Testicular Cancer

TESTICULAR CANCER

Testicular cancer is a cancer that originates in one or both testicles, or testes. The testes are the male reproductive glands located inside the pouch of skin located underneath the penis (the scrotum). The testes are responsible for producing sperm and the hormone, testosterone.

Testicular cancer most often begins with changes in the cells in the testicles that produce sperm (germ cells). These germ cell tumors account for a little less than 100 percent of testicular cancers.

There are two main types of germ cell tumors:

• Seminomas are testicular cancers that grow slowly. These are usually confined to the testes, though in some cases the lymph nodes may also be involved.
• Nonseminomas are the more common form of testicular cancer. This type not only grows faster, it is most likely to spread to other parts of the body.

Testicular cancer can also occur in the tissues that produce hormones. These are called gonadal stromal tumors.

Although it can occur at any age, testicular cancer is the most commonly diagnosed cancer in men between ages 15 to 35.

It also happens to be one of the most treatable cancers, even if it spreads to other areas.

THE TESTICLES

With a single testicle called a testis, the testicles are part of the male reproductive system. The 2 organs are a little smaller than a golf ball in adult males. They're found within a sac of skin called the scrotum. The scrotum hangs under the base of the penis.

Testicles have 2 main functions:

• They make sperm, the male cells needed to fertilize a female egg cell to initiate a pregnancy.
• They make androgens (male hormones) such as testosterone.

Sperm cells are made in the seminiferous tubules (long, thread-like tubes inside the testicles). They are stored in a small coiled tube behind each testicle called the epididymis, where they mature.

During ejaculation, sperm cells are carried from the epididymis through the vas deferens to the seminal vesicles where they mix with fluids made by the vesicles, prostate gland, and other glands to form semen. The semen then enters the tube in the center of the penis through which both urine and semen leave the body (the urethra).

TYPES OF TESTICULAR CANCER

The testicles are made up of many types of cells. Each of these types can develop into one or more types of cancer. Because cancers differ in how they're treated and in their prognosis, it's always important to know the type of cell the cancer began in and what kind of cancer it is. This can be determined by doctors after looking at the cells under a microscope.

• Seminomas

There are 2 main sub-types of these tumors. They are classical seminomas and spermatocytic seminomas.

Generally, seminomas tend to grow and spread more slowly than non-seminomas.

Classical seminoma: Most of seminomas are classical and they usually occur in men between age 25 and 45.

Spermatocytic seminoma: This type of seminoma though rare, occurs often in older men (average age 65). Spermatocytic tumors tend to grow more slowly and unlike classical seminomas, they are less likely to spread to other parts of the body.

• Some seminomas increase blood levels of a protein called human chorionic gonadotropin (HCG). However, HCG can be checked with a simple blood test and is considered a tumor marker for certain types of testicular cancer. It can also be used for diagnosis and to check how the patient is responding to treatment.

• Germ cell tumors

Almost all of testicular cancers start in the cells that make sperm (germ cells). The main types of germ cell tumors (GCTs) in the testicles are seminomas and non-seminomas.

A lot of testicular cancers contain both seminoma and non-seminoma cells. Because they grow and spread like non-seminomas, these mixed germ cell tumors are treated as non-seminomas.

• Non-seminomas

These are germ cell tumors that usually occur in men within the late teens and early 30s. There are four (4) main types of non-seminoma tumors;

• Embryonic carcinoma,
• Yolk sac carcinoma,
• Choriocarcinoma, and

Most of these tumors are a mix of different types (sometimes even with seminoma cells), but this doesn't change the treatment of most non-seminoma cancers.

