Diagnosis and Treatment of Testicular Cancer

Testicular cancer is the most common solid tumor in young men between the ages of 20 and 35 and is one of the most curable forms of cancer.¹ According to the American Cancer Society, the 5-year survival rates for stage I, II, and III testicular cancer are 99%, 96%, and 72%, respectively. It is estimated, however, that there will be approximately 8010 new cases of testicular cancer diagnosed in 2005, with an estimated 390 men dying from this disease.²

Men at risk for the development of testicular cancer include those with a prior history or positive family history of testicular cancer, cryptorchidism, and Klinefelter's syndrome. Other risk factors in which a direct causal relationship has not been definitively established include male children of women exposed to diethylstilbestrol or oral contraceptives, a history of direct testicular trauma, viral orchitis, vasectomy, and those infected with HIV.^1,3

Common symptoms include persistent testicular pain, swelling, and/or hardness. A painless testicular mass occurs in only a minority of patients. Symptoms of a more advanced stage may include the following: lumbar pain, lower abdominal pain, or renal colic (possibly indicating retroperitoneal lymph node involvement); dyspnea, cough, hemoptysis, or chest pain (suggestive of extensive pulmonary metastases); or headache, confusion, dementia, or focal neurologic syndromes (possibly associated with brain metastases).^1,4

If an intratesticular mass is identified on physical examination or by ultrasound, an inguinal orchiectomy will be performed for pathologic confirmation and primary treatment. Further diagnostic workup such as a computed tomographic (CT) scan, chest x-ray, and/or magnetic resonance imaging may be indicated if clinical signs and symptoms of metastatic disease are present. Measurement of circulating tumor markers alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG) are utilized as part of the initial diagnostic workup and for monitoring therapy. Serum lactate dehydrogenase (LDH) also is determined in all patients.^1,3,4

Once all of the above diagnostic studies have been completed, the clinical stage is categorized and the appropriate treatment determined. Stage I disease is confined only to the testis; stage II disease is restricted to the retroperitoneum (involving abdominal lymph nodes); and stage III disease involves other distant nodal sites (mediastinum or supradiaphragm) or visceral metastases.^1,4 For patients with metastatic disease, a further prognostic grouping tool is utilized for treatment decisions and eligibility for clinical trials. This system is defined by the International Germ- Cell Cancer Collaborative Group and stratifies patients into 3 main groups based on serum HCG, AFP, LDH, and pattern of disease. These 3 groups include good-, intermediate-, and poor-prognosis disease.⁵

The majority (95%) of malignant tumors arising from the testes are germ cell tumors. Non-germ cell tumors and lymphomas comprise less than 5% of testicular cancers. Germ cell tumors are classified into 2 major subgroups: seminomas or nonseminomas.^1,3,4

Seminomas

Seminomas are clinically less aggressive than nonseminomas. Seminomas are associated with an increased serum concentration of HCG.³ Following inguinal orchiectomy, patients with stage I disease are treated with adjuvant radiotherapy to the infradiaphragmatic area, including para-aortic lymph nodes. In those unable to tolerate radiation therapy, surveillance is an alternative. Cure rates approach 100% with either strategy. In those who do not undergo adjuvant radiotherapy, however, 15% to 20% of patients may relapse.^3,6 For patients with stage II disease, adjuvant radiotherapy is administered to the infradiaphragmatic area as in stage I above, in addition to the ipsilateral iliac lymph nodes.³

Relapses that occur after treatment of a stage I or II seminomas are treated with chemotherapy. For good-risk germ cell tumors, chemotherapy (Table) may consist of 4 cycles of etoposide plus cisplatin (EP) or 3 cycles of bleomycin, etoposide, and cisplatin (BEP).^3,7,8 Those patients with intermediate-or poor-risk tumors are treated with 4 cycles of BEP or placed in a clinical trial.³

Patients with advanced-stage seminomas (stage IIC and III) are treated according to risk status. Good-risk patients receive 4 cycles of EP or 3 cycles of BEP (Table).^3,7,8 Those with intermediate-or poor-risk disease receive 4 cycles of BEP. Cure rates approach 90% with these regimens.³

Nonseminomas

Nonseminomas often are associated with an elevated serum concentration of HCG and AFP. Nonseminomas are considered more radioresistant than seminomas and may be associated with higher relapse rates and slightly lower cure rates. Multiple cell types such as embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma may be present.^3,4

For patients diagnosed with stage I disease, treatment options consist of observation, nerve-sparing retroperitoneal lymph node dissection (RPLND), or chemotherapy. Observation is recommended only for extremely compliant patients who can follow a very intense follow-up program (frequent CT scans, tumor markers, and chest x-rays). For most patients, RPLND is the preferred treatment option. In those unable to undergo surgery, 2 cycles of BEP is an option. Treatment options for patients with stage II disease include RPLND (with or without adjuvant chemotherapy) or primary chemotherapy alone (EP or BEP). The choice of therapy is dependent on whether tumor markers are negative or persistently elevated, whether the tumor is completely resected, and/or whether other lymphnode metastasis is present.^3,4

Advanced-stage nonseminoma patients are initially treated with chemotherapy according to risk status. Good-risk germ cell tumors are treated with either 4 cycles of EP or 3 cycles of BEP (Table).^3,7,8 Cure rates approach 90% with either regimen. The cure rates for intermediate-and poor-risk patients who receive 4 cycles of BEP are 70% and less than 50%, respectively. Enrollment in a clinical trial is preferred for poor-risk patients. If a complete response is observed following chemotherapy and tumor markers are negative, patients may undergo RPLND or surveillance. Any sites of residual disease that may be found following chemotherapy may undergo surgical resection.³

Salvage Therapy

Previously treated patients who do not respond or who relapse after firstline therapy may achieve a complete response with salvage chemotherapy. Successful chemotherapy regimens (Table) include VeIP (vinblastine, ifosfamide, and cisplatin), VIP (etoposide, ifosfamide, and cisplatin), and TIP (paclitaxel, ifosfamide, and cisplatin).^9-11 Other treatment options currently under investigation include high-dose chemotherapy plus autologous peripheral stem cell support and newer chemotherapeutic agents such as gemcitabine, irinotecan, and oxaliplatin.^4,5

Toxicities Associated with Treatment

Any of the therapeutic interventions utilized in the management of testicular cancer may compromise fertility. Any fertility concerns should be discussed thoroughly with the patient's physician prior to the initiation of treatment.

The most common acute toxicities associated with chemotherapy include nausea and vomiting, alopecia, myelosuppression, infection, allergic reactions, anorexia, and pneumonitis. Generally, these toxicities can be managed by general supportive care measures. Some of the delayed side effects associated with chemotherapy include cardiovascular and cerebrovascular disease, hypercholesterolemia, secondary malignancies such as leukemia or malignant melanoma, peripheral and autonomic neuropathies, pulmonary fibrosis, and renal complications.⁴

Dr. Saadeh is an associate professor of pharmacy practice at Ferris State University and works with the Sparrow Health System, Department of Pharmacy.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@ascendmedia.com.