Testicular Cancer

1. Clinical Overview

Testicular Cancer is the most common solid malignancy in men aged 15-44 years. The vast majority (95%) are Germ Cell Tumors (GCTs). Despite its malignancy, it is the "Poster Child" of modern oncology: it is one of the most curable cancers, with a 5-year survival rate > 95% even with metastatic disease, largely due to the extreme chemosensitivity of GCTs to Cisplatin.

The fundamental clinical distinction is between Seminomas (slow growing, radiosensitive, elderly men) and Non-Seminomatous GCTs (NSGCTs - aggressive, early metastasis, young men).

Clinical Pearl:

The "Back Pain" Trap: Any young man presenting with persistent back pain who is not a manual laborer needs a scrotal exam. Large retroperitoneal lymph node metastases can compress the psoas muscle or nerve roots. Do not label it "musculoskeletal" until you check the testes.

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2. Epidemiology

• Incidence: Increasing globally. ~1% of all male cancers.
• Age:
  • NSGCT: Peak 25-35 years.
  • Seminoma: Peak 35-45 years.
  • Lymphoma: The most common testicular tumor in men > 60 years.
• Race: 5x more common in White men than African-American men.
• Risk Factors:
  • Cryptorchidism (Undescended Testis): Risk is increased 4-6x. Orchiopexy reduces risk but does not eliminate it. intra-abdominal testes have highest risk.
  • Family History: Brothers have 8-10x risk.
  • Previous Cancer: 2% risk of cancer in the contralateral testis.
  • GCNIS: Germ Cell Neoplasia In Situ (precursor lesion). 50% progress to cancer within 5 years.

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3. Pathophysiology & Classification

1. Seminoma (50%)

• Arise from seminiferous epithelium.
• Markers: bHCG elevated in 15%. AFP is NEVER elevated in pure Seminoma. (If AFP is high, treat as NSGCT).
• Behavior: Lazy. Metastasizes late via lymphatics to Para-aortic nodes.
• Sensitivity: Highly sensitive to Radiotherapy and Chemotherapy.

2. Non-Seminomatous GCT (NSGCT) (40%)

• A mixed bag of more primitive cells. Roughly 4 types:
  • Embryonal Carcinoma: Aggressive, undifferentiated.
  • Yolk Sac Tumor: Most common in children. Produces AFP.
  • Choriocarcinoma: Rare, deadly. Produces massive bHCG. Early hematogenous spread (Brain/Lungs).
  • Teratoma: Differentiated tissue (hair, teeth). Resistant to chemo (needs surgery).
• Behavior: Aggressive. Early hematogenous spread.

3. Stromal Tumors (5%)

• Leydig Cell Tumor: Can secrete testosterone (precocious puberty) or estrogen (gynecomastia). usually benign.
• Sertoli Cell Tumor.

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4. Clinical Assessment

History

• The Lump: Usually painless hardness. "Heavy" or "Dragging" sensation in scrotum.
• Pain: Acute pain occurs in 10% (hemorrhage into tumor), mimicking torsion or epididymo-orchitis.
• Metastatic Symptoms:
  • Back pain (Retroperitoneal nodes).
  • Dyspnea/Cough (Lung mets).
  • Bone pain.
  • Exophthalmos (Retro-orbital mets - rare).

Physical Examination

• Examination of the Testis:
  • Hard, irregular, non-tender mass.
  • Unlike a hydrocele, you cannot get above it (it is the testis itself) but it does not transilluminate (it is solid).
  • Check the other side! (Atrophy/Tumor).
• General Exam:
  • Abdomen: Palpate for Para-aortic mass (deep, midline).
  • Neck: Supraclavicular nodes (Virchow's).
  • Chest: Gynecomastia (Estrogen or bHCG effect).

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5. Tumor Markers (The "Liquid Biopsy")

Must be drawn BEFORE orchidectomy (for baseline) and AFTER (to check half-life clearance).

Critical Rule: If a "Seminoma" on pathology has an elevated AFP, it is treated as a Non-Seminoma (NSGCT) because there must be occult non-seminomatous elements missed by the pathologist.