• Embryonal carcinoma: These cells are found in about almost half of all testicular tumors. Under a microscope, these tumors sometimes look like tissues of very early embryos. This type of non-seminoma grows rapidly and spreads outside the testicle. Embryonal carcinoma can increase blood levels of a tumor marker protein called alpha-fetoprotein (AFP), as well as human chorionic gonadotropin (HCG).
• Yolk sac carcinoma: This is the most common form of testicular cancer in children (especially in infants), they are so named because their cells look like the yolk sac of an early human embryo. Other names for this cancer include yolk sac tumor, infantile embryonal carcinoma, or orchidoblastoma. Pure yolk sac carcinomas (which do not have other types of non-seminoma cells in them) are rare in adults. These tumors are usually treated successfully when they occur in children, but when they are pure and occur in adults they're of more concern. The yolk sac carcinomas respond very well to chemotherapy, even if they have spread.
• Choriocarcinoma: A rare and fast-growing type of testicular cancer in adults. Pure choriocarcinoma is very likely to spread and rapidly too, to other parts of the body, (e.g. the lungs, bones, and brain). More often, the choriocarcinoma cells are seen with other types of non-seminoma cells in a mixed germ cell tumor. Generally, mixed tumors have a better outlook than pure choriocarcinomas, although the presence of choriocarcinoma is always worrisome. This type of tumor increases blood levels of HCG (human chorionic gonadotropin).
• Teratoma: Under a microscope, Teratomas are germ cell tumors with areas that look like each of the 3 layers of a developing embryo (The endoderm, mesoderm and ectoderm). Pure Teratomas of the testicles are rare. They do not increase AFP (alpha-fetoprotein) or HCG (human chorionic gonadotropin) levels. Most often, Teratomas are seen as parts of mixed germ cell tumors.

There are 3 main types of Teratomas:

1. Teratomas with somatic type malignancy are very rare. These cancers have some areas that look like mature Teratomas but have other areas where the cells have become a type of cancer that normally develops outside the testicle (e.g. sarcoma, adenocarcinoma, or even leukemia).
2. Mature Teratomas are tumors formed by cells a lot like the cells of adult tissues. They seldom spread, and can usually be cured with surgery, but some recur after treatment.
3. Immature Teratomas are less well-developed cancers with cells that look like those of an early embryo. This type is more likely than a mature teratoma to grow into (invade) nearby tissues, spread (metastasize) outside the testicle, and come back (recur) years after treatment.

• Carcinoma in situ of the testicle

Sometimes, testicular germ cell cancers begin as non-invasive forms of the disease called carcinoma in situ (CIS). Testicular CIS cells look abnormal under the microscope, but they have not yet spread outside the walls of where sperm cells are formed (the seminiferous tubules). Carcinoma in situ doesn't always progress to invasive cancer.

It's always difficult to find CIS before it becomes an invasive cancer because it hardly causes any symptoms or form a lump that you or the doctor can feel. The only way to diagnose testicular CIS is to have a biopsy. Sometimes CIS is found incidentally (by accident) when a testicular biopsy is done for another reason (e.g. infertility).

Since CIS doesn't always become an invasive cancer, experts disagree about the best treatment for CIS. A lot of doctors though consider observation (watchful waiting) to be the best option for treatment.

When CIS of the testicle becomes invasive, its cells would no longer just in the seminiferous tubules, they would have grown into other structures of the testicle. These cancer cells can then spread either to the lymph nodes, through lymphatic vessels, or through the blood to other parts of the body.

• Stromal tumors

Tumors can also initiate in the supportive and hormone-producing tissues, or stroma, of the testicles. These are known as gonadal stromal tumors. The main types are Leydig cell tumors and Sertoli cell tumors.

• Leydig cell tumors: These tumors start in the Leydig cells in the testicle that normally make androgens like testosterone (male sex hormones). Leydig cell tumors can develop in both adults and children. These tumors often make androgens (male hormones), but sometimes they make female sex hormones (estrogens). Most Leydig cell tumors are benign (not cancer). They seldom spread beyond the testicle and can often be cured with surgery. Yet, a small number of Leydig cell tumors do spread to other parts of the body. These usually have a poor outlook because they usually don't respond well to chemo or radiation therapy.
• Sertoli cell tumors: These tumors start in normal Sertoli cells, which support and nourish the sperm-making germ cells. Just like the Leydig cell tumors, these tumors are usually benign. However, if they spread, they usually do not respond well to chemo or radiation therapy.

