Testicular Cancer

What is Testicular Cancer?

Testicular cancer is the most common type of cancer found in men aged 15 to 45 years old. It’s commonly treatable and curable, especially if found and treated early. It makes up 1% of all tumors in men and 5% of urological cancers. It’s important to note that the number of cases of testicular cancer has been rising over the years and it has become more significant because both the disease and its treatment can affect a person’s life in the long run. In fact, the incidence of testicular cancer has doubled in the last 40 years.

With effective treatment, the chances of recovery are excellent, over 90% of patients are cured and more than 95% survive five years or more after diagnosis. Various environmental and genetic factors contribute to the development of testicular cancer; common risk factors include undescended testicles, having a relative with testicular cancer, a personal history of testicular cancer in the other testicle, age, and ethnicity. The first steps in diagnosing testicular cancer include going over the patient’s medical history and physical exam, checking for tumor markers and carrying out a scrotal ultrasound. If a solid tumor inside the testicle is found, the testicle is removed via surgery both for diagnosis and treatment. Further treatment is decided based on the stage of the tumor and can include monitoring the patient closely, chemotherapy, surgery to remove lymph nodes in the back of the abdomen, and radiation therapy.

What Causes Testicular Cancer?

Testicular cancer has both genetic and environmental factors that can contribute to its development.

Epidemographic or population-based risk factors: The risk of getting testicular cancer can increase due to certain conditions or situations. Some of these include cryptorchidism (a condition where one or both of the testes fail to descend), cases of reduced sperm production leading to fertility issues, sexual development disorders, having a family history of testicular tumors in close relatives, and having certain types of tumors or cancerous cells in the testes.

The environment also plays a role in the risk of testicular cancer. Common environmental risk factors are listed below:

– Undescended testes (cryptorchidism) can increase the risk 2–4 times. Since cryptorchidism is more common on the right side, there is a slight increase in right-sided testicular cancer cases.
– A family history of testicular cancer increases the risk 6–10 times in brothers or sons of affected men.
– Certain infections like HPV, Epstein-Barr virus, Cytomegalovirus, Parvovirus B-19, and HIV are also considered risk factors.
– Physical injury to the testes.
– High levels of estrogen in mothers.
– Previous history of testicular cancer or non-testis germ cell tumors.

DNA and genetics can also factor into the risk. Different changes in the genetic makeup have been linked to testicular cancer. Certain types of genetic patterns (like the isochromosome of the short arm of chromosome 12) are consistently found in adult germ cell tumors (GCTs; a type of cell that can develop into eggs or sperm), as well as a specific type of cancerous cells located in the testes. Also, variations in the PTEN tumor suppressor gene (a gene that slows down cell division and prevents uncontrolled growth) and related risk of testicular cancer have been discovered. Genetic markers indicate disruptions in certain fetal germ cells’ development, thought to be a cause for certain cancerous cells and germ cell tumors. Finally, certain single-letter changes in the DNA sequence (SNPs) are linked to an increased risk of testicular cancer.

Despite these genetic findings, however, researchers have yet to pinpoint a single genetic cause that significantly ups the risk of testicular cancer. There is also overlap in the development of two types of testicular cancer (seminoma and embryonal carcinoma) as some atypical seminoma cases show signs of cell markers typically found in embryonal carcinoma.

Risk Factors and Frequency for Testicular Cancer

Testicular cancer is most frequently found in Western and Northern Europe, with 8.7 and 7.2 cases per 100,000 men respectively. It’s also been noted that death rates are highest in Western Asia, though this is gradually decreasing due to early detection methods and better treatment options.

In the United States, testicular cancer mostly strikes men aged 20 to 34, making up 51% of all cases. The average age of diagnosis is 33. It seems to affect men from different racial backgrounds differently as well; White males have an incidence rate of 7.1 per 100,000 people, followed by Hispanic men at 5.4, and African American men with 1.7.

Interestingly, the overall incidence rate of testicular cancer in the U.S. has been slowly growing over the past 40 years and is now at 6.3 per 100,000 people. This is up from 3.7 per 100,000 in 1975. It’s more common in industrialized countries compared to developing ones, and white men have a higher incidence rate. However, non-white and immigrant men in the U.S. are seeing an uptick in cases for reasons that are still unknown. On a different note, a small percentage of cases also show tumors in both testicles.

