Testicular cancer is the most common cancer in men aged 15-to-45 years and represents one of the most curable malignancies when identified promptly.
Testicular cancer is a rare disease, representing 1 per cent of male cancers and 5 per cent of urological cancers worldwide.1 Its incidence has increased in the past few years, however, especially in Western and industrialised countries.
It is also the most common cancer found in young men aged between 15 and 34 years, and approximately 173 men are diagnosed with testicular cancer in Ireland each year.7
Mortality associated with testicular cancer is relatively low at approximately 0.1 per cent of all annual cancers, and cure rates are greater than 90 per cent for all stages, with over 95 per cent five-year survival rates.1,9
The rise of testicular cancer in Western and industrialised countries in recent years is possibly due to an increased exposure to aetiological factors. The highest incidence of testicular cancer is observed in Western and Northern Europe at 8.7 and 7.2 per 100,000 men, respectively.9
Testicular cancer includes several types of cancer such as germ cell tumours (GCT), sex cord-gonadal stromal tumours, and secondary testicular tumours. About 90-to-95 per cent of testicular tumours arise from germ cells to generate the GCT, followed by 5-to-10 per cent gonadal stromal tumours, mixed GCT and secondary tumours.2
The testes (male gonads) are located in a skin-covered, highly pigmented, muscular sack called the scrotum that extends from the body behind the penis. They produce both sperm and androgens such as testosterone and are active throughout the reproductive lifespan of the male. Paired ovals, the testes are approximately 4-to-5cm in length and are surrounded by two distinct layers of protective connective tissue. The outer tunica vaginalis is a serous membrane that has both a parietal and a thin visceral layer. Beneath the tunica vaginalis is the tunica albuginea, a tough, white, dense connective tissue layer covering the testis, which also inverts to form septa that divide the testis into 300-to-400 structures called lobules. Within the lobules, sperm develop in structures called seminiferous tubules.8
The main non-modifiable risk factors for testicular cancer are cryptorchidism (undescended testicle), family history, previous history of testicular cancer, genetic predisposition, ethnicity, congenital abnormalities, and infertility.2
In cryptorchidism, the undescended testicle remains in the abdomen or groin, and the risk of developing the disease does not change even after surgery to move the testicle into the scrotum. In patients with cryptorchidism, the relative risk of developing testicular cancer ranges from 2.9- to-6.3. The risk is increased in both testes, although the risk is much higher in the ipsilateral testis (6.3 vs 1.7).5 Family history correlates to an increased risk, and testicular cancer risk is significant in men whose father or brother had the disease. Patients with a father or brother with testicular cancer have a 3.8- and 8.6-times greater risk, respectively.5
Those diagnosed with cancer in one testicle are also more likely to get cancer in the other testicle. Patients with a personal history of testicular cancer have a 12-times greater risk of developing a contralateral testicular cancer than the general population. However, the greatest risk is in the first five years after diagnosis and the 15-year cumulative risk is 1.9 per cent.5
Genetic and environmental factors play an important role in the genesis and development of testicular cancer. Several genes are implicated in its pathogenesis and different environmental factors have been investigated.1 Klinefelter’s syndrome, caused by a chromosomal abnormality, has been associated with testicular cancer and other cancer types, and congenital abnormalities of the testicles, penis, or kidneys may also contribute to an increased risk of testicular cancer.
Age wise, the highest incidence of GCT is found in men between 15 and 35 years of age.
Infertility is also strongly associated with testicular cancer.
Caucasian men have a higher chance of getting the disease than Afro-Caribbean or Asian men.1,3
Testicular cancer may present as a painless scrotal mass, an incidental radiologic finding, post-traumatic symptom, or scrotal pain.5 An enlarged testicle or a small lump or area of hardness are usually the first signs of testicular cancer. Any lump, enlargement, hardness, pain, or tenderness in the testicle should be evaluated as soon as possible. Other symptoms of testicular cancer usually do not appear until after the cancer has spread to other parts of the body.