• Secondary testicular cancers

They are cancers that start in another organ and then spread (metastasize) to the testicle, and so they are only secondary testicular cancers. These are not real testicular cancers because they don't start in the testicles. Cancers are named and treated based on where they started.

The most common secondary testicular cancer is Lymphoma. Testicular lymphoma is more common in men older than 50. The outlook will depend on the type and stage of lymphoma. The usual treatment is surgical removal, otherwise by radiation and/or chemotherapy.

In males with acute leukemia, the leukemia cells can sometimes form a tumor in the testicle. Aside chemotherapy to treat the leukemia, this condition might require treatment with radiation or surgery to remove the testicle.

Cancers of the prostate, lung, skin (melanoma), kidney, and other organs can also spread to the testicles. The prognosis for these cancers tends to be poor because these cancers would usually have spread widely to other organs as well. Treatment will depend on the specific type of cancer.

CAUSES

The exact cause of most testicular cancers is not known. But scientists have linked the disease with a number of other conditions.

Researchers are trying to reveal how certain changes in a cell's DNA can cause the cell to become cancer. DNA is the chemical in each human cell that makes up the genes. Genes tell cells how to function. They are packaged in long strands of DNA in each cell (chromosomes). Most cells in the body have 2 sets of 23 chromosomes (one set of chromosomes comes from each parent). We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look.

Some genes control when our cells actually grow, divide into new cells, and die.

Certain genes too have the job of helping cells grow and divide. They are called oncogenes.

There are others that slow down cell division or make cells die at the right time. They are called tumor suppressor genes.

Cancers can be caused by changes in chromosomes that turn on oncogenes or turn off tumor suppressor genes.

SYMPTOMS OF TESTICULAR CANCER

People with testicular cancer may experience a variety of signs or symptoms even as some men with testicular cancer do not have any of these changes. Or, the cause of a symptom may be a different medical condition that is not cancer. Therefore, having these symptoms does not mean that a man definitely has cancer.

Usually, an enlarged testicle or a small lump or area of hardness are the first signs of testicular cancer. Any lump, enlargement, hardness, pain, or tenderness should be evaluated by a doctor as soon as possible. Some other symptoms of testicular cancer usually does not appear until after the cancer has spread to other parts of the body.

Symptoms of testicular cancer may include:

• A dull ache in the lower abdomen or groin.
• A sudden buildup of fluid in the scrotum
• A painless lump or swelling on either testicle. If found early, a testicular tumor may be about the size of a pea or a marble, but it can still grow much larger.
• Pain, discomfort, or numbness in a testicle or the scrotum, with or without swelling.
• Change in the way a testicle feels or a feeling of heaviness in the scrotum. One testicle may for example become firmer than the other testicle.

• Breast growth or tenderness. Although it is rare, some testicular tumors make hormones that cause breast tenderness or growth of breast tissue, a condition called gynecomastia.
• Shortness of breath, lower back pain, chest pain, and bloody sputum or phlegm can be symptoms of later-stage testicular cancer.
• Shortness of breath, swelling of one or both legs or from a blood clot can be symptoms of testicular cancer. A blood clot in a large vein is called deep venous thrombosis or DVT. A blood clot in an artery in the lung is called a pulmonary embolism and both causes shortness of breath.

If a person is concerned about changes they experience, doctors would be the best people to speak with to help figure out the cause of the problem, called a diagnosis.

If cancer is diagnosed, relieving symptoms remains an important part of cancer care and treatment. This may be called Supportive care, Palliative care or Hospice care.

• Supportive care arose specifically to combat toxicities of cancer treatment.
• Palliative care, which has historic roots in end-of-life
• Hospice care, Hospice care is a type of health care that focuses on the palliation of a terminally ill patient's pain and symptoms and attending to their emotional and spiritual needs at the end of life.

These specialized areas of care have now established themselves as medical specialties dedicated to helping patients with serious illness live as well as possible. It often begins soon after diagnosis and continued throughout treatment.

RISK FACTORS

A risk factor is anything that increases a person's chance of developing a condition. Although risk factors often influence the development of cancer, they may not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do.

