Testicular cancer

More than 95% of testicular tumours arise from the germ cells. Testicular germ cell tumours can be subdivided into seminoma and non-seminomatous germ cell tumours (NSGCTs). Of the germ cell tumours, about 50% are seminomas and 50% are non-seminomas.

Since the introduction of combination chemotherapy in the 1970s, survival rates for testicular cancer have risen every year. One year survival is close to 100% and both 5 and 10 year survival are more than 95%. Even metastatic disease should be seen as potentially curable.¹

Types of testicular cancer (classification)

Testicular cancers are defined based on their cell type.

The 2016 updated World Health Organization (WHO) histopathological classification characterises testicular cancers as follows:²

• Germ cell tumours.

• Derived from germ cell neoplasia in situ (GCNIS):

  • Seminoma.

  • Embryonal carcinoma.

  • Yolk sac tumour, post-pubertal type.

  • Trophoblastic tumour.

  • Teratoma, post-pubertal type.

  • Teratoma with somatic-type malignancies.

  • Mixed germ cell tumours.

• Germ cell tumours unrelated to GCNIS including spermatocytic tumour, yolk sac tumour, pre-pubertal type, Mixed germ cell tumour, pre-pubertal type.

• Sex cord/stromal cell tumours including Leydig cell tumour, Sertoli cell tumour, granulosa cell tumour.

• Thecoma/fibroma group of tumours.

• Other sex cord/gonadal stromal tumours.

• Tumours containing both germ cell and sex cord/gonadal stromal - eg, gonadoblastoma

• Miscellaneous non-specific stromal cell tumours including tumours of paratesticular structures

How common is testicular cancer? (Epidemiology)²³

• Testicular cancer accounts for around 1% of all new cancer cases in the UK, and is the 17th most common cancer for men.

• The incidence peaks at 30-34 and only 1% of cases are diagnosed in men aged 75 or over.

• The incidence of testicular cancer varies by ethnic origin and is lower in those of Asian origin compared to the White ethnic group. It is more common in developed compared to developing countries.

• Testicular tumours are far more common in adults than in children. Seminoma is rare in boys younger than 10 years of age but is the most common testicular tumour in men older than 60 years.

Risk factors

These include:²⁴

• Cryptorchidism or testicular maldescent.

• Klinefelter's syndrome.

• Family history (multiple genetic associations have been found, but no single gene analogous to the BRCA gene).

• Male infertility (increases risk by a factor of three).

• Low birth weight, young maternal age, young paternal age, multiparity, breech delivery.

• Infantile hernia.

• Height - taller men are more at risk of developing germ cell tumours.

• Infection with human papilloma virus, Epstein-Barr virus, cytomegalovirus, parvovirus B-19, or HIV.

Of the factors associated with the risk of developing germ cell tumours of the testis, cryptorchism and malignancy in the contralateral testis are by far the strongest.

Testicular microlithiasis, vasectomy, and scrotal trauma are not risk factors for testicular cancer. ⁵

Genetic factors⁶

Many malignancies are due to genetic damage. This genetic damage may be caused in the intrauterine environment for tumours of testis and breast. Virtually all testicular tumours display an abnormality on chromosome 12. Up to 20% of men may carry the testicular germ cell tumour 1 (TGCT1) gene on their X chromosome. Possession of this gene may increase risk of testicular malignancy by up to 50 times. It may also be involved in families with a history of cryptorchism, and families of men who develop bilateral disease are also more likely to carry this gene.

Signs and symptoms of testicular cancer (presentation)²⁷

Symptoms

• More than 95% present with a lump in the body of the testis, which is usually painless. See the separate Lumps in the groin and scrotum article.

• Testicular pain and/or abdominal pain.

• Dragging sensation.

• Recent history of trauma; it is probably the trauma that leads the man to examine himself and find the tumour rather than the trauma being the cause of malignant change.

• Hydrocele.

• Gynaecomastia from beta human chorionic gonadotrophin (beta-hCG) production (this is rare but important as it can sometimes precede a palpable lump).

• Metastasis - seminomas metastasise to para-aortic nodes and produce back pain; teratomas undergo blood-borne spread to the liver, lung, bone and brain.

Signs

• A lump is usually palpable.

