Screening And Early Detection Of Testicular Germ Cell Tumors

Introduction

Over the past few decades, the incidence of testicular cancer has increased. However, compared to other cancers, the incidence is relatively low. Early detection and prompt treatment play a pivotal role in increasing the chances of survival.¹

The United States Preventive Service Task Force (USPSTF) does not recommend screening tests for asymptomatic males to detect testicular cancer. It is unclear whether testicular cancer can be detected earlier by the testicular screening test in healthy males without symptoms.²

Cancers with good prognoses, such as testicular germ cell tumour (GCT), are not significantly reduced by screening tests.² Also, the incidence of testicular GCT is low in the non-white population. For that reason, screening might not be productive for the general population.³ To date, there is no widely accepted screening program for testicular cancer.

Tumour-related morbidity and mortality can deprive these young patients of their most productive years. Therefore, detecting and starting the therapy at the earliest possible time is of the utmost importance.

Understanding testicular germ cell tumours

Germ cell tumours (GCT) are diverse tumours that can affect either people assigned female or male at birth (AFAB or AMAB). Around 95% of testicular cancers are GCT. Young people AMAB between the ages of 15 and 34 are more likely than older inidividuals to develop testicular GCT.⁴

Types of germ cell tumours of testes

• GCT derived from germ cell neoplasia (uncontrolled growth of cells) in situ
• GCT derived from non-germ cell neoplasia in situ
• Mixed and unclassified GCT⁴

Risk factors for testicular GCT

The exact cause of testicular GCT remains unknown. However, the known risk factors, that increase the risk of getting testicular GCT are:

• Undescended testes
• Family history of testicular cancer
• Low birth weight
• Prenatal or postnatal exposure to endocrine hormone disruptors^5,6,7

Patients with isolated cryptorchidism (undescended testes) have three times the risk of developing testicular cancer than those without such a presentation.⁸ The risk of testicular cancer can increase up to 6-fold in a first-degree relative with testicular cancer.⁶ Despite the good prognosis of testicular cancer, self-examination by high-risk groups can help lower cancer-related deaths.³

Clinical presentation of testicular GCT

Most commonly, testicular GCT presents as a scrotal swelling or lump in the testes, with or without pain. It can also present as dull aching abdominal pain. The other symptoms include fever, non-specific respiratory symptoms, and gynecomastia. A patient can present with a testicular lump or abdominal mass and lymphadenopathy (swollen lymph glands) on clinical examination.^5,9

Screening methods for testicular GCT

Self-examination of the testes, clinical examination by a general practitioner (GP), and screening of high-risk groups can reduce the incidence of death. Also, it can reduce complications such as infertility, heart disease, and respiratory illnesses in the later stages of life among survivors.^1,10,11 Delays in the diagnosis of testicular GCT of more than 16 weeks can result in decreased survival and increased morbidity.^1,11

Failure to detect the testicular mass in suspected cancer is estimated to reduce the five-year survival rate from 99% to 74%.¹¹ It is crucial to make the cancer diagnosis as soon as possible in cases where the prognosis is good to excellent and newer therapies have significantly decreased the death rate. After a physical examination and initial work-up, further investigations such as imaging, blood testing, and biopsy are required to confirm testicular GCT.^9,12

Diagnosis of testicular cancer

There are different cancerous and non-cancerous tumours of the testes. Other testicular tumours, such as lymphoma, mesothelioma, and leiomyosarcoma, also need consideration during the initial workup.⁹ To rule out other testicular non-GCT and confirm testicular GCT, a series of diagnostic tests is required. These are:

• Imaging
• Tumor markers
• Histopathological examination (HPE)^9,12,13

Imaging

Scrotal ultrasonography is the preferred imaging method to evaluate testicular masses. Staging or assessing the extension of the testicular tumour to other parts requires other imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI).^9,13

There are mimics of testicular GCT in imaging. Hence, additional tests, such as the measurement of tumour markers and HPE, are done to confirm the diagnosis of testicular GCT.^9,13

Tumour markers

The measurement of serum tumour markers such as alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and lactate dehydrogenase (LDH) has revolutionised the management of testicular GCT in recent years.^9,12

Role of tumour markers in testicular cancers:

• Diagnosis of testicular cancers
• Monitoring the response to therapy
• Detection of cancer recurrence¹²

Histopathological examination and tumour staging

Unlike other cancers, where biopsy is the gold standard, a biopsy of a testicular lump is not advised. A biopsy can injure the testes and spread cancer to the scrotum or other body parts. A combination of imaging and tumour markers is sufficient to diagnose testicular cancer.

