What Do the Testicles Do?
The testicles are the paired organs of male fertility (“gonads”) suspended in the loose scrotal sac. The testicles provide the hormonal signals for maleness, and begin to generate sperm (“spermatozoa”) after puberty. A hormone is a chemical substance produced in one area of the body that has its effects in a different area-- thus it is a “chemical messenger”. Specifically, the testicles produce “androgens” which are male hormones. The best known androgen is testosterone. Male hormones are even produced in the womb (by other glandular tissue); they signal the “Y” sex chromosome to activate and develop the penis and testicles. Androgens circulate in the bloodstream to all of the other tissues of the body, to tell them about the male sex. Thus, in the growing male the breasts stay small, the voice deepens, facial hair becomes coarse, the upper torso enlarges, and the red blood cell count is higher.
The testicles are best known for producing sperm, the male seed (“gamete”) which they do from puberty through old age. Although the amount of sperm decreases as a man ages, males can produce an unlimited number of sperm over their lifetimes. This is in contrast to females, who’s number of eggs (“ova” or female “gametes”) are predetermined by the time of birth. Each sperm contains one-half of the total genetic information needed to produce a new human being; the other necessary one-half of the genetic information is found in the female egg (“ovum”). The formation of gametes utilizes a unique form of division found only in the testicles and ovaries, called “meiosis.” This process uses “reduction divisions” to halve the parent genetic material. After all, if each parent gave their full amount of genetic material, we would have twice as much as necessary to build a new human. Meiosis contrasts with the much more common process of “mitosis”, which keeps the same amount of genetic material in every cell produced. The other non-gamete body (“somatic”) cells and all cancer cells divide by mitosis. When a viable sperm and egg meet, the process of fertilization occurs resulting in a “zygote.” The zygote cells divide into increasingly specialized (“differentiated”) cells to form the embryo, then fetus, infant, and ultimately viable adult human. Interestingly, each sperm or egg produced can have a unique content of genetic material, since the process of “halving” the parent’s genetic code is random (the genes are “re-assorted” differently into each sperm or egg cell). This explains why siblings have different genetic makeup (“genotype”) and appearance (“phenotype”). Only identical twins, resulting from one zygote splitting (“mitosing”) into two exactly identical zygotes, have the precise same genotype.
The paired testicles are each one and one-half to two inches in length in the adult male, and inch in breadth, and an inch in depth. The left testicle is usually slightly larger, they weigh about one and one-half onces apiece. The testicles are also called “testes” for short, they are contained within the scrotum which protects them and keeps them at the proper temperature. The “cremasteric” muscle controls how closely the testes are held to the body are from which they dangle, called the “perineum”. The perineum is the area between the anus and the base of the penis. Sperm are best produced at a temperature slightly below the normal body temperature of 98.6 degrees F. (38 C.). When sensing cold, the testicles are drawn up toward the body and held snug by the cremasteric muscle; which relaxes as the testicles warm up. Immature sperm are produced within the testes by cells called “spermatogonia,” these line the “seminiferous tubules” where sperm start. The newly minted sperm travel through a network called the “rete testes,” and then in the “efferent ducts” exiting each testicle. During this journey, which can take several weeks, the young sperm are maturing. They are then delivered into the “vas deferense” which is a twisted tube taking them out of the scrotum, and eventually sending them to the part of the “urethra” housed within the “prostate gland.” The urethra carries both urine from the bladder and sperm from the testes out through the penis, but not at the same time (owing to control valves). Within the “prostatic portion” of the urethra, sperm are mixed with “prostatic fluid” produced by the “seminal vesicals” atop the prostate gland. This mixing with the high-sugar (fructose) fluid from the prostate gives the sperm their yellowish color and energy when they are “ejaculated” out of the tip of the penis. This energy is crucial to “capacitate” the sperm and enable them to swim up into the woman’s cervix to fertilize an egg resting on her uterine lining. It takes about 70 days to produce new, capacitated sperm ready to fertilize an egg. Spermatogenesis is a complex and elegant process; normally 60 million sperm are found in each ejaculate.
Male hormones are made by different cells within the testes, the “Sertoli-Leydig” cells. These cells also provide support for the inner structures of the seminiferous tubules. When a male child is forming in the womb, and to a small degree afterward, androgens like testosterone are synthesized by the “adrenal glands” atop each kidney. In adult males, about 95% of their androgens are made by the testes and 5% by these adrenal glands. If the testicles are removed (“castration”) prior to a boy reaching puberty, he will be a “eunich”. Besides for being unable to father children (“infertile”), a eunich will have more body fat, a higher pitched voice, larger breasts, and less facial hair. However, when castration occurs after puberty, most of these “secondary sexual characteristics” of maleness will stay intact-- although he will be infertile, he won’t become a eunich. Recall that some young boys used to be castrated in earlier cultures to either guard the King’s harem or keep their pre-pubescent singing voices.
The testicles are formed in a pre-born baby boy’s abdomen. They “migrate” down through a special canal (“inguinal canal”) into the scrotum shortly before or after birth. If they fail to “descend”, and remain in the abdomen or trapped in the canal, they stay too warm and will wither over time. This is called “cryptorchidism”. Nowadays, young boys with undescended testicles will have them surgically brought down into their proper home in the scrotum. Normally the inguinal canal seals up after the testicles descend. An “inguinal hernia” is when the canal fails to close and tissue from the abdomen (such as intestine) improperly gets caught in it (“incarcerated”). Hernias can be fixed with no danger to the normal testicle(s).
The blood supply to the testes is via the “gonadal arteries” which come from the body’s main artery, the aorta. These gonadal arteries form smaller arteries which nourish the spermatic cord, and ultimately the substance of the testicles. Other smaller arteries from the pelvic circulation “collateralize” with the gonadal arteries to provide more bloodflow. The scrotal sac gets blood from the deep pelvic arteries (“pudic artery”), not from the gonadal. However, all of the arteries suppying the area can be traced back to the aorta. Blood returning to the heart from the testes drains back to the main low body vein, the “vena cava.” The pattern of circulation is important in tracing the spread of infections or cancers from the testicles.
