Testicular Cancer¶
Chapter 93 | Part 4: Oncology and Hematology
KEY CLINICAL POINTS¶
- Testicular germ cell tumors (GCTs) account for 95% of all testicular neoplasms, with non-GCTs being rare.
- Seminomas (50% of cases) are radiosensitive, while nonseminomatous GCTs (NSGCTs) are chemosensitive.
- Staging is based on TNM classification: Stage I (testis only), Stage II (retroperitoneal lymph nodes), Stage III (distant metastases).
- Cisplatin-based chemotherapy (BEP/EP/VIP) is the cornerstone of treatment for metastatic disease.
- Retroperitoneal lymph node dissection (RPLND) is used for staging and treatment in select cases.
1. DEFINITION & OVERVIEW¶
Testicular germ cell tumors (GCTs) are the most common malignancy in adolescents and young adult males (15–39 years). They arise from primordial germ cells and include seminomas and nonseminomatous GCTs (NSGCTs). NSGCTs are further classified into embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma. GCTs are highly curable with modern therapies, earning them the title 'a model for a curable neoplasm.'
Table 93-1: International Germ Cell Consensus Classification System¶
| RISK GROUP | SEMINOMA | NSGCT |
|---|---|---|
| Good | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent | Gonadal or retroperitoneal primary; nonpulmonary visceral metastases absent; AFP <1000 ng/mL; hCG <5000 mIU/mL; LDH <1.5 × ULN |
| Intermediate | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent; one of the following: AFP 1000–10,000 ng/mL; HCG 5000–50,000 mIU/mL; LDH 1.5–10 × ULN | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases present |
| Poor | N/A | Mediastinal primary; nonpulmonary visceral metastases present; or one of the following: AFP >10,000 ng/mL; HCG >50,000 mIU/mL; LDH >10 × ULN |
1.1 Subtopic¶
GCTs are divided into seminomas (50% of cases) and NSGCTs (50% of cases). Seminomas are radiosensitive, while NSGCTs are chemosensitive. Molecular analysis reveals isochromosome 12p (i[12p]) in most cases, with KITLG locus on chromosome 12 being a major risk factor.
2. EPIDEMIOLOGY¶
In 2023, ~9,200 cases of testicular GCTs were diagnosed in the U.S., with 470 deaths. Incidence is highest in Scandinavia, Western Europe, and Australia/New Zealand; lowest in Africa and Asia. Risk factors include cryptorchidism (4–6x increased risk), family history (heritability ~50%), and prior GCT. NSGCTs are more common in Caucasians, while African Americans have lower incidence.
2.1 Demographics¶
Peak incidence in 15–39-year-olds. Incidence increases in men over 50. Seminomas peak in the fourth decade; NSGCTs peak in the third decade.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
GCTs originate from primordial germ cells. Genetic analysis shows i(12p) in most cases. NSGCTs have multiple independent loci, with KITLG on chromosome 12 being the strongest risk factor. Molecular events include chromosomal abnormalities and mutations in genes like KIT and TP53.
3.1 Molecular Basis¶
Isochromosome 12p (i[12p]) is common in GCTs. KITLG locus on chromosome 12 is a major risk factor. NSGCTs have higher heritability (~50%) than seminomas.
4. CLINICAL FEATURES¶
Painless testicular mass is the most common presentation. Other symptoms include testicular swelling, discomfort, back/flank pain, cough, hemoptysis (lung metastases), and gynecomastia (elevated hCG). Physical exam may reveal testicular atrophy, suprapubic masses, or inguinal lymphadenopathy.
4.1 Complications¶
Retroperitoneal metastases may cause back pain. Lung metastases may present with cough, hemoptysis. Liver/bone metastases are less common. Testicular atrophy and infertility are common sequelae.
5. DIFFERENTIAL DIAGNOSIS¶
Epididymitis/orchitis, hydrocele, varicocele, and testicular torsion. A trial of antibiotics may be considered for suspected infection. Scrotal ultrasound is essential to differentiate between benign and malignant masses.
6. INVESTIGATIONS & DIAGNOSIS¶
Scrotal ultrasound is the first-line imaging modality. Serum tumor markers AFP, hCG, and LDH are measured. CT of abdomen/pelvis and chest x-ray are used for staging. PET/CT may be used for residual masses post-chemotherapy.
Table 93-1: International Germ Cell Consensus Classification System¶
| RISK GROUP | SEMINOMA | NSGCT |
|---|---|---|
| Good | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent | Gonadal or retroperitoneal primary; nonpulmonary visceral metastases absent; AFP <1000 ng/mL; hCG <5000 mIU/mL; LDH <1.5 × ULN |
| RISK GROUP | SEMINOMA | NSGCT |
|---|---|---|
| Intermediate | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent; one of the following: AFP 1000–10,000 ng/mL; HCG 5000–50,000 mIU/mL; LDH 1.5–10 × ULN | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases present |
| Poor | N/A | Mediastinal primary; nonpulmonary visceral metastases present; or one of the following: AFP >10,000 ng/mL; HCG >50,000 mIU/mL; LDH >10 × ULN |
6.1 Diagnostic Criteria¶
Hypoechoic testicular mass on ultrasound. Elevated AFP (60–70% NSGCTs), hCG (choriocarcinoma), or LDH. Normalization of markers post-orchiectomy indicates stage I disease.
7. MANAGEMENT & TREATMENT¶
Radical inguinal orchiectomy is the initial treatment. Chemotherapy (BEP/EP/VIP) is used for metastatic disease. RPLND is considered for staging and treatment in select cases. Postchemotherapy surgery is required for residual masses >3 cm or viable tumor.
Table 93-1: International Germ Cell Consensus Classification System¶
| RISK GROUP | SEMINOMA | NSGCT |
|---|---|---|
| Good | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent | Gonadal or retroperitoneal primary; nonpulmonary visceral metastases absent; AFP <1000 ng/mL; hCG <5000 mIU/mL; LDH <1.5 × ULN |
| Intermediate | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases absent; one of the following: AFP 1000–10,000 ng/mL; HCG 5000–50,000 mIU/mL; LDH 1.5–10 × ULN | Any primary site; normal AFP, any hCG, any LDH; nonpulmonary visceral metastases present |
| Poor | N/A | Mediastinal primary; nonpulmonary visceral metastases present; or one of the following: AFP >10,000 ng/mL; HCG >50,000 mIU/mL; LDH >10 × ULN |
7.1 Treatment Algorithms¶
Stage I: Active surveillance, adjuvant carboplatin, or RPLND. Stage II: Radiation or chemotherapy. Stage III: Cisplatin-based chemotherapy with postchemotherapy RPLND. Relapsed disease is managed with salvage chemotherapy based on risk stratification.
8. PROGNOSIS & COMPLICATIONS¶
Testicular GCTs have an ~95% cure rate with modern therapies. Complications include infertility (30% azoospermia), retrograde ejaculation, and secondary malignancies from radiation/chemotherapy. Long-term survivors may experience sexual dysfunction and metabolic side effects.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: No specific risks, but chemotherapy may affect fertility. Pediatrics: Cryptorchidism increases risk; orchidopexy reduces but does not eliminate risk. Elderly: Higher incidence in men over 50; treatment considerations include comorbidities.
10. KEY POINTS & CLINICAL PEARLS¶
- Testicular GCTs are highly curable with modern therapies.
- Serum tumor markers (AFP, hCG, LDH) are critical for staging and monitoring.
- Radical inguinal orchiectomy is the first step in management.
- Cisplatin-based chemotherapy is the standard for metastatic disease.
- Postchemotherapy RPLND is required for residual masses >3 cm or viable tumor.