Testicular Cancer

Background

• Testicular cancer refers to a germ cell tumor arising in the testis. This includes both:
  • seminoma, originating in the germinal epithelium of the seminiferous tubules
  • nonseminoma testicular cancer, which encompasses all other germ cell tumors, both pure and mixed
• Types of nonseminoma testicular cancer include:
  • choriocarcinoma
  • yolk sac tumor
  • teratoma (mature or immature)
  • embryonal cell carcinoma
  • mixed germ cell tumor
  • seminomas with elevated alpha fetoprotein (AFP)
• Testicular germ cell tumors are the most common solid tumor in men aged 20-34 years. The incidence has increased in the United States over the last 2 decades with an estimated 8,430 new cases in 2015.
• Key risk factors include a personal or familiar history of testicular cancer, cryptorchidism, or genetic syndromes such as Klinefelter syndrome.
• The pathogenesis involves distinct abnormalities of gene expression in germ cells and different levels of DNA methylation that may produce the various histologic subtypes.

Evaluation

• The most common presentation is a painless testicular mass, but some may present with testicular discomfort or swelling. Other potential presentations due to the spread of the cancer include back pain, cough, hemoptysis, or headaches.
• The physical exam should include palpation of both testes for the presence of a firm, unilateral nodule.
• Initial testing includes a testicular ultrasound to confirm mass, blood tests (complete blood count, electrolytes and creatinine, liver function tests, and serum tumor markers such as beta-human chorionic gonadotropin (beta-hCG), lactate dehydrogenase (LDH), alpha fetoprotein [AFP]), and a chest x-ray (Strong recommendation).
• A biopsy should not be performed if a hypoechoic mass is found on the ultrasound, or if microcalcifications are found with no other abnormalities (Strong recommendation).
• Consider a contralateral testicular biopsy if there are suspicious ultrasound results with intratesticular abnormalities, cryptorchid testis, or significant testicular hypertrophy (Weak recommendation).
• Perform a radical inguinal orchiectomy to confirm diagnosis and help determine staging (Strong recommendation).
• Postdiagnostic evaluation (after orchiectomy) to determine staging:
  • Obtain a computed tomography (CT) of the abdomen and pelvis with or without chest imaging; for seminoma, obtain a CT of the chest if there is an abnormal chest x-ray or abnormal abdominal CT (Strong recommendation).
  • Repeat serum tumor markers (Strong recommendation); TNM staging is based on postorchiectomy values.
  • Consider a magnetic resonance imaging (MRI) of the brain and bone scan if metastasis to those locations is suspected (Weak recommendation).

Management

General management

• Discuss sperm banking for patients of reproductive age due to complication of infertility (Strong recommendation).
• Consider risk stratification to guide treatment selection for primary chemotherapy (Weak recommendation).

Management of seminoma

• Primary treatment:
  • For patients with clinical stage IA or IB disease:
    • Offer surveillance for patients with pT1-pT3 tumors as the preferred first-line therapy (Strong recommendation)
    • Consider either chemotherapy with carboplatin or radiation therapy as alternative treatment options (Weak recommendation).
  • For patients with clinical stage IS disease, repeat evaluation of serum markers and abdominal/pelvic CT scan to determine extent of disease (Strong recommendation).
  • For patients with clinical stage IIA disease, consider radiation therapy (including para-aortic and ipsilateral iliac lymph nodes) as the preferred first-line therapy, or consider chemotherapy as an alternative treatment option in cases of multiple positive lymph nodes (Weak recommendation).
  • For patients with clinical stage IIB disease, consider chemotherapy as the preferred first-line therapy, or consider radiation therapy (including para-aortic and ipsilateral iliac lymph nodes) as an alternative treatment option in nonbulky cases (Weak recommendation).
  • For patients with clinical stage IIC and III disease, offer chemotherapy (Strong recommendation).
• Adjuvant treatment for clinical stage II-III treated with primary chemotherapy:
  • If there is a residual mass or mass ≤ 3 cm and normal tumor markers, consider surveillance (Weak recommendation).
  • If there is a residual mass > 3 cm with normal tumor markers, consider a positron emission tomography (PET) scan at 6 weeks after completion of chemotherapy (Weak recommendation):
    • If the PET scan is negative, consider surveillance (Weak recommendation).
    • If the PET scan is positive, consider retroperitoneal lymph node dissection if feasible, or second-line chemotherapy for metastatic disease (Weak recommendation).
  • If disease progression is evident (growing mass or increasing tumor markers), treat as second-line chemotherapy for nonseminoma (Strong recommendation).
• Surveillance includes a periodic history and physical exam, assessment of serum tumor markers, abdominal and pelvic CT, and chest x-ray.