Testicular cancers are defined based on their cell type. The most common histology of testicular cancer is germinal-seminoma and non-seminoma. About 95 per cent of testicular cancers begin in germ cells, specialised cells in the testicles that make sperm. While these tumours typically start in the testicles they also occasionally arise in the abdomen, chest, or other areas of the body, even if there is no evidence of cancer in or near the testicles. Seminomas make up about half of all GCTs. They usually grow slowly and are less likely to metastasise to other parts of the body. Non-seminomas are often more aggressive than seminomas, and more likely to spread beyond the testicle. Approximately 5 per cent of testicular cancers start in stromal cells, which make testosterone. Testicular stromal tumours are often benign.3
Evaluation by clinicians is guided by a complete history of the presenting symptoms, physical examination, and assessment for risk factors. Testicular examination should include the affected and unaffected testis for comparison. The normal testis is 3.5-5cm in length, smooth, homogenous, movable, and detached from the epididymis. Hard, firm, or fixed areas within or adjacent to the testes are abnormal and warrant further investigation. Physical examination should also include evaluation of the inguinal and supra-clavicular lymph nodes, the abdomen, and the chest for gynaecomastia.5 It is important to ask specifically about the history of cryptorchidism, orchiopexy, or inguinal hernia repair as an infant. A family history of testicular cancer in the father or a brother should be elicited. Physical examination findings of any solid intra-testicular mass should be considered to be testicular cancer until proven otherwise.9
Many signs and symptoms of testicular cancer are similar to those caused by non-cancerous conditions such as a spermatocele, varicocele, hydrocele, inguinal hernia, lymphoma, epididymo-orchitis or epididymitis, and differential diagnosis is important.4
Blood tumour markers include Alpha-fetoprotein (AFP), beta human chorionic gonadotrophin (bHCG), and Lactate dehydrogenase (LDH).6
Scrotal ultrasonography can confirm the presence of a mass, and has a sensitivity of 92-to-98 per cent and specificity of 95-to-99.8 per cent.5
Once a solid intra-testicular tumour is identified, radical inguinal orchiectomy is performed both for diagnostic and therapeutic purposes.12 A biopsy of the suspect mass will be carried out and when suspicion for metastatic disease is present, additional imaging with CT of the chest and abdomen may be done for staging.5
Staging is determined by the size of the tumour, lymph node involvement, whether the cancer has spread and if tumour markers are present.10 Tumour staging guides further management with options including active surveillance, chemotherapy, retroperitoneal lymph node dissection, and radiation therapy.9
Stages are based on four categories:11,12
Once the individual T, N, M, and S components are scored, they are combined to determine the overall testicular cancer stage group.
Stage 0: The cancer cells have not spread beyond the testicle. At this stage, tumours are also referred to as carcinomas in situ.
