Testicular Tumours and Cancer

Testicular Tumours

• Over 90% are germ-cell tumours
• Bilateral occurrence in 1-2% of cases
• 1% of testicular tumours are metastatic from another site

Epidemiology of Testicular Cancer

• Approximately 176 men are diagnosed with testicular cancer in Ireland each year, a number that is slowly increasing
• Testicular cancer accounts for 1% of all male cancers
• It is the most common solid cancer in men aged 15-35 years
• The overall survival rate at 10 years is 96%

Risk Factors for Testicular Cancer

• Testicular Dysgenesis: Cryptorchidism increases the risk by 5-15 times compared to those with normally descended testes; also associated with infertility and hypospadias; 3x risk if pexy occurs before age 13, versus being 6x if pexy after age 13
• Family History: A 4x increased risk if the father is affected, 8x if a brother is affected
• Contralateral Tumour/GCNIS: A 12x increased risk if there is a previous tumour; 50% of GCNIS cases develop into testicular cancer within 5 years
• Age: Most common in men aged 20-40
• Race: More prevalent in white individuals with a 3:1 ratio compared to black individuals
• Maternal Oestrogen Exposure: Potential contributing factor
• Genetics: Implication of 12p in all Germ Cell Tumours (GCT)

Histological Classification of Tumours

• Germ-cell tumours
  • Seminoma
  • Non-seminomatous GCT: Embryonal carcinoma, Choriocarcinoma, Yolk sac tumour, Teratoma, Mixed tumours
• Gonadal stromal tumours
  • Leydig-cell tumours
  • Sertoli-cell tumours
  • Gonadoblastoma
  • Mixed
• Other tumours
  • Epidermoid cyst
  • Adenomatoid tumours
  • Carcinoid
  • Adenocarcinoma of the rete testis
  • Metastatic tumours

History and Examination

• History may reveal painless unilateral testicular swelling or nodule
• Sensation of heaviness in the scrotum
• Scrotal or lower abdominal pain
• Trauma draws attention to a previously existing nodule
• Metastases may be symptomatic
• 10-15% present with pain
• Examination: enlarged testis
• Protruding nodule may be palpable
• 10% have a secondary hydrocoele
• Epididymis may be difficult to palpate
• Paraaortic or inguinal lymphadenopathy
• Hepatomegaly
• Signs of distant metastases
• May mimic acute epididymo-orchitis

Diagnosis of Testicular Cancer

• Urine examination is not recommended as there are no specific urinary markers
• Blood tests include serum markers;
  • AFP (50-70% NSGCT)
  • bhCG (40-60% NSGCT, 30% Seminoma)
  • LDH (Non-specific)
• Imaging: Ultrasound is nearly 100% sensitive, plus CT and MRI to check for metastases

Staging – TNM

• Tis: ITGCN (Intratubular Germ Cell Neoplasia)
• T1: Confined to testes without vascular/lymph involvement; no tunica vaginalis involvement
• T2: Limited to testes with vascular/lymph involvement; possible tunica vaginalis involvement
• T3: Invades spermatic cord
• T4: Invades scrotum
• N1: Lymph node mass less than 2cm, multiple lymph nodes all less than 2cm
• N2: Lymph node mass between 2-5cm; more than 5 lymph nodes positive, all less than 5cm; extranodal extension
• N3: Lymph node mass greater than 5cm
• M1: Non-regional lymph node involvement; lung metastases (a), Other sites (b)
• Serum Markers:
  • S1: LDH less than 1.5x ULN, hCG less than 5k, AFP less than 1k
  • S2: LDH between 1.5-10x ULN, hCG between 5k-50k, AFP between 1k-10k
  • S3: LDH greater than 10x ULN, hCG greater than 50k, AFP greater than 10k

Royal Marsden Classification

• Stage 1: Testis lesion only
• Stage 2: Nodes are affected only below the diaphragm
• Stage 3: Nodes are affected above the diaphragm
• Stage 4: Pulmonary/hepatic metastases present

Treatment

• Radical Orchidectomy
  • Is curative in 75% of patients
• Lymphatic drainage of the scrotum and testes differs: Testes (lumbar and para-aortic lymph nodes), Scrotum (superficial inguinal lymph nodes)
• Sperm banking should ideally be offered preoperatively

Adjuvant Treatments

• Orchidectomy is curative in 75% of cases
• Seminoma has a 15% recurrence rate, usually within 2 years
• Non-Seminomatous Germ Cell Tumours (NSGCT) recur in 15-50% of cases, depending on risk factors
• Staging is important, involving CT TAP and serial tumour markers
• Adjuvant options include surveillance, chemotherapy (NSGCT are chemosensitive), radiotherapy (Seminomas are radiosensitive), and surgery
• Seminoma and NSGCT should be considered as distinct diseases for adjuvant treatments

How to check your testicles

• The best time to examine yourself is after a warm bath or shower when the skin of your scrotum is relaxed
• Most lumps found on the testicles are not cancer, but any changes in size, shape or weight should be checked
• Support the scrotum in the palm of your hand and become familiar with the size and weight of each testicle
• Examine each testicle by rolling it between your fingers and thumb
• Gently feel for lumps, swellings or changes in firmness
• Each testicle has a soft tube at the top (epididymis) which carries sperm to the penis, this is normal

Penile Tumour

• Rare cancer
• 630 men/year in the UK are diagnosed
• Higher incidence in Africa and Asia
• Most commonly diagnosed in men > 60 years
• Associated with HPV, HIV, smoking, and phimosis
• HPV sub-types: 6, 16, 18
• Circumcision is protective

Classification of Penile Tumours

• 95% are squamous cell carcinoma
• Other types include basal cell carcinoma, sarcoma, melanoma, and small cell carcinoma

Clinical Manifestations

• Palpable or ulcerating lesion on the penis, usually on the glans
• Typically painless
• It may bleed or discharge
• Inguinal lymphadenopathy is present in 30-60% of cases
• Patients may complain of dysuria

Investigations

• Biopsy to confirm diagnosis
• CT TAP for staging
• PET CT for determination of lymphadenopathy

Penile Cancer TNM Staging Classification

• Stage I: T1a - invades subepithelial connective tissue; grade 1 or 2; N0, M0
• Stage II: T1b - grade 3; T2 - invades corpus spongiosum; T3 - invades corpus cavernosum; N0, M0
• Stage III: T1-T3; N1 - Metastasis in 1-2 inguinal lymph nodes; N2 - Metastasis in more than 2 lymph nodes OR bilateral lymph nodes; M0
• Stage IV: T4 - invasion of adjacent structures; Any T; N0-2; N3 - pelvic lymph nodes OR extranodal extension of any lymph nodes; Or M1 disease: distant metastasis

Penile cancer management

• Surgical Management
• Topical Chemotherapy agent e.g. Imiquimod or 5-FU
• Laser treatment
• Glans resurfacing

Surgical Management

• Organ sparing treatment when disease is confined to the glans
  • Local excision
  • Partial glansectomy
  • Total glansectomy with reconstruction
• Invasive penile cancer
  • Partial amputation with reconstruction
  • Total penectomy with perineal ureterostomy
  • Neo-adjuvant radiotherapy or chemotherapy

Prognosis

• The Overall 5-year Survival Rate (5YSR) is 50% (for all stages)
• 85% 5YSR if diagnosed at T1 stage
• 12% 5YSR if distal metastases are present at diagnosis