The lymphatic drainage means the way that the tissue fluid which bathes the cells manages to return to the bloodstream. The lymph fluid is the liquid portion of the blood which migrates through the delicate walls of the smallest blood vessels (“capillaries”) and bathes individual body cells with food and oxygen. It drains into special one-way channels called “lymph channels”, and ultimately to pea-sized glands called “lymph nodes”. These nodes help purify the lymph fluid, filtering out infectious agents and cancer cells. Lymph nodes are normally filled with White Blood Cells and are a crucial part of the “immune system”. Other immune system cells are found within the testicle tissue itself. When foreign cells become trapped in lymph nodes, they react and swell. This is called “lymphadenopathy”, and is said to exist when lymph nodes become larger than about 1 cm. (1/2 inch) across. There are groups of local and regional lymph nodes to which body fluids drain. If this system gets clogged up, involved limbs or the scrotum may swell (“edema”). Ultimately the purified lymph fluid is collected from groups of lymph nodes and sent back to the heart, to rejoin the circulating blood. The drainage of the testes is along the “aortic lymph nodes”-- these are called the “para-aortic chain”. The lymphatic drainage of the scrotal tissues is into the “inguinal nodes” in each groin. Again, the lymph system can act as either a barrier or a conduit of spread for infections, cancer, or both.
The nerve supply to the testes is from the “sympathetic chain” along the thoracic spine, this is joined by filaments from the “parasympathetic pelvic chain” which accompany the artery of the Vas Deferens (Ref. Gray's Anatomy). Both these sympathtetic and parasympathetic inputs are necessary for erection and ejaculation, respectively. The nerves to the scrotal sac are from the large internal pudic nerve. It is important to know that surgeries which cut the above nerves can cause impotence.
What is Testicular Cancer?
As alluded to above, there are several different types of cells within the testicles, and each has a designated function and “life cycle”. If a cancer starts in the testes, the particular type will depend upon the normal cell counterpart it arose from. Since there are different types of cells within the testicles, there are different types of cancers which may arise from them, as will be discussed. Firstly, we must understand that all cell division in the testicles is under tight control of the “genes” within each cell. Testicular cancer, like all cancers, starts in just one cell. When the genes within a particular cell become damaged, that cell may start dividing out of control, and form a clump called a “tumor”. A tumor merely means a swelling, which may be caused by infection, inflammation or anything-- it is not necessarily a cancer. When a tumor grows only within its local area (although it may become very large) it is called “benign”, and is not cancer. However, when a tumor’s cells have the capacity to spread to other areas of the body, it is called “malignant”, and it is cancer. When a cancer spreads, it is called “metastasis”. At first, the spread is just individual cells too small to be seen, that is called “micrometastasis” or “seeding”. Eventually, those “seeds” may get trapped in distant body areas (e.g. lungs, liver, lymph nodes, bone, brain) and grow into large tumors there. Thus, all tumors that can develop a metastasis are malignant, and all those that cannot are benign. As a cancer grows in its local area, its chances for spread increase. It is the quality of spread for malignant tumors that makes uncontrolled cancer so dangerous.
How Common is Testicular Cancer?
There are about 6000 new cases of testicular cancer each year in the U.S.A., which causes perhaps 400 deaths. Dramatic improvement in survival rates in the past three decades have greatly reduced the numer of men dying of it. In fact, survival has increased from just 10% five decades ago to over 90% today for most subtypes. About 3 in 100,000 men per year develop testicular cancer, and it is the most common cancer in young men between the ages of 15 and 35 years old. Overall, an average man has a 0.1% lifetime risk for testicular cancer, and this risk has actually doubled over the past 50 years. Still, however, testicular cancer represents less than 1% of all new cancers each year. About 3% of patients have “bilateral” disease, that is in both testicles. These cancers may occur at the same time (“simultaneously”) or at successive times (“metachronously”). White males get testicular cancer 6 times as commonly as African-American or Asian males. While young men predominantly get “germ cell tumors” derived from sperm, men over age 60 tend to get a completely different type of cancer, called lymphoma, arising from immune cells. In young boys, acute leukemia (ALL) tends to go to the testicles and swell them, but the treatment for this follows that of the primary disease. Only a cancer which actually starts in the testicles is called “primary testicular cancer”. A cancer spreading to them from some other area (this is rare) is NOT considered testicular cancer, but is named according to the originating area. Again, the risk of testicular cancer has been steadily rising over the past 5 decades; some possible reasons are outlined below.
What Causes, or Increases the Risk for Testicular Cancers?
As for any cancer, the exact reason why one man gets testicular cancer and another does not remains unknown. Recall that cancer starts due to particular gene damage within a susceptible cell; thus it is ultimately a disease of the genes. Several factors, called “risk factors”, have been noted to increase the risk of testicular cancer:
1) Undescended Testicles (“cryptorchidism”) is strongly related to developing a germ cell tumor of the testicles. The risk various from 4 to 48 times greater than for a man with normally descended testicles. The risk partly depends upon just where the testicle is stuck. If it is retained in the abdomen, the chance is 1 in 20 it will become cancerous; it it is stuck in the inguinal canal (which leads down into the scrotum) the chance is just 1 in 80. Another factor is how much time elapses between discovery of the condition and surgical correction. Surgical placement of the stuck testicle(s) into the scrotum prior to 6 years of age will reduce the subsequent chance for cancer by more than one-half. Interestingly, Just 75% of cases occur in within the previously trapped testicle, this is also known in medical parlance as the “ipsilateral” testicle. The other 25% of testis (singular for testes) cancers in patients with a undescended testicle occur in the other (“contralateral”) normal, fully descended testicle! One testicle appears to somehow affect the other, perhaps by hormonal influences.Overall, however, just 10% of patients with testicular cancer have a history of cryporchidism.