However, if one knows their risk factors and discuss them with doctors, it may help with more informed lifestyle and health care choices.

The following factors can raise a man's risk of developing testicular cancer. However, it is important to reiterate the fact that the cause of testicular cancer is not known.

• Family history - A man who has a close relative, who has had testicular cancer has an increased risk of developing testicular cancer.
• Personal history - Men who have had cancer in 1 testicle previously, have an increased risk of developing cancer in the other testicle.
• Age - More than fifty percent (50%) of the men who are diagnosed with testicular cancer are between ages 20 and 45. However, the fact is men of any age can develop this disease, including teenage males and those in their 60s.
• Cryptorchidism – This is an undescended testicle, meaning that 1 or both testicles did not move down into the scrotum before birth as they should. Men with this condition have an increased risk of developing testicular cancer.

However, this risk may be lowered if the condition is fixed before puberty. Some doctors recommend surgery for cryptorchidism between ages 6 months and 15 months to reduce the risk of infertility. Cryptorchidism is often fixed at a young age, many men may not know if they had the condition.

• Race - Men of any race can develop testicular cancer, but white men are more likely than men of other races to be diagnosed with testicular cancer. Testicular cancer is very rare among black men. Strangely however, black men with testicular cancer are more likely to die of the cancer than white men, especially if the cancer spread to the lymph nodes or other parts of the body at the time of diagnosis.
• Human immunodeficiency virus (HIV). Men with HIV or acquired immune deficiency syndrome (AIDS) caused by HIV have a slightly higher risk of developing seminoma.

WHEN TO SEE A DOCTOR

People should endeavor to see their doctor if they detect any pain, swelling or lumps in the testicles or groin area, more so if these signs and symptoms last longer than two weeks.

DIAGNOSIS

Self-Exam

The best time to do a testicular self-exam is after a warm bath or shower, while standing, when the scrotum is relaxed. It only takes a few minutes.

To begin;

• Feel for lumps, swelling or things that don't seem right. Lumps or bumps are not normal (even if they do not cause pain). Pain is not normal.
• Check each testicle - Gently but firmly roll each testicle between the thumb and forefingers. Feel the whole surface. The firmness of the testis should be the same all around. It's normal for one testis to be slightly larger than the other.
• Find the epididymis and vas deferens - Soft, tube-like structures above and behind the testicle. These tubes collect and carry sperm. One has to become familiar with how the cords feel.

One needs to check himself at least once per month and during the process should look for changes in size, shape, or texture.

People should take notice of lumps or any changes over time. It may not be anything serious, but if it is testicular cancer, it can spread very quickly. If found early, testicular cancer is very curable.

Medical Examinations

Health record and physical exam: Doctors will examine the scrotum, abdomen, lymph nodes, and other parts to look for signs of cancer. Whilst doing that, they will look for lumps, firmness or signs of swelling.

• Testicular ultrasound: This imaging test is used to see the inside of the scrotum and to check suspicious lumps. Other scans or x-rays may be done if the doctor would like to see inside the chest or abdomen. This is to determine if the cancer has spread to lymph nodes, the lungs or the liver. MRIs are rarely used, but will still be needed to check the brain and spinal cord.
• Blood test: A blood test is taken to check proteins and hormones made by some testicular cancers (tumor markers). But many testicular cancers will not produce tumor markers. Therefore, just because tumor markers are normal does not mean that one is free of cancer.
• Serum Tumor Marker Test: If cancer is found, tumor marker tests will be repeated after treatment to track how well the treatment is going over time. Some medicines and even marijuana can create false positive levels of Human chorionic gonadotropin HCG, which is a hormone produced by cells that are surrounding a growing embryo (syncitiotrophoblast initially), eventually, this forms the placenta after implantation.

Though over the counter urinary pregnancy tests do check for HCG levels in the urine they are not reliable tests for testicular cancer.

STAGES

If the urologist finds cancer through the examinations, they will want to learn the exact cancer cell-type and if it has spread. This is called 'staging'. This process will help the doctor learn which treatments are best.

