Testicular Cancer: Understanding the Causes, Identifying Symptoms, and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Testicular cancer is the most common solid malignancy in males aged 15-35 years and the most curable solid tumour in oncology, with overall 5-year survival exceeding 95%. Approximately 9,000 new cases are diagnosed per year in the United States, and incidence has been rising over the past several decades, particularly in Caucasian men. Over 95% of testicular cancers are germ cell tumours (GCTs), which are classified into two major subtypes: seminoma (approximately 55%), arising from primitive germ cells and characterised by exquisite radiosensitivity and chemosensitivity, and non-seminomatous germ cell tumour (NSGCT, approximately 45%), a heterogeneous group comprising embryonal carcinoma, yolk sac tumour, choriocarcinoma, and teratoma either in pure forms or — more commonly — as mixed GCT. Bilateral testicular GCT occurs in 1-2% of patients. The International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification categorises metastatic GCT into good, intermediate, and poor prognosis groups based on primary tumour site, serum tumour marker levels (AFP, beta-HCG, LDH), and presence of non-pulmonary visceral metastases, guiding chemotherapy intensity.

Cryptorchidism (undescended testis) is the strongest established risk factor for testicular GCT, conferring a 3-8-fold increased risk even after surgical orchidopexy; the risk remains elevated if orchidopexy is performed after age 12. A contralateral undescended testis confers increased risk to both testes. Additional risk factors include: personal history of a previous testicular GCT in the contralateral testis (3-5% risk in ipsilateral treated patients); first-degree family history of testicular cancer (4-6-fold increased risk, suggesting polygenic predisposition); testicular atrophy; Klinefelter syndrome (47,XXY, associated with mediastinal extragonadal GCT and primary gonadal GCT); and in utero diethylstilbestrol (DES) exposure (modestly elevated risk). Germ cell neoplasia in situ (GCNIS), formerly called intratubular germ cell neoplasia, is the universally recognised precursor of invasive GCT and is found in adjacent seminiferous tubules in virtually all resected GCT specimens. The molecular hallmark of GCT is isochromosome 12p (i(12p)) — present in over 90% of all seminoma and NSGCT — which results from duplication of the short arm of chromosome 12, and serves as a diagnostic marker. Epidemiological data suggest that westernised diet, endocrine disruptor exposure (phthalates, bisphenol A), and maternal oestrogen levels during gestation may contribute to the rising incidence.

The most common and classic presentation is a painless unilateral testicular lump or firmness, often noted incidentally during self-examination or by a sexual partner. Approximately 30-40% of patients report a dull ache or heaviness in the affected testis or ipsilateral lower abdomen. Acute testicular pain, mimicking epididymo-orchitis, occurs in approximately 10% of cases and is a classic pitfall for delayed diagnosis: any acute testicular episode that does not respond to antibiotics within 2 weeks requires scrotal ultrasound. Gynecomastia — unilateral or bilateral — results from beta-HCG secretion by choriocarcinoma elements and should prompt testicular evaluation in any male. Back or flank pain from retroperitoneal lymph node enlargement is a common presenting symptom of advanced NSGCT in young men. Dyspnoea, haemoptysis, or an incidental pulmonary nodule from lung metastases may be the presenting feature of choriocarcinoma, which metastasises haematogenously at an early stage. Rare presentations include bilateral leg oedema from caval compression by large retroperitoneal disease, or brain metastases with neurological symptoms. Incidental testicular mass detected on ultrasound performed for other indications (varicocele, epididymal cyst) is increasingly common.

Scrotal ultrasound is the first-line imaging modality, providing high sensitivity (approximately 100%) and specificity (approximately 95-99%) for distinguishing intratesticular from extratesticular masses. Any hypoechoic intratesticular mass should be considered a GCT until proven otherwise. Serum tumour markers — alpha-fetoprotein (AFP), beta human chorionic gonadotrophin (beta-HCG), and lactate dehydrogenase (LDH) — must be obtained before orchiectomy; elevated AFP is incompatible with pure seminoma and mandates reclassification as NSGCT. Radical inguinal orchiectomy is both the primary diagnostic procedure and therapeutic step, providing histological diagnosis and definitive pathological information including tumour type, extent of rete testis invasion, lymphovascular invasion, and margins. CT chest, abdomen, and pelvis with IV contrast is mandatory staging. MRI brain is required in IGCCCG poor-risk patients, those with elevated beta-HCG, and in NSGCT with high metastatic burden. Post-orchiectomy serum tumour marker half-life decline is monitored to confirm adequate clearance and detect persistent disease. IGCCCG staging classifies patients into good (5-year OS more than 90%), intermediate (approximately 80%), and poor prognosis (approximately 48-50%) groups. Retroperitoneal lymph node size and distribution on CT categorise nodal staging (CS IIA: nodes 1-2 cm; CS IIB: 2-5 cm; CS IIC: greater than 5 cm).

