Testicular cancer

What is testicular cancer?

Testicular cancer is a cancer that develops in the tissues of one or both testicles. The testicles, or testes, are part of the male reproductive system. They make male hormones and sperm. They are two egg-shaped glands inside the scrotum, a sac of loose skin that lies below the penis. You can get cancer in one or both testicles.

Who is most likely to develop testicular cancer?

Testicular cancer is very rare. You can get it at any age, but it is most common in men between the ages of 20 and 39. It is also more common in those who:

• Have had abnormal testicle development
• Have had an undescended testicle, a condition in which one or both testicles fail to move into the scrotum before birth
• Have had testicle cancer before
• Have a family history of the cancer
• Are White

What are the symptoms of testicular cancer?

The symptoms of testicular cancer may include:

• A painless lump or swelling in either testicle
• A change in how the testicle feels
• A dull ache in the lower abdomen (belly) or the groin (the area where the thigh meets the abdomen)
• A sudden build-up of fluid in the scrotum
• Pain or discomfort in a testicle or in the scrotum

How is testicular cancer diagnosed?

To find out if you have testicular cancer, your health care provider may use:

• A physical exam.
• Blood tests.
• An ultrasound of the testicles.
• An inguinal orchiectomy, which is a procedure to remove the entire testicle. A tissue sample from the testicle is viewed under a microscope to check for cancer cells.

What are the treatments for testicular cancer?

Testicular cancer can usually be cured.The treatment options include:

• Surgery (if the testicle has not already been removed during diagnosis).
• Radiation therapy.
• Chemotherapy.
• High-dose chemotherapy with stem cell transplant.
• Surveillance, which might be done after surgery. It means that your provider will closely follow your condition with regular exams and tests. You won't get any further treatment unless there are changes in your test results.

Some of the treatments may also cause infertility. If you may want to have children later on, you should consider sperm banking before treatment.

After you have finished your treatment, you will need regular follow-up testing to make sure that the cancer has not come back. If you have had cancer in one testicle, you have a higher risk of getting cancer in the other testicle. So it's important to check the other testicle regularly and let your provider know if you notice any changes or unusual symptoms.

NIH: National Cancer Institute

Source: MedlinePlus, U.S. National Library of Medicine

Signs and symptoms

One of the first signs of testicular cancer is often a lump or swelling in the testicles. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for testicular cancer in asymptomatic males, including routine testicular self-exams. However, the American Cancer Society suggests that some men should examine their testicles monthly, especially if they have a family history of cancer, and the American Urological Association recommends monthly testicular self-examinations for all young men.

Symptoms may also include one or more of the following:

a lump in one testis which may or may not be painful

sharp pain or a dull ache in the lower abdomen or scrotum

a feeling often described as "heaviness" in the scrotum

breast enlargement (gynecomastia) from hormonal effects of β-hCG

low back pain (lumbago) due to the cancer spreading to the lymph nodes along the back

It is not very common for testicular cancer to spread to other organs, apart from the lungs. If it has, however, the following symptoms may be present:

shortness of breath (dyspnea), cough or coughing up blood (hemoptysis) from metastatic spread to the lungs

a lump in the neck due to metastases to the lymph nodes

Testicular cancer, cryptorchidism, hypospadias, and poor semen quality make up the syndrome known as testicular dysgenesis syndrome.

Causes

A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). It is generally believed that the presence of a tumor contributes to cryptorchidism; when cryptorchidism occurs in conjunction with a tumor, then the tumor tends to be large. Other risk factors include inguinal hernias, Klinefelter syndrome, and mumps orchitis. Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormones.

Higher rates of testicular cancer in Western nations have been linked to the use of cannabis. A mounting pattern of studies over time suggesting this possible, but still inconclusive linkage has convinced some doctors and researchers to recommend younger men, especially those with a family history of cystic fibrosis or indirect hernias, to quit or avoid cannabis use as an extra precaution.

Diagnosis

The main way testicular cancer is diagnosed is via a lump or mass inside a testis. More generally, if a young male has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer.

Other conditions may also have symptoms similar to testicular cancer:

Prostate infections or inflammations (prostatitis), bladder infections or inflammations (cystitis), or kidney (renal) infections (nephritis) or inflammations which have spread to and caused swelling in the vessels of the testicles or scrotum

Infection, inflammation, retro-peritonitis, or other conditions of the lymph nodes or vessels near the scrotum, testicles, pubis, anorectal area, and groin

Benign tumors or lesions of the testicles

Metastasis to the testicles from another primary tumor site(s)

The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine the exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed, or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases.

The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy—that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.

Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A trans-scrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy, only the retroperitoneal route exists.

Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. Alpha-fetoprotein, human chorionic gonadotropin (the "pregnancy hormone"), and LDH-1 are the typical tumor markers used to spot testicular germ cell tumors.

A pregnancy test may be used to detect high levels of chorionic gonadotropin; however, the first sign of testicular cancer is usually a painless lump. Note that only about 25% of seminomas have elevated chorionic gonadotropin, so a pregnancy test is not very sensitive for making out testicular cancer.

Stressful experiences

The stressful event of testicular cancer not only affects the patient who is diagnosed but also affects the caregiver. The psychological stress model consists of stressful experiences that a patient with testicular cancer may go through after diagnosis, that caregivers may want to look out for. The stressful experiences consist of 4 main categories:

These side effects may need physical and emotional care, which in turn, can cause the caregiver an emotional burden.

Screening

The American Academy of Family Physicians recommends against screening males without symptoms for testicular cancer.

Staging

After removal, the testicle is fixed with Bouin's solution because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. In broad terms, testicular cancer is staged as follows:

Stage I: the cancer remains localized to the testis.

Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or paraaortic lymph nodes (lymph nodes below the diaphragm).

Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and paraaortic lymph nodes. Stage 3 is further subdivided into non-bulky stage 3 and bulky stage 3.

Further information on the detailed staging system is available on the website of the American Cancer Society.

Classification

Although testicular cancer can be derived from any cell type found in the testicles, more than 95% of testicular cancers are germ cell tumors (GCTs). Most of the remaining 5% are sex cord–gonadal stromal tumours derived from Leydig cells or Sertoli cells. A correct diagnosis is necessary to ensure the most effective and appropriate treatment. To some extent, this can be done via blood tests for tumor markers, but definitive diagnosis requires examination of the histology of a specimen by a pathologist. Testicular tumors are best classified by radical inguinal orchiectomy, which allows for histologic evaluation of the whole testicle and provides local tumor control.

Most pathologists use the World Health Organization classification system for testicular tumors:

Germ cells derived from germ cell neoplasia in situ

Specific forms of intratubular germ cell neoplasia

Germ cell tumors unrelated to germ cell neoplasia in situ

Testicular neuroendocrine tumor, prepubertal type

Mixed teratoma and yolk sac tumor, prepubertal type

Sex cord-stromal tumor not otherwise specified

Treatment

The three basic types of treatment are surgery, radiation therapy, and chemotherapy.

Surgery is performed by urologists; radiation therapy is administered by radiation oncologists; and chemotherapy is the work of medical oncologists. In most patients with testicular cancer, the disease is cured readily with minimal long-term morbidity. While treatment success depends on the stage, the average survival rate after five years is around 95%, and stage 1 cancer cases, if monitored properly, have essentially a 100% survival rate.

Testicle removal

The initial treatment for testicular cancer is surgery to remove the affected testicle (orchiectomy). While it may be possible, in some cases, to remove testicular cancer tumors from a testis while leaving the testis functional, this is seldom done, as the affected testicle usually contains pre-cancerous cells spread throughout the entire testicle. Thus, removing the tumor alone without additional treatment greatly increases the risk that another cancer will form in that testicle.

Since only one testis is typically required to maintain fertility, hormone production, and other male functions, the affected testis is almost always removed completely in a procedure called inguinal orchiectomy. (The testicle is rarely removed through the scrotum; an incision is made beneath the belt line in the inguinal area.) In the UK, the procedure is known as a radical orchidectomy.

Retroperitoneal lymph node dissection

In the case of non-seminomas that appear to be stage I, surgery may be done on the retroperitoneal/paraaortic lymph nodes (in a separate operation) to accurately determine whether the cancer is in stage I or stage II and to reduce the risk that malignant testicular cancer cells that may have metastasized to lymph nodes in the lower abdomen. This surgery is called retroperitoneal lymph node dissection (RPLND). However, this approach, while standard in many places, especially in the United States, is out of favor due to costs and the high level of expertise required to perform successful surgery. Sperm banking is frequently carried out before the procedure (as with chemotherapy), as there is a risk that RPLND may damage the nerves involved in ejaculation, causing ejaculation to occur internally into the bladder rather than externally.

Many patients are instead choosing surveillance, where no further surgery is performed unless tests indicate that the cancer has returned. This approach maintains a high cure rate because of the growing accuracy of surveillance techniques.

Adjuvant treatment

Since testicular cancers can spread, patients are usually offered adjuvant treatment— in the form of chemotherapy or radiotherapy— to kill any cancerous cells that may exist outside of the affected testicle. The type of adjuvant therapy depends largely on the histology of the tumor (i.e., the size and shape of its cells under the microscope) and the stage of progression at the time of surgery (i.e., how far cells have 'escaped' from the testicle, invaded the surrounding tissue, or spread to the rest of the body). If the cancer is not particularly advanced, patients may be offered careful surveillance by periodic CT scans and blood tests, in place of adjuvant treatment.