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6. Investigations

1. Scrotal Ultrasound (First Line)

• Findings: Hypoechoic, solid, vascular mass. Microcalcifications (Microlithiasis).
• Pearl: Can distinguish solid tumor from cystic hydrocele or inflammatory epididymitis with ~100% sensitivity.

2. Diagnosis: Radical Inguinal Orchidectomy

• NEVER BIOPSY A TESTICULAR MASS. Trans-scrotal biopsy violates lymphatic planes and can seed cancer into the scrotum/inguinal nodes.
• Procedure: Incision in groin (inguinal). Clamp cord at internal ring. Remove testis + cord en-bloc.

3. Staging: CT Chest/Abdomen/Pelvis

• Required: To look for metastases.
• Lymphatic Spread: Follows embryological origin. Testis starts at T10 (Renal level).
  • Right Testis: Spreads to Inter-Aortocaval nodes.
  • Left Testis: Spreads to Para-aortic nodes (near Renal Hilum).
  • Inguinal Nodes: ONLY involved if tumor breaches scrotal skin or patient had previous scrotal surgery (orchiopexy).

TNM-S Staging (S = Serum Markers)

• Unique to testicular cancer. Markers are part of staging.
• S0: Markers normal.
• S3: Massive elevation (LDH > 10x, hCG > 50,000, AFP > 10,000) = Poor Prognosis.

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7. Management: Principles

Fertility Preservation (Mandatory Step 0)

• Sperm banking must be offered to all patients before Chemotherapy or RPLND (Retroperitoneal Lymph Node Dissection), as these cause azoospermia (often permanent). Even if counts are low initially (due to cancer stress), bank what you can.

The Treatment Algorithm

graph TD
    A[Testicular Mass] --> B[Radical Inguinal Orchidectomy]
    B --> C{Histology?}
    
    C --> D[Seminoma]
    C --> E[Non-Seminoma NSGCT]
    
    D --> F{Stage?}
    F -->|Stage I Confined| G[Surveillance Preferred]
    F -->|Stage I Risk Factors| H[Carboplatin Single Dose]
    F -->|Metastatic II/III| I[Radiotherapy or BEP Chemo]
    
    E --> J{Stage?}
    J -->|Stage I Confined| K[Surveillance Preferred]
    J -->|Stage I Risk Factors| L[1 cycle BEP Chemo]
    J -->|Metastatic II/III| M[3-4 cycles BEP Chemo]
    M --> N{Residual Mass?}
    N -->|Yes (> 1cm)| O[RPLND Surgery]

1. Stage I Disease (Confinded to Testis)

• Surveillance: Gold Standard. CT scans + Markers every 3-6 months for 5 years. Relapse rate 15-30% (but salvageable). Avoids overtreatment.
• Adjuvant Chemo:
  • Seminoma: Single dose Carboplatin (AUC7). Reduces relapse to ~3%.
  • NSGCT: Single cycle BEP. Reduces relapse to less than 3%.

2. Metastatic Disease (Stage II/III)

• Chemotherapy (BEP Protocol):
  • Bleomycin + Etoposide + Cisplatin (Platinol).
  • Usually 3 cycles (Good Risk) or 4 cycles (Intermediate/Poor Risk).
  • Cure Rate: > 90% for good risk.

3. Residual Masses (Post-Chemo)

• Seminoma: If mass less than 3cm, observe (PET scan if unsure). Usually fibrosis.
• NSGCT: If mass > 1cm, Review for RPLND. Teratoma does not respond to chemo and will grow/transform if left behind.

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8. Complications of Treatment

Acute (Chemotherapy)

• Nausea/Vomiting: Cisplatin is highly emetogenic. Requires extensive anti-emetics (NK1 inhibitors).
• Neutropenic Sepsis: Risk with Etoposide.
• Bleomycin Toxicity: Pulmonary Fibrosis. Watch for cough/dyspnea. Avoid high FiO2 (Scuba diving, Anesthesia) life-long.