Treatment is stage, histology, and risk-stratified. Stage I seminoma: active surveillance (the preferred strategy for T1-T2 lesions, with 5-year relapse rate approximately 15-20% but salvage chemotherapy achieves cure in almost all relapsers), single-dose carboplatin AUC7 (reducing relapse to approximately 5%), or para-aortic radiotherapy 20-25 Gy (effective but increasingly avoided due to second malignancy risk). Stage I NSGCT: active surveillance (preferred for low-risk; 5-year relapse approximately 15-20%), nerve-sparing RPLND (diagnostic and therapeutic), or one cycle of BEP chemotherapy (risk-adapted approach). Stage IIA/B seminoma: radiotherapy or BEP chemotherapy (BEP x3 or EP x4). Stage IIA/B NSGCT: primary nerve-sparing RPLND or BEP chemotherapy. Metastatic GCT (Good-risk by IGCCCG): BEP x3 cycles (bleomycin 30 IU days 1, 8, 15; etoposide 100 mg/m² days 1-5; cisplatin 20 mg/m² days 1-5, every 21 days); alternatively EP x4. Intermediate/Poor-risk: BEP x4 cycles; poor-risk patients should be treated at specialised centres with clinical trial access. Residual retroperitoneal masses after chemotherapy for NSGCT: post-chemotherapy RPLND is recommended for any mass greater than 1 cm; seminoma residual masses greater than 3 cm are evaluated with PET. Salvage chemotherapy: TIP (paclitaxel-ifosfamide-cisplatin) or VIP (vinblastine/etoposide-ifosfamide-cisplatin); high-dose chemotherapy plus autologous SCT for chemorefractory disease. Sperm banking should be offered to all patients before initiation of chemotherapy.

While the primary causes of testicular GCT are not fully modifiable, several evidence-based measures reduce risk or enable early detection. Orchidopexy for cryptorchidism is recommended before 12 months of age (or at the latest before 18 months) to reduce the risk of testicular malignancy and preserve fertility, as recommended by the European Association of Urology and the American Urological Association guidelines. Earlier orchidopexy is associated with lower cancer risk than surgery performed after puberty. Regular testicular self-examination (TSE) is advocated by patient advocacy groups and many clinicians to identify new testicular lumps at the earliest possible stage; however, there is no robust trial evidence demonstrating TSE reduces testicular cancer mortality given the excellent overall prognosis. Males with a history of previous GCT in one testis should undergo annual scrotal ultrasound surveillance of the contralateral testis, as metachronous contralateral GCT occurs in 1-2% of patients. Individuals with known genetic risk factors — Klinefelter syndrome, family history of GCT — should be educated about self-examination and should have a low threshold for testicular ultrasound. Avoidance of environmental endocrine disruptors and promotion of healthy dietary patterns may reduce the modestly elevated epidemiological risk associated with westernisation.

Any young male aged 15-45 who notices a new testicular lump, hardness, or change in the shape or consistency of a testicle should seek medical evaluation within 1-2 weeks. Even if the lump is painless, this is not reassuring — the majority of testicular GCTs are painless at initial presentation. Any scrotal swelling or hardness that does not clearly resolve within 2 weeks with conservative management (e.g., following minor trauma) should be evaluated with a scrotal ultrasound rather than simply attributed to epididymo-orchitis or varicocele. Pain in the back or abdomen in a young man without clear musculoskeletal cause should prompt consideration of retroperitoneal lymphadenopathy from testicular GCT. Gynecomastia — breast tissue enlargement in a male — should always prompt examination and ultrasound of both testes. Dyspnoea or haemoptysis in a young otherwise healthy male warrants chest imaging and testicular evaluation to exclude metastatic choriocarcinoma. Males with known cryptorchidism history — even after orchidopexy — should be vigilant about testicular self-examination and should not delay seeking evaluation for any abnormality. All concerns should be evaluated by a urologist with ultrasound, as early-stage testicular cancer is nearly universally curable.

Stage I seminoma and NSGCT: 5-year OS greater than 99%. Good-prognosis metastatic GCT (IGCCCG): 5-year OS greater than 90%. Intermediate prognosis: approximately 80%. Poor prognosis: approximately 48-50%. Overall 5-year testicular cancer survival exceeds 95%, making it one of the most curable cancers in oncology regardless of stage. Even chemorefractory patients may achieve cure with high-dose salvage chemotherapy and autologous SCT. The prognosis for Testicular Cancer: Understanding the Causes, Identifying Symptoms, and Treatment varies depending on severity at diagnosis, the patient's overall health, and how promptly treatment is initiated. With early diagnosis and appropriate management, many patients achieve good outcomes and maintain quality of life. Regular follow-up with healthcare providers is essential to monitor progress, adjust treatment as needed, and detect any complications early. Adherence to prescribed treatments and lifestyle modifications significantly improves long-term prognosis.