2) Testicular Feminization Syndrome is a rare genetic disease where hidden testicles are trapped up in the abdomen of what appears to be a girl. This is sometimes called “Penis at age 12” syndrome, after a group of girls in San Juan who spontaneously sprouted penises in adolescence (much to their parent’s shock!). The testicles of such individuals are commonly removed as they are discovered, and they continue to be raised as girls. Very rarely, a person may have both testicles and ovaries, this is a true “hermaphrodite”. Unfortunately, these genetic disease tend to result in total infertility (“sterility”). There is a ~40 times greater risk that the testicles in such patients will become cancerous (much like cryptorchidism above). These cancers often occur in both retained testicles (“bilateral disease”).
3) Radiation Exposure is thought to be a risk factor for getting testicular cancer (as well as many other types) but the exact risk is unknown. This is because it is difficult to do studies on normal individuals, irradiating their testicles and surveilling for cancer development! Patients who are getting therapeutic X-rays to the pelvis for some other cancer generally get very low dose to the testicles (owing to the exactitude of modern radiation techniques) and were not “normal” in terms of cancer risk anyway. The sperm generating cells are killed at very low doses of radiation (about 6 Gray in a single exposure, 12 Gray in multiple expo- sures). This compares to the Leydig Hormone Producing cells in the testes (which require about 25 Gray to annihilate testosterone production). Thus a person may be sterilized by radiation while still producing male hormones. The chances of getting a cancer induced by radiation are greater if the exposure was at a young age. Often decades go by (“latent period”) before the cancer manifests. This is because the gene damage “induced” by radiation may be “promoted” by other substances (such as dietary chemicals and hormones) to become overtly cancerous at a later time.
4) Chemicals abound in our enviroment, and the observation that the rates of testicular cancer are increasing (even as the cure rates increase) correlates with the contaminants we breath, eat and are surrounded by. Carcinogens are chemicals known or strongly suspected to cause cancer; these chemicals often exert their effects directly on the DNA within the genes. Chimney sweep boys in England’s 19th century frequently developed scrotal cancer (which is not the same as testicular cancer). Many aromatic hydrocarbons like benzene and coal tar are carcinogenic-- even though cigarette smoke has not been linked to testicular cancer. Organophosphate pesticides are associated with testicular lymphoma. More study is required to say which agents are the worst carcinogens. Hormones like testosterone, produced by the testicles themselves and adrenal glands, stimulate cell development within the seminiferous tubules. While strong- ly linked to prostate cancer (testosterone stimulates prostate growth), hormones are weakly linked to testicular cancer development (“carcinogenesis”). However, they may act as promotors to get previously abnormal cells to divide. The more often cells divide (especially irritated or abnormal ones), the greater the chance for acquiring a “gene mutation” which results in cancer. We are sustaining gene damage all the time, and much of it is successfully repaired. Fortunately, only a tiny minority of the myriad possible gene damages results in “transformation” to cancer. Even if a cell does “transform”, the immune system often recognizes it as abnormal and destroys it before a tumor can form. A weakened immune system (e.g. from AIDS, malnutrition or certain medications) may let the incipient cancer cell escape and begin uncontrolled growth. Immune detection and destruction of the original cancer or its metastatic seeds is the theory of “immunosurveillance.”
5) Testicular Injury or chronic irritation (as from an inflammatory condition) can raise the risk for later cancer development. Specifically, blunt trauma (such as a kick to the groin) or having them get twisted up (“torsion”) are implicated. After an injury cells normally divide more quickly to replace damaged or dead ones, and this contributes to the “genetic instability” which may presage cancer. It is difficult to thresh out whether the injury actually caused the cancer, or just made the man pay more attention to his testicles (so he noticed a prior cancer there).
***Alcohol and Tobacco use have not been linked to testicular cancer.
What are the Signs and Symptoms of Testicular Cancer?
The way a patients first appears when they go to their physician is called their “presentation,” and this consists of “signs” and “symptoms.” A “sign” is something that can be measured, such as fever, weight loss, or breast growth. A “symptom” is something the patient fells, such as pain, nausea or hot flashes. There is often a 2 month delay prior to diagnosing testicular cancer which can be felt (“palpated”) by an examining hand. This delay is thought due to both patient and doctor denial of cancer. As the condition progresses it becomes more obvious. Common “findings” include:
1) Painless Testicle Swelling is the most common sign, seen in over 50% of new patients. It feels like a lump or hardness of the testes, occasionally acompanied by a dull or aching sensation in the lower belly and scrotum.
2) Acute Testicular Pain is the “presenting symptom” in 10% of patients, and is seen overall in 40% of patients. The pain is usually accompanied by swelling. The pain may be caused by simultaneous infection or a cut off of the crucial blood supply (“infarction”) to the testes. The “torsion” injury when the stalk of the the testes (which contains its blood and nerve supply) becomes twisted usually leads to acute pain. Of course, most cases of torsion do not indicate cancer. If the testicle has stayed up in the abdomen, symptoms mimic appendicitis.
3) Signs of Infection include redness, heat, pain, and swelling. If the epididymis tube which drains the testes of sperm becomes infected, the symptoms may resolve with antibiotic therapy but still be masking a small tumor. In general, having a cancer increases local infection risk, and both processes can be going on simultaneously. This may cause local lymph nodes in the groin (the superficial inguinals) or along the vertebral column (presacral and para-aortics) to swell (“lymphadenopathy”) in an immune system attempt to fight something foreign. About 25% of patients have a presentation suggesting active infection.
4) Breast Swelling (“gynecomastia”) is seen in about 10% of patients, due to the production of female hormones (HCG) by some tumors, as will be described.
5) Back Pain results from spread of cancer to lymph glands along the aorta (the para-aortic chain). The lymph nodes are normally smaller than 1 cm. but can enlarge to huge sizes; when occuring along the spine this is “retroperitoneal lymphadenopathy”. Retroperitoneal means behind the glisteny sheets of a protective membrane (“fascia”) called the “peritoneum” lining the abdominal and upper pelvic organs. In a patient with known cancer, new back pain means spread of cancer there in ~70% of the time. The pain may be partially relieved by leaning forward, suggesting the retroperitoneal location.
6) Infertility means inability to father children, this is the “presenting complaint” in 3% of patients. Infertility will also occur if the testicles fail to descend and are not surgically brought down into the scrotum on time. This is because normal internal body temperature is too warm for the testis, which will wither (“atrophy”) over time if it is trapped in the abdomen or inguinal canal. This “cryptorchidism” is itself a risk factor for testicular cancer, as was described. As will be seen, treatment of testicular cancer may result in infertility, so some men are urged to save viable seed in a “sperm bank” prior to therapy.
