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Testicular Cancer
Aka: Testicular Cancer, Testicular Neoplasm, Testicular Tumor
- See Also
- Testicular Mass
- Epidemiology
- Accounts for 1% of all cancers in males
- Age of onset
- Peak age: 30-34 years old (ranges 12 to 35)
- Most common cancers in males ages 15 to 34 years
- Rare in early childhood
- Incidence: Has doubled since 1960s
- New cases in U.S. (2017): 8560 (410 deaths)
- Cases per 100,000: 5.6 (14.6 at age 30-34 years old)
- Geographic variation
- Highest rates: Scandanavia and Germany, hispanic, native alaskan and native american
- Lowest rates: Asia and Africa
- Risk Factors
- Cryptorchidism (Undescended Testicle)
- Accounts for 10% of cases
- Confers 2.9 to 6.3 fold increased risk
- Risk increases
- Intraabdominal Testicle (contrast with inguinal)
- Bilateral crytorchidism
- Repair after age 12 years old (5 fold increased risk)
- 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
- Father with Testicular Cancer increases Relative Risk 3.8 fold
- Brother with Testicular Cancer increases risk 6-10 fold
- Testicular Germ Cell Tumor 1 (Chromosome Xq27)
- Tobacco Abuse
- 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
- Pathophysiology
- Germinal or Germ Cell Tumors (95-97%)
- Seminoma (most common, 50% of germ cell tumors)
- Non-Seminoma Germ Cell tumors (NSGCT)
- Embryonal cell carcinoma
- Yolk Sac tumor (postpubertal)
- Teratoma (postpubertal)
- Trophoblastic Tumor (e.g. Choriocarcinoma)
- Nongerminal tumors (sex cord-stromal tumors)
- Leydig cell tumor (associated with Precocious Puberty)
- Sertoli cell tumor
- Granulosa Cell Tumor
- Mixed germ cell and stromal tumors
- Gonadoblastoma
- Miscellaneous tumors
- Hemangioma
- Hematolymphoid tumors
- 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)
- Lymphoma
- Leukemia
- Metastatic Disease
- Evaluate for Gynecomastia (as well as Precocious Puberty signs)
- Overall 10% of patients (30% of Leydig cell tumors) produce bHCG
- Evaluate for systemic disease (metastases present in 5% of patients)
- Hemoptysis, cough or Dyspnea from pulmonary metastases
- Supraclavicular mass from lymph node metastases
- Abdominal mass from retroperitoneal spread
- Lumbar back pain from Vertebral metastases
- Differential Diagnosis
- See Testicular Mass
- Staging
- Based on TNMS classification
- T: Tis (carcinoma in situ) to T4 (tumor invades Scrotum)
- T1: Tumor limited to Testis (T1a < 3cm in size)
- T2: Lymphovascular invasion or other spread short of spermatic cord
- T3: Spermatic cord involvement
- T4: Scrotal involvement
- N: N0 (no lymph nodes involved) to N3 (one lymph node and 5 cm mass)
- N1: One or more lymph node masses <2 cm
- N2: One or more lymph node masses 2-5 cm
- N3: Lymph node masses >5 cm
- M: M0 (no distant metastases) to M1 (distant metastases present)
- M1a: Nonretroperitoneal nodal or pulmonary metastases
- M1b: Nonpulmonary visceral metastases
- S: S0 (normal Tumor Markers) to S3 (Tumor Markers significantly increased)
- Staging Summary (* denotes ANY)
- Note: Each stage is subdivided (Ia-b, IIa-c, IIIa-c )
- Stage I: Testicular Cancer involving Testicle only (T* N0 M0 S0)
- LDH <1.5x normal, bHCG <5k mIU/ml, AFP <1k ng/ml
- Stage II: Metastases to retroperitoneal nodes (T* N* M0 S0-1)
- LDH 1.5-10x normal, bHCG 5-50k mIU/ml, AFP <1-10k ng/ml
- Stage III: Metastases above diaphragm or to viscera (T* N* M1 S*)
- LDH >10x normal, bHCG >50k mIU/ml, AFP >10k ng/ml
- Imaging
- Scrotal and Testicular Ultrasound
- Differentiate intratesticular mass (presumed cancer) from extratesticular mass
- Efficacy in Testicular Cancer
- Test Sensitivity: 92-98%
- Test Specificity: 95-99.8%
- Additional studies for cancer staging and evaluation for metastases
- CT Abdomen and Pelvis
- Chest XRay or CT Chest
- Labs: Tumor Markers
- Alpha fetoprotein (aFP)
- Secreted by non-seminoma GCT or mixed tumors
