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Sahdev V, Aning J. GPs should have a high index of suspicion for testicular cancer. Practitioner April 2021;265(1847):11-14

GPs should have a high index of suspicion for testicular cancer

22 Apr 2021

AUTHORS

Mr Varun Sahdev BSc BMBS MRCS Specialist Registrar in Urology

Mr Jonathan Aning BMBS BMed Sci DM FRCS (Urol),Consultant Urological Surgeon

Competing interests: None

Article

Testicular cancer accounts for 1% of male cancers and is the most common solid cancer in men aged between 15 and 49 years old. Most men present with a lump that they have identified in their scrotum. Although the scrotal swelling is usually painless, pain is the first symptom in around 20% of patients, typically a dull or dragging ache in the testicle or a heaviness in the scrotum. Examination should include visual inspection and palpation of the abdomen for abdominal masses and scars. Orchidopexy is performed through a small groin and scrotal incision and it is important to look for these scars as patients may not recall the surgery being performed in early life. A scrotal examination should be performed lying and standing to determine whether left and right testicles are present in the scrotum and palpate any abnormalities of the testicle. The differential diagnosis includes inguinal hernia, varicocele, epididymal cyst and orchitis. NICE recommends that all men who have a non-painful enlargement or change in shape or texture of their testis should be referred urgently to urology using the two-week wait pathway. In men who have unexplained or persistent testicular symptoms, an urgent direct access testicular ultrasound scan should be requested. Scrotal ultrasound is the key investigation to determine whether there is a solid tumour within the testicle. All men diagnosed with testicular cancer on ultrasound should have a testicular tumour marker blood test.


Testicular cancer accounts for 1% of male cancers overall and is the most common solid cancer in men aged between 15 and 49 years old. The estimated lifetime risk of testicular cancer for men born after 1960 is 1 in 215 in the UK. Around 2,300 new diagnoses are made each year in the UK.1

At present a full time GP is likely to diagnose one or two new cases of testicular cancer during their career. However, it is important to recognise that the incidence rates for testicular cancer have risen 24% since the early 1990s and are projected to rise by a further 12% in the UK between 2014 and 2035.1

Early diagnosis of testicular cancer is associated with excellent outcomes and as such GPs should maintain a high level of suspicion for this disease.

The precise aetiology of testicular cancer is unknown but recognised risk factors include:

• A history of undescended testicles (cryptorchidism). Boys born with their testicles inside their abdomen are 3-6 times more likely to develop testicular cancer than those whose testicles have descended into the scrotum by birth.2 The risk is higher in both testes although more so on the affected side.3

Even if boys have an early orchidopexy to fix the affected testis in the scrotum there remains a two-fold higher risk compared with the general population4

• A family history. Men whose father or brother has had testicular cancer have a four- or eight-fold higher risk of developing the disease, respectively5

• Previous testicular cancer. Men with a history of testicular cancer have at least a twelve-fold increased risk of developing cancer in their other testicle compared with the general population5

• Testicular cancer is up to three times more common in Caucasians and Northern Europeans than non-Caucasians

• A history of subfertility6

• HIV increases the risk of developing testicular seminoma7

Presentation

Most men will attend their GP to discuss a lump that they have identified in their scrotum, which may or may not be related to their testicle.

Usually the scrotal swelling will be painless, however around 20% of patients may report pain as the first symptom they notice. A dull or dragging ache in the testicle or a heaviness in the scrotum may be described alone and 10% of men presenting with testicular pain will have a delayed diagnosis of a testicular tumour made.8,9

Rarely men may present with signs of metastatic testicular cancer which include: an abdominal mass, cervical or supraclavicular lymphadenopathy, back pain, weight loss, cough, shortness of breath, nausea, vomiting, gastrointestinal bleeding, central or peripheral nervous system symptoms.

Despite testicular cancer awareness campaigns explaining the importance of routine self-examination and the need

to present to a GP if any abnormality is found or suspected when they check themselves; many men still feel embarrassed and frightened when they talk about their reason for consulting.

Men should be reassured during their consultation that testicular cancer is one of the most treatable cancers and currently at least 95% of men will survive at least five years after their diagnosis.1

Examination

A thorough history should be taken and full abdominal examination should be performed on every patient who presents with suspected testicular cancer. The abdominal examination should be performed in a warm room where the patient’s privacy can be maintained.

The examination should include visual inspection and palpation of the abdomen for abdominal masses and scars.