7) Signs of Distant Spread (“metastasis”) are the presenting signs in 5% of patients. Fortunately, testicular cancers usually spread in an orderly manner up the testicular stalk and then along the para-aortic lymph nodes. Eventually lymph node spread may be seen as a neck “mass” (hard swelling). A cancer can metastasize to any area of the body. Thus is can go to the liver, lung, bone or brain causing symptoms in those areas. Rarely, it can even spread behind the eye, underneath the breastbone (sternum) to the “mediastinal” area in front of the heart, or to the intestines.
How is Testicular Cancer Diagnosed and Evaluated?
When a patient’s “presentation” is suspicious for possible testicular cancer, we routinely do:
1) Complete History and Physical Exam will include careful examination through feeling (“palpating”) the testicles and local lymph glands trying to obviate (“rule-out” ) other conditions besides cancer. The “differential diagnosis” means a listing of other conditions that could be causing the symptoms and signs noted. Testicular torsion, epididymitis infection, or orchitis (infection of the testicles proper) can all mimic cancer. If the testicular swelling is filled with fluid and a strong light can be shown through it (“transilluminated”) it is probably a benign “hydrocele” (fluid filled sac)-- although 10% of testicular cancers have hydroceles! If there is severe pain, fever, and pus in the urine, this suggests epididymitis-- although acute pain and infection are seen with 10% -25% of testicular cancers. Swollen veins in the scrotum (“vericoceles”) feel like a “bag of worms”, and hernias are usually easy to detect. Spermaceles are when a lump of sperm hardens (“concretizes”) and gets trapped in the testes; they can also be associated with cancer development. Unfortunately, acute swelling testis tortion, inflammations of the testicle, and blood clots can all demand a surgery to prove they are not cancer. Thorough exam of the lymph node areas in the groin (inguinals), armpit (axillary) and neck (cervical) is crucial; heart, lung, chest, neurological and rectal exams are performed.
2) Routine Laboratory Tests include Complete Blood Count (CBC) checking for anemia (low red blood cell count) or infection (often a high white blood cell count). A Blood Chemistry Panel (SMA) is an inexpensive way to get multiple chemistry tests. Standarly included are sodium, potassium, calcium, phosphorus, blood sugar (glucose), cholesterol, protein (albumin) and indicators of heart (CPK), Liver (AST, ALT, LDH) and Kidney (BUN, Creatinine) function. A Urinalysis (UA) looks for blood, pus, sugar, protein, or signs of infection in the urine.
3) Special Laboratory Tests for testicular (and germ cell tumors in other body areas) are called “tumor markers”. These are usually done as simple blood tests. They include “Human Chorionic Gonadotropin” (HCG) and “Alpha-Feto- Protein (AFP) which are normally produced by developing embryos. AFP in particular is not specific to testicular cancer, since it can be elevated with lung, liver, pancreas or salivary gland tumors. Regarding testicular tumors, these tests help tell whether the cancer is a “pure seminoma”, exclusively derived from sperm, or whether it contains “non-seminomatous” elements. If neither HCG nor AFP is elevated, the tumor is generally a pure seminoma. However, while 15% of pure seminomas can produce some HCG, the AFP is never high unless except if “non-seminomatous” components exist. Another marker for more advanced disease is Lactate Dehydrogenase (LDH) but it is also not very specific-- it can be elevated with liver or blood cell damage. If these “markers” are initially high, they can be used to monitor the progress of therapy. HCG goes down by one-half (half-life by metabolism) in 24 hours, while AFP does so in 5 days. Thus, if the tumor is removed, we should see prompt drops in the markers.
4) Imaging Tests are done in the radiology department to get a better look at the tumor and areas of possible spread. Routine tests include Chest X-ray to look for tumor or infection in the chest, and a complete CT scan of the chest, pelvis and abdomen. CT scan is like a series of multiple X-rays that is superior to a single X-ray for imaging small area(s) of abnormality and localizing their exact positions. CT scan with contrast utilizes a “radio-opaque” dye injected into an arm vein to highlight blood vessels and swellings (edema) around abnormal areas. If getting a CT scan with contrast, insist on “omnipaque” brand contrast or equivalent; it is more expensive but also more comfortable and less likely to cause allergic reactions or kidney damage. Magnetic Resonance Imaging (MRI) does not use radiation and is excellent for imaging soft tissue in the body. It can also be done with a different type of contrast (“gadolinium”) but is about 3 times expensive as CT scan (~$1200) for the complete scan. It is thus discouraged by most insurers who feel a CT scan should be enough. A simple Ultrasound (US) also does not use ionizing radiation (sound waves instead) and is the best initial test for distinguishing fluid filled cysts (such as hydroceles) from solid tumors, which are more likely to be cancerous. An older test uncommonly performed today is “lymphangiography”, where some dye is injected into the leg veins and it migrates up toward the heart. Plain X-rays are then taken of where the dye accumulates in abnormal lymph nodes. It has been mostly supplanted by CT and MRI, which also show large lymph nodes in the pelvis, inguinal and para-aortic areas with considerable acuracy (~85%). One advantage of lymphangiography (which is uncomfortable and has possible complications of leg blood clots) is that the dye tends to stay in the lymph nodes, and X-rays can be taken months later to see their response to therapy. Thus, a few specialized centers still do the procedure. Other radiology tests such as barium enemas, gallium scans, CT scans of the brain and bone scans are only done for specific signs and symptoms of spread, AND when the results of these tests may change the planned therapy.