- Not secreted by a pure seminoma or Choriocarcinoma
- Falls to <25 ng/ml by 25-35 days after orchiectomy
- Human chorionic gonadotropin (bHCG)
- Secreted by 50% non-seminoma GCT or mixed tumors
- Secreted by 10% of seminomas
- Undetectable by 5 to 8 days after orchiectomy
- Lactate Dehydrogenase (LDH, especially LDH-1)
- Elevated in 60% of patients with non-seminoma GCT
- Increases with tumor burden (esp. widespread and metastatic cancer)
- Other lab testing
- Comprehensive metabolic panel
- Management: Treatments
- Surgery: Radical orchiectomy by inguinal approach
- High ligation spermatic cord (to Internal Inguinal Ring)
- Further therapy directed by histology
- Chemotherapy
- Agents (typically Cisplatin combined with one or both of the other agents)
- Carboplatin
- Cisplatin (Platinol)
- Etoposide (Vepesid)
- Bleomycin (Blenoxane)
- Indications
- Advanced spread of disease
- Advanced stage seminoma and non-seminomas
- Radiotherapy
- Indicated for early-stage seminomas
- Management: Seminoma
- Radical orchiectomy is performed for all stages
- Stage I (T1-T3 tumors)
- Active surveillance (preferred) OR
- Single-agent carboplatin or Radiotherapy
- Stage II
- Stage IIA
- Radiotherapy (preferred) OR
- Etoposide-Cisplatin for 4 cycles OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles
- Stage IIB
- Etoposide-Cisplatin for 4 cycles (preferred) OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles (preferred) OR
- Radiotherapy of regional lymph nodes
- Stage IIC
- Etoposide-Cisplatin for 4 cycles OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles
- Stage III
- Etoposide-Cisplatin for 4 cycles OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles
- Management: Nonseminoma
- Radical orchiectomy is performed for all stages
- Stage I (IA and IB)
- Active surveillance (preferred for IA) OR
- Retroperitoneal lymph node dissection (RPLND) OR
- Bleomycin-Etoposide-Cisplatin for 1-2 cycles (if Stage IB)
- Stage II (IIA to IIC)
- Etoposide-Cisplatin for 4 cycles OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles OR
- Radiotherapy (for Stage IIA and select Stage IIB cases)
- Stage III
- Stage IIIA
- Etoposide-Cisplatin for 4 cycles OR
- Bleomycin-Etoposide-Cisplatin for 3 cycles OR
- Stage IIIB
- Bleomycin-Etoposide-Cisplatin for 4 cycles
- Stage IIIC
- Bleomycin-Etoposide-Cisplatin for 4 cycles OR
- Etoposide-Ifosfamide-Cisplatin for 4 cycles (in select cases)
- Monitoring: Five year
- Surveillance after initial management is typically for 5 years
- Exact monitoring protocols vary by tumor type and stage
- This section summarizes more specific guidelines
- History and physical
- Initially every 2-3 months, then every 3-6 months and then annually
- Abdominal and Pelvic CT
- Initially every 3-6 months, then every 6-12 months
- PET/CT surveillance may be obtained in higher stage cancers
- Chest XRay
- As indicated in Stage I Seminoma, and in other tumors every 2-6 months initially, then every 6-12 months
- CT Chest may be indicated in symptomatic patients
- Tumor Markers (Serum bHCG, AFP levels, Lactate Dehydrogenase)
- Obtained at each history and physical
- Optional in Stage I and IIA Seminoma
- 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)
- Stage I Five year survival: 98%
- Stage II Five year survival: 97%
- 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
- Infertility
- Radiation-related
- Cardiac toxicity
- Leukemia or other secondary malignancy
- Chemotherapy-related
- General: Azoospermia, Leukemia or other secondary malignancy
- Cardiovascular mortality increases 5-fold in the first year after Chemotherapy
- Fung (2015) J Clin Oncol 33(28): 3105-15 [PubMed]
- Bleomycin: Lung toxicity
- Etoposide: Neurotoxicity with secondary Peripheral Neuropathy
- Cisplatin: Nephrotoxicity, Ototoxicity
- Resources
- NCCN Clinical Practice Guidelines: Testicular Cancer
- 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]