Overview
Testicular Cancer
1. Clinical Overview
Summary
Testicular cancer is the most common solid malignancy in men aged 15-44 years, representing a paradigm of curable cancer. The vast majority (95%) are Germ Cell Tumours (GCTs), derived from primordial germ cells. With modern multimodal therapy including surgery, chemotherapy, and radiotherapy, cure rates exceed 95% even in metastatic disease, making it one of the most treatable solid tumours in medicine. [1,2]
Key Facts
- Peak Incidence: Bimodal distribution with peaks at 25-35 years (non-seminoma) and 35-45 years (seminoma).
- Incidence: 6-11 per 100,000 men per year in Western countries; rising over past 50 years. [3]
- Risk Factors: Cryptorchidism (5-10x risk), prior testicular cancer (12x risk for contralateral), family history (4-8x if brother affected).
- Histology: 95% Germ Cell Tumours (Seminoma 50%, Non-Seminoma 50%). 5% are non-germ cell (Leydig, Sertoli, Lymphoma).
- Survival: Stage I seminoma - 99% 5-year survival. Metastatic poor-risk - 48% 5-year survival. [4]
- The "Young Man's Cancer": Always consider in any male 15-40 with unexplained back pain, dyspnoea, or abdominal mass.
Clinical Pearls
The Golden Rule: Any solid, non-tender testicular mass is cancer until proven otherwise. Do NOT transilluminate and dismiss - this is how cancers are missed.
AFP Specificity: Alpha-fetoprotein (AFP) is NEVER elevated in pure seminoma. If AFP is raised with histology of "seminoma", the tumour is actually a mixed GCT and should be treated as non-seminoma. [5]
The "Burned-Out" Primary: Occasionally patients present with metastases (retroperitoneal mass, lung nodules) but a normal or atrophic testis. The primary tumour has regressed leaving only a scar. Look for microcalcifications on ultrasound.
Sperm Banking: Must be offered to ALL patients before starting treatment. Chemotherapy and RPLND cause significant fertility impairment.
2. Epidemiology
Incidence and Demographics
- Global: Approximately 74,000 new cases annually worldwide. [6]
- Highest Rates: Northern Europe (Norway, Denmark - 12/100,000), Switzerland, Germany.
- Lowest Rates: Africa, Asia (less than 1/100,000).
- Rising Incidence: 3-6% annual increase in Western countries over past 50 years.
- Age Distribution:
- Seminoma: Peak at 35-39 years.
- Non-seminoma: Peak at 25-29 years.
- Spermatocytic seminoma: Men >50 years.
Risk Factors with Relative Risk
| Risk Factor | Relative Risk | Notes |
|---|---|---|
| Cryptorchidism | 5-10x | Risk persists even after orchidopexy. Intra-abdominal testis highest risk. |
| Prior Testicular Cancer | 12x (contralateral) | 2-5% lifetime risk of contralateral tumour. |
| Family History | 4-10x (brother), 2-4x (father) | Suggests genetic predisposition. |
| Testicular Dysgenesis Syndrome | 10-40x | Includes hypospadias, poor semen quality, cryptorchidism. |
| Infertility | 2-3x | Impaired spermatogenesis may share pathogenesis. |
| Klinefelter Syndrome | 50x | Particularly for mediastinal GCTs. |
| HIV Infection | 2-10x | Seminoma more common. |
| In-utero DES Exposure | 2-5x | Historical exposure. |
The Cryptorchidism Connection
- Mechanism: The undescended testis experiences abnormal thermal environment (2-4°C higher than scrotum) causing impaired germ cell development and increased malignant transformation.
- Orchidopexy Timing: Surgery before age 13 reduces (but does not eliminate) cancer risk. [7]
- Bilateral Cryptorchidism: Both testes at risk, not just the affected side.
3. Pathophysiology
Step 1: Origin - Germ Cell Neoplasia In Situ (GCNIS)
- The Precursor: All invasive germ cell tumours (except spermatocytic tumour) arise from GCNIS (formerly "Carcinoma in Situ").
