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Background

Epidemiology

• Prevalence: rare, only 8K-9K cases per year
• Age: most common cancer in 20-40yo men
• Stage at presentation: majority (~2/3) present with Stage I, < 15% present with Stage III disease
• Bilateral disease: 2%, usually metachronous within 5yrs of initial presentation
• Extragonadal primary: seen in 5%, usually in retroperitoneum or mediastinum

Risk factors

• Intratubular germ cell neoplasia (ITGCN): 50% testis cancer risk in 5yrs
• Cryptorchidism: 4-6x, 2-3x if pexied pre-puberty, 1.74x risk in contralateral testis
• Family hx: increased risk if first-degree relative with testis cancer
• Personal hx: 12x compared to general population, but 15yr incidence is only 2% (because testis cancer is overall rare)
• Other potential risks: HIV, gonadal dysgenesis with Y chromosome, infertility (2-3x risk), Klinefelter syndrome (increased extragonadal risk), CHEK2 mutation (4x risk)
• Non-risk factors: atrophy, trauma (increases chances of diagnosis), microlithiasis (incidental finding only)

Types

• Germ cell tumors: seminoma (~55%) vs non-seminoma germ cell tumor (NSGCT, ~45%)
• NSGCT: includes choriocarcinoma, yolk sac, embryonal, and teratoma
• Seminoma: doesn't make AFP, XRT-sensitive
• Choriocarcinoma: can spread hematogenously, cause hemorrhagic metastases
• Teratoma: chemo-resistant, can rapidly grow, can transform into somatic malignancies (sarcoma, etc), no difference in adults between immature and mature
• Embryonal carcinoma: presence in orchiectomy specimen increases risk for occult metastases
• Yolk sac tumor: more common in mediastinal and pediatric tumors, almost always make AFP, do not make HCG

Presentation and Workup

Symptoms/Signs

• Symptoms: painless swelling, pain (10% from hemorrhage/infarction), chest/back/abdominal pain, cough/dyspnea
• Signs: hard/enlarged testicle, abdominal mass, subclavicular lymphadenopathy, gynecomastia

Imaging workup

• Scrotal US: solid testis mass is testis cancer until proven otherwise
• Staging: obtain CT C/A/P to assess for retroperitoneal and other lymphadenopathy, CT misses 30% metastatic disease
• Chest imaging: can get CXR instead of CT chest if low risk for thoracic metastases
• Brain imaging: consider if HCG > 5K, AFP > 10K, neurologic symptoms, extensive lung mets, or non-pulmonary visceral mets
• Bone imaging: only if specific clinical indication
• Observation: if mass < 1cm and normal STMs, can consider repeating labs and US in 6-8 weeks (may be benign lesion), consider MRI for inconclusive lesions

Serum Tumor Markers (STMs)y

• LDH: nonspecific marker produced by 20% GCT, magnitude correlates w/ disease bulk, also seen with lymphoma and infection/inflammation
• AFP: produced by yolk sac and embryonal (elevated AFP = NSGCT), never produced by pure choriocarcinoma or seminoma, also seen with infants < 1yo, lung, biliary, stomach, panc, liver cancer, liver disease, ataxia telangiectasia, and tyrosinemia
• bHCG: produced by 10-30% NSGCT (always if choriocarcinoma present) and 10-15% seminomas, also seen with liver, panc, stomach, biliary, lung, breast, kidney, bladder cancer, marijuana use, hyperthyroid hypogonadism (cross-reactive with LH)
• Do not treat solely based on elevated LDH (non-specific) or elevated AFP < 25 (can be normal)
• Half-Life: AFP (5-7 days), LDH (3-5 days), bHCG (24-36 hours)
• S0: normal STMs
• S1: LDH < 1.5x normal, AFP < 1K, bHCG < 5K
• S2: LDH 1.5-10x normal, AFP 1-10K, bHCG 5-50K
• S3: LDH > 10x normal, AFP > 10K, bHCG > 50K

Sperm Banking

• Discuss sperm banking prior to orchiectomy (standard of care)
• Pre-orchiectomy findings: 50% have abnormal semen parameters and 10% have azoospermia at presentation
• Cisplatin chemotherapy: causes azoospermia, 50% recovery by 2yrs, 80% by 5yrs
• XRT: > 6 Gy causes azoospermia, oligospermia is dose dependent below 6 Gy
• RPLND: 80% have permanent ejaculatory dysfunction, reduced to 10% w/ nerve-sparing techniques

Orchiectomy

Tips for Minimizing Cancer Recurrence

• Approach: perform orchiectomy via inguinal (not scrotal) incision (standard of care), removes spermatic cord and does not alter lymphatic drainage
• Local recurrence rates 2.5% with scrotal violation (vs 0% via inguinal approach)
• If able, place testis prosthesis
• Contralateral testis biopsy: consider if atrophic testis, history cryptorchidism, or younger than 40yrs (36% risk ITGCN vs baseline 5-9% ITGCN in contralateral testis)

Testis-Sparing Surgery

• Indications: mass < 2-3cm, equivocal US findings, negative STM, solitary testis, and/or b/l tumors
• Obtain biopsies from normal adjacent tissue (look for ITGCN)
• Increased recurrence risk overall, especially local recurrence (11% vs 0%)
• If ITGCN present, offer XRT or orchiectomy due to higher risk of recurrence
• Risks: need for intraoperative orchiectomy, ipsilateral atrophy (3%), hypogonadism (7%)

Scrotal violation management

• Trans-scrotal biopsy and orchiectomy should not be performed
• Local recurrence risk: increases to 2.5% from 0%
• pT4 suspected: excise portion of scrotum en bloc during inguinal orchiectomy
• Scar excision after scrotal orchiectomy: 9% had residual disease
• Surveillance: perform groin exams, check inguinal/pelvic nodes on imaging