• Most cases of testicular cancer occur in Western and Northern Europe.
• Death rates are highest in Western Asia but are decreasing thanks to early detection and treatment.
• The majority of U.S. cases are in men aged 20 to 34, with an average diagnosis age of 33.
• White men in the U.S. have the highest incidence rate at 7.1 per 100,000, followed by Hispanic men at 5.4 and African American men at 1.7.
• The overall rate of U.S. testicular cancer has increased over the last 40 years.
• Testicular cancer is more common in industrialized countries, and particularly in white men.
• However, non-white and immigrant men in the U.S. are seeing an increase in testicular cancer rates for unknown reasons.
• In 0.6% of cases, tumors are found in both testicles at the same time, and in 1.9% of cases, a tumor is found in the other testicle at a later date.

Signs and Symptoms of Testicular Cancer

Testicular cancer typically shows up as a lump or swelling in one testicle, often discovered accidentally. Sometimes, it can cause a dull or sharp pain. While an injury to the testicles doesn’t cause cancer, it might lead to a check-up that discovers it. During a physical check-up, doctors can usually find a hard spot inside the testicle. Sometimes, it can be difficult to feel the whole testicle if there’s a build-up of fluid around it (hydrocele). If this is the case, ultrasound, a kind of imaging, can be useful to confirm the presence of a tumor. It’s also important to check the other testicle, as a very small percentage (0.6%) of patients have tumors in both testicles at the same time.

Slightly more uncommon are symptoms due to the cancer spreading to other parts of the body. These symptoms include:

• General body symptoms: Feeling very tired, not wanting to eat, losing weight
• Lung involvement: Coughing or finding it hard to breathe
• Spread to neck glands: Swollen neck or collarbone lymph nodes
• Spread to lower back area: Back pain or varicocele (swelled veins in testicles) due to tumors compressing blood vessels
• Vascular obstruction or clotting: Swelling in lower limbs
• Spread to digestive tract: Nausea, throwing up, or bleeding internally
• Spread to the nervous system: Symptoms related to the brain, spinal cord, or peripheral nerves

It’s important to diagnose and treat testicular cancer as soon as possible because it responds very well to treatment. Modern therapies, including platinum-based chemotherapy, radiation, and surgeries (like removal of the testicle or lymph nodes in the lower back), have been very successful in curing this disease.

Testing for Testicular Cancer

To evaluate testicular cancer, doctors start with a detailed interview about your health history and conduct a thorough physical exam. They will ask about certain symptoms you may be experiencing. You might also be asked if you’ve ever had concerning conditions like undescended testicles, testicular surgery or an inguinal hernia repair as a baby. If anyone in your immediate family, like your father or brother, had testicular cancer, it’s important to let your doctor know. During the physical exam, if a hard lump is found inside your testicle, your doctor will suspect testicular cancer until other tests confirm otherwise. Signs related to cancer spread might also be found.

Your doctor may use an ultrasound, a scan that uses sound waves to create images of your testicles, which can reveal abnormalities like lumps in the testicles. Ultrasound is good at catching testicular cancer, especially when combined with a physical exam. Different types of testicular cancers show slightly different features on ultrasound.

If cancer is suspected, blood tests to check the levels of certain tumor markers (substances produced by some types of cancer) like AFP, HCG, and LDH will be carried out. If you need to have the testicle removed (orchiectomy), you should be counseled about potential fertility issues and the option of storing sperm for future use.

The primary way to treat and confirm testicular cancer is a surgery called radical inguinal orchiectomy, which removes the testicle. Biopsies (removing a small sample of tissue for testing) should not be done because they carry a risk of spreading the cancer.

The spread pattern of testicular cancer via certain routes, called lymphatic channels, is well known. Depending on whether the cancer is on the right or left testis, it might spread to different areas. An essential imaging type called computed tomography (CT) – a series of X-ray images from different angles – can help identify this spread, especially in the abdomen and pelvis areas.

Anyone with testicular cancer should undergo CT imaging of the abdominopelvic area. If tumor markers in your blood are high, your doctor may recommend CT scans for your chest, abdomen, and pelvis. In some cases, just having a chest X-ray in combination with a CT scan of your abdomen and pelvis could be enough. In select cases, imaging of the brain may be necessary.

Certain substances in your blood, known as tumor markers, play a crucial role in evaluating and managing testicular cancer. They help stage the cancer, monitor treatment responses and track signs of recurrence. High levels of substances like LDH, AFP and β-hCG could indicate a high burden of the tumor. Still, other non-cancerous conditions and some types of cancers can also raise these levels. So, researchers are studying the role of new factors like circulating microRNAs in the management of testicular cancer.

Newly discovered markers in the cancerous tissue, examined under the microscope, are aiding in the diagnosis. They include substances like PLAP, which are present in different types of the cancer cells.

