The treatment of testicular cancer is a success story in oncology. With available methods, 95% of men with this condition can be cured. Emphasis is shifting toward maintaining high cure rates and reducing or effectively managing late effects of treatment. A new review article on this topic comes from Dr. Nasser Hanna and Lawrence Einhorn at the Indiana University School of Medicine.
Fifty years ago, a diagnosis of metastatic testicular cancer meant a 90% chance of death within 1 year. Today, a cure is expected in 95% of all patients who have received a diagnosis of testicular cancer and in 80% of patients with metastatic disease.
•Describe the epidemiology and clinical presentation of testicular cancer.
In the United States, the incidence of testicular cancer, which is highest among whites and lowest among blacks, has increased steadily over the past 20 years. In some parts of northern Europe, the incidence has doubled, and in Denmark and Norway, 1% of men will receive a diagnosis of testicular cancer during their lifetime. Genetic and environmental factors appear to play a role in this increase in incidence. The risk of testicular cancer is 8 to 10 times as high in a brother of a person with testicular cancer and 4 to 6 times as high in a son of a person with testicular cancer as in a brother or son of an unaffected family member. Genetic disorders, including Down’s syndrome and the testicular dysgenesis syndrome, are also associated with increased risks of testicular cancer. Cryptorchidism, which occurs in 2 to 5% of boys born at term, is the most well-characterized risk factor for testicular cancer. The timing of orchiopexy influences the future risk of testicular cancer. However, 90% of persons with testicular cancer do not have a history of cryptorchidism. Recent investigations have shed light on the malignant transformation of normal gonocytes into germ-cell tumors. Germ-cell tumors appear to develop as a result of a tumorigenic event in utero that leads to a precursor lesion classified as intratubular germ-cell neoplasia. Most patients with testicular cancer receive a diagnosis when the disease is in stage I and present with a testicular mass. Less frequently, patients report back pain (secondary to enlarged retroperitoneal lymph nodes) or symptoms of metastatic disease, including cough, hemoptysis, pain, and headaches.
Table 1. Staging and Risk Stratification of Germ-Cell Tumors.
• What is the treatment for Stage I and Stage II seminoma?
Most patients with clinical stage I seminoma are cured with orchiectomy. Adjuvant radiation therapy was standard treatment for many years and was instrumental to the cure before the advent of effective chemotherapy. Over the past 20 years, the dose and field of radiation have been considerably reduced, and in many instances radiotherapy has been eliminated altogether. Most patients today are treated with active surveillance, although some still receive radiation therapy consisting of 20 Gy to the ipsilateral retroperitoneal lymph nodes (sometimes including the inguinal lymph nodes, depending on whether the patient had undergone prior surgery involving the inguinal, pelvic, or scrotal areas) or adjuvant carboplatin therapy. More relapses are associated with surveillance than with radiotherapy or chemotherapy (20% vs. 4%), but the long-term survival is nearly 100%, irrespective of the initial option chosen. For some patients with low-volume stage II seminoma (disease confined to the retroperitoneal lymph nodes, with the lymph nodes <3 cm in diameter), 30 to 36 Gy of radiation to the paraaortic and ipsilateral iliac lymph nodes remains a standard treatment. In other patients, the preferred treatment is chemotherapy with bleomycin, etoposide, and cisplatin (also known as BEP) for three cycles or etoposide and cisplatin for four cycles. Chemotherapy is preferred for patients with bulkier disease, since the rate of relapse is higher with radiotherapy alone. Cures are achieved in 98% of patients.
Table 2. Treatment Options for Stage I Seminoma.
Morning Report Questions
Q: How are the nonseminiferous germ-cell tumors managed?
A: Most patients with a nonseminomatous germ-cell tumor present with clinical stage I disease. Treatment options after orchiectomy include active surveillance, nerve-sparing retroperitoneal lymph-node dissection, and adjuvant BEP for one or two cycles; each of these options is associated with 99% long-term cure rates. Patients are characterized as high risk (relapse rates of 50% with surveillance) or low-risk (relapse rates of 15% with surveillance) according to the presence or absence of lymphovascular invasion. Patients with a low-volume stage II nonseminomatous germ-cell tumor (disease confined to the retroperitoneal lymph nodes, with the lymph nodes <3 cm in diameter) and normal beta-hCG [beta human chorionic gonadotropin] and AFP [alpha-fetoprotein] levels after orchiectomy are generally treated with retroperitoneal lymph-node dissection, although care must be individualized. Patients with higher-volume stage II disease or increasing levels of markers should receive chemotherapy (BEP for three cycles or etoposide and cisplatin for four cycles). Cures are achieved in 95 to 99% of patients.
Table 3. Treatment Options after Orchiectomy for Stage I Nonseminomatous Germ-Cell Tumor.
Q: What are long-term risks of treatment for a patient with testicular cancer?
A: Since most patients will survive after a diagnosis of testicular cancer, clinicians must be vigilant to reduce the long-term risks of therapy and limit unnecessary morbidity and early mortality. Therapeutic radiation has been recognized as a risk factor for secondary cancers. However, studies also implicate chemotherapy in the risk of cancers of the kidney, thyroid, soft tissue, bladder, stomach, and pancreas, as well as in the risk of lymphoma and leukemia. Survivors of testicular cancer are also at risk for later relapse of disease (defined as relapse >2 years after remission), as well as for the metabolic syndrome; cardiovascular disease; infertility; neurotoxic, nephrotoxic, and pulmonary toxic effects; Raynaud’s phenomenon; psychosocial disorders; and hypogonadism, which may confer a predisposition to sexual dysfunction, fatigue, depression, and osteoporosis. Retrograde ejaculation may develop postoperatively in men who have undergone retroperitoneal lymph-node dissection. The most comprehensive study to date is under way to understand the genetic susceptibility to the long-term toxic effects of platinum-based chemotherapy in survivors of testicular cancer.