Long Term (The Survivor's Burden)

• Infertility: BEP causes azoospermia. Recovery takes 2-3 years, may be incomplete.
• Second Malignancy: Risk of Leukemia (Etoposide) and solid tumors (Radiotherapy) is doubled.
• Cardiovascular: Metabolic Syndrome (Obesity, HTN, High Cholesterol) is very common in survivors. 2x risk of MI.
• Raynaud's Phenomenon: Cisplatin vascular damage.
• Ototoxicity/Nephrotoxicity: Cisplatin damages ears (tinnitus) and kidneys.

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9. Integrated Care

• Psychology: Diagnosis strikes at peak "invincibility" years. Body image (loss of testis) and sexual function/fertility fears are major.
• Prosthesis: Discussion about Saline testicular prosthesis insertion (can be done at time of orchidectomy or delayed).
• Cardiology: Long-term monitoring of BP and Lipids is the job of the GP.

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10. Prognosis (IGCCCG Classification)

Survival depends on Histology, Site of Mets (Lung vs Visceral), and Marker Levels.

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11. Evidence & Guidelines

Landmark Trials

• Einhorn (1977): The discovery that Cisplatin cures testicular cancer. Changed survival from 5% to 95%.
• TE08 / TE24: Established that surveillance is safe for Stage I NSGCT to avoid toxicity.
• SWENOTECA: Scandinavian protocols defining the modern management of Stage I disease.

Guidelines (EAU / NCCN)

• Imaging: MRI Brain is NOT routine unless choriocarcinoma or high volume mets.
• PET CT: Only useful for Seminoma residual masses. Not useful for NSGCT (Teratoma is PET negative but dangerous).

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12. Future Horizons

• miRNA-371: A new "Liquid Biopsy" marker. Outperforms AFP/bHCG sensitivity/specificity significantly. Likely to replace current markers soon.
• TIP Chemo: Paclitaxel + Ifosfamide + Cisplatin for relapse/salvage.
• High Dose Chemo + Stem Cell Transplant: For multiple relapses.

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13. Special Populations

A. Extragonadal GCT

• Tumor arises in midline (Mediastinum, Retroperitoneum, Pineal Gland) without a testicular mass.
• Mediastinal Non-Seminoma: Associated with Klinefelter's Syndrome and Hematologic malignancy. Poor prognosis.

B. The Solitary Testis

• Man with previous orchidectomy develops cancer in the remaining testis.
• Management: Organ-sparing surgery (Partial Orchidectomy) if tumor less than 30% of volume, to create internal testosterone (though fertility is lost). Otherwise, bilateral orchidectomy + lifelong T-replacement.

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14. Patient Education

Testicular Self-Exam (TSE)

• Who: All men 15-45.
• When: Once a month, in specific warmth (shower relaxes the scrotum).
• How: Roll testis between thumb and fingers. Feel for the epididymis (soft rope at back) and distinguish it from a hard lump in the body.

"Chemo Brain"

• Cognitive fog is real and can persist. Validate the patient's experience.

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15. Case Mastery: Clinical Scenarios

Case 1: The "Epididymitis" That Won't Go

Patient: 25yo male. Treated with Doxycycline for 4 weeks for "swollen epididymis". No pain relief. Swelling firm. Error: Assuming infection in painless mass. Action: Urgent Ultrasound. 10% of cancers have inflammation/pain.

Case 2: The "Gynecomastia"

Patient: 30yo bodybuilder. Complains of new breast tissue. Denies steroid use. Clue: High bHCG or Estrogen from Leydig Cell/Choriocarcinoma. Action: examine the testes! (And thyroid/liver).

Case 3: The "Post-Chemo Mass"

Patient: Finished BEP for Stage 2 NSGCT. CT shows 2cm para-aortic node remaining. Markers normal. Diagnosis: Teratoma. (Chemo killed the cancer, but Teratoma remains). Action: RPLND (Surgery). If you leave it, it grows and compresses bowel/ureters ("Growing Teratoma Syndrome").

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16. Appendix: Additional Resources

Useful Abbreviations

Online Tools

• It's In The Bag (Testicular Cancer Support)
• Movember Foundation