation is a concern, scrotal ultrasonography must be performed to aid in the diagnosis.

Indications

Surgery is indicated not only for the initial treatment of nonseminomatous germ cell tumors (NSGCTs) but also for diagnosis.

Contraindications

Radical (inguinal) orchiectomy has no contraindications, other than potential anesthetic risks and uncontrolled bleeding diathesis. In such high-risk patients, preoperative clearance and preparation may be required, but radical orchiectomy should still be performed at the earliest opportunity.


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