Testis Cancer

Testis cancer is a highly curable disease entity when treated appropriately.

In 2015, it is estimated that 8,400 U.S. men were diagnosed with testis cancer and 380 men died from testis cancer. Testis cancer is most commonly diagnosed in the second and third decade of life, with the average age of diagnosis being 33 years. For unknown reasons, testis cancer is becoming more prevalent in the U.S. and elsewhere.

Just as self-examination for breast cancer is taught to young women, testicular self-examination should be encouraged among young men. Advanced medical techniques in diagnosis and treatment exist that effectively address this form of cancer, with low risk of complications. As with many forms of cancer, early detection and treatment can significantly enhance prognosis.

More than ninety-percent of testis cancers develop from germ cells, which are responsible for making sperm. There are two main types of germ cell tumors and the diagnosis is made under the microscope.

• Seminoma
• Non-seminoma
• Embryonal carcinoma
• Yolk sac carcinoma
• Choriocarcinoma
• Teratoma

Stromal tumors, which are often benign, account for 5% of adult testis cancers and are comprised of: (1) Leydig cell tumors and (2) Sertoli cell tumors.

Risks & Causes

Cryptorchidism (or undescended testis) can increase the risk of developing cancer in the affected testis, as well as the opposite testis, even if it is normally descended. The degree to which surgical correction of cryptorchidism (called "orchidopexy") can decrease this risk has not been determined, although there appears to be a protective effect when surgery is performed prior to puberty.

Individuals who have had testis cancer in one testis have about a 3-4% chance of developing cancer in the opposite testis. All individuals who have a history of cryptorchidism or testis cancer require lifelong surveillance by examination. White men versus Black and Asian men have a four- to five-times higher risk for developing testis cancer. Evidence for other risk factors has been lacking. Although patients often report a history of preceding testicular trauma, this event usually leads to self-examination and incidental discovery of a mass that is not associated with the trauma.

HIV patients have a greater risk of developing other tumors such as lymphoma and sarcoma that can affect the testes; however, these patients' risk of GCT appears to be the same as seen in the overall population.

Patients with Klinefelter's syndrome are at greater risk of forming GCT outside of the testes, notably inside the chest (mediastinum). Exposure of pregnant women to diethylstilbesterol (DES) appears to increase the incidence of testis cancer in their male children. However, the effect of DES on adult men does not appear to increase the risk of developing testis cancer.

Some have proposed that increased scrotal temperature, which may occur in those with a sedentary lifestyle, may be a putative factor in the formation of testicular neoplasia. Investigations thus far are inconclusive.

Symptoms & Evaluation

Testis cancer is suspected with the finding of any mass involving the body of the testicle, although germ cell tumors (GCTs) are found outside of the testis in about 10% of cases.

Classically, these testicular masses are described as painless, firm lesions ranging in size from millimeters to a few centimeters. However, it is common for there to be some degree of pain or swelling in the involved testicle or other associated testicular structures, possibly caused by bleeding or inflammation within the tumor.

Other, non-neoplastic processes can also cause these findings, necessitating further tests to confirm the diagnosis before considering surgery. A full examination including lymph node and rectal exam should be performed as well as urine and, when indicated, blood tests. A scrotal ultrasound is a safe and non-invasive test often used to determine the anatomic relationship between the mass and the testis, as well as to identify components of fluid and blood flow.

Diagnosis of a testicular GCT requires microscopic tissue examination by a pathologist. Tissue is obtained by surgical removal of the involved testis (inguinal orchidectomy) through a groin incision using an approach similar to performing a hernia repair.

GCT can spread to other parts of the body through the lymphatic drainage from the testicle, so further imaging tests are performed, including chest x-ray and computed tomography (CT scan) of the abdomen and pelvis, to look for evidence of tumor growth in the lymph nodes or other sites.

Further treatment largely depends on the type of GCT found by the pathologist and the results of imaging tests for staging. Germ cell tumors of the testis are divided into two broad categories based on microscopic findings: seminoma and nonseminomatous tumors.

• Seminoma is the most common type of testis cancer, occurring in roughly 50% of all cases. Seminomas are very sensitive to both radiation and chemotherapy treatments and are considered highly curable cancers with excellent long-term disease free survival when treated appropriately.
• The group of nonseminomatous tumors includes embryonal carcinoma, choriocarcinoma, yolk sac tumor and teratoma.

