Testicular cancer is the most common solid tumor in young men aged 15–35, though it accounts for only about 1% of all male cancers. The American Cancer Society estimates approximately 9,760 new cases of testicular cancer are diagnosed in the United States each year, with roughly 410 deaths. Testicular cancer is one of the most curable cancers in medicine—even when metastatic—with an overall five-year survival rate exceeding 95%.
The remarkable curability of testicular cancer is largely attributed to the exquisite sensitivity of germ cell tumors to cisplatin-based chemotherapy. The development of combination chemotherapy regimens by Dr. Lawrence Einhorn in the 1970s transformed testicular cancer from a frequently fatal disease to one with cure rates above 95%. This success story remains one of the greatest achievements in medical oncology.
Types of Testicular Cancer
Over 90% of testicular cancers are germ cell tumors (GCTs), which arise from the cells that produce sperm. GCTs are divided into two major categories with distinct biology, treatment approaches, and prognosis:
Seminoma
Accounts for approximately 50–55% of testicular germ cell tumors. Seminomas tend to grow more slowly, typically occur in men aged 25–45, and are exquisitely sensitive to both radiation and chemotherapy. Pure seminomas do not elevate alpha-fetoprotein (AFP); elevated AFP in the presence of seminoma histology indicates a non-seminomatous component and the tumor should be treated accordingly. Subtypes include classical seminoma (most common) and spermatocytic seminoma (rare, typically in older men, excellent prognosis).
Non-Seminoma Germ Cell Tumors (NSGCTs)
Account for approximately 45–50% of testicular GCTs and tend to occur in a slightly younger age group (15–35). NSGCTs are more likely to grow rapidly and metastasize early. They are classified into four subtypes, which frequently occur in mixed combinations:
- Embryonal carcinoma — Aggressive, often mixed with other types. Can elevate AFP and/or HCG.
- Yolk sac tumor (endodermal sinus tumor) — The most common testicular cancer in prepubertal boys. Characteristically elevates AFP.
- Choriocarcinoma — Rare and highly aggressive. Characteristically elevates HCG, sometimes to very high levels. Propensity for hemorrhagic metastases.
- Teratoma — Contains differentiated tissue elements (hair, cartilage, bone). Mature teratoma is chemoresistant and requires surgical excision. Immature teratoma can be more aggressive.
Tumor Markers
Serum tumor markers are essential for diagnosis, staging, treatment planning, and post-treatment surveillance:
| Marker | Elevated In | Clinical Significance |
|---|---|---|
| AFP (Alpha-Fetoprotein) | Yolk sac tumor, embryonal carcinoma, mixed GCTs | Never elevated in pure seminoma. Elevated AFP with seminoma histology indicates NSGCT treatment. |
| HCG (Human Chorionic Gonadotropin) | Choriocarcinoma, embryonal carcinoma, some seminomas | Markedly elevated in choriocarcinoma. Mildly elevated in ~15% of seminomas. |
| LDH (Lactate Dehydrogenase) | Both seminoma and NSGCT | Correlates with tumor burden. Used in IGCCCG risk classification for metastatic disease. |
Risk Factors
- Cryptorchidism (undescended testicle) — The strongest known risk factor, increasing risk 4–8 fold. Orchiopexy (surgical correction) before puberty reduces but does not eliminate the risk.
- Personal history — A prior testicular cancer increases the risk of cancer in the contralateral testicle by approximately 5–12 fold.
- Family history — Brothers of affected men have an 8–10 fold increased risk; sons of affected fathers have a 4–6 fold increased risk.
- Testicular dysgenesis syndrome — Includes cryptorchidism, hypospadias, low sperm count, and testicular cancer.
- Germ cell neoplasia in situ (GCNIS) — The precursor lesion found in the contralateral testicle of approximately 5% of testicular cancer patients.
- Race/ethnicity — Testicular cancer is 4–5 times more common in White men than Black men in the U.S.
Staging and Risk Classification
| Stage | Description | 5-Year Survival Rate |
|---|---|---|
| Stage I | Confined to the testicle, no evidence of spread | ~99% |
| Stage II | Spread to retroperitoneal lymph nodes (IIA: <2 cm; IIB: 2–5 cm; IIC: >5 cm) | ~96% |
| Stage III | Distant metastasis (lung, liver, brain, bone) or markedly elevated markers | ~73% |
For metastatic disease, the International Germ Cell Cancer Collaborative Group (IGCCCG) classification divides patients into good, intermediate, and poor prognosis groups based on primary site, sites of metastasis, and marker levels. Good-prognosis patients have five-year survival rates of approximately 92%, while poor-prognosis patients (primarily NSGCTs with very high markers or non-pulmonary visceral metastases) have five-year survival rates of approximately 48%.
Treatment Options
Radical Inguinal Orchiectomy
The initial treatment for virtually all testicular cancers is radical inguinal orchiectomy—surgical removal of the affected testicle through a groin incision. This provides both the definitive diagnosis (histological subtype) and local tumor control. A testicular prosthesis can be placed at the time of surgery or later. Sperm banking should be offered before any treatment, as chemotherapy and radiation can affect fertility.
Stage I Management
- Active surveillance — The preferred approach for Stage I seminoma and low-risk Stage I NSGCT. Involves regular physical exams, tumor marker checks, and CT imaging. Relapse occurs in approximately 15–20% of seminoma and 15–30% of NSGCT patients on surveillance, but virtually all are cured with salvage treatment.
- Adjuvant carboplatin (seminoma) — A single cycle of carboplatin reduces relapse risk to approximately 3–4% and is an alternative to surveillance.
- Retroperitoneal lymph node dissection (RPLND) — An option for Stage I NSGCT, particularly when lymphovascular invasion or predominant embryonal carcinoma is present. Nerve-sparing techniques preserve ejaculatory function in most patients.
Advanced Disease (Stages II–III)
- BEP chemotherapy — Bleomycin, etoposide, and cisplatin. The standard regimen for metastatic GCTs. Good-prognosis patients receive 3 cycles; intermediate- and poor-prognosis patients receive 4 cycles. BEP cures approximately 90% of good-prognosis and 50–70% of poor-prognosis patients.
- EP chemotherapy — Etoposide and cisplatin (4 cycles). An alternative for patients with contraindications to bleomycin (e.g., impaired pulmonary function).
- Radiation therapy — Used selectively for Stage IIA/IIB seminoma as an alternative to chemotherapy. Excellent control rates with limited toxicity when retroperitoneal fields are used.
- Post-chemotherapy RPLND — Performed in NSGCT patients with residual retroperitoneal masses after chemotherapy. Pathology reveals necrosis/fibrosis in ~45%, mature teratoma in ~40%, and viable GCT in ~15%.
Salvage Therapy for Relapsed Disease
Even patients who relapse after first-line chemotherapy have a significant chance of cure. Standard salvage approaches include:
- Salvage chemotherapy — TIP (paclitaxel, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin) regimens followed by high-dose chemotherapy with autologous stem cell transplant (HDCT/ASCT).
- High-dose chemotherapy with ASCT — Cures approximately 50% of patients who relapse after first-line BEP. The TIGER trial is comparing conventional-dose versus high-dose salvage as initial salvage treatment.
- Late relapse surgery — Patients who relapse more than 2 years after initial treatment often have chemoresistant teratoma or somatic-type malignancy that requires surgical excision rather than further chemotherapy.