With testicular cancer, cells are looked at after surgery is done to remove the cancerous tissue unlike the processes with other cancers. Thus the doctor would not take a biopsy before surgery.

Testicular Cancer Stages

• Stage 0: Also called Germ Cell Neoplasia in Situ (GCNIS). At this stage, it is not really a cancer, but a warning that cancer could grow. GCNIS may be found in the seminal tubules and nowhere else.
• Stage I (IA, IB, IS): At this stage cancer is found only in the testicle. It has not spread to nearby lymph nodes.
• Stage II (IIA, IIB, and IIC): Cancer has spread to one or more lymph nodes in the abdomen, but has not spread to other parts of the body.
• Stage III (IIIA, IIIB, and IIIC): The cancer at this stage has spread beyond the lymph nodes in the abdomen. Cancer may be found far from the testicles, like in distant lymph nodes or the lungs. Tumor marker levels are high.

TREATMENT

Depending on the stage of the cancer, one may be treated with one or more options however, there are three general categories of treatments used for testicular cancer.

• Surgery

Surgery can be employed to remove one or both of a person's testicles and some surrounding lymph nodes to both stage and treat cancer.

• Radiation therapy

Radiation therapy involves the use of high-energy rays to kill cancer cells. This may be administered externally or internally.

External radiation uses a machine that aims the radiation at the cancerous area. Internal radiation involves the use of radioactive seeds or wires placed into the affected area. The latter form is often successful in treating seminomas.

• Chemotherapy

This is a systemic treatment, which means it can kill cancer cells that have traveled to other parts of the body. Chemotherapy involves the use medication to kill cancer cells. When it's taken orally or through the veins, it travels through the bloodstream to kill cancer cells.

In very advanced cases of testicular cancer, a high-dose of chemotherapy may be followed by a stem cell transplant. So that after the chemotherapy has destroyed the cancer cells, the stem cells are administered and develop into healthy blood cells.

LIVING AS A TESTICULAR CANCER SURVIVOR

Care for people diagnosed with cancer does not end when active treatment has ended. The health care team will continue to check for the recurrence of the cancer, manage any side effects, and monitor the patient's overall health (follow-up care).

A follow-up care may include regular physical examinations, medical tests, or both. Doctors would want to keep track of the recovery in the months and years ahead. Most men who had testicular cancer usually receive follow-up screening for at least 10 years after the end of their treatment.

Watching out for recurrence

One major goal of follow-up care is to check for recurrence. Cancer recurs because small areas of cancer cells may remain undetected in the body. Over time, these cells may increase in number until they show up on test results or cause signs or symptoms. During follow-up care, a doctor familiar with your medical history can give personalized information about the risk of recurrence. Some people may have blood tests or imaging tests done as part of regular follow-up care, however testing recommendations depend on several factors including the type and stage of cancer originally diagnosed and the types of treatment given.

Managing long-term side effects

Most people expect to experience some side effects when receiving treatment. However, it is often surprising to survivors that some side effects may linger beyond the treatment period. These are called long-term side effects. Other side effects called late effects may develop months or even years afterwards. Long-term and late effects may include both physical and emotional changes.

If the patient had a treatment that is known to cause specific late effects, doctors may have certain physical examinations, scans, or blood tests done to help find and manage them.

Below are some of the long-term side effects that are possible after treatment for testicular cancer.

• Lung problems. Bleomycin can cause lung damage for about 5% of men with testicular cancer and is even fatal for a few of men who receive the drug. Lung scarring is another possible long-term side effect. It is rare to have lung effects without these risk factors
• Previous lung injury
• Being older than 70
• Smoking
• Previous radiation therapy to the chest
• Poor kidney function

If 4 cycles of chemotherapy is needed, Ifosfamide can be used instead of bleomycin, but it is linked with more short-term side effects (e.g. infections). Bleomycin also makes the lungs a lot more sensitive, and patients who need to receive extra oxygen during surgery may have a higher risk of lung damage from bleomycin.