Stage 1 testicular cancer: The cancer has invaded tissues next to the testicle, but has not spread to lymph nodes, or more distant sites in the body. Levels of tumour marker proteins may be normal or elevated. The three subcategories of stage 1 testicular cancer are:
Stage 2 testicular cancer: Testicular cancers at this stage have invaded tissues next to the testicle and can now be found in at least one nearby lymph node. Tumour marker levels may be normal or slightly elevated. Stage 2 testicular cancer has three subcategories:
Stage 3 testicular cancer: Testicular cancers at this stage have spread to distant lymph nodes or organs. Stage 3 testicular cancer has three subcategories:
Treatment options for testicular cancer include surgery, radiation therapy, chemotherapy and stem cell transplant. Sometimes more than one type of treatment might be used including chemotherapy and/or radiotherapy.9
The management of seminomas depends on the extent of spread of the cancer. Surgery, radiotherapy, and chemotherapy are used to treat seminomas and the stage of cancer will decide treatment options. Non-seminomas are usually treated with surgery and chemotherapy.10
When a diagnosis of testicular cancer is suspected based on physical examination and ultrasound findings, radical inguinal orchiectomy is performed, which removes the testicle, epididymis, and spermatic cord up to the level of the internal inguinal ring. In this procedure, these structures are delivered through an inguinal incision made along Langer’s lines in the groin. If the mass is too large to pass through a standard 3-to- 5cm inguinal incision, the incision can be carried inferiorly to the anterior scrotum to allow for removal of the testis in its tunics along with the spermatic cord. Trans-scrotal orchiectomy or biopsy is contraindicated, as doing so alters the lymphatic drainage patterns and impacts further management. Further surgery or radiotherapy or chemotherapy will be based on the disease’s stage and response to the initial management.9
Following radical inguinal orchiectomy, patients should avoid heavy lifting and high-impact activities for four weeks and should wear supportive underwear to prevent scrotal swelling or haematoma. Retroperitoneal lymph node dissection is major intra-abdominal surgery, after which dedicated post-operative rehabilitation should be undertaken.9
Removing one testicle does not affect libido or the ability to have an erection providing the remaining testicle is normal. The removal of a testicle may be traumatic, especially for a young man, and a testicular prosthesis can be placed in the scrotum at the time of surgery. Fertility can be compromised by testicular cancer treatment. However, the potential to father children should not be greatly affected provided the other testicle is normal. Chemotherapy, however, does affect sperm production in this testicle and it is recommended that patients with testicular cancer arrange to freeze sperm in case there are problems with fertility later on.7 Adequate counselling should be given regarding the possibility of infertility, sperm-banking and also regarding the placement of a testicular prosthesis if required.9
Prognosis is determined by the histology, extent of distant tumour spread, and extent of tumour marker elevations. For men with disseminated seminomas, the main adverse prognostic variable is the presence of metastases to visceral organs other than the lungs. A tumour that originated in the mediastinum has a worse prognosis when compared to a tumour that originated within the testicle.9
There is no national screening programme for detecting testicular cancer in Ireland.6 Testicular self-examination is one of the simplest and most effective ways to identify testicular cancer early, although there is controversy about its efficacy.7 Despite opportunities for an early diagnosis, most men seek medical help only after some time has passed, when symptoms have intensified, or after receiving information about the condition from someone else or the media. Despite the fact that knowledge about testicular cancer and testicular self-examination in developed counties is higher, testicular self-examination is still rarely performed. Most patients present with a testicular mass, which suggests that testicular self-examination could aid early detection.1
It is important to educate men of all ages about testicular cancer and testicular self-examination and that healthcare professionals, especially nurses, are well informed and able to discuss it with their patients. Healthcare professionals play a key role in providing information about testicular cancer risk factors and symptoms and in explaining the importance of testicular self-examination.7
Men tend to seek help late for testicular problems for many reasons such as anxiety and fear of receiving an undesired diagnosis. Others feel ashamed, deprived of their masculinity and are too embarrassed to talk about it with anyone, even a partner. Researchers have found that when men are properly educated about testicular self-examination they are more likely to carry it out and recognise symptoms of testicular cancer.1
Testicular cancer is the most common cancer in men aged 15-to-45 years and represents one of the most cur-able malignancies when identified promptly and treated with a multimodal approach.9 It has excellent survival rates and having awareness about the disease and seeking prompt healthcare attention is of the utmost importance. Since treatment is successful for most men with testicular cancer, one of the major future goals is to reduce the side-effects of treatment for those with early-stage cancer. In addition, treatments for poor-risk and recurrent cancers are being studied in clinical trials, along with research on the causes and genetics of testicular cancer. Stem cell transplant is most often used to treat testicular cancers that have re-occurred after treatment with chemotherapy. Current studies are looking at whether a stem cell transplant may be valuable as part of the first treatment for some patients with advanced germ cell cancers. Clinical trials are also underway to find better ways of reducing symptoms and side-effects of current testicular cancer treatments, so as to improve patients’ comfort and quality-of-life.13
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