Testicular Germ Cell Tumors

Importance: Testicular cancer is the most common solid malignancy among males aged 15 to 40 years in the US, with approximately 10 000 new cases diagnosed each year. Between 90% and 95% of testicular cancers are germ cell tumors (GCTs). Observations: The mean age at diagnosis for testicular cancer is 33 years. GCTs are categorized as seminomas and nonseminomatous GCTs (NSGCTs) based on their embryonic origins and path of differentiation. Risk factors include cryptorchidism, family history of testicular cancer, gonadal dysgenesis, infertility, cannabis use, and genetic conditions such as Klinefelter syndrome. The most common presenting symptom of testicular cancer is a painless testicular mass. History, physical examination, scrotal ultrasound, laboratory assessment of GCT-associated serum tumor markers (α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase), and prompt referral to a urologist are indicated when testicular cancer is suspected. Early diagnosis and treatment, starting with a radical inguinal orchiectomy, are important to optimize outcomes. At diagnosis, GCT is stage I (localized to the testicle) in 70% to 75% of patients, stage II (metastatic only to the retroperitoneal lymph nodes) in 20%, and stage III (widely metastatic) in 10%. Treatment of GCTs is guided by histology, clinical staging, and risk classification, with 5-year survival rates of 99%, 92%, and 85% for those diagnosed at stages I, II, and III, respectively. Optimal treatment often involves a multidisciplinary team at high-volume, experienced medical centers and may include surveillance (serum tumor markers [α-fetoprotein, β-human chorionic gonadotropin, and lactate dehydrogenase] and imaging of the chest, abdomen, and pelvis), surgery (retroperitoneal lymph node dissection), chemotherapy, and/or radiation. Treatment decisions should consider long-term survivorship concerns, including body image, fertility, hypogonadism, mental health, financial cost, adherence to follow-up, and late adverse effects of therapy such as cardiovascular disease, secondary malignancies, and potential psychosocial effects such as anxiety, depression, and social isolation. Conclusions and Relevance: Testicular cancer is the most common solid malignancy in young men in the US, and 90% to 95% are GCTs. Patients with testicular GCT have a 5-year survival rate of 99%, 92%, and 85% for stages I, II, and III, respectively. Prompt diagnosis and treatment are important to optimize outcomes, and treatment decisions should balance oncologic control with survivorship concerns to minimize long-term adverse effects of treatment.