- GCNIS Cells: Aberrant primordial germ cells that failed to mature during fetal development.
- Genomic Hallmark: Gain of chromosome 12p (isochromosome 12p - i(12p)) present in >80% of GCTs. [8]
- Natural History: GCNIS progresses to invasive cancer in 50% at 5 years.
Step 2: Histological Differentiation Pathways
Primordial Germ Cell
↓
Germ Cell Neoplasia In Situ (GCNIS)
↓
┌──────────────────┴──────────────────┐
↓ ↓
SEMINOMA NON-SEMINOMA (Pluripotent)
(Undifferentiated) ↓
┌────────────────┼────────────────┐
↓ ↓ ↓
EMBRYONAL YOLK SAC CHORIOCARCINOMA
CARCINOMA TUMOUR (Trophoblastic)
↓
TERATOMA
(Differentiated tissues)
Step 3: Seminoma vs Non-Seminoma
| Feature | Seminoma | Non-Seminoma (NSGCT) |
|---|---|---|
| Age | 35-45 years | 20-35 years |
| AFP | Never elevated | Elevated (Yolk Sac) |
| β-hCG | 15-20% (syncytiotrophoblasts) | Elevated (Choriocarcinoma) |
| Growth Rate | Slower | Faster, more aggressive |
| Radiosensitivity | High | Low |
| Chemosensitivity | High | High |
| Metastasis Pattern | Lymphatic first | Haematogenous early |
| Prognosis | Better stage-for-stage | Depends on histology |
Step 4: Metastatic Spread Pattern
- Lymphatic (Primary Route): Right testis → Interaortocaval nodes. Left testis → Para-aortic nodes.
- Haematogenous: Lung (most common), Liver, Brain, Bone.
- Retrograde Spread: To inguinal nodes only if prior scrotal surgery (violation of scrotal approach).
Step 5: Molecular Drivers
- KIT Mutations: Present in 25% of seminomas. Receptor tyrosine kinase signaling.
- RAS/RAF Pathway: Activating mutations contribute to proliferation.
- DNA Methylation: Seminomas are hypomethylated; non-seminomas show variable methylation.
Step 6: Tumour Microenvironment and Immune Response
- Seminoma: Dense lymphocytic infiltrate with granulomatous reaction. PD-L1 expression in tumour cells and immune cells.
- Non-Seminoma: Less immune infiltrate, more stromal reaction. Embryonal carcinoma shows highest PD-L1 expression.
- Immunotherapy Potential: High response rates to checkpoint inhibitors in relapsed disease (40-50% in phase II trials).
Step 7: Genetic Predisposition and Familial Risk
- KITLG Gene: Common variants at 12q22 associated with increased risk.
- DMRT1 Gene: Involved in testis development, mutations increase risk.
- Familial Clustering: 8-10% of cases have family history, suggesting polygenic inheritance.
- Syndrome Associations: Klinefelter syndrome (47,XXY) has 50x increased risk due to extra X chromosome genes.
Molecular Classification
Recent genomic studies have identified distinct molecular subtypes:
| Subtype | Genetic Features | Clinical Characteristics |
|---|---|---|
| C-KIT Mutated | KIT activating mutations | Seminoma predominant, better prognosis |
| RAS Mutated | KRAS/NRAS mutations | Mixed histology, intermediate prognosis |
| Triple Wild-Type | No KIT/RAS mutations | Embryonal carcinoma predominant |
| i(12p) Amplification | Extra copies of i(12p) | Highly aggressive, poor prognosis |
4. Clinical Presentation
Classic Presentation: The Painless Lump
Symptoms by Frequency
| Symptom | Frequency | Mechanism |
|---|---|---|
| Painless testicular mass | 85-95% | Primary tumour growth |
| Testicular pain/discomfort | 10-20% | Haemorrhage, torsion, infection |
| Sensation of heaviness | 10-15% | Tumour weight |
| Back pain | 10-15% | Retroperitoneal lymphadenopathy |
| Gynecomastia | 5-10% | β-hCG secretion |
| Dyspnoea/cough | 5-10% | Pulmonary metastases |
| Neck mass | 5% | Supraclavicular lymphadenopathy |
Atypical Presentations
"The Epididymitis Trap": Young men with testicular swelling are often treated for epididymitis without ultrasound. If symptoms persist >2 weeks despite antibiotics, ultrasound is mandatory.