5) Biopsy of the Tumor remains the only definite way of confirming or denying a cancer. Unfortunately, the only accepted approach to sampling the tumor is by permanently removing the suspicious testicle through the inguinal canal. This procedure is called an “inguinal orchietomy”. Previously, surgeons sometimes used a “trans-scrotal” approach, that is cutting open the scrotal sac to remove the offending testicle. However, this led to a high number of relapses of cancer in the local area. Using a needle or knife to remove a small part of the testicle is not recommended owing the the ease of missing cancer and spreading it around; only total removal of the testicle is advocated. This operation is done by a “urologist”, that is a surgeon specialing in urinary and male genital cancers. The scrotal sac is itself not cut into nor pieces of it removed unless it is overtly invaded by cancer. A small round plastic ball can be sewn into the scrotal sac afterward to retain the appearance of having testes. The patient may elect to have sperm banking done prior to the orchiectomy to help ensure they are able to father offspring in the future, via a “test tube” baby technique. The removed testicle is examined by a “pathologist”, that is a physician specializing in the diagnosis of disease from tissue samples. If cancer is found, the particular subtype is identified in the pathologist’s report.
What are the Types of Testicular Cancer?
There are several different types of testicular cancer, with different treatments and results. Various “histologic classifications” have been advocated over the past 40 years to proper classify the various subtypes. The first major distinction is between “seminomatous” (“pure seminoma”) and the “non-seminomatous” (“mixed”) types.
Pure Seminoma arises from sperm and has a counterpart in women’s eggs called “germinoma”. The typical, classic type of Pure Seminoma accounts for 80% of all seminomas and occurs mostly between 30 and 40 years of age. “Anaplastic Seminoma” is about 10% of cases and these tend to be more aggressive tumors that metastasize earlier. Basically it means the Seminoma cells are rapidly dividing and look markedly abnormal, hallmarks for cancerous activity. “Spermatocytic Seminoma” accounts for about 10% of all Pure Seminoma cases, occuring mostly in men over 50 years old. In contrast to the Anaplastic variety, the Spermatocytic type tends to be non-aggressive (“indolent”) and rarely metastasizes.
Other Non-Seminomatous types have mixtures of other components of the human embryo in them. Specifically, “Embryonal Carcinoma” looks like a young embryo and produces HCG, the same hormone used to detect pregnancy in women. Recally, however, that 15% of Pure Seminomas also produce some HCG. Embryonal cancers are further broken down into two categories-- those arising from the placental tissues around the embryo (“synctiotrophoblast”) which manufacture HCG, and those from the embryo itself (“cytotrophoblast”) which makes AFP. The main cancers from the tissues around the embryo are “Choriocarcinoma” (which always makes HCG) and “Yolk Sac Carcinoma”, also called “Endodermal Sinus Tumor” (which always makes AFP). The main cancer developing from the embryo itself is “Teratoma”. These can be “mature” (having fully formed tissue elements like teeth, skin, and hair) or “immature” (having only partially developed tissues). They may or may not act cancerous (with capacity for distant spread). Testicular Cancers are often a mixture of the above types. In general, 60% of testicular cancers have just one type of cancer, and 40% have some mixing of varieties. A “mixed” tumor will tend to behave as does the most aggressive component cancer.
Another totally different type of testicular tumor is that arising from the Sertoli-Leydig cells, these commonly produce masculinizing androgen hormones. These are sometimes called “Gonadal Stromal Tumors” since they occur in the cells which makes up and support the seminiferous tubules. In general, they have less aggressively (with less tendency for distant spread) than the Seminomatous variety.
Overall, the most common type of testicular cancer of the Seminomatous or Non-Seminomatous variety, arising from sperm, which makes up 95% of total cases. Pure Seminoma is found in 40%, Embryonal Carcinoma in 20%, Teratoma in 5%, Choriocarcinoma in 3%, and Yolk Sac Carcinoma in 1%. Sertoli-Leydig tumors make up 5% of the total. Most of the remainder of the cancers are of mixed type, and very rarely primary lymphoma (from immune cells) or sarcoma (from muscle, fat or cartilage) is seen. Again, the particular type of cancer is called its “histology” and is determined by the pathologist’s examination of the biopsy specimen.
How is the Extent of Testicular Cancers Gauged?
Like all cancers, the extent of testicular cancer is given by the “Stage”. Several staging systems have been developed for testicular cancers, most notably the Walter Reed (Military) staging, the simple three part Boden and Gibb Staging (confined to testicle, beyond testicle, or distant disease) and the widely used AJCC system:
“Stage I” means the cancer is limited to one testicle with no spread.
“Stage II’ means the cancer has spread to the scrotum or spermatic cord.
“Stage III” means the cancer invades a single lymph node which is on the same side as the involved testicle, and swells it up to 5 cm.
“Stage IV” means the cancer involves multiple lymph nodes, or a lymph node has swelled up beyond 5 cm. It can also mean that the cancer has spread to distant organs, like lung, liver , bone or brain.
What is the Survival from Testicular Cancer?
This depends upon many factors, such as the stage, type of tumor, extent of the disease, and treatment selected. In particular, survivals are somewhat poorer for the Non-Seminomatous than the Pure Seminoma variety. Average 5 year survivals:
Seminomatous Non Seminomatous Stage 5-year survival Stage 5-year survival I 98% I 95% II 80% II 70% III 70% III 60% IV 50% IV 40%
It is crucial to understand that the above survivals, from textbooks, include demise from all causes, including accidents, heart attacks, and other cancers. No one can say just how long any particular patient with testicular cancer will live. Many patients live many years of quality life even with incurable cancer. Also, survivals have been improving with the latest effective treatments.
What is the Conventional Treatment for Testicular Cancer?
Historically, the conventional treatment for testicular cancer was surgery alone, and survival afterward ranged from 90% for very favorable patients (i.e. Pure Seminoma stage I) to less than 10% for those with aggressive Non-Seminomatous cancers which had spread. In the 1950’s, radiation therapy was applied which significantly increased survival for patients with local (but not distant) disease spread. The problem continued to be “distant failure”, that is finding metastasis in other areas such as the lungs, liver, bone and brain from aggressive cancers. We became able to recognize early features of these aggressive subtypes, such as Non-Seminomatous histology (subtype), invasion of the scrotum, and lymph node involvement. In the 1970’s chemotherapy was used successfully on “high risk” patients who previously would have probably died. The specifics of each of these conventional therapies are now described, along with their results and side-effects.
