Testicular Cancer

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Original Editors Brandon Davis as part of the Bellarmine University's Pathophysiology of Complex Patient Problems project.

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Definition/Description

-Testicular cancer occurs when cells in one or both testicles become malignant.
-There are three stages of testicular cancer.
-Stage I-the cancer is refined to the testicle
-Stage II-The cancer has spread to the retroperitoneal lymph nodes, located in the posterior abdominal cavity below the diaphragm and between the kidneys.
-Stage III-The cancer has spread beyond the lymph nodes to remote sites in the body, including the lungs, brain, liver, and bones.
-Germ cell tumors (origin in the primordial germ cells) make up more than 95% of testicular tumors, whereas the remaining neoplasms are mostly tumors of stromal or sex cord origin.

-Carcinoma in situ usually becomes an invasive germ cell tumor in a median period of
approximately 5 years.
-The neoplastic transformation of a germ cell results in either a seminoma, an undifferentiated tumor, or a nonseminomatous tumor comprised of embryonal carcinoma teratoma, choriocarcinoma, or yolk-sac carcinoma (endodermal-sinus tumor).
-Primary testicular tumors are divided into two histogenic categories: seminoma and nonseminoma.

-Seminomas are the most common testicular cancers, accounting for approximately 40% to 50% of germ cell tumors and most often appearing in the fourth decade of life.
-Seminomas appear as a solid, grey-white growth and are rarely necrotic or cystic.¹  The entire testis can be replaced by the tumor.
-The incidence of nonseminomas peaks in the third decade of life, hemorrhage, necrosis, or cystic changes are more common.
-Yolk-sac tumors are the most common germ cell tumors of infants.  These tumors result in enlarged testes, which appear grossly as poorly defined lobulated masses.  Focal areas of hemorrhage are common.
-Metastatic tumors to the testis from primary neoplasm elsewhere in the body are uncommon, although involvement by lymphoma may occur in older men.

Prevalence

-Testicular cancer is relatively rare and occurs most often in young men between the ages of 15 and 35 years old, although any male can be affected at any time (including infants).
-Testicular cancer in the most common solid organ tumor in young men.
-Testicular cancer is the second most common malignancy from age 35 to 39 years with a white-to-black incidence ratio of 5 to 1.
-According to the National Cancer Institute’s Surveillance, about 8,000 men are diagnosed with testicular cancer each year (390 deaths annually).
-The incidence of testicular cancer around the world has doubled in the past 30 to 40 years.
-There are considerable geographic and ethnic variations in the global incidence of  testicular cancer.
-The disease mainly affects Western populations, with an increasing incidence since the middle of the twentieth century.
-Average rates in developed areas of the world are six times higher than those in developing areas.
-Approximately 79,200 new cases of testicular cancer were estimated to occur in the United States in 2007.

Characteristics/Clinical Presentation

-A lump in either testicle
-Any enlargement, swelling, or hardness of a testicle
-Significant loss of size in one of the testicles
-Feeling of heaviness in the scrotum and/or lower abdomen
-Dull ache in the lower abdomen or in the groin
-Sudden collection of fluid in the scrotum
-Pain or discomfort in a testicle or in the scrotum
-Enlargement or tenderness of the breasts
-Unexpected fatigue or malaise
-Infertility
-Low back pain (metastases to retroperitoneal lymph nodes)

-The most common initial sign of testicular cancer is enlargement of the testis with diffuse testicular pain, swelling, hardness, or some combination of these findings.
-The condition may go undetected if no pain is experienced and the male is not periodically performing testicular self-examination.
-The enlargement may be accompanied by an ache in the abdomen or scrotum or a sensation of heaviness in the scrotum.
-Metastasis, with little or no local change, is noted in the scrotum.
-Retroperitoneal primary tumors may present with back pain and/or groin or pelvic pain (psoas muscle invasion).
-Metastatic testicular cancer can present as back pain (may be the primary presenting complaint), abdominal mass, hemoptysis, or neck or supraclavicular adenopathy.
-Up to 21% of men with testicular germ cell cancer have back pain as the primary presenting symptoms.
-Pain may be the sole presenting symptom in metastasis to the retroperitoneal, cervical, and supraclavicular lymphatic chains.
-Approximately 20% of all cases have involved lymph nodes.
-Bone metastasis is a late event, often combined with metastasis to the retroperitoneal lymph nodes, lung, and liver.
-Occurring during the prime of life for most men and potentially affecting sexual and reproductive capabilities, testicular cancer has a major emotional impact and can affect overall quality of life.