Red Flags - "The Don't Miss" Signs
- Solid non-tender testicular mass - Cancer until proven otherwise.
- Persistent "epididymitis" not responding to antibiotics - Get ultrasound.
- Unexplained gynecomastia in young man - Check β-hCG, examine testes.
- Young man with large retroperitoneal mass - Primary testicular tumour?
- New back pain in 20-40 year old male - Consider retroperitoneal nodes.
- Multiple lung nodules in young man - Metastatic GCT high on differential.
Primary Symptom (95%)
Painless, unilateral testicular mass or swelling.
Pain
Present in 10-20% (due to hemorrhage or infarction within tumour).
Duration
Often present for weeks to months before presentation (mean delay 3-6 months).
5. Clinical Examination
Structured Testicular Examination
General Inspection
- Patient standing and supine.
- Compare both sides for asymmetry.
- Note any scrotal skin changes, scars, or sinuses.
Palpation Technique
- Warm hands - Cold hands cause cremasteric reflex.
- Examine normal testis first - Establish baseline.
- Bimanual palpation - Thumb anteriorly, two fingers posteriorly.
- Examine systematically: Epididymis (posterior), Vas deferens, Testis proper.
Key Examination Findings
| Finding | Significance |
|---|---|
| Hard, irregular mass within testis | Primary malignancy |
| Non-tender (usually) | Differentiates from epididymitis |
| Loss of testicular landmarks | Large tumour replacing testis |
| Cannot get above swelling | Excludes inguinal hernia |
| Transillumination negative | Solid mass (vs. hydrocele) |
| Secondary hydrocele | Present in 10% of tumours |
Beyond the Testis - Metastatic Examination
| Site | Examination | Significance |
|---|---|---|
| Abdomen | Palpate for retroperitoneal mass | Bulky nodal disease |
| Supraclavicular | Left > Right (Virchow's node) | Distant spread |
| Chest | Auscultate, percuss | Pleural effusion, lung mets |
| Breast | Gynecomastia | β-hCG effect |
| Legs | Oedema | IVC compression |
Special Tests
- Transillumination: Negative (solid) - distinguishes from hydrocele.
- Cremasteric Reflex: May be absent with large tumours.
- Prehn's Sign: Elevation does NOT relieve pain (vs. epididymitis).
6. Investigations
First-Line Investigations
1. Scrotal Ultrasound (USS)
- Sensitivity: >95% for detecting testicular masses.
- Findings:
- Hypoechoic or heterogeneous intratesticular mass.
- Microcalcifications (associated with GCNIS).
- Loss of normal testicular echotexture.
- Bilateral Examination: Mandatory - 5% have contralateral abnormality.
2. Tumour Markers (Pre-Orchidectomy)
| Marker | Normal | Elevated In | Half-Life | Clinical Use |
|---|---|---|---|---|
| AFP | less than 10 ng/mL | Yolk Sac Tumour, Embryonal, Mixed | 5-7 days | Never elevated in pure seminoma |
| β-hCG | less than 5 mIU/mL | Choriocarcinoma, Seminoma (20%) | 24-36 hours | Gynecomastia correlation |
| LDH | less than 250 U/L | All GCTs | Variable | Tumour bulk, prognosis |
The AFP Rule: If AFP is elevated with "seminoma" histology, treat as non-seminoma (mixed tumour with yolk sac component not sampled).
3. Baseline Bloods
- FBC, U&E, LFTs, Bone profile.
- Pre-operative assessment.
Staging Investigations (Post-Diagnosis)
1. CT Chest-Abdomen-Pelvis
- Retroperitoneal Nodes: Primary drainage site.
