Testicular Cancer

Germ cell tumors (seminoma and non-seminomatous subtypes) and sex cord-stromal tumors — the most curable solid malignancy with cisplatin-based chemotherapy achieving >95% cure in localized disease

Key Points

• Testicular cancer is the most common solid malignancy in men aged 15–35 and one of the most curable cancers — overall 5-year survival exceeds 95%, with stage I seminoma approaching 99% cure following orchiectomy alone or adjuvant therapy.
• Germ cell tumors (GCTs) account for ~95% of testicular cancers and are classified as seminoma (~50%) or non-seminomatous germ cell tumors (NSGCTs — ~50%); NSGCTs include embryonal carcinoma, yolk sac tumor, choriocarcinoma, teratoma, and mixed GCT containing two or more elements.
• Serum tumor markers — AFP (alpha-fetoprotein), β-hCG (beta-human chorionic gonadotropin), and LDH — are essential for diagnosis, staging, prognosis (IGCCCG risk classification), and response monitoring; pure seminoma never elevates AFP.
• BEP chemotherapy (bleomycin + etoposide + cisplatin) is the standard systemic regimen for metastatic GCT; cisplatin-based chemotherapy transformed metastatic testicular cancer from nearly universally fatal to curable in ~70–80% of good-risk and ~50% of intermediate-risk patients.
• Sex cord-stromal tumors (Leydig cell tumors and Sertoli cell tumors) account for ~5% of testicular neoplasms; they are almost always benign but can produce excess sex hormones causing gynecomastia, precocious puberty, or infertility; testis-sparing surgery is appropriate when the diagnosis can be confirmed intraoperatively.
• Retroperitoneal lymph node dissection (RPLND) plays a critical role in staging and treatment of NSGCTs — post-chemotherapy RPLND for residual masses >1 cm is standard; nerve-sparing RPLND techniques preserve ejaculatory function in the majority of patients.

Epidemiology and Classification

Testicular cancer is diagnosed in approximately 9,000–10,000 men annually in the United States, representing ~1% of all male malignancies but the most common solid cancer in young men aged 15–35. Incidence has been rising ~1–2%/year over the past 40 years in developed nations for unclear reasons. White men are affected at 4–5× the rate of Black men. Bilateral testicular cancer occurs in ~2–5% (metachronous or synchronous). **Risk factors:** Cryptorchidism (3–5× increased risk, even after orchiopexy), personal or family history of GCT, Klinefelter syndrome (mediastinal GCTs), testicular…

Germ Cell Tumor Subtypes

**Seminoma:** The most common GCT subtype; peak incidence age 25–45. Clinically presents as painless testicular enlargement; may spread to retroperitoneal lymph nodes and, in advanced disease, to mediastinum and lungs. Lymphatic spread is predictable and orderly (retroperitoneal LNs first). Hematogenous spread is a late event. Seminoma is uniquely radiosensitive — historically treated with adjuvant radiation to the paraaortic field. AFP must be normal; any AFP elevation reclassifies as mixed GCT requiring NSGCT management. **Embryonal Carcinoma:** The most undifferentiated NSGCT element;…

Sex Cord-Stromal Tumors

Sex cord-stromal tumors (SCSTs) account for ~5% of testicular neoplasms and are overwhelmingly benign in adults. They arise from the supporting stroma of the testis rather than germ cells; they are i(12p)–negative and AFP/β-hCG–negative. Hormonal activity is a defining clinical feature of many SCSTs. **Leydig Cell Tumors (~75% of SCSTs):** The most common SCST; arise from interstitial Leydig cells that normally produce testosterone. Typical presentation: small, painless testicular nodule incidentally discovered; gynecomastia in ~30% (due to excess estrogen from aromatization of elevated…

Diagnosis, Staging, and Tumor Markers

**Clinical Presentation:** The classic presentation is a firm, painless unilateral testicular mass or swelling. Up to 30% have dull aching or heaviness. Acute pain occurs in ~10% (may mimic epididymo-orchitis — a common diagnostic delay). Gynecomastia (~5% of GCTs, more common with SCST) may be the presenting symptom. In metastatic disease: back pain (retroperitoneal LN mass compressing lumbar nerve roots), dyspnea/hemoptysis (pulmonary metastases), supraclavicular lymphadenopathy, neurologic symptoms (brain metastases — choriocarcinoma), or lower extremity edema (vena cava obstruction).…

Treatment by Stage and Histology

**Stage I Seminoma:** Following radical inguinal orchiectomy, 3 management options exist for the ~15–20% at risk of occult retroperitoneal micrometastases: - *Active surveillance (preferred for most patients):* No adjuvant therapy; CT and markers at scheduled intervals; relapse rate ~15–20%; virtually all relapses are salvageable with chemotherapy or radiation; avoids overtreatment in 80–85% of patients - *Adjuvant carboplatin (1–2 cycles, AUC7):* Reduces relapse rate to ~3–5%; comparable outcomes to adjuvant radiation (MRC TE19 trial); avoids radiation toxicity - *Adjuvant paraaortic…

Surveillance, Fertility, and Long-term Considerations

**Surveillance Schedules:** Risk-adapted follow-up; schedules vary by institution and initial stage: - Stage I on surveillance: Physical exam, markers, and CT every 3–4 months for years 1–2, every 6 months for years 3–5, then annually; CT frequency varies by protocol (radiation exposure concern) - Post-chemotherapy: Physical exam and markers every 2 months for year 1, every 3–4 months for year 2, then 6-monthly to 5 years; annual CT thereafter **Fertility Preservation:** Fertility must be addressed before orchiectomy and before chemotherapy in all patients: - Sperm banking is standard of…