• Whereas the normal testis is rather delicate and the inflamed testis is very tender, the malignant testis tends to lack the normal level of sensation.

• Lymphatics from the scrotum drain to the inguinal nodes but from the testes they go deeper. Hence, inguinal lymph nodes are unlikely to be enlarged.

Patients presenting with a swelling in the scrotum should be examined carefully and an attempt made to distinguish between lumps arising from the testis and other intrascrotal swellings. An ultrasound scan should be performed to make a distinction.

Differential diagnosis²

• Epididymo-orchitis.

• Torsion.

• Lymphoma.

• Other scrotal lumps - eg, hydrocele, haematocele, epididymal cyst, hernia, varicocele.

• Infection - eg, tuberculosis, syphilis, mumps.

Diagnosis of testicular cancer (investigations)⁸⁹

• The National Institute for Health and Care Excellence (NICE) says that we should 'consider a suspected cancer pathway referral for testicular cancer in men if they have a non-painful enlargement or change in shape or texture of the testis' and consider an ultrasound for all men with unexplained or persistent testicular symptoms. This referral should not be delayed by waiting for an ultrasound scan.

• Investigations in secondary care may include CT, and tumour markers (alpha-fetoprotein (AFP) is produced by yolk sac elements but not produced by seminomas, whereas beta-hCG is produced by trophoblastic elements and so there may be elevated levels both in teratomas and in seminomas).

Staging of testicular tumours¹⁰

• I - no evidence of disease outside the testis.

• IM - as above but with persistently raised tumour markers.

• II - infradiaphragmatic nodal involvement.

  • IIA - maximum diameter <2 cm.

  • IIB - maximum diameter 2-5 cm.

  • IIC - maximum diameter >5-10 cm.

  • IID - maximum diameter >10 cm.

• III - supradiaphragmatic and infradiaphragmatic node involvement:

  • Abdominal nodes A, B, C, as above.

  • Mediastinal nodes M+.

  • Neck nodes N+.

• IV - extralymphatic metastases:

  • Abdominal nodes A, B, C, as above.

  • Mediastinal or neck nodes as for stage III.

  • Lungs:

    • L1 <3 metastases.

    • L2 multiple metastases <2 cm maximum diameter.

    • L3 multiple metastases >2 cm in diameter.

  • Liver involvement H+.

  • Other sites specified.

Management of testicular cancer¹⁰

Management is dependent on the type of tumour and stage. It may include surgery, chemotherapy, and radiotherapy. A testicular prosthesis should be offered before surgery. Sperm storage should be offered to men who may require chemotherapy or radiotherapy.

Complications of testicular cancer

• Most survivors of testicular cancer regain a normal quality of life. Some patients become hypogonadal after orchidectomy and fertility may be reduced after chemotherapy.

• Peripheral neuropathy, Raynaud's phenomenon, and hearing loss caused by chemotherapy may persist for years.

• After chemotherapy 2.0- to 3.7-fold increased risks for cancers of the small intestine, bladder, kidney and lung have been observed.¹¹

• There is also an increased risk of cardiac events. ¹²

• Overall quality of life scores are similar to those in the general population, but anxiety associated with fear of recurrence, economic worries, alcohol misuse, and sexual difficulties are common in survivors.

• Late relapse (new tumour growth more than two years after at least three cycles of chemotherapy) occurs in 2-3% and does not have a good response to chemotherapy.¹³

Prognosis of testicular cancer^{1 14}

There has been decline in mortality rates reported in Western countries. The prognosis is dependent on stage, tumour type, and presence of low, medium or high levels of markers.

• If the tumour is diagnosed early, over 95% of men are cured and treatment can be less intensive.

• For NSGCTs, the overall results are less favourable than for seminomas.

• Choriocarcinomas have the worst prognosis of any of the testicular malignancies.

Early detection of testicular cancer¹⁵

Public information campaigns have encouraged men to check for any scrotal lumps regularly and to see a GP if they have any concerns. Patients with increased clinical risk factors for testicular cancer, including a family history of testicular cancer, undescended testis (cryptorchidism) or testicular atrophy should be informed of their potential increased risk of testicular cancer and particularly encouraged to self-examine. There is no national screening programme for testicular cancer and this decision is not being actively reviewed by the National Screening Committee.