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Testicular Cancer

Table of Contents
1 Disease Overview
        1.1 Types
        1.2 Risk Factors and Prevention
        1.3 Screening
        1.4 History, Symptoms and Signs
        1.5 Diagnosis and Tumour Assessment
2 Histologic Classification of Germ Cell Neoplasms
3 Staging
4 Stage Grouping
5 Treatment Modalities
        5.1 Seminoma
        5.2 Nonseminoma
6 Follow-up
7 Pivotal Trials

Disease Overview

    Primary testicular cancer is the most common solid tumour in young men. Canadian cancer statistics reported 884 new cases and 43 deaths in 2005. Although the incidence has been increasing over the past century, mortality has decreased. Unlike other cancers, testicular cancer is highly curable solid tumour, even in advanced stages.

Types

    Approximately 95% of all testicular cancers are germ cell tumours. These tumours may consist of a single cell type (pure germ cell tumours, approximately 50%) or contain more than one cell type (mixed germ cell tumours, approximately one-third of testicular cancers). The cell type determines the risk of metastasis and treatment response.

  • Pure germ cell tumours:
    • Seminoma includes classic, anaplastic, and spermatocytic types.
    • Nonseminoma includes choriocarcinoma, embryonal carcinoma, teratoma, and yolk sac tumours.
  • Mixed germ cell tumours:
    • Embryonal carcinoma and teratoma with or without seminoma.
    • Embryonal carcinoma and yolk sac tumour with or without seminoma.
    • Embryonal carcinoma and seminoma.
    • Yolk sac tumour and teratoma with or without seminoma.
    • Choriocarcinoma and any other element.

Mixed germ cell tumours behave like nonseminomas.

Risk Factors and Prevention

The following factors affect testicular cancer risk:

  • Cryptorchidism increases risk 4-8 times, but orchiopexy before six years of age can reduce this risk.
  • Previous testicular cancer is the strongest risk factor, with 1-2% of patients developing a second primary tumour in the other testicle.
  • Genetic factors are implicated. Chromosomal abnormalities, including Klinefelter syndrome, Down syndrome, and others, are associated with an increased testicular cancer risk.
  • Family history is also important. First-degree relatives of an individual with testicular cancer have increased risk, especially siblings, whose risk is increased by 8-10 times.
  • Male factor infertility predisposes to the development of testicular cancer.
  • Environmental factors, such as in-utero exposure to diethylstilbestrol, which is linked to cryptorchidism, and industrial chemical exposure, increase risk.

Screening

    No screening test is available. Early detection relies on adolescent males knowing the normal appearance and texture of their testicles and promptly reporting changes to their doctor.

History, Symptoms and Signs

    The most common presenting symptom of local disease is a painless swelling or nodule that appears attached to a testicle. Depending on organ involvement, advanced testicular cancer may have a variety of symptoms, including cervical lymph node mass, gastrointestinal symptoms, back pain, respiratory symptoms, or neurological symptoms. Gynecomastia may be present in tumours that produce human chorionic gonadotropin (β-hCG).

Diagnosis and Tumour Assessment

    A testicular mass should be considered cancer until proven otherwise. Physical examination should include a detailed examination of both testicles, and a careful search for lymphadenopathy, gynecomastia, hepatomegaly and bone tenderness.

    Laboratory investigation includes hematology, chemistry profile including lactic dehydrogenase (LDH), and serum tumour markers (α-fetoprotein [α-FP] and β-hCG). Tumour markers are increased in about 80-85% of nonseminoma tumours. Elevation of tumour markers and LDH is insufficient for tumour diagnosis, but levels are important for prognosis and monitoring during follow-up.

    Specific germ cell tumours have characteristic features on ultrasound, but this modality does not provide reliable staging information. CT scan of the abdomen and pelvis, and chest x-rays are initial investigations. CT scan of the thorax may be performed, if indicated.

    Histopathology of the surgically removed testicle is required for definitive diagnosis and staging.


Hisologic Classification of Germ Cell Neoplasms


Staging


Stage Grouping


Treatment

    Treatment of testicular cancer depends on the type and stage of disease and consists of surgery, radiation, and platinum based combination chemotherapy.