Orchidopexy is performed through a small groin and scrotal incision. It is important to look for these scars as patients may not recall the surgery being performed as it is usually carried out when boys are very young, after the age of 8 months.

A scrotal examination should be performed lying and standing to elicit whether left and right testicles are present in the scrotum and palpate any abnormalities of the testicle.

Whether or not the healthcare professional performing the examination detects a testicular abnormality; the patient should always be asked to check that where you are palpating during the examination is consistent with where he palpated any perceived abnormality.

Important negative differential diagnoses which can clearly be identified at examination should be looked for and include: inguinal hernia, varicocele, epididymal cyst and orchitis.

If metastatic disease is suspected, it is appropriate to perform respiratory and neurological examinations.

Investigation

NICE guidance recommends that all men who have non-painful enlargement or a change in shape or texture of their testis should be referred urgently to urology using the two-week wait pathway for suspected cancer referrals.10

In men who have unexplained or persistent testicular symptoms an urgent direct access testicular ultrasound scan should be requested. An ultrasound should also be requested if the patient has significant risk factors for testicular cancer or a previous history of testicular cancer in the contralateral testicle and the healthcare professional has a high suspicion that testicular cancer may be an underlying diagnosis. If the option of a direct access ultrasound scan is not available then consider referring the patient to urology under the two-week wait pathway.10

A recent large study of the clinical features of testicular cancer in primary care highlighted other findings that GPs should be alert to. Men with persistent testicular pain or unresolving epididymo-orchitis should be referred for urgent review. Men aged under 50 years old with a new clinically significant hydrocele should also be referred for review. 11

Confirming diagnosis

Scrotal ultrasound is the key investigation to determine whether there is a solid tumour within the testicle (see figure 1). This is performed urgently in all men with suspected testicular cancer. The sensitivity and specificity of testicular ultrasound is 92-99% and 95-98% respectively.12

All men diagnosed with testicular cancer on ultrasound should have a testicular tumour marker blood test performed at diagnosis.

Alpha-fetoprotein (AFP), beta-human chorionic gonadotrophin (β-hCG) and lactate dehydrogenase (LDH) are the testicular tumour markers measured.

The levels of the tumour markers at diagnosis can help indicate what type of testicular cancer is present and can also be used to evaluate response to treatment.

Testing for testicular tumour markers can be carried out in the community if clinically GPs have a high suspicion of a testicular cancer diagnosis but this should not delay referral to urology.

In secondary care all men diagnosed with a testicular cancer will be booked to undergo an urgent CT scan of the chest, abdomen and pelvis to exclude metastatic spread.

Management

The primary treatment for testicular cancer is usually a radical orchidectomy where the entire abnormal testicle is removed through an inguinal incision. This is normally performed as an urgent procedure as soon as possible after diagnosis.

All patients should be offered the opportunity to bank sperm prior to orchidectomy. There will be local protocols in place but all men choosing to bank sperm will have to undergo blood tests to exclude hepatitis B, C and HIV. If these blood tests come back positive, sperm banking can only be offered at two highly specialised centres in the UK.

From 12 months after treatment patients may be offered sperm analysis to determine whether continued sperm storage is necessary.

During the consent process for radical orchidectomy men should be offered a testicular prosthesis. This artificial implant is placed in the empty scrotum at the end of the operation to give the appearance of a testicle being present in the scrotum. There is a small risk of prosthesis related infection after surgery (0.6-2%) so patients should be given the option of having an implant inserted at a later date.13

There are certain circumstances when radical orchidectomy is not carried out or a more nuanced approach is considered. These are when:

• The tumour is present in the patient’s only testis or both testicles – in these cases partial orchidectomy may be possible

• There is a small non palpable mass < 50% of testicular volume on ultrasound scan – in these cases partial orchidectomy may be considered

• There is reduced androgen function

• Men have symptoms and signs and are unwell with metastatic testicular cancer. In these cases chemotherapy may be required prior to orchidectomy

Monitoring and follow-up

All patients diagnosed with testicular cancer are managed by a multidisciplinary team (MDT) including cancer nurse specialists, radiologists, urologists and oncologists. Once radical orchidectomy has been performed the pathological tissue diagnosis is combined with the staging imaging information and used by the MDT to advise patients on whether additional treatment is recommended and what should constitute appropriate follow-up.

Testicular tumours are broadly subclassified into seminoma and non seminomatous germ cell tumours. The Union for International Cancer Control clinical staging system is used to form prognostic groups and guide further management.14 Depending on the

stage of their tumour, after radical orchidectomy patients may be offered active surveillance, chemotherapy, radiation or further surgery to remove lymph nodes located at the back of the abdomen in the form of a retroperitoneal lymph node dissection.