Tumors may be composed of a mix of these different cell types, including seminoma, and are treated as nonseminomatous cancer. These tumors are somewhat more difficult to treat than pure seminoma due to their more aggressive biology and diminished response to chemotherapy.

Serum Markers

Some GCTs release products into the blood stream that can be detected in the laboratory. These products, referred to as tumor markers, include alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH). Unfortunately, these markers are not always present in the blood of patients with GCT and are not reliable as a screening test for cancer. When markers are detectable, they provide clues in diagnosing the type of GCT present and in following the response to treatment. Higher marker values are correlated with greater extent of disease. A summary of these markers and their expression by different tumor cell types is provided in table 1.

Tumor Marker (normal range) Tumor type producing marker
AFP (<5 ng/ml) Embryonal Carcinoma, Yolk Sac Tumor
HCG (<5 ng/ml) Choriocarcinoma, Embryonal, Seminoma
LDH (<200 ng/ml) Any (nonspecific marker)

Staging

There are three stages of tumor progression related to the anatomical sites in which cancer is found (table 2).

1. Stage I cancer is limited to the testicle with no evidence of lymph node involvement.
2. Stage II disease signifies the presence of lymph node involvement at predictable sites known for tumor spread within the abdomen or pelvis (retroperitoneum) and can be evaluated with CT scan.
3. With Stage III, the cancer has spread to areas outside of these usual sites and may involve the lungs, distant lymph nodes, or other organs. Patients with Stage III cancer may have very high tumor marker concentrations on blood tests without evidence of tumor spread seen.

Natural Progression

Natural progression of testis tumors is typically fairly rapid. Therefore, intensive follow-up of men treated for testis tumors is needed for the first several years after initial therapy.

Unfortunately, late recurrence of testis tumors can also occur. Several subsets of men with testis cancer need longer follow-up or more intensive treatment than has been previously proposed. Men who have had tumors of the retroperitoneum (the lymph nodes in the back of the abdomen) need to have complete removal of all lymph nodes, not just removal of obviously affected nodes or a limited number of lymph nodes. For those men who have had lymph node sampling alone should have a complete surgical lymph node resection.

In addition, men who have had apparently successful treatment may remain at risk for late recurrences many years after initial treatment, especially after chemotherapy. Chemotherapy may reduce aggressive tumors to teratomas or other "benign" lesions that may subsequently degenerate into aggressive cancers that are relatively resistant to standard chemotherapy and may require surgical treatment. Yearly follow-up has been suggested by some for men rendered "disease-free" by chemotherapy.

Treatment Options

Following radical orchiectomy, imaging and serum tumor markers give information about the testicular type (seminoma versus non-seminoma) and cancer stage.

For men with Stage I non-seminoma, surveillance may be an appropriate option and may provide a cure in approximately 70% of men without the risks of chemotherapy or surgery. A recent study by Sharir et al., looked closely at the best means of detecting tumor spread in a group of 170 patients being followed by surveillance. As expected, almost 30% had disease progression within 2 years after initial diagnosis and were treated. The most important tools for diagnosing these patients included history, physical examination, tumor markers and CT scanning at regularly performed intervals, starting 2 months after initial orchiectomy. Even with this extremely close follow-up, one patient died of cancer.

Two cycles of chemotherapy is also an option for men with Stage I non-seminoma. The advantage of this approach is to treat the 30% of men who may have residual disease; however, the disadvantage are the side effects of chemotherapy, which include potential damage to hearing and/or to the kidneys. Side effects can also include neuropathy, or hypersensitivity to cold and heat, and numbness or tingling sensations in the hands or feet.

Retroperitoneal lymph node dissection (RPLND) is surgical removal of the lymph nodes where testicular cancer may land. Advances in surgical approaches to RPLND have significantly decreased the complications from this procedure. The developments of nerve sparing surgery and modified template dissections have limited the previously encountered problems of retrograde ejaculation following this operation. Although this was traditionally performed using an open surgical approach, faculty at Weill Cornell offer a minimally invasive approach with robotic assistance. This shortens the length of hospitalization to an overnight stay and leads to shorter return to activities of daily living.

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