Testicular Cancer

See Also

Testicular Mass

Epidemiology

Accounts for 1% of all cancers in males
Age of onset
1. Peak age: 30-34 years old (ranges 12 to 35)
2. Most common cancers in males ages 15 to 34 years
3. Rare in early childhood
Incidence: Has doubled since 1960s
1. New cases in U.S. (2018): 8850 (410 deaths)
2. Cases per 100,000: 5.6 (14.6 at age 30-34 years old)
3. Geographic variation
  1. Highest rates: Scandanavia and Germany, hispanic, native alaskan and native american
  2. Lowest rates: Asia and Africa

Risk Factors

Cryptorchidism (Undescended Testicle)
1. Accounts for 10% of cases
2. Confers 2.9 to 6.3 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)
  4. Even with early orchiopexy, Testicular Cancer Relative Risk is still 2.2
Caucasian (4-5 fold increased risk)
Testicular Cancer in the contralateral Testicle (Relative Risk 12)
Family History of Testicular Cancer
1. Father with Testicular Cancer increases Relative Risk 3.8 fold
2. Brother with Testicular Cancer increases risk 6-10 fold
Testicular Germ Cell Tumor 1 (Chromosome Xq27)
Tobacco Abuse
1. Ongoing Tobacco use with a >12 pack year history confers 2 fold risk
Infertility (Relative Risk 1.6 to 2.8)
Testicular atrophy
Testicular dysgnesis
HIV Infection

Pathophysiology

Germinal or Germ Cell Tumors (95-97%)
1. Seminoma (most common, 50% of germ cell tumors)
2. Non-Seminoma Germ Cell tumors (NSGCT)
  1. Embryonal cell carcinoma
  2. Yolk Sac tumor (postpubertal)
  3. Teratoma (postpubertal)
  4. Trophoblastic Tumor (e.g. Choriocarcinoma)
Nongerminal tumors (sex cord-stromal tumors)
1. Leydig cell tumor (associated with Precocious Puberty)
2. Sertoli cell tumor
3. Granulosa Cell Tumor
Mixed germ cell and stromal tumors
1. Gonadoblastoma
Miscellaneous tumors
1. Hemangioma
2. Hematolymphoid tumors
3. Adenocarcinoma of the collecting duct or rete Testis

Symptoms

Painless, firm Testicular Mass found incidentally
Dull ache in Scrotum
Scrotal heaviness
Vague Abdominal Pain

Symptoms
Red Flag Presentations

Minor Scrotal Trauma causes significant injury (Scrotal Hematoma, Hydrocele)
Epididymitis with swelling or tenderness that fails to improve with Antibiotic therapy

Signs

Painless asymmetric, hard, firm Testicular Mass
Transilluminate for reactive Hydrocele
Evaluate for Inguinal Lymphadenopathy (as well as Supraclavicular Lymphadenopathy)
1. Lymphoma
2. Leukemia
3. Metastatic Disease
Evaluate for Gynecomastia (as well as Precocious Puberty signs)
1. Overall 10% of patients (30% of Leydig cell tumors) produce bHCG
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

Differential Diagnosis

See Testicular Mass

Staging

Based on TNMS classification
1. T: Tis (carcinoma in situ) to T4 (tumor invades Scrotum)
  1. T1: Tumor limited to Testis (T1a < 3cm in size)
  2. T2: Lymphovascular invasion or other spread short of spermatic cord
  3. T3: Spermatic cord involvement
  4. T4: Scrotal involvement
2. N: N0 (no Lymph Nodes involved) to N3 (one Lymph Node and 5 cm mass)
  1. N1: One or more Lymph Node masses <2 cm
  2. N2: One or more Lymph Node masses 2-5 cm
  3. N3: Lymph Node masses >5 cm
3. M: M0 (no distant metastases) to M1 (distant metastases present)
  1. M1a: Nonretroperitoneal nodal or pulmonary metastases
  2. M1b: Nonpulmonary visceral metastases
4. S: S0 (normal Tumor Markers) to S3 (Tumor Markers significantly increased)
Staging 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)
  1. LDH <1.5x normal, bHCG <5k mIU/ml, AFP <1k ng/ml
3. Stage II: Metastases to retroperitoneal nodes (T* N* M0 S0-1)
  1. LDH 1.5-10x normal, bHCG 5-50k mIU/ml, AFP <1-10k ng/ml
4. Stage III: Metastases above diaphragm or to viscera (T* N* M1 S*)
  1. LDH >10x normal, bHCG >50k mIU/ml, AFP >10k ng/ml

Imaging

Scrotal and Testicular Ultrasound
1. Differentiate intratesticular mass (presumed cancer) from extratesticular mass
2. Efficacy in Testicular Cancer
  1. Test Sensitivity: 92-98%
  2. Test Specificity: 95-99.8%
Additional studies for cancer staging and evaluation for metastases
1. CT Abdomen and Pelvis
2. Chest XRay or CT Chest