The minimum recommended follow-up based on European guidelines for patients diagnosed with early and advanced disease are illustrated in tables 1, 2 and 3.15

The risk of a second contralateral tumour is 1% so all patients should continue self-examination routinely after treatment for testicular cancer.

Potential future complications

Although testicular cancer has a high survival rate, some men may suffer irreversible morbidity from their treatment. Men treated with radiotherapy and chemotherapy are at increased risk of leukaemia and solid organ cancers compared with the general population. Cisplatin based chemotherapy can be associated with ototoxicity, peripheral neuropathy, or nephrotoxicity. Bleomycin chemotherapy can cause pulmonary toxicity.16

Despite the availability of sperm banking, infertility may be a significant survivorship issue for men who have undergone treatment. Patients with testicular cancer have abnormal semen parameters prior to treatment in up to 50% of cases.17 Radical orchidectomy followed by chemotherapy or radiotherapy may cause testicular dysgenesis syndrome. Retroperitoneal lymph node dissection is associated with the risk of retrograde ejaculation. 

Assisted reproduction techniques may be required after testicular cancer treatment to achieve successful conception.

Hypogonadism resulting from treatment is common.16 GPs should routinely evaluate men post treatment for symptoms and assess hormonal status accordingly. Decisions to administer testosterone replacement therapy should be made based on clinical symptoms and initiated in secondary care. GPs should refer men with confirmed low testosterone levels and symptoms of hypogonadism to secondary care according to their local protocols.

 

Conclusion

Although uncommon, testicular cancer is one of the most treatable cancers with excellent survival rates. GPs have a key role to play in the early diagnosis of testicular cancer and supporting men diagnosed with the disease. Most men will live a long life after treatment and GPs must be alert to these men’s holistic needs and identify and manage men’s long term survivorship needs.

REFERENCES

1 Cancer Research UK Testicular cancer statistics www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/testicular-cancer  [Last accessed 17 April 2021]

2 Akre O, Pettersson A, Richiardi L. Risk of contralateral testicular cancer among men with unilaterally undescended testis: a meta analysis. Int J Cancer 2009;124(3):687-89

3 Lip SZ, Murchison LE, Cullis PS et al. A meta-analysis of the risk of boys with isolated cryptorchidism developing testicular cancer in later life. Arch Dis Child 2013;98(1):20-26

4 Pettersson A, Richiardi L, Nordenskjold A et al. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med 2007;356(18):1835-41

5 Hemminki K, Li X. Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer 2004;90(9):1765-70

6 Walsh TJ, Croughan MS, Schembri M et al. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med 2009;169(4):351-56

7 Manecksha RP, Fitzpatrick JM. Epidemiology of testicular cancer. BJU Int 2009;104(9 pt B):1329-33

8 Germa-Lluch JR, Garcia del Muro X, Maroto P et al. Clinical pattern and therapeutic results achieved in 1490 patients with germ-cell tumours of the testis: the experience of the Spanish Germ-Cell Cancer Group (GG). Eur Urol 2002;42:553-62

9 Moul J. Timely diagnosis of testicular cancer. Urol Clin North Am 2007;34:109-17

10 National Institute for Health and Care Excellence. NG12. Suspected cancer: recognition and referral. NICE. London. 2015. www.nice.org.uk/guidance/ng12 Updated 2021 [Last accessed 17 April 2021]

11 Shephard EA, Hamilton WT. Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records. Br J Gen Pract 2018;68:e559-65

12 Coursey Moreno C, Small WC, Camacho JC et al. Testicular tumors: what radiologists need to know — differential diagnosis, staging, and management. Radiographics 2015;35(2):400-15

13 Marshall S. Potential problems with testicular prostheses. Urology 1986;28:388-90

14 Brierley JE et al. The TNM classification of malignant tumours 8th edition. 2016.  www.uicc.org/resources/tnm/publications-resources

15 The European Association of Urology Guidelines on Testicular Cancer 2020: https://uroweb.org/guideline/testicular-cancer

16Travis LB, Fosså SD, Schonfeld SJ et al. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst 2005;97(18):1354-65

17 Djaladat H, Burner E, Parikh PM et al. The association between testis cancer and semen abnormalities before orchiectomy: a systematic review. J Adolesc Young Adult Oncol 2014;3(4):153-59