- Lung Metastases: Most common haematogenous site.
- Liver Metastases: Less common.
2. MRI Brain
- Indication: β-hCG >5000 mIU/mL, choriocarcinoma histology, or neurological symptoms.
- Risk: Choriocarcinoma has high propensity for brain metastases.
3. PET-CT
- Role in Seminoma: Useful for assessing residual masses post-chemotherapy.
- Not for NSGCT: Teratoma is not FDG-avid.
Staging Systems
TNM Staging (AJCC 8th Edition)
| Stage | Description |
|---|---|
| pT1 | Tumour limited to testis and epididymis, no LVI |
| pT2 | Tumour with LVI or invading hilar soft tissue |
| pT3 | Tumour invades spermatic cord |
| pT4 | Tumour invades scrotum |
| N1 | Lymph nodes ≤2 cm |
| N2 | Lymph nodes 2-5 cm |
| N3 | Lymph nodes >5 cm |
| M1a | Non-retroperitoneal nodal or lung metastases |
| M1b | Other visceral metastases |
Serum Marker Staging (S-Stage)
| S-Stage | LDH | β-hCG (mIU/mL) | AFP (ng/mL) |
|---|---|---|---|
| S0 | Normal | Normal | Normal |
| S1 | less than 1.5x ULN | less than 5000 | less than 1000 |
| S2 | 1.5-10x ULN | 5000-50,000 | 1000-10,000 |
| S3 | >10x ULN | >50,000 | >10,000 |
7. Management
Management Algorithm
TESTICULAR MASS SUSPECTED
↓
┌─────────────────────────────────────────┐
│ URGENT SCROTAL ULTRASOUND │
│ + Serum Markers (AFP, β-hCG, LDH) │
└─────────────────────────────────────────┘
↓
Solid Intratesticular Mass?
↓
┌─────┴─────┐
NO YES
↓ ↓
Reassess RADICAL INGUINAL
Consider ORCHIDECTOMY
Alternative (NEVER Scrotal)
↓
↓
┌─────────────────────────────────────────┐
│ POST-ORCHIDECTOMY STAGING │
│ - CT CAP │
│ - Post-op markers (day 5-7) │
│ - Consider MRI brain if high β-hCG │
└─────────────────────────────────────────┘
↓
┌───────┴───────┐
↓ ↓
SEMINOMA NON-SEMINOMA
↓ ↓
┌──────┴──────┐ ┌─────┴─────┐
Stage I II/III Stage I II/III
↓ ↓ ↓ ↓
Surveillance Chemo RPLND or Chemo
or Carbo x1 or RT Surveillance (BEP)
Surgical Management
1. Radical Inguinal Orchidectomy
- Approach: Inguinal incision (NEVER scrotal) to avoid scrotal contamination and lymphatic seeding.
- Technique: High ligation of spermatic cord at internal ring.
- Sperm Banking: Must be offered pre-operatively.
- Histology: Determines subsequent management.
2. Retroperitoneal Lymph Node Dissection (RPLND)
- Indication: Stage I NSGCT (alternative to surveillance), Residual mass post-chemo (NSGCT).
- Template: Nerve-sparing (preserves ejaculation in 95%).
- Complications: Retrograde ejaculation, chylous ascites, lymphocele.
Chemotherapy Regimens
BEP Regimen (First-Line NSGCT)
- B: Bleomycin 30 units weekly.
- E: Etoposide 100 mg/m² days 1-5.
- P: Cisplatin 20 mg/m² days 1-5.
- Cycles: 3 cycles (good prognosis) or 4 cycles (intermediate/poor).
EP Regimen (Seminoma/Bleomycin Contraindicated)
- Etoposide + Cisplatin (4 cycles).
- Use: Age >40, pulmonary disease, or prior bleomycin toxicity.
Salvage Regimens
- TIP: Paclitaxel, Ifosfamide, Cisplatin.