Surgery was, and remains, typically a “radical orchiectomy” which is removal of the whole testicle. This both establishes the diagnosis and is also an essential part of the treatment. As mentioned, a urologist performs the surgery, and the testicle is always pulled up and removed through the same inguinal canal it originally descended through. Cutting into the scrotum to remove a testicle was associated with a high rate of contamination of the local area with spilled cancer cells, and later “local relapse”-- so this is not done anymore. Patients who have bilateral disease (that is in both testicles) will need to have both removed. Furthermore, patients with a high suspicion for cancer spread to local lymph nodes may have some of them surgically removed. Any obviously grossly swollen lymph nodes in the inguinal (groin) area will be removed at surgery; the question is whether to removed non-enlarged lymph nodes along the para-aortic chain to check them (under the microscope) for cancer spread. Depending upon the particular cancer type, “subclinical” (too small to be seen with the naked eye) spread may have occured and result in later treatment failure. The operation done to check for this was called a “Retroperitoneal Lymph Node Dissection” (RPLND) done at the same time as orchiectomy. This operation was considered both diagnostic (to see if the cancer had spread) and therapeutic (to remove it if it had). Patients who had an RPLND were found to have subclinical cancer spread to the removed lymph nodes 15% of the time if they had Seminoma, and 30% of the time if they had Non-Seminomatous disease. Interestingly, however, even patients who have grossly enlarged lymph nodes will have only infection or inflammation found in them, and no sign of cancer, about 30% of the time. The main problem with an extensive RPLND is that was a major operation, not every lymph node could possibly be removed, and over 75% of patients were rendered permanently impotent due to nerve damage from the original surgery. Also, the risks for surgeon induced (“iatrogenic”) infection and swelling (“edema”) in the lower extremities and scrotum was about 20%. This operation has been mostly replaced today with imaging studies (CT and MRI) that are quite accurate (~85%) in detecting lymph node enlargment. Still, grossly enlarged nodes will be removed for analysis. However, when patients have retroperitoneal lymph nodes removed today, it is with a modified technique that better preserves potency (described under Latest Therapy).
If patients are fertile prior to surgery, and may wish to father children, sperm banking
is recommended. On average, it is 60% - 80% successful for patients who have sufficient sperm (~60 million per ejaculate) prior to surgery. However, only about 30% of testicular cancer patients have sufficient sperm for the “cryopreservation” (freezing) technique used in banking. Patients generally give multiple samples to be “banked”.
The actual orchiectomy operation is a relatively minor one, it is not “castration” in the sense that the scrotal sac remains intact. Risks of surgery include operative death (“mortality”) of less than 1% from General Anesthesia or other factors, and side-effects (“morbidity”) of infection (5%), formation of fluid cysts that require later draining (5%) and urinary problems (2%). Also expected are possible impotence, erectile and ejaculation problems depending upon the extent of the surgery, and the amount of testosterone produced by the remaining testicle. The average rate of sexual problems from unilateral orchietomy (just one testicle being removed) in an otherwise healthy male is 15%. As mentioned, a prosthetic can be placed in the scrotum to mimic the appearance of an intact testicle.
The recovery from surgery is generally complete within 3 weeks, after which patients can do heavy lifting. Surgery is also used to remove residual tumors in the groin and abdomen, particularly the Non-Seminomatous type, which failed to entirely disappear with radiation therapy and chemotherapy (as described below). Not all residual “tumors” harbor cancer after treatment; they may merely be scar tissue. The general rule is that all lymph nodes or persistant tumors over 3 cm. (~1 inch) in diameter will need to be surgically removed for the best chance of cure in Non-Seminomatous and Mixed tumors. For the Seminomatous variety, which tend to be more sensitive to radiation and chemotherapy, residual tumor is more likely scar tissue instead of cancer, and may not need to be surgically removed. Radiation Therapy is a standard and effective treatment for testicular cancer. In particular, Pure Seminoma is very easily killed by radiation (“radiosensitive”). The Non-Seminomatous varieties are less sensitive, but still “locally controlled” by adequate doses of radiation. Radiation tends to kill cancer cells when they try to divide (“mitotic death”) and so tumors can continue to shrink after treatments are completed. Radiation is a local, or at best regional therapy-- we cannot use high enough doses to treat the whole body without undue side effects (“toxicity”). The prescription of radiation, along with the design and construction of a proper radiation field is an elegant art performed by a “Radiation Oncologist”. This is a physician who specializes in treating cancers with radiation. For testicular cancer, radiation has been used for ~5 decades and modern techniques make it very safe and effective.
When a patient is first diagnosed with testicular cancer, upon removal of the involved testicle, there is a 10% - 30% chance (depending upon the subtype of cancer) that is has already spread to the lymph glands which drain the testicles. The most likely area the cancer will recur is in along the para-aortic lymph node chain, with a much smaller chance (1/10 as high) that it will reappear in the pelvis. The chance that it will reappear within the scrotum itself if minute (unless the scrotum was actively invaded). Radiation treatment will dramatically reduce the risk of the patient’s cancer recurring in local lymph nodes, and the ultimate risk of it spreading to distant body areas. Thus, urologists standardly refer patients for consideration of radiation treatment.
After the patient is evaluated by the radiation oncologist, and their questions about radiation are answered, they sign consent and are scheduled for a “simulation.” This means they are placed on a mock-up treatment machine, and the area to be treated is marked out. The actual scrotum is almost never treated. Instead, the areas treated are those at highest risk for lymph node involvement-- specifically the para-aortic and pelvic lymph nodes [note-- the terms “lymph node” and “lymph gland” are used interchangeably). The pelvis is a much lower risk for involvement, as above. In fact, some radiation oncologists SKIP the pelvis treatment altogether, since the risk there is often less than 3%, and just treat the para-aortics. These para-aortics run up along the low and mid-back vertebral column, and there are “paired chains” of them along either immediate side of the vertebal column. The area to be treated is first marked out with watercolor pens, and eventually tiny permanent tattoos placed to forever designate the area treated. The patient is asked not to wash off the watercolor marks during the treatment period. X-rays are taken during the simulation to show the positioning relative to the hard treatment table. The “simulation” is painless and takes about an hour. The patient then goes home. Information from the simulation and CT scans is then placed into a “treatment planning computer” which develops a “plan” for inspection by the radiation oncologist. It is also reviewed by a radiation physicist.