Importantly:

Patients who smoke must quit smoking for many health reasons, especially to reduce the risk of lung damage from bleomycin. The doctor would examine the patient's lungs before each cycle of chemotherapy and will stop giving bleomycin if lung damage is seen.

• Damage to Kidneys. The medication Cisplatin, can cause kidney damage. However, it is a very important drug to treat testicular cancer. Again, Cisplatin has fewer side effects than carboplatin, which has been shown to be less effective. In preventing this problem, Cisplatin should be flushed out by giving the patient at least 1 liter of IV fluid before and after the drug is given to reduce the risk of kidney damage.
• Problems with heart and blood vessels. A condition that makes the blood vessels narrow and the skin turn white, then blue, and then red when exposed to triggers, such as cold may also be caused by Bleomycin. It is called Raynaud's phenomenon. However, it has been established that more men develop this condition when vinblastine is combined with bleomycin. However, this regimen is outdated and it's not ever used again. Avoiding the triggers (e.g. preventing the fingers from becoming cold), is just about the main treatment. Men who receive BEP chemotherapy (chemotherapy drug combination: Bleomycin; Etoposide; Platinum), may have higher cholesterol and blood pressure levels and an increased risk of heart disease and/or stroke. An increased risk of heart disease has also been linked to Radiation therapy, however the necessity to treat the cancer always outweighs this increased risk. The side effects are more important when the doctor considers chemotherapy or radiation therapy to prevent the cancer from coming back for men with clinical stage I disease. A healthy diet, exercise, not smoking, and medications to lower cholesterol, control high blood pressure, or treat diabetes are ways to reduce the risk of heart disease and stroke.
• Nerve damage. The medicine Cisplatin, sometimes causes feelings of numbness or 'pins and needles' and can even damage the nerves. This often occurs, during the chemotherapy but reduces and goes away with time. It may take months or even years to completely go away. Though rare, it can affect a person's functioning, such as being clumsy when buttoning a shirt.
• Hearing problems. Some men who received Cisplatin actually noticed that they could no longer hear high-pitch sounds. This is even more common with higher doses. It is more likely for older men or men who had previous problems with hearing. It rarely affects young men but may be relevant for musicians or others who depend on having very fine hearing abilities. Another side effect of Cisplatin may be tinnitus (i.e. ringing in the ears).
• Secondary cancers. Men who receive chemotherapy and/or radiation therapy for testicular cancer would also have an increased risk of developing other types of cancer in the future. The thought of developing another cancer can be concerning and difficult to face. However, if the testicular cancer has spread to other sites in the body by metastasis (stage II or III), then the cancer is fatal unless it is treated effectively. When the goal is to cure the disease, Chemotherapy and radiation therapy often play important roles in treating testicular cancer. Even though they pose risks, chemotherapy and radiation therapy are sometimes the best options for controlling cancer growth and extending a patient's life. Secondary cancers may be particularly important for men with stage I disease and early stage II disease that can be cured with surgery alone. In such cases, men may have a choice between surgeries alone versus surgery plus chemotherapy or radiation therapy.
• The issue of fertility in men with testicular cancer is rather a complex topic because patients with testicular cancer often have a lower sperm count before any treatment is given. Any man who has fertility problems after treatment should talk with his doctor about these factors:
• How long ago the treatment was given
• Sperm count before chemotherapy
• Whether he received chemotherapy or radiation therapy
• Whether an experienced surgeon performed a nerve-sparing RPLND to preserve ejaculation. Though a low sperm count does not necessarily mean that a man will be infertile after treatment, most patients will develop very low to no sperm counts while receiving chemotherapy. The chance of fertility returning after treatment actually increases over time but is lower for men with no or low sperm counts before chemotherapy.

• Low testosterone. In addition to damage to the ability to make sperm, the cells that make testosterone may be damaged during the treatment. If a man has a low testosterone level, then hormone replacement therapy can be used. Symptoms of a reduced testosterone level include decreased sex drive, inability to achieve a normal erection and orgasm, fatigue, hot flashes, depression, mood changes etc.