Key Facts

Testicular cancer is one of the great success stories of modern oncology, with cure rates exceeding 95% even in metastatic disease. Cisplatin-based combination chemotherapy and multidisciplinary management are key to these outcomes.

Epidemiology

• UK incidence: approximately 2,400 new cases per year
• Peak incidence: 25-35 years
• Incidence has been rising over the past 50 years (reason unclear)
• Caucasian men have highest incidence worldwide
• Mortality: approximately 60 deaths per year in the UK (reflects high cure rate)

Aetiology

• Cryptorchidism: strongest risk factor (4-8× risk; not eliminated by orchidopexy but allows better surveillance)
• Previous testicular cancer: 2-5% risk of contralateral tumour
• Family history: first-degree relative 4-8× risk
• Klinefelter syndrome (47,XXY): increased risk of mediastinal germ cell tumours
• Testicular microlithiasis: controversial risk factor; surveillance if symptomatic
• Germ cell neoplasia in situ (GCNIS): precursor lesion; 50% progress to invasive cancer within 5 years

Pathophysiology

• Seminoma: uniform cells resembling primordial germ cells; radiosensitive; slower growth; good prognosis
• Non-seminomatous germ cell tumours (NSGCT): includes embryonal carcinoma (aggressive), yolk sac tumour (AFP production), choriocarcinoma (βhCG, haematogenous spread), teratoma (mature/immature)
• Mixed germ cell tumours: contain both seminomatous and non-seminomatous elements; treated as NSGCT
• Spread: lymphatic to retroperitoneal lymph nodes (para-aortic) → haematogenous to lungs, liver, brain, bone
• Excellent chemosensitivity due to high mitotic rate and intact apoptotic pathways

Typical Presentation

• Painless testicular swelling or lump (most common)
• Sensation of heaviness in scrotum
• Dull ache in testis, groin, or lower abdomen
• Detected incidentally after trauma

Advanced Disease

• Back pain (retroperitoneal lymphadenopathy)
• Dyspnoea, cough (pulmonary metastases)
• Gynaecomastia (βhCG-producing tumours)
• Neck mass (supraclavicular lymphadenopathy)

Red Flags

• Any new testicular lump in a young man
• Rapidly enlarging testis
• Gynaecomastia in young man
• Unexplained back pain in young man with testicular abnormality
• Elevated AFP or βhCG

Bedside

• Testicular examination (size, consistency, tenderness, transillumination)
• Abdominal examination (retroperitoneal mass)
• Supraclavicular lymph nodes

Bloods

• Tumour markers (pre-orchidectomy):
  • AFP: raised in yolk sac tumour and embryonal carcinoma; NEVER raised in pure seminoma
  • βhCG: raised in choriocarcinoma and 10-20% of seminomas
  • LDH: non-specific; reflects tumour burden
• FBC, U&Es, LFTs
• Semen analysis and sperm banking: BEFORE orchidectomy/chemotherapy

Imaging

• Scrotal USS: first-line; hypoechoic intratesticular mass is cancer until proven otherwise
• CT chest/abdomen/pelvis: staging (retroperitoneal lymph nodes, pulmonary metastases)
• MRI brain: if choriocarcinoma (high risk of brain metastases) or neurological symptoms

Special Tests

• Serial tumour markers: post-orchidectomy; half-lives: AFP 5-7 days, βhCG 24-36 hours
• Histopathology after orchidectomy: definitive diagnosis, subtype classification
• PET-CT: role in post-chemotherapy assessment of residual seminoma masses (>3cm)

Non-pharmacological

• Sperm banking BEFORE orchidectomy (30-50% of men have impaired spermatogenesis at diagnosis)
• Testicular prosthesis option
• Psychological support
• Long-term follow-up (late effects of treatment)

Pharmacological

• Stage I seminoma (post-orchidectomy options):
  • Active surveillance (98-99% cure; relapse 15-20%, salvaged with treatment)
  • Single-dose carboplatin AUC7 (reduces relapse to 5%)
  • Adjuvant radiotherapy to para-aortic nodes (20 Gy; reduces relapse to <5%)
• Stage I NSGCT (post-orchidectomy options):
  • Active surveillance (70-80% cure without further treatment; 30% relapse)
  • Adjuvant BEP × 1 cycle (reduces relapse to <3%)
• Metastatic seminoma and NSGCT:
  • BEP: bleomycin 30,000 IU days 1, 8, 15 + etoposide 100mg/m² days 1-5 + cisplatin 20mg/m² days 1-5; q21 days
  • Good prognosis: 3 cycles BEP (or 4 × EP if bleomycin contraindicated)
  • Intermediate/poor prognosis: 4 cycles BEP
  • Bleomycin pulmonary toxicity: monitor PFTs; stop if TLCO falls >25%
• Post-chemotherapy residual mass:
  • NSGCT: retroperitoneal lymph node dissection (RPLND) if residual mass >1cm
  • Seminoma: PET-CT at 6 weeks; surgery only if PET-avid and >3cm
• Salvage chemotherapy: TIP (paclitaxel + ifosfamide + cisplatin) or high-dose chemotherapy with autologous stem cell rescue

Surgical/Interventional

• Radical inguinal orchidectomy: diagnostic and therapeutic; approach through inguinal incision (NOT trans-scrotal)
• RPLND: post-chemotherapy for residual NSGCT masses; nerve-sparing technique to preserve ejaculation
• Metastasectomy: resection of residual pulmonary or other metastases

Referral Criteria

• Any testicular lump in a young man: urgent USS within 2 weeks
• Confirmed testicular cancer: urgent referral to specialist supra-network centre
• All patients: sperm banking before any treatment
• Follow-up: long-term surveillance for relapse and late effects

• Overall cure rate: >95%
• Stage I: 99% cure rate with surveillance and salvage treatment
• Good prognosis metastatic (IGCCCG): 92% 5-year survival
• Intermediate prognosis: 80% 5-year survival
• Poor prognosis: 48% 5-year survival
• Long-term effects of treatment: cardiovascular disease (2× risk), secondary malignancy, nephrotoxicity, ototoxicity (cisplatin), pulmonary toxicity (bleomycin), infertility, metabolic syndrome
• Late relapse (>2 years): occurs in 2-3%; often chemo-resistant; surgery is primary treatment

IGCCCG Prognostic Classification

Tumour Marker Interpretation