- VeIP: Vinblastine, Ifosfamide, Cisplatin.
- High-Dose Chemotherapy + ASCT: For relapsed disease.
Radiotherapy
- Seminoma Stage I/II: Para-aortic strip RT (20-30 Gy).
- Declining Use: Chemotherapy often preferred (fertility, second malignancy risk).
Stage-Specific Management
Stage I Seminoma Options
- Surveillance (Preferred): 85% cure with orchidectomy alone.
- Single-dose Carboplatin AUC7: Reduces recurrence to 4%.
- Adjuvant RT: 20 Gy dogleg field (historical, declining use).
Stage I NSGCT Options
- Surveillance: If markers normalize, no LVI, low-risk.
- Primary RPLND: Nerve-sparing technique.
- Adjuvant BEP x1: If high-risk features (LVI, embryonal predominance).
Metastatic Disease
- Good Prognosis: BEP x3 (90% cure).
- Intermediate Prognosis: BEP x4 (80% cure).
- Poor Prognosis: BEP x4 or clinical trial (48% cure). [9]
8. Complications
Treatment-Related Complications
Chemotherapy Toxicities
| Complication | Agent | Management |
|---|---|---|
| Pulmonary Fibrosis | Bleomycin | Limit cumulative dose less than 400 units |
| Nephrotoxicity | Cisplatin | Aggressive hydration, avoid NSAIDs |
| Ototoxicity | Cisplatin | Audiometry monitoring |
| Neuropathy | Cisplatin | Dose reduction if severe |
| Secondary Malignancy | All | Leukaemia risk 0.2-0.5% |
| Cardiovascular | All | Long-term CVD risk 2-3x increased |
Surgical Complications
| Complication | Incidence | Prevention |
|---|---|---|
| Retrograde Ejaculation | 1-10% (RPLND) | Nerve-sparing technique |
| Infertility | 30-50% | Pre-treatment sperm banking |
| Lymphocele | 5-10% | Meticulous ligation |
| Contralateral Tumour | 2-5% lifetime | Surveillance, self-examination |
Disease Complications
- Metastatic Disease: Occurs in 15-30% at presentation.
- Relapse: 15-20% of stage I patients relapse (curable with salvage therapy).
- Second Primary Testicular Cancer: 2-5% lifetime risk.
9. Prognosis and Outcomes
IGCCCG Prognostic Classification
Good Prognosis (56% - Seminoma, 90% - NSGCT)
- Seminoma: Any primary site, no non-pulmonary visceral mets.
- NSGCT: Testis/retroperitoneal primary, no non-pulmonary visceral mets, good markers.
- 5-Year Survival: 91%.
Intermediate Prognosis (28% - Seminoma, 10% - NSGCT)
- Seminoma: Non-pulmonary visceral mets present.
- NSGCT: Testis/RP primary, no non-pulmonary visceral mets, intermediate markers.
- 5-Year Survival: 79%.
Poor Prognosis (NSGCT only - 16%)
- Mediastinal primary, OR non-pulmonary visceral mets, OR poor markers.
- 5-Year Survival: 48%.
Long-Term Survivorship Issues
- Cardiovascular Disease: 1.5-2x increased risk (cisplatin effect).
- Second Malignancies: 1.2-1.5x increased risk over 20 years.
- Metabolic Syndrome: Higher rates post-treatment.
- Hypogonadism: May require testosterone replacement.
- Psychosocial: Anxiety, fertility concerns, body image.
Surveillance Protocols (Stage I)
Seminoma Surveillance
- Year 1-3: CT every 4-6 months, Markers every 3-4 months.
- Year 4-5: CT every 6-12 months, Markers every 6 months.
- Year 6-10: Annual review.
NSGCT Surveillance
- Year 1: CT every 2-3 months, Markers monthly.
- Year 2: CT every 3-4 months, Markers every 2 months.
- Year 3-5: CT every 6-12 months, Markers every 3-6 months.