Associated Co-morbidities/Prognosis

-No co-morbidities found in our two books.  Will research further.
-Long-term sequelae of cisplatin use may include leukemia, cardiovascular events, and reports that circulating cisplatin can be detected in the plasma as long as 20 years after treatment.
-The most serious long-term complications of chemotherapy or radiotherapy are cardiovascular toxicity and second malignancies; each has a 25-year risk of approximately 16%.
-Chemotherapy-related cardiovascular toxicity may be the result of both direct endothelial damage induced by cisplatin and indirect hormonal and metabolic changes.
-There is an increased incidence of metabolic syndrome in long-term survivors that is most likely caused by the lower testosterone levels.
-Current therapeutic regimens have significantly improved survival but often adversely affect fertility; cisplatin-based chemotherapy results in 30% to 50% infertility rates in men with testicular cancer who are treated with chemotherapy.
-Other chemotherapy-induced complications include chronic neurotoxicity (50%), permanent ototoxicity and renal function impairment (30%), pulmonary fibrosis (5% to 10% when treated with bleomycin); and late relapse.

Medications

-No known preventive strategies exist including the use of medications.
-Will research further to see if any oral medications are used in the treatment of testicular cancer.

Diagnostic Tests/Lab Tests/Lab Values

-A thorough urologic history and physical examination are the basis for making a diagnosis of testicular cancer.
-A painless testicular mass is highly suggestive of testicular cancer.
-Transillumination of the scrotum may also reveal a testicular mass.
-Serum tumor markers (e.g., alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and lactate dehydrogenase (LDH)) are increased in 40% to 60% of all cases and may be used to guide treatment and follow-up.
-Testicular ultrasound is used to differentiate a variety of scrotal disorders besides cancer (e.g., epididymitis, orchitis, hydrocele, or hematocele).
-The modalities used to assess metastatic spread include CT scans and MRI.
-MR lymphography may replace the currently used tomography scanning or MRI used to noninvasively stage retroperitoneal lymph nodes.
-Biopsy with microscopic examination of testicular tissue by a pathologist is the best way to make a definitive diagnosis.  

-The American Cancer Society recommends monthly self-exam of the testicles for adolescents and men, starting at age 15.

-Testicular self-examination is an effective way of getting to know this area of the body and thus detecting testicular cancer at a very early, curable stage.
-The self-exam is best performed once each month or after a warm bath or shower when the heat has relaxed the scrotum.

Causes/Risks

-The etiology of testicular cancer is not well understood.
-Although the cause is unknown, hormonal balance at various life stages appear to be related.
-Congenital and acquired factors have been associated with the development of testicular cancer; familial clustering has been observed particularly among siblings.
-The first susceptibility gene for testicular cancer has been located and named TGCT1 on the long arm of chromosome X, inherited from the mother; its presence increases a man’s risk of testicular cancer by up to 50 times.
-There is some evidence that cancer stem cells are derived from normal stem cells that have gradually accumulated various genetic defects; a group of tumor-specific antigens known as cancer/testis antigens (CTAs) may be expressed at early stages during embryogenesis in germ cell precursors eventually leading to testicular cancer.
-The most significant factor in testicular cancer is the association of cryptorchidism (the testes not descending into the scrotum).
-The incidence of testicular cancer is 35 times higher in males with a cryptoid testis.
-Risk is higher than average for boys born with an undescended testicle (cryptorchidism).  The cancer risk for boys with this condition is increased even if surgery is done to move the testicle to the scrotum.
-In the case of unilateral cryptorchidism, the risk of testicular cancer is increased in the normal testicle as well.  This fact suggests testicular cancer is due to whatever caused the undescended testicle.
-Having a brother or father with testicular cancer also increases an individual’s risk.
-There is now strong evidence that prenatal or postnatal environmental estrogen exposures (e.g., endocrine-mimicking environmental pollutants, pesticides, industrial chemicals, or chemical contaminants in drinking water) contributes to testicular cancer; this remains under further investigation.
-Other risk factors still under investigation may include mothers who took exogenous estrogen during pregnancy (diethylstilbestrol), scrotal trauma, exposure to high levels of radiofrequency/microwave radiation in radar technicians, first-born sons, and nonidentical twins.
-Other risk factors may include occupation (e.g., miners, oil and gas workers, leather workers, food and beverage processing workers, janitors, firefighters, utility workers) and HIV infection.
-Men with Kleinfelter’s syndrome (a sex chromosome disorder characterized by low levels of male hormones, sterility, breast enlargement, and small testes) are also at greater risk of developing testicular cancer.
-Lifestyle and occupational exposures occurring later in life may play a role in promoting the disease, but they are not likely involved in the initiation of the cancer development.
-A previous history of testicular cancer and history of infertility and poor semen quality or infection have been associated with an increased risk of developing testicular cancer.
-A causal relationship has not been established between infertility and infection and testicular cancer.
-The risk of testicular cancer among white American men is about 5 to 10 that of African American men and more than twice that of Asian American men.
-The risk for Hispanics is between that of Asians and non-Hispanic whites.  The reason for this difference is unknown.
-The testicular cancer rate has more than doubled among white Americans in the past 40 years but has not changed for African Americans.
-Worldwide, the risk of developing this disease is highest among men living in the United States and Europe and lowest among African and Asian men.
 

