Testicular Cancer

1. Epidemiology
   1. Accounts for 1% of all cancers in males
   2. Age of onset
      1. Peak age: 32 years old (ranges 12 to 35)
      2. Most common cancers in males ages 15 to 34 years
      3. Rare in early childhood
   3. Incidence: Doubled since 1960s
      1. New cases in U.S. (1998): 7600
      2. Cases per 100,000: 4.2
      3. Geographic variation
         1. Highest rates: Scandanavia and Germany
         2. Lowest rates: Asia and Africa
2. Risk Factors
   1. Cryptorchidism (Undescended Testicle)
      1. Accounts for 10% of cases
      2. Confers 2.5 to 11 fold increased risk
      3. Risk increases
         1. Intraabdominal Testicle (contrast with inguinal)
         2. Bilateral crytorchidism
         3. Repair after age 12 years old (5 fold increased risk)
   2. Caucasian (4-5 fold increased risk)
   3. Family History of Testicular Cancer
      1. Brother with Testicular Cancer increases risk 6-10 fold
   4. Testicular Germ Cell Tumor 1 (Chromosome Xq27)
   5. Tobacco abuse
      1. Ongoing Tobacco use with a >12 pack year history confers 2x risk
   6. Testicular atrophy
   7. Testicular dysgnesis
3. Pathophysiology
   1. Germinal or Germ Cell Tumors (97%)
      1. Seminoma (most common)
      2. Non-Seminoma Germ Cell tumors (NSGCT)
         1. Embryonal cell carcinoma
         2. Teratoma
         3. Choriocarcinoma
   2. Nongerminal tumors
      1. Leydig's cell tumors
      2. Sertoli's cell tumors
      3. Gonadoblastoma
4. Symptoms
   1. Painless testicular mass found incidentally
   2. Dull ache in Scrotum
   3. Scrotal heaviness
   4. Vague Abdominal Pain
5. Symptoms: Red Flag Presentations
   1. Minor scrotal trauma causes significant injury (Scrotal hematoma, Hydrocele)
   2. Epididymitis that fails to improve with antibiotic therapy
6. Signs
   1. Painless asymmetric, firm testicular mass
   2. Transilluminate for reactive Hydrocele
   3. Evaluate for Inguinal Lymphadenopathy
   4. Evaluate for Gynecomastia
      1. Overall 10% of patients (30% of Leydig cell tumors) produce bHCG
   5. Evaluate for systemic disease (metastases present in 5% of patients)
      1. Hemoptysis, cough or Dyspnea from pulmonary metastases
      2. Supraclavicular mass from lymph node metastases
      3. Abdominal mass from retroperitoneal spread
      4. Lumbar back pain from Vertebral metastases
7. Staging
   1. Based on TNMS classification
      1. T: Tis (carcinoma in situ) to T4 (tumor invades Scrotum)
      2. N: N0 (no lymph nodes involved) to N3 (one lymph node and 5 cm mass)
      3. M: M0 (no distant metastases) to M1 (distant metastases present)
      4. S: S0 (normal Tumor Markers) to S3 (Tumor Markers significantly increased)
   2. Summary (* denotes ANY)
      1. Note: Each stage is subdivided (Ia-b, IIa-c, IIIa-c )
      2. Stage I: Testicular Cancer involving Testicle only (T* N0 M0 S0)
      3. Stage II: Metastases to retroperitoneal nodes (T* N* M0 S0-1)
      4. Stage III: Metastases above diaphragm or to viscera (T* N* M1 S*)
8. Imaging
   1. Scrotal and Testicular Ultrasound
      1. Differentiate intratesticular mass (presumed cancer) from extratesticular mass
   2. Additional studies for cancer staging and evaluation for metastases
      1. Abdominal CT
      2. Chest XRay or CT Chest
9. Labs: Tumor Markers
   1. Alpha fetoprotein (aFP)
      1. Secreted by non-seminoma GCT or mixed tumors
      2. Not secreted by a pure seminoma or Choriocarcinoma
      3. Falls to <25 ng/ml by 25-35 days after orchiectomy
   2. Human Chorionic Gonadotropin (bHCG)
      1. Secreted by 50% non-seminoma GCT or mixed tumors
      2. Secreted by 10% of seminomas
      3. Undetectable by 5 to 8 days after orchiectomy
   3. Lactate Dehydrogenase (LDH, especially LDH-1)
      1. Elevated in 60% of patients with non-seminoma GCT
      2. Increases with tumor burden (esp. widespread and metastatic cancer)
10. Management
    1. Surgery: Radical orchiectomy by inguinal approach
       1. High ligation spermatic cord
       2. Further therapy directed by histology
    2. Chemotherapy
       1. Agents (typically Cisplatin combined with one or both of the other agents)
          1. Cisplatin (Platinol)
          2. Etoposide (Vepesid)
          3. Bleomycin (Blenoxane)
       2. Indications
          1. Advanced spread of disease
          2. Advanced stage seminoma and non-seminomas
    3. Radiation
       1. Indicated for early-stage seminomas
11. Monitoring: Serum bHCG and AFP levels
    1. Follow if previously elevated to monitor for recurrence
12. Prevention
    1. Testicular Self-Exam
13. Prognosis
    1. Overall 5 year survival > 95% (Previously 63% in 1963)
       1. Stage I Five year survival: 98%
       2. Stage II Five year survival: 97%
       3. Stage III Five year survival: 72%
    2. Cure rate is 99% for early Testicular Cancer without metastases
    3. When relapse occurs, it is typically within 18 months of Chemotherapy
    4. Risk of cancer in opposite Testicle: 2 to 5%
14. Complications
    1. Testicular Cancer related
       1. Infertility
    2. Radiation-related
       1. Cardiac toxicity
       2. Leukemia or other secondary malignancy
    3. Chemotherapy-related
       1. General: Azoospermia, Leukemia or other secondary malignancy
       2. Bleomycin: Lung toxicity
       3. Etoposide: Neurotoxicity with secondary Peripheral Neuropathy
       4. Cisplatin: Nephrotoxicity, Ototoxicity
15. References
    1. Walsh (1998) Campbell's Urology, Saunders, p. 2411-45
    2. Horwich (2006) Lancet 367: 754-65
    3. Kinkade (1999) Am Fam Physician 59(9):2539-44
    4. Shaw (2008) Am Fam Physician 77: 469-76