Labs
Tumor Markers

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
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
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)
Other lab testing
1. Comprehensive metabolic panel

Management
Treatments

Surgery: Radical orchiectomy by inguinal approach
1. High ligation spermatic cord (to Internal Inguinal Ring)
2. Further therapy directed by histology
Chemotherapy
1. Agents (typically Cisplatin combined with one or both of the other agents)
  1. Carboplatin
  2. Cisplatin (Platinol)
  3. Etoposide (Vepesid)
  4. Bleomycin (Blenoxane)
2. Indications
  1. Advanced spread of disease
  2. Advanced stage seminoma and non-seminomas
Radiotherapy
1. Indicated for early-stage seminomas

Management
Seminoma

Radical orchiectomy is performed for all stages
Stage I (T1-T3 tumors)
1. Active surveillance (preferred) OR
2. Single-agent Carboplatin or Radiotherapy
Stage II
1. Stage IIA
  1. Radiotherapy (preferred) OR
  2. Etoposide-Cisplatin for 4 cycles OR
  3. Bleomycin-Etoposide-Cisplatin for 3 cycles
2. Stage IIB
  1. Etoposide-Cisplatin for 4 cycles (preferred) OR
  2. Bleomycin-Etoposide-Cisplatin for 3 cycles (preferred) OR
  3. Radiotherapy of regional Lymph Nodes
3. Stage IIC
  1. Etoposide-Cisplatin for 4 cycles OR
  2. Bleomycin-Etoposide-Cisplatin for 3 cycles
Stage III
1. Etoposide-Cisplatin for 4 cycles OR
2. Bleomycin-Etoposide-Cisplatin for 3 cycles

Management
Nonseminoma

Radical orchiectomy is performed for all stages
Stage I (IA and IB)
1. Active surveillance (preferred for IA) OR
2. Retroperitoneal Lymph Node dissection (RPLND) OR
3. Bleomycin-Etoposide-Cisplatin for 1-2 cycles (if Stage IB)
Stage II (IIA to IIC)
1. Etoposide-Cisplatin for 4 cycles OR
2. Bleomycin-Etoposide-Cisplatin for 3 cycles OR
3. Radiotherapy (for Stage IIA and select Stage IIB cases)
Stage III
1. Stage IIIA
  1. Etoposide-Cisplatin for 4 cycles OR
  2. Bleomycin-Etoposide-Cisplatin for 3 cycles OR
2. Stage IIIB
  1. Bleomycin-Etoposide-Cisplatin for 4 cycles
3. Stage IIIC
  1. Bleomycin-Etoposide-Cisplatin for 4 cycles OR
  2. Etoposide-Ifosfamide-Cisplatin for 4 cycles (in select cases)

Monitoring
Five year

Surveillance after initial management is typically for 5 years
1. Exact monitoring protocols vary by tumor type and stage
2. This section summarizes more specific guidelines
History and physical
1. Initially every 2-3 months, then every 3-6 months and then annually
Abdominal and Pelvic CT
1. Initially every 3-6 months, then every 6-12 months
2. PET/CT surveillance may be obtained in higher stage cancers
Chest XRay
1. As indicated in Stage I Seminoma, and in other tumors every 2-6 months initially, then every 6-12 months
2. CT Chest may be indicated in symptomatic patients
Tumor Markers (Serum bHCG, AFP levels, Lactate Dehydrogenase)
1. Obtained at each history and physical
2. Optional in Stage I and IIA Seminoma
3. False Negatives in up to 35% of non-seminoma recurrence

Prevention

Testicular Cancer screening is not recommended in asymptomatic men (USPTF, NCI, AAFP)
Testicular Self-Exam

Prognosis

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%
Cure rate is 99% for early Testicular Cancer without metastases
When relapse occurs, it is typically within 18 months of Chemotherapy
Risk of cancer in opposite Testicle: 2 to 5%

Complications

Testicular Cancer related
1. Infertility
Radiation-related
1. Cardiac toxicity
2. Leukemia or other secondary malignancy
Chemotherapy-related
1. General: Azoospermia, Leukemia or other secondary malignancy
  1. Cardiovascular mortality increases 5-fold in the first year after Chemotherapy
    1. Fung (2015) J Clin Oncol 33(28): 3105-15 [PubMed]
2. Bleomycin: Lung toxicity
3. Etoposide: Neurotoxicity with secondary Peripheral Neuropathy
4. Cisplatin: Nephrotoxicity, Ototoxicity

Resources

NCCN Clinical Practice Guidelines: Testicular Cancer
1. https://www.nccn.org/professionals/physician_gls/default.aspx

References

Walsh (1998) Campbell's Urology, Saunders, p. 2411-45
Baird (2018) Am Fam Physician 97(4):261-8 [PubMed]
Horwich (2006) Lancet 367: 754-65 [PubMed]
Kinkade (1999) Am Fam Physician 59(9):2539-44 [PubMed]
Shaw (2008) Am Fam Physician 77: 469-76 [PubMed]