Treatment Options for Testicular Cancer

Staging is a crucial part of managing testicular cancers. It helps doctors understand the cancer’s progress and plan the treatment accordingly. The International Germ Cell Cancer Collaborative Group (IGCCCG) has developed a clinical staging system that categorizes patients into four categories: Stage 0, I, II or III. Stage 0 involves the cancer cells staying within the testicles, Stage I is when the cancer is limited to the testicles, Stage II includes the spread of cancer to the lymph nodes, and Stage III is when the cancer has spread to distant parts of the body.

In Stage 0, decisions need to be made together by the patient and the doctor, options include close monitoring, removal of the infected testicle (orchiectomy), or radiation therapy. However, radiation can result in 40% of men requiring hormone replacement therapy or dealing with subfertility issues.

In Stage I, removal of the affected testicle is the first step. What happens next depends on the type of tumor. For tumors known as seminomas, there’s a 15-18% chance of the cancer returning after the removal of the testicle without additional treatment. Therefore, treatments like chemotherapy, surveillance or radiation therapy are considered. Tumors known as non-seminomatous have a 14-22% chance of returning without extra treatment. These can be managed with chemotherapy or more surgery.

In Stage IIA and IIB, the infected testicle is removed first, and subsequent treatments depend on the type of tumor. Seminomas can be managed with radiation therapy or chemotherapy. Non-seminomatous tumors are typically treated with chemotherapy or more surgery.

In Stage IIC and III, aggressive chemotherapy is used involving drugs like BEP (bleomycin, etoposide, and cisplatin), EP (etoposide and cisplatin), VIP (etoposide, ifosfamide, cisplatin) or VeIP (vinblastine, ifosfamide, cisplatin). The exact treatment regimen depends on how severe the cancer is. For patients whose tumor markers don’t decrease satisfactorily after the first round of chemotherapy, more intensive chemotherapy might be considered.

To manage any residual cancer left after chemotherapy, patients with seminomas are typically observed or undergo surgery if the leftover tumor is large (over 3cm in size). For non-seminomas, surgical resection is often required for leftover tumors larger than 1cm.

Relapsed or resistant cancers are typically managed with more rounds of intensive chemotherapy followed by surgical removal of residual tumors.

Treatment for testicular cancer varies widely based on the stage and type of cancer. Discussions between the patient and doctor are essential to make the best decision for each individual situation.

What else can Testicular Cancer be?

Typically, a tough lump within the testicle is a telltale sign of testicular cancer. However, it’s essential not to jump to conclusions as there are other conditions that could cause a lump in the testicle. Some of these include:

• Epididymo-orchitis (inflammation of the testicle and sperm-carrying tube)
• Hematoma (localised bleeding outside of blood vessels)
• Inguinal hernia (a condition in which the intestine or fat pushes through muscles at the top of the inner thigh)
• Hydrocele (fluid-filled sac around a testicle)
• Spermatocele or epididymal head cyst (fluid-filled cyst in the long, tightly coiled tube that lies above and behind each testicle)
• Varicocele (enlargement of the veins within the scrotum)
• Lymphoma (common in older men with lumps in both testicles)
• Metastasis from other cancers such as lung, prostate, or skin cancer
• Syphilitic gumma (soft, non-cancerous growth due to syphilis)
• Tuberculoma (mass formed during a stage of tuberculosis)

Doctors often use ultrasonography (a type of imaging test) to help understand what’s causing the lump. The standard treatment for diagnosis often involves surgically removing the testicle through the groin, a process known as radical inguinal orchiectomy.

Surgical Treatment of Testicular Cancer

If there’s a suspicion of testicular cancer based on physical examination or ultrasound results, a procedure known as a radical inguinal orchiectomy is performed to remove the testicle, epididymis, and spermatic cord, which are the tubes that transport sperm. This procedure is done through a small incision in the groin area. If the tumor is too big to get through the regular incision, the doctor might extend the incision towards the scrotum to complete the removal. Performing the operation via the scrotum directly is highly discouraged, since it can alter the regular patterns of lymph fluid flow and negatively impact future management plans.

Partial orchiectomy, which means removing only a portion of a testicle, is not recommended when the other testicle is normal. It can be considered in rare cases involving small lesions in solitary testicles, but only after taking a sample from the surrounding testicle area for testing and ensuring that it doesn’t have any precancerous cells or cancer lesions. This procedure is also done through a groin incision.