The “plan” tells tells how much radiation is going to the suspected areas of cancer spread, and how much is going to surrounding normal tissues. Fortunately, modern techniques allow exquisite acuracy in delivering radiation. Special metal “blocks” may be cut which shape the “field” and limit the radiation going to normal tissues; they fit into the head of the treatment machine.
The patient returns several days later to begin treatment. They are placed onto a hard table in a room by themselves, and aligned into position with laser lights. A “Linear Accelerator” or LINAC for short is usually used; some facilities use a radiation source called Cobalt-60. With a LINAC, the radiation is only produced when the machine is turned on, much like an electric light. With a Cobalt-60 machine, radiation is always being produced, but is shielded when the machine is inactivated. Treatment is given with photons, the same type of entity that makes up visible light but at higher energies. Patients are treated Monday through Friday for 2 - 3 weeks for most Pure Seminoma tumors and perhaps 3- 4 weeks for Non-Seminomatous tumors (which get a higher dose). The therapy takes only a couple of minutes each day. For Pure Seminomas, a typical dose is 20 - 30 Gray (units of radiation) given at about 1.5 Gray each treatment day. For Non-Seminomatous tumors, doses of 30 - 50 Gray are appropriate. Treatment is painless; the patient does not lose their scalp hair or become “radioactive”.
Expected side-effects (“toxicity”) of radiation are grouped into “acute” and “late” effects. Acute effects occur during the actual treatment period or shortly thereafter, while Late effects may occur months to years following completion of treatment. Anticipated Acute effects include some nausea, and possible vomiting or diarrhea shortly after the treatments. Some patients even experience “anticipation nausea” just prior to each treatment. Nausea is due to some intestine being irradiated in the lower abdomen. It can usually be controlled with anti-nauseant (“anti-emetic”) medications, like compazine, or excellent but expensive ones like ondansetron (“Zofran”). Some oncologists try marijuana oil (“Marinol”) available by prescription. If the nausea a big problem, unrelieved by medication, then the radiation dose per treatment can be reduced. In this case, more treatments are given to arrive at the full prescribed dose. Some skin redness (“erythema”) may be noted in the treatment field area, but actual skin peeling (“desquamation”) is rare with these relatively low doses (i.e. compared to brain or bone cancer). Some urinary frequency or irritation (“dysuria”) may be seen as the bladder dose builds up, we often check for a urinary tract infection if this is persistant. Medications can be given to comfort irritation in the urinary tract, such as phenazopyridine (“Pyridium”), a urinary tract anesthetic that turns urine orange. Diarrhea can usually be well controlled by lomotil, which slows gut spasms. Occasionally stronger medicine like opium in alcohol (“Paragoric”) may be needed. In general, treatment is very well tolerated.
Possible Late effects include long-term problems like chronic diarrhea (5%), later bowel obstruction (from scarring called “adhesions”) requiring surgery to relieve it (2%), testicular swelling (1%) infertility from radiation itself (1%) and development of a second cancer in the treatment area caused by radiation administration (“radiation carcinogenesis”) in less than 1% of patients. Since the doses of radiation, both daily and t tal, are relatively low for most testicular cancers (especially Pure Seminoma) the risk of any late problems are less than when higher doses are given for primary rectal, prostate or bladder cancers. Any combination of chemotherapy with radiation can increase both acute and late effects, especially agents like cyclophospamide, adriamycin, bleomycin and mitomycin-C. If patients get simultaneous (“concomittant”) radiation and chemotherapy, the doses for each may need to be proportionately lowered to avoid excessive “toxicity”.
The results of conventional radiation therapy, culled from many studies, show a reduction in recurrence for Pure Seminoma from 10% - 15% to less than 3%, and for Non-Seminomatous tumors from 30% to 10%. Thus, radiation is a safe, effective treatment for preventing local relapse of most testicular cancers. Radiation is also useful for rapidly shrinking tumors which have metastasized to distant sites, such as brain or bone. In practice, patients who are suitable for cure despite widespread disease are treatmed primarily with chemotherapy. Chemotherapy, that is giving chemicals into the bloodstream to poison cancer cells anywhere in the body, has seen remarkable advancement within the past 2 decades. In fact, testicular cancer is considered a “paradigm” (prime example) of the success of modern chemotherapy. In general, chemotherapy is less effective for solid tumors (e.g. lung cancer) than bloodborne ones (e.g. leukemia), but testicular cancer is an exception-- especially Pure Seminoma which is highly “chemosensitive”. Chemotherapy treatments are administered by a “Medical Oncologist”, who is usually an Internal Medicine doctor who studied 3 more years to subspecialize in cancer. Chemotherapy, like radiation, primarily kills rapidly dividing cells. While both methods are effective for localized testicular cancer, in practice chemtherapy is considered a more “drastic” treatment. Thus it is usually reserved for less favorable, more widespread, or relapsed cancers-- NOT for routine treatment of early disease. Chemotherapy will be used if the AFP, HCG or both remain elevated after primary treatment with surgery and radiation, showing that cancer is still present in the treatment area or has spread elsewhere. Chemotherapy is the only treatment which goes to every area of the body, that is “systemic” rather than “local” therapy. Also, chemotherapy will be used instead of radiation therapy for Non-Seminomatous tumors with bulky lymph nodes (>3 cm.) in the abdomen (mesenteric or para-aortic ndoes). If these lymph nodes do not become normal after chemotherapy, then they are usually removed with surgery, since they may still harbor cancer up to 30% of the time (as opposed to Pure Seminoma, which rarely harbors cancer after treatment, even if the nodes remain swollen).
The conventional chemotherapy for disseminated testicular cancer is with 3 agents (that is “combination chemotherapy”). These agents are often Bleomycin, Cisplatin and Etoposide. The combination “regimen” may be abbreviated as “BEP”. The rationale for using more than one drug is that we can help kill the cancer with a cocktail of drugs, especially selected so that they do not have “additive” side effects. That is, the side effects of each drug tend to be different, so even though there are more “low-grade” adverse reactions, there are few “high-grade” or severe reactions.