10. Evidence and Guidelines
Key Guidelines
| Guideline | Organization | Key Recommendations |
|---|---|---|
| EAU Guidelines | European Association of Urology | Stage I surveillance preferred, RPLND for NSGCT |
| ESMO Guidelines | European Society for Medical Oncology | BEP as standard chemo, bleomycin omission criteria |
| NCCN Guidelines | National Comprehensive Cancer Network | Risk-adapted management, surveillance protocols |
Landmark Trials
1. MRC TE10 Trial (1994) [11]
- Question: Carboplatin vs RT for stage I seminoma?
- N: 1,447 patients.
- Result: Single-dose carboplatin non-inferior to RT.
- Impact: Carboplatin is now a standard option for adjuvant seminoma.
2. SWENOTECA Study (2011) [12]
- Question: Risk-adapted management for stage I NSGCT?
- N: 745 patients.
- Result: 1 cycle BEP reduces relapse from 41% to 3% in high-risk.
- Impact: Established risk stratification using LVI.
3. 111 Trial - MRC/EORTC (2014) [13]
- Question: 3 vs 4 cycles BEP for good prognosis metastatic GCT?
- N: 812 patients.
- Result: 3 cycles BEP equivalent in good prognosis.
- Impact: Reduced toxicity without compromising cure.
4. Indiana University Series (1997) [14]
- Question: Outcomes after high-dose chemo + ASCT for relapse?
- N: 184 patients.
- Result: 63% long-term survival in relapsed disease.
- Impact: Established salvage therapy paradigm.
11. Patient and Layperson Explanation
What is Testicular Cancer?
Testicular cancer starts in one of the testicles (the egg-shaped glands in the scrotum that make sperm and testosterone). It usually appears as a painless lump or swelling. The good news is that testicular cancer is one of the most curable cancers, with more than 95% of men surviving, even if it has spread.
Who Gets It?
It mainly affects younger men aged 15-44. Risk factors include:
- An undescended testicle in childhood.
- Previous testicular cancer in the other testicle.
- Family history (brother or father affected).
What Are the Warning Signs?
- A painless lump or swelling in either testicle.
- A feeling of heaviness in the scrotum.
- A dull ache in the lower belly or groin.
- Breast tenderness or growth (rare).
How is it Diagnosed?
- Ultrasound: A quick, painless scan of the testicle.
- Blood Tests: Check for tumour markers (AFP, hCG, LDH).
- Surgery: The testicle is removed through a cut in the groin (not the scrotum) to confirm the diagnosis.
How is it Treated?
- Surgery: Removal of the affected testicle (you can have a prosthetic implant).
- Chemotherapy: Very effective - often uses a combination called "BEP".
- Radiotherapy: Sometimes used for seminoma type.
- Surveillance: For early-stage cancer, close monitoring may be all that's needed.
What About Fertility?
- One testicle is usually enough for normal testosterone levels and fathering children.
- We offer sperm banking before any treatment starts.
- Some treatments can temporarily or permanently affect fertility.
When to Seek Help
- Any lump or swelling in a testicle - get it checked within 2 weeks.
- Testicle pain that doesn't go away.
- Unexplained back pain that persists.
- Unexplained weight loss or fatigue.
- Shortness of breath or chest pain.
Follow-Up and Support
After treatment, regular check-ups are important to monitor for recurrence. Many men experience anxiety about the possibility of recurrence, and psychological support may be helpful. Fertility preservation and testosterone replacement are important considerations for long-term quality of life.
Psychological Impact and Support Needs
- Anxiety and Depression: Up to 30% of survivors experience significant anxiety about recurrence.
- Body Image Concerns: Loss of one testicle and potential prosthetic concerns.
- Sexual Function: Chemotherapy can cause erectile dysfunction and reduced libido.
- Support Resources: Cancer support groups, psychological counseling, survivorship clinics.
- Fertility Counseling: Discussion of sperm banking outcomes and ART options.
12. References
Primary Sources
- Cheng L, et al. Testicular cancer. Lancet. 2018;392:1711-1723. PMID: 30285908.
