What is the management approach for germ cell tumors?

Management of Germ Cell Tumours

Germ cell tumours require a systematic, risk-stratified approach beginning with radical inguinal orchiectomy, followed by risk-adapted treatment based on histology, stage, and prognostic markers, with excellent cure rates exceeding 95% for localized disease when managed by experienced oncologists. 1, 2

Initial Diagnosis and Surgical Management

Diagnostic Workup

• Obtain serum tumour markers (AFP, β-HCG, LDH) before any surgical intervention to establish baseline values for diagnosis, staging, and subsequent monitoring 1, 2, 3
• Perform high-frequency testicular ultrasound to confirm intratesticular mass 2
• Complete staging with CT chest and abdomen to evaluate for metastatic disease 1
• Add brain MRI (or CT if unavailable) when β-HCG >10,000 IU/L or >10 lung metastases 1
• Consider bone scan in patients with advanced metastatic disease 1

Surgical Approach

• Perform radical inguinal orchiectomy through an inguinal incision, resecting the tumour-bearing testicle with spermatic cord at the internal inguinal ring 1, 2
• Never use a scrotal approach due to higher local recurrence rates 2
• Orchiectomy should be timely but is NOT an emergency unless life-threatening metastatic disease is present 1, 4
• In patients with life-threatening metastases and unequivocally elevated AFP or HCG, initiate urgent chemotherapy first and postpone orchiectomy until completion of treatment 1

Pre-Treatment Considerations

• Offer sperm cryopreservation before any treatment (chemotherapy or radiotherapy) as this is the most cost-effective fertility preservation strategy 1, 2, 4
• Counsel patients about risks of hypogonadism and infertility 2
• Remeasure tumour markers post-orchiectomy and follow until normalization to determine half-life kinetics (AFP <7 days; β-HCG <3 days) 1, 4

Risk Stratification and Staging

International Germ Cell Consensus Classification (IGCCCG)

Stage I patients are subdivided based on vascular invasion presence 1:

• Low risk (20% relapse rate): No vascular invasion
• High risk (40-50% relapse rate): Vascular invasion present

Metastatic disease classification 1, 3:

• Good prognosis: AFP <1,000 ng/mL AND β-HCG <5,000 IU/L AND LDH <1.5× ULN AND non-mediastinal primary AND no non-pulmonary visceral metastases
• Intermediate prognosis: AFP 1,000-10,000 ng/mL OR β-HCG 5,000-50,000 IU/L OR LDH 1.5-10× ULN AND non-mediastinal primary AND no non-pulmonary visceral metastases
• Poor prognosis: AFP >10,000 ng/mL OR β-HCG >50,000 IU/L OR LDH >10× ULN OR mediastinal primary OR non-pulmonary visceral metastases present

Contralateral Testis Biopsy

• Consider contralateral biopsy in high-risk patients: testicular volume <12 mL and age <30 years (34% risk of TIN) 1
• Perform biopsy at time of orchiectomy and preserve in Stieve's or Bouin's solution (NOT formalin) 1
• In extragonadal germ cell tumours, approximately one-third harbour TIN in one or both testicles 1

Treatment by Histology and Stage

Non-Seminomatous Germ Cell Tumours (NSGCT)

Stage I Disease:

• Low-risk (no vascular invasion): Surveillance protocol is recommended 1, 2
• High-risk (vascular invasion present): Adjuvant chemotherapy with BEP × 2 cycles 1, 2
• Nerve-sparing retroperitoneal lymph node dissection (RPLND) is an exceptional alternative only if chemotherapy not possible 1

Metastatic Disease (Stages II-IV):

• Good prognosis: BEP × 3 cycles (bleomycin 30,000 IU days 1,8,15; etoposide 100 mg/m² days 1-5; cisplatin 20 mg/m² days 1-5) 1, 2, 5
• Intermediate or poor prognosis: BEP × 4 cycles 1, 2, 5
• For adjuvant BEP, etoposide may be reduced to 360 mg/cycle 1

Pure Seminoma

Stage I Disease:

• Surveillance is the preferred option (category 1) for pT1 and pT2 disease 2
• Alternative options include adjuvant carboplatin (1-2 cycles, AUC × 7) or adjuvant radiotherapy (20 Gy in 10 fractions) to para-aortic lymph nodes 2
• Disease-specific survival is 99% regardless of management strategy 2

Testicular Intraepithelial Neoplasia (TIN)

• Radiotherapy to affected testis (20 Gy/10 fractions over 2 weeks), orchiectomy, or surveillance 1, 2
• If untreated, 70% develop invasive tumour within 7 years 1

Post-Chemotherapy Management

Response Evaluation

• Assess response by tumour marker measurement prior to each treatment cycle and repeat CT scans post-treatment 1
• Patients with residual masses post-chemotherapy should have them resected wherever possible by a specialist surgeon 1, 6, 5
• Surgery remains an essential component of care even after complete marker normalization 5

Salvage Therapy

• Ifosfamide plus cisplatin-containing standard dose therapy or high-dose carboplatin plus stem-cell rescue are potentially curative options 7, 5
• Ifosfamide is FDA-approved for third-line chemotherapy of germ cell testicular cancer in combination with other agents and should be used with mesna for hemorrhagic cystitis prophylaxis 7

Follow-Up Protocols

Surveillance Patients (Stage I)

• Monthly for year 1: Clinical review, chest X-ray, tumour markers 1, 2
• Every 2 months for year 2: Same assessments 1, 2
• Every 4 months for year 3: Same assessments 1
• Every 6 months to year 5: Same assessments 1, 2
• CT scans at 3,6,9,12, and 24 months 1, 2

Post-Chemotherapy Patients

• Every 2 months for year 1: Clinical review, chest X-ray, tumour markers 1, 2
• Every 3 months for year 2: Same assessments 1, 2
• Every 6 months to year 5, then annually: Same assessments 1, 2
• CT scans only as clinically indicated 1, 2

Special Considerations and Pitfalls

Testis-Sparing Surgery

• Consider only in highly selected patients with masses <2 cm, solitary testis, or bilateral synchronous tumours 2
• Counsel about higher local recurrence risk and need for intensive monitoring 2
• This approach is highly experimental and should be limited to experienced centres 1

Critical Marker Interpretation

• Elevated AFP absolutely excludes pure seminoma and indicates non-seminomatous histology regardless of pathology 4, 3
• False β-HCG elevations can occur from hypogonadism or heterophilic antibodies 3
• LDH elevation alone requires careful clinical correlation due to numerous non-malignant causes 3

Treatment Coordination

• All patients should be treated by an oncologist with experience in testicular cancer management 1
• Prognosis is excellent (98-100% for Stage I) regardless of management option chosen, so decisions should balance efficacy against toxicity 1
• Overall 5-year survival rates: 99% Stage I, 92% Stage II, 85% Stage III 2