Treatment of testicular GCT

The available treatment options are surgery, chemotherapy and radiotherapy.Surgery

Patients undergo orchidectomy or surgical removal of the involved testes. After the surgery, the specimen undergoes HPE for staging, typing, and immunohistochemistry. Recognizing the components of GCT using HPE is required to modify the treatment protocol and assess the probability of recurrence.^,14 In the United Kingdom, the 3-stage system is widely used for staging.

Chemotherapy and radiotherapy

After the successful completion of the surgery, chemotherapy follows. In some cases, there are recommendations for radiotherapy as well. Cancer deposits in lymph nodes and lungs are removed by surgical interventions, if not completely eliminated by chemotherapy. 

Role of the individualized treatment plan

The cancer team should consider the following factors when deciding which treatment to offer:

• Type of testicular GCT
• Stage
• Deposits in lymph nodes and lungs
• Risk of recurrence
• Concerns related to infertility
• Patient preferences about treatment procedures

Thus, patients nowadays receive treatment plans tailored to their specific requirements rather than following a uniform, common protocol.

Prognosis and survivorship 

In recent years, there has been a significant improvement in treatment modalities, resulting in a 90% cure rate and a 95% 5-year survival rate.^5,15

Factors affecting prognosis

• Type of testicular GCT (seminoma vs non-seminoma)
• Stage of the tumour
• Whether the tumour is confined to the testes or extended to distant organs
• Level of tumour markers^9,16

Testicular cancer survival rate and follow-up

For stage 1 tumour, the 5-year survival rate is more than 94%, and for stage 2 and stage 3, it is 87.5% and 66.7%, respectively. Similarly, for typical testicular seminoma and testicular seminoma combined embryonal carcinoma, the 5-year survival rates are 93.1% and 87.5%, respectively.¹⁶

After completing the treatment, some people find adjusting to the new environment quite challenging. Due to the removal of the testes, patients with testicular GCT, the majority of whom are young, may struggle with low self-esteem, sexual dissatisfaction, and negative body image issues.¹⁷ Therefore, a holistic approach is required to address such psychosocial problems.

In the case of testicular cancer, the cancer team advises follow-up, as recurrence is possible within 2 to 3 years. In the United Kingdom, the National Health Services cancer treatment centres also offer free sperm banking services to young patients with a likelihood of infertility. If patients present with symptoms of testosterone deficiency, testosterone replacement therapy is also provided.

Prevention and health promotion

Testicular self-examination 

The understanding regarding self-examination of the testes for early detection of testicular cancer is poor in most parts of the world. The best way to create awareness among youth is through campaigns and programmes related to the importance of testicular self-assessment and its techniques.^18,19

Lifestyle modifications

In the course of treating cancer, patients suffer physical, mental, and emotional trauma. The long-term health problems in testicular cancer such as heart and lung illness are well known.¹⁰

The following lifestyle changes can help the body to recover early from cancer:

• Weight management
• Healthy diet
• Healthy habits such as quitting smoking or drinking alcohol 
• Physical activity²⁰

It is also imperative that high-risk familial GCT patients undergo genetic counselling, testing, and assessment, to improve their management.²¹

Summary

Testicular GCT has become the model for curable cancer in recent decades. The sensitive diagnostic tools, advanced treatment strategies, and testicular GCT’s response to chemotherapeutic agents contribute to a high survival rate.

The success stories of screening tests for cervical and colorectal cancer prevention are well known. Worldwide, there has been a significant reduction in the incidence of these cancers since the introduction of screening programs.

Unfortunately, the screening test for testicular cancer could not produce similar outcomes. Hence, before introducing any testicular cancer screening, more studies are required on parameters such as the sensitivity of the test, impact on survival rate and cost-effectiveness.

In the recent period, due to personalized medicine and risk-adjusted therapies, there has been a marked increase in survival rates. The focus should also be on decreasing cancer-associated morbidity. Providing long-term support to young cancer survivors and discussing post-treatment issues related to physical and mental health is as important as diagnosing and treating testicular GCT.