Systemic Involvement

-Men can experience back pain (as well as hip, groin, SI, and sacral pain) caused by referred pain from the male reproductive system.
-Back pain, changes in bladder function, and sexual dysfunction are the most common symptoms associated with male reproductive disorders.
-Metastases occur via the blood or lymph system.
-The most common place for the disease to spread is to the lymph nodes in the posterior part of the abdomen.  Therefore, lower back pain is a frequent symptom of later stage testicular cancer.
-If cancer has spread to the lungs, persistent cough, chest pain, and/or shortness of breath can occur.  Hemoptysis (sputum with blood) may also develop.
-Back pain associated with cancer is usually constant, intense, and worse at night or with weight-bearing activities, although vague, diffuse back pain can be an early sign of non-Hodgkins lymphoma and multiple myeloma.
-Pain with metastasis to the spine may become quite severe before any radiologic manifestations appear.
-Back pain associated with malignant retroperitoneal lymphadenopathy or testicular cancers is characterized as persistent, poorly localized low back pain present at night but relieved by forward flexion.
-Pain may be so excruciating while lying down that the patient can sleep only while sitting in a chair hunched forward over a table.
-Typically systemic back pain is not relieved by recumbency.
-In fact the bone pain of metastasis or myeloma tends to be more continuous, progressive, and prominent when the client is recumbent.
-Beware of the client with acute backache who is unable to lie still.
-Almost all clients with regional or nonspecific backache seek the most comfortable position (usually recumbency) and stay in that position.
-In contrast, individuals with systemic backache tend to keep moving trying to find a comfortable position.
-Back pain that is unrelieved by rest or change in position, or pain that does not fit the expected mechanical or neuromusculoskeletal pattern, should raise a red flag.
-When the symptoms cannot be reproduced, aggravated, or altered in any way during the examination, additional questions to screen for medical disease is indicated.
-Pain at night can signal a serious problem such as tumor, infection, or inflammation.
-Long-standing night pain unaltered by positional change suggests a space-occupying lesion, such as a tumor.
-Systemic back pain may get worse at night, especially when caused by vertebral osteomyelitis, septic discitis, Cushing’s disease, osteomalacia, primary and metastatic cancer, Paget’s disease, ankylosing spondylitis, or tuberculosis (of the spine).

Medical Management (current best evidence)

-Management of testicular cancer has changed substantially in the last 20 years, primarily because of the ability of cisplatin-containing combination chemotherapy to cure advanced disease.
-Even over the last 5 years, the management of stage 1 testis cancer has changed tremendously.
-Chemotherapy is used in cases of relapse after radiation therapy or when there is a high risk for occult metastatic disease.
-The recommendation of which therapies to include is based on pathologic findings from the orchidectomy and results of the CT and MRI procedures.
-Second-line conventional-dose or high-dose chemotherapy with stem cell rescue may cure 25% to 50% of men with recurrent testicular tumors.
-New chemotherapeutic agents, including the taxanes gemcitabine and oxaliplatin, may also be used.
-Organ-sparing surgery has become an accepted approach to treat malignant and nonmalignant tumors of a single testis.Combined with adjuvant radiotherapy to the retroperitoneal and ipsilateral pelvic lymph nodes, this approach has proven as effective as orchidectomy.
-Nerve-sparing retroperitoneal lymph node dissection is an integral part of testis cancer management strategies for both early and advanced-stage disease.
-Nerve-sparing techniques help preserve sexual function and prevent incontinence.
-As many as 50% of men with clinical stage 1 testis cancer can be treated with close surveillance instead of immediate adjuvant treatment.
-Testicular-sparing management of testicular cancer is an alternative to radial orchidectomy and allows for preservation of sperm and hormonal function without endangering survival rates.  Sperm collection and cryopreservation before the initiation of therapy is an available reproductive technology.  Only a few sperm are needed for successful in vitro fertilization.

Physical Therapy Management (current best evidence)

Will research further.

Alternative/Holistic Management (current best evidence)

Will research further.

Differential Diagnosis

-Men can experience back pain (as well as hip, groin, SI, and sacral pain) caused by referred pain from the male reproductive system.
-Back pain, changes in bladder function, and sexual dysfunction are the most common symptoms associated with male reproductive disorders.

Case Reports

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Resources

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Recent Related Research (from Pubmed)

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