Management of nonseminoma testicular cancer

• Primary treatment:
  • For patients with clinical stage IA disease, consider surveillance as the preferred first-line therapy, or nerve-sparing retroperitoneal lymph node dissection (RPLND) as an alternate therapy (Weak recommendation).
  • For patients with clinical stage IB disease, consider either nerve-sparing RPLND or primary chemotherapy, or surveillance in cases of pT2 tumors (Weak recommendation).
  • For patients with clinical stage IIA disease with negative tumor markers, consider either nerve-sparing RPLND or primary chemotherapy (Weak recommendation).
  • For patients with clinical stage IIB with negative tumor markers:
    • If lymph node metastases are evident within lymphatic drainage sites, consider either primary chemotherapy or nerve-sparing RPLND (Weak recommendation).
    • If multifocal, symptomatic, or lymph node metastases with aberrant lymphatic drainage are evident, consider primary chemotherapy (Weak recommendation).
  • For patients with clinical stage IS, IIA-C, or IIIA-C disease with persistently elevated tumor markers, offer primary chemotherapy (Strong recommendation).
  • For patients with brain metastases, consider primary chemotherapy with or without radiation therapy and with or without surgery if clinically indicated (Weak recommendation).
• Adjuvant treatment:
  • For patients with clinical stages IIA-B disease with negative tumor markers after chemotherapy:
    • In patients with a residual mass ≥ 1 cm on a CT scan, consider nerve-sparing RPLND (Weak recommendation).
    • In patients with no mass or a residual mass < 1 cm on a CT scan, consider either surveillance, or nerve-sparing RPLND in select cases (Weak recommendation).
  • For patients with clinical stage IS, IIA-IIC, or IIIA-IIIC with persistent marker elevation after chemotherapy:
    • If there is a complete response to chemotherapy (negative markers) and original stage IS, consider surveillance (Weak recommendation).
    • If there is a complete response to chemotherapy (negative markers) and original stage IIA-IIC or IIIA, consider surveillance or bilateral RPLND with or without nerve sparing in select cases (Weak recommendation).
    • If there is a partial response to chemotherapy (residual masses with normal alpha fetoprotein [AFP] and beta-human chorionic gonadotropin [beta-hCG] levels), consider surgical resection of all residual masses (Weak recommendation).
      • If only teratoma or necrosis are found, consider surveillance (Weak recommendation).
      • If residual embryonal, yolk sac, choriocarcinoma, or seminoma elements are found, consider primary chemotherapy or second-line chemotherapy (Weak recommendation).
    • If there is an incomplete response, consider second-line chemotherapy (Weak recommendation).
  • For patients with clinical stage IA, IB, IIA, or IIB disease after nerve-sparing RPLND:
    • If pN0 disease, consider surveillance (Weak recommendation).
    • If pN1 disease, surveillance is the preferred adjuvant therapy, but second-line chemotherapy may be considered as an alternative treatment option (Weak recommendation).
    • If pN2 disease, second-line chemotherapy is the preferred adjuvant therapy, but surveillance may be considered as an alternative treatment option (Weak recommendation).
    • If pN3 disease, consider second-line chemotherapy (Weak recommendation).
• Treatment of relapsed or refractory disease:
  • In patients with relapse within 2 years, enrollment in a clinical trial is preferred; for a list of trials for testicular cancer that are currently recruiting patients, see clinicaltrials.gov.
    • In patients with favorable prognosis having progression or relapse after first-line chemotherapy, consider conventional- or high-dose chemotherapy (Weak recommendation).
    • In patients with unfavorable prognosis after first-line chemotherapy, consider conventional- or high-dose chemotherapy, or salvage surgery if the relapse is in a solitary site (Weak recommendation).
  • In patients with disease recurrence > 2 years after the completion of primary treatment, consider:
    • surgical salvage as the preferred treatment in cases of resectable disease (Weak recommendation)
    • second-line chemotherapy (conventional- or high-dose) as an alternative treatment (Weak recommendation)
• Surveillance includes a periodic history and physical exam, assessment of serum tumor markers, abdominal and pelvic CT, and chest x-ray.