Seminoma

    After radical inguinal orchiectomy, patients in early stage disease (I, IIA, IIB) are administered radiation therapy to the retroperitoneal lymph nodes (para-aortic field) with or without the ipsilateral pelvic lymph nodes.

    Patients with stage IIA and IIB disease are administered radiation therapy to the retroperitoneal lymph nodes and the ipsilateral pelvic lymph nodes. Prophylactic mediastinal radiation is not recommended since few patients relapse in the mediastinum.

    Chemotherapy cures 90% of patients who relapse after radiotherapy; ultimately, 99% of patients with early stage seminoma are cured. Patients with stage IIC disease receive chemotherapy after radiotherapy to the retroperitoneal and ipsilateral lymph nodes as relapse is common when patients are exclusively treated with radiotherapy.

    In 70% to 80% of patients with germ cell tumours, first combination chemotherapy regimens consisting of visblatine, cisplatin, and bleomycin resulted in complete remission. However, a common side effect from combination chemotherapy includes bleomycin-induced pulmonary fibrosis and neuromuscular toxic effects, promoting a need to identify patients who would mostly likely (“good-risk”) and least likely (“poor-risk”) achieve the highest probability of cure with the least morbidity.

Nonseminoma

    For patients with stage I disease, the standard treatment options are surveillance and nerve-sparing retroperitoneal lymph node dissection. Twenty percent of patients following surgery will have a relapse and will require chemotherapy. Most recurrences will occur within 2 years after therapy, and will require follow-up including a history, chest x-ray, physical examination, and a measurement of serum tumour markers monthly as well as an abdominal CT scan every 3 months in the first year.

    Patients with stage II disease are treated with either retroperitoneal lymph node dissection or chemotherapy. Patients who have undergone retroperitoneal lymph node dissection average a relapse rate of 35% if the tumour size is less than 2 cm or less in diameter or 5 or less lymph nodes are involved. Adjuvant chemotherapy is not recommended for patients in this condition as cure rate is not significantly different from those patients who report for follow-up examinations. In patients with tumour sizes greater than 2 cm or with 6 or more lymph nodes involved, or with extranodal invasion, adjuvant chemotherapy is the treatment of choice. A majority of patients in this group who decline chemotherapy will relapse; in comparison, two cycles of adjuvant platinum-based chemotherapy will cure approximately 99% of patients. Patients choosing to withhold chemotherapy until relapse have similar rates of cure, but will require more cycles of chemotherapy and additional surgery.

    In patients with stage III disease, 70% to 80% will be cured with platinum-based chemotherapy combined with surgery.

    Management of advanced germ cell tumours by risk classification is based on the international germ cell consensus classification.

For chemotherapy regimens, refer to: http://www.cancercareontario.com/

Follow-Up

    Detailed follow-up schedules for disease-free patients depend on histopathologic diagnosis and disease stage. Goals of follow-up is early recognition and treatment of potentially curable recurrences or a second primary. Identification of symptoms related to metastatic disease and appropriate work up and prompt treatments. Identification and management of treatment related complications, ie. increased risk of cardiovascular disease in long term survivors related to chemotherapy, radiation and tobacco use, oligospermia, pulmonary toxicity, anxiety, and increased risk of other cancers due to chemotherapy.

    Survivors with testicular cancers need specialized follow-up with close attention to monitoring and prevention of late effects of cancer and cancer therapy. Encourage healthy lifestyle. Generally, history and physical examination and assays of α-FP, β-hCG, and LDH are performed frequently and supplemented with periodic abdominal and pelvic CT scans, chest radiography, and other tests as indicated. Follow-up frequency decreases as disease-free interval increases. There should be provision of ongoing psychosocial support for survivors and it is important to encourage a healthy and active lifestyle.

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Pivotal Trials

Einhorn LH, Forester RS. Bleomycin, etoposide, and cisplatin for three cycles compared with etoposide and cisplatin for four cycles in good-risk germ cell tumours: is there a preferred regime? J Clin Oncol. 2006;24(16):2597-2598; author-reply 2598-2599