- Gilligan TD, et al. American Society of Clinical Oncology Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors. J Clin Oncol. 2010;28:3388-3404. PMID: 20530298.
- Trabert B, et al. International patterns and trends in testicular cancer incidence. Int J Cancer. 2015;136:E285-E295. PMID: 25200513.
- IGCCCG. International Germ Cell Consensus Classification: a prognostic factor-based staging system. J Clin Oncol. 1997;15:594-603. PMID: 9053482.
- Albers P, et al. EAU Guidelines on Testicular Cancer. Eur Urol. 2023. PMID: 35815957.
- Sung H, et al. Global Cancer Statistics 2020. CA Cancer J Clin. 2021;71:209-249. PMID: 33538338.
- Pettersson A, et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356:1835-1841. PMID: 17476009.
- Kanetsky PA, et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 2009;41:811-815. PMID: 19483682.
- Einhorn LH. Treatment of testicular cancer: a new and improved model. J Clin Oncol. 1990;8:1777-1781. PMID: 1700077.
- Laguna MP, et al. EAU Guidelines on Testicular Cancer: 2020 Update. Eur Urol. 2022;79:440-456. PMID: 35200039.
- Oliver RT, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma. Lancet. 2005;366:293-300. PMID: 16039331.
- Tandstad T, et al. Risk-adapted treatment in clinical stage I nonseminomatous germ cell testicular cancer. J Clin Oncol. 2009;27:2122-2128. PMID: 19307506.
- de Wit R, et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy. J Clin Oncol. 2001;19:1629-1640. PMID: 11250990.
- Nichols CR, et al. High-dose chemotherapy and autologous bone marrow transplantation for recurrent germ cell tumors. J Clin Oncol. 1992;10:558-563. PMID: 1312584.
- Motzer RJ, et al. Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer. J Clin Oncol. 2000;18:2413-2418. PMID: 10893129.
- Mead GM, et al. A randomized trial comparing high-dose chemotherapy with autologous peripheral-blood stem-cell transplantation and weekly chemotherapy in relapsed germ-cell tumors. J Clin Oncol. 2005;23:5136-5142. PMID: 16051954.
- Kollmannsberger C, et al. Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors. J Clin Oncol. 1998;16:3386-3391. PMID: 9779708.
- Travis LB, et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst. 2005;97:1354-1365. PMID: 16174854.
- Haugnes HS, et al. Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol. 2010;28:4649-4657. PMID: 20921457.
- Rossen PB, et al. Psychosexual adjustment in men who have undergone radical orchidectomy for testicular cancer. J Clin Oncol. 1995;13:2580-2585. PMID: 7595709.
13. Examination Focus
Common Exam Questions
MRCP Oncology/Genitourinary Questions:
-
"A 28-year-old man presents with a painless left testicular mass. What is the most likely diagnosis?"
- Answer: Germ cell tumour (95% of testicular masses in young men are malignant).
-
"What tumour markers are elevated in testicular cancer and what do they tell you about histology?"
- Answer: AFP (never in pure seminoma, indicates yolk sac component), β-hCG (elevated in both but choriocarcinoma has highest), LDH (tumour burden).
-
"A patient has stage I seminoma. What are the management options?"
- Answer: Surveillance (preferred), single-dose carboplatin AUC7, or adjuvant radiotherapy (declining use due to second malignancy risk).
-
"How do you manage metastatic non-seminomatous germ cell tumour?"
- Answer: BEP chemotherapy regimen (bleomycin, etoposide, cisplatin) for 3-4 cycles based on prognosis group.
-
"What is the most important prognostic factor in testicular cancer?"
- Answer: Histology (seminoma vs non-seminoma) and IGCCCG prognostic group for metastatic disease.
Viva Points
Opening Statement: "Testicular cancer is the most common solid malignancy in men aged 15-44, with over 95% being germ cell tumours. It presents classically as a painless testicular mass and has excellent prognosis with cure rates exceeding 95% even in metastatic disease, making it one of medicine's greatest success stories in cancer treatment."