There is also a procedure called retroperitoneal lymph node dissection that is aimed at removing all lymphatic tissue in a specific region in order to prevent the spread of cancer. This area is located in the lower back area with boundaries defined by certain landmarks such as renal vessels, ureters, and the iliac vessels. To remove lymphatic tissue in this region, a technique known as “split and roll” is used where bundled nodes of lymph tissue are removed from around the major blood vessels. In addition, the vein that served the testicle and the stump of the spermatic cord are also removed. It’s also possible to identify and spare certain nerve fibers during this procedure if indicated.

What to expect with Testicular Cancer

The outcomes for testicular cancer patients largely depend on the type of cancer cells present in the tumor (histology), how far the tumor has spread away from the original location (extent of distant tumor spread), and abnormal levels of certain biological substances produced by the tumor (tumor markers). For men suffering from a type of testicular cancer called ‘seminomas’, the disease’s prognosis worsens if the cancer has spread to other organs aside from the lungs. Furthermore, if the cancer starts in the area situated among the lungs (mediastinum) rather than the testicles, it generally leads to worst outcomes. However, even patients with advanced cancer spread, including brain metastases, may potentially be cured and should be treated accordingly.

Numerous studies have suggested that larger tumors (at least 3 to 4 centimeters in size) may indicate a higher chance of the testicular cancer recurring in the future. Moreover, cancer cells spreading into the network of tubules in the testicles (rete testis) and blood or lymph vessels can also indicate a high chance of reoccurrence. A new biomarker, CXC-chemokine ligand 12 (CXCL12) – a form of molecule present in our body, has been preliminarily found to predict the recurrence in a specific type of testicular cancer called ‘non-seminomatous germ cell tumors’ independently.

Possible Complications When Diagnosed with Testicular Cancer

Testicular cancer can lead to a variety of complications. These can be divided into two categories: those caused by the disease itself and those as a result of the treatment.

Issues that arise from the disease itself include:

• Chronic fatigue
• Anxiety disorders
• Complications from the cancer spreading
• Blood clots

On the other hand, complications from treatment can include:

• Hypogonadism, which can cause depression, sexual problems, and decreased physical well-being
• Peripheral neuropathy – a condition affecting nerves (which can be caused by a drug called cisplatin)
• Hearing loss (which can be caused by the use of cisplatin)
• Constant ringing or buzzing in the ears, known as tinnitus (again as a result of taking cisplatin)
• Raynaud’s phenomenon – a condition where cold temperatures or stress cause fingers or toes to feel numb and cool (which can be a side effect of cisplatin use)
• Secondary cancers
• Heart disease
• Infertility
• Infections
• Surgical complications like failure of antegrade ejaculation (ejaculation that is obstructed) and small bowel obstruction

Recovery from Testicular Cancer

After having a radical inguinal orchiectomy, which is a surgical procedure to remove a testicle, patients should refrain from heavy lifting and intense physical activities for four weeks. They should also wear supportive underwear to help prevent swelling in the scrotum or a hematoma, which is a collection of clotted blood within the tissue.

If patients have undergone something called a Retroperitoneal lymph node dissection – a significant surgical procedure where lymph nodes in the abdomen are removed – it’s important they engage in dedicated post-surgery rehabilitation to aid a successful and healthy recovery.

Preventing Testicular Cancer

The testicles, found in the scrotum, are the glands that produce sperm in males. Sometimes cells in these glands may grow out of control and develop into testicular cancer. This type of cancer is most commonly seen in young men and thankfully, is one of the most curable types of all cancers. In fact, more than 95% of men diagnosed with testicular cancer beat their disease.

Usually, the first sign of testicular cancer is a hard, painless lump in one of the testicles, though it can occasionally occur in both. If the cancer spreads to other parts of the body like the lungs, brain, abdomen, neck, etc., symptoms such as nausea, vomiting, upset stomach, cough, shortness of breath, fatigue, abnormal sensations, abdominal pain, lumps in the neck or groin, and back pain can occur.

It’s very important to get checked by a doctor if you notice any unusual changes, as an early diagnosis can lead to simpler and more effective treatment. Doctors may use tests and imaging procedures, like an ultrasound of the testicles, blood tests for cancer markers, and CT scans of the chest and abdomen to confirm the presence and spread of the disease.

Typically, the initial step to manage this condition involves surgically removing the lump and the affected testicle. Subsequent treatment, like additional surgery, radiotherapy, or chemotherapy, is based on the stage of the disease and its response to the first treatment. The good news is that testicular cancer is one of the most curable cancers. Knowledge about this disease and prompt attention to any symptoms are key to a successful outcome.