Before 1970, survival rates from testicular cancer were low. Since the introduction of adjuvant chemotherapy, chiefly platinum-based drugs like cisplatin and carboplatin, the outlook has improved substantially. Although 7000 to 8000 new cases of testicular cancer occur in the United States yearly, only 400 men are expected to die of the disease.

In the UK, a similar trend has emerged: since improvements in treatment, survival rates have risen rapidly to cure rates of over 95%.

Radiation therapy

Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for non-seminoma.

Non-seminoma

Chemotherapy is the standard treatment for non-seminoma when the cancer has spread to other parts of the body (that is, stage 2B or 3). The standard chemotherapy protocol is three, or sometimes four, rounds of Bleomycin-Etoposide-Cisplatin (BEP). BEP as a first-line treatment was first reported by Professor Michael Peckham in 1983. The landmark trial published in 1987 which established BEP as the optimum treatment was conducted by Dr. Lawrence Einhorn at Indiana University. An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP).

Lymph node surgery may also be performed after chemotherapy to remove masses left behind (stage 2B or more advanced), particularly in the cases of large non-seminomas.

Seminoma

As an adjuvant treatment, the use of chemotherapy as an alternative to radiation therapy in the treatment of seminoma is increasing, because radiation therapy appears to have more significant long-term side effects (for example, pelvic radiation disease, increased risks of secondary malignancies, etc. See also: Radiation therapy#Late side effects). Two doses, or occasionally a single dose of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy. The concept of carboplatin as a single-dose therapy was developed by Tim Oliver, Professor of Medical Oncology at Barts and The London School of Medicine and Dentistry. However, very long-term data on the efficacy of adjuvant carboplatin in this setting do not exist.

Since seminoma can recur decades after the primary tumor is removed, patients receiving adjuvant chemotherapy should remain vigilant and not assume they are cured 5 years after treatment.

Prognosis

Treatment of testicular cancer is one of the success stories of modern medicine, with sustained response to treatment in more than 90% of cases, regardless of stage. In 2011 overall cure rates of more than 95% were reported, and 80% for metastatic disease—the best response by any solid tumor, with improved survival being attributed primarily to effective chemotherapy. By 2013 more than 96 percent of the 2,300 men diagnosed each year in the U.K. were deemed cured, a rise by almost a third since the 1970s, the improvement attributed substantially to the chemotherapy drug cisplatin. In the United States, when the disease is treated while it is still localized, more than 99% of people survive 5 years.

Surveillance

For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate, and patients will undergo surveillance instead. The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients who need it. The number of patients ultimately cured is the same using surveillance as post-operative "adjuvant" treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.

For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumor markers, chest x-rays, and CT scanning. However, the requirements of a surveillance program differ according to the type of disease since, for seminoma patients, relapses can occur later, and blood tests are not as good at indicating relapse.

CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest X-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT.

The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimizing radiation exposure.

For patients treated for stage I non-seminoma, a randomized trial (Medical Research Council TE08) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage.

For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomized trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST. This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation, and so, if it is shown to be as good at detecting relapses, it may be preferable to CT.

For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary based on the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse.

Fertility

A man with one remaining testis may remain fertile. However, sperm banking may be appropriate for men who still plan to have children, since fertility may be adversely affected by chemotherapy and/or radiotherapy. A man who loses both testicles will be infertile after the procedure, though he may elect to bank viable, cancer-free sperm before the procedure.

Epidemiology

Globally, testicular cancer resulted in 8,300 deaths in 2013, up from 7,000 deaths in 1990. Testicular cancer has the highest prevalence in the U.S. and Europe, and is uncommon in Asia and Africa. Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand.

Although testicular cancer is most common among men aged 20-40 years, it has three peaks: infancy through the age of four as teratomas and yolk sac tumors, ages 25–40 years as post-pubertal seminomas and non-seminomas, and from age 60 as spermatocytic tumors.

Germ cell tumors of the testis are the most common cancer in young men between the ages of 15 and 35 years.

United States

In the United States, about 9,810 cases are diagnosed each year. The risk of testicular cancer in white men is approximately 4–5 times the risk in black men, and more than three times that of Asian American men. The risk of testicular cancer in Latinos and American Indians is between that of white and Asian men. The cause of these differences is unknown.

United Kingdom

In the UK, approximately 2,000 people are diagnosed each year. Over a lifetime, the risk is roughly 1 in 200 (0.5%). It is the 16th most common cancer in men. It accounts for less than 1% of cancer deaths in men (around 60 men died in 2012).

Source: Wikipedia, The Free Encyclopedia · CC BY-SA 4.0