Key Facts to Mention:
- Bimodal age distribution (seminoma 35-45, NSGCT 20-35 years)
- Cryptorchidism increases risk 5-10 fold
- AFP >10 ng/mL excludes pure seminoma diagnosis
- Radical inguinal orchidectomy is the initial treatment (never scrotal approach)
- BEP chemotherapy is the standard regimen for metastatic disease
- 5-year survival for metastatic disease is 48% (poor prognosis) to 91% (good prognosis)
Classification to Quote: "The International Germ Cell Cancer Collaborative Group (IGCCCG) classifies metastatic GCT into good, intermediate, and poor prognosis groups based on primary site, presence of non-pulmonary visceral metastases, and serum markers."
Evidence to Cite:
- "The MRC TE10 trial (2005, n=1447) showed single-dose carboplatin was non-inferior to radiotherapy for stage I seminoma"
- "The 111 trial (2001, n=812) demonstrated 3 cycles of BEP were equivalent to 4 cycles for good prognosis metastatic disease"
Structured Answer Framework:
- Epidemiology (30 seconds): Most common cancer in young men, rising incidence, cryptorchidism major risk factor.
- Pathophysiology (45 seconds): Germ cell neoplasia in situ (GCNIS) precursor, 95% germ cell tumours, seminoma vs non-seminoma.
- Clinical Features (45 seconds): Painless mass (85-95%), markers (AFP/β-hCG/LDH), red flags for metastatic disease.
- Investigations (30 seconds): USS shows solid intratesticular mass, markers guide histology, CT staging.
- Management (60 seconds): Orchidectomy first, then risk-adapted approach - surveillance vs chemo vs RPLND.
- Prognosis (30 seconds): >95% cure rate, IGCCCG classification, long-term survivorship issues.
Common Mistakes
What fails candidates:
- ❌ Forgetting to mention AFP NEVER elevated in pure seminoma
- ❌ Not knowing BEP chemotherapy regimen doses
- ❌ Missing cryptorchidism as major risk factor
- ❌ Not appreciating excellent prognosis (95%+ cure rate)
- ❌ Quoting outdated radiotherapy as first-line for seminoma
Dangerous Errors to Avoid:
- ⚠️ Delaying orchidectomy for "trial of antibiotics" in epididymitis
- ⚠️ Performing scrotal rather than inguinal orchidectomy (violates lymphatics)
- ⚠️ Not offering sperm banking pre-treatment
- ⚠️ Missing elevated β-hCG indicating choriocarcinoma component
Outdated Practices (Do NOT mention):
- Routine RPLND for all stage I NSGCT (now surveillance preferred)
- Radiotherapy as first-line for stage I seminoma (second malignancy risk)
- Using AFP elevation to diagnose seminoma (it excludes pure seminoma)
Examiner Follow-Up Questions
Expect these follow-up questions:
-
"How would you differentiate between seminoma and non-seminoma on histology?"
- Answer: Seminoma has uniform cells, clear cytoplasm, lymphocytic infiltrate; NSGCT shows mixed histology (embryonal, yolk sac, choriocarcinoma, teratoma).
-
"What are the components of the BEP regimen?"
- Answer: Bleomycin 30 units weekly, Etoposide 100 mg/m² days 1-5, Cisplatin 20 mg/m² days 1-5, repeated every 3 weeks.
-
"What are the contraindications to bleomycin?"
- Answer: Pulmonary disease, age >40, prior bleomycin exposure (>400 units cumulative dose increases pulmonary fibrosis risk).
-
"How do you manage a patient who develops bleomycin-induced pneumonitis?"
- Answer: Stop bleomycin immediately, supportive care with oxygen, consider corticosteroids if severe, monitor pulmonary function.
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"What are the long-term complications of testicular cancer treatment?"
- Answer: Cardiovascular disease (2x risk), second malignancies (leukaemia risk 0.5%), infertility (RPLND/chemotherapy), hypogonadism requiring testosterone replacement.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.