The BEP regimen is given into the veins (“intravenously”), usually every 3 weeks for 4 “cycles.” Blood counts are carefully monitored before each new cycle is started. Over 70% of patients will get a “complete response” (“CR”) with this type of treatment, meaning that no further cancer can be detected in their bodies with today’s technology. Another 25% will get a “partial response” (“PR”), meaning that the tumor(s) shrink significantly or at least stop growing. Less than 5% of patients will get “no response” (“NR”) meaning the tumors keep growing despite the drugs. If patients fail to obtain a “complete response,” or “fail” after initially responding, then “salvage treatment” is employed. Failure may be either “local” (in the original tumor area) or “distant” (in some other body area). Salvage chemotherapy often uses more Cisplatin (a derivative of the metal platinum) along with Vinblastine and Ifosphamide. It is commonlly given for 2 “cycles” past maximum response. Typically 6 cycles or so are administered. Again, if residual disease is present, or suspected, it is surgically removed. No scan can currently distinguish scar tissue from residual cancer, but tumors which continue to grow after treatment are likely still cancerous.
Side effects (“toxicity”) of chemotherapy depend upon the agents used, the doses to which they are given, and invididual patient tolerance. In general combination chemotherapy will have greater toxicity than just using “single agent”, and if radiation is given simultaneously local reactions (such as skin redness or nausea) will be greater. Again, chemotherapy works by killing the most rapidly growing cells in the body, poisoning their metabolic processes. Cancer cells tend to be very rapidly dividing, accounting for the “therapeutic gain” (preferential cancer cell killing) seen with chemotherapy. However, other quickly dividing cells, such as blood cells, hair cells, and gut cells, are also killed-- resulting in anemia, baldness (“alopecia”), nausea and diarrhea. There is usually good “recovery” from chemotherapy, with normalization of blood counts and new hair growth over time. This time can vary from days to months. However, sterility caused by chemotherapy tends to be permanent. Additionally, each chemotherapy agent has its own particular side-effects. Bleomycin can cause long-term heart and lung damage, especially in smokers. Cisplatin can cause nerve damage, hearing loss and reduced kidney function. Etoposide causes marked lowering of White Blood Cell Counts (“leukopenia”), and especially lowering of the crucial neutrophils (“neutropenia”) which makes the patient susceptible to infections. The salvage drug Vinblastine causes severe muscle cramps, while Ifophamide can cause sloughing of the bladder lining (“hemorrhagic cystitis”) with blood in the urine. All of these drugs must only be given under the watchful eye of an expert Medical Oncologist, with frequent monitoring of signs, symptoms and blood counts. If patients become severely anemic, neutropenic or dehydrated during therapy, they must be seen at the hospital for prompt medical intervention.
Chemotherapy has had a major impact in survival for unfavorable testicular and other germ cell tumors, raising it from 10% to 90% overall. As it continues to evolve, less toxic agents with better anti-cancer activities will replace the current ones. Medicines that reduce the toxicity of chemotherapy, such as anti-emetic drugs (Zofran) and agents which increase fallen blood counts (Epogen for red cells and Neupogen for White Cells) will continue to make chemotherapy easier to take than ever before.
Since most patients present with early disease, the actual overall survival for testicular cancers is now over 90%. Refinements have been made in all areas of conventional treatment, and surgery, radiation and chemotherapy are still used today. In fact, the Latest Effective Treatment is just fine-tuning of the conventional treatment.
Surgery advancements include only taking the testicle through the inguinal canal, and never through the scrotal sac which may spread the cancer. The continuing improvements in anesthesia, surgical techniques and antibiotics makes surgery today very safe, and it is the current initial treatment for testicular cancers. Further, the recognition that residual tumor mass after treatment for the Non-Seminomatous variety may show persistent, and that such masses should be surgically removed, has helped cure rates.
Radiation advancements include precise targeting of the radiation beam to areas at risk, using three-dimensional treatment planning. Medicines like Zofran and Marinol which reduce nausea help patients tolerate treatment, as mentioned. The scrotum can be well shielded to prevent radiation from sterilizing the remaining testicle, and modern techniques of sperm freezing and banking can help some patients father future children. Importantly, some Radiation Oncologists now omit treatming the pelvis if there is no evident cancer there, and instead only treat the para-aortics-- since the abdomen has at least 5 times higher risk of relapse than the pelvis. Some patients decide NOT to get radiation treatment at all after orchiectomy for Pure Seminoma, since 85% of them will never relapse anyway. If this option, called “surveillance,” is selected, it is critical to carefully “follow” the patient with serial examinations and CT scans every 6 months or so for at least 5 years to be sure the cancer has not returned. After 5 years, the chance of cure is so great that further monitoring is usually not necessary. If the cancer does relapse, they can get salvage radiation and/or chemotherapy at that time. In practice, this is only recommended for very responsible patients who are scrupulous about keeping follow-up appointments.
Chemotherapy advancements include the use of salvage chemotherapy for the 30% of patients who do not have a complete response (“CR”) to initial radiation or chemotherapy. We have recognized that radiation is usually NOT NECESSARY to be used in combination with chemotherapy for bulky disease in the abdomen , just chemotherapy and surgery are usually used for these patients. Radiation in this setting does still reduce the risk of “local relapse”, but is also damages the local bone marrow, reduces blood counts, and thus reduces the amount of effective chemotherapy that can be given. The response to treatment can often be accurately measured by the fall of HCG or AFP, and if these levels increase afterwards, then the cancer has most certainly recurred.
Bone Marrow Transplant is the most aggressive, most modern treatment for testicular cancers which fail to be cured by other methods. Most commonly, the patient’s own bone marrow is used, called an “autologous” transplant. The bone marrow is either gotten from multiple thick needle insertions into both hips, or by a “peripheral stem cell” harvest (which means collecting it from the bloodstream, a much less intrusive procedure but which may require multiple sessions). The patients is then given “high dose chemotherapy” (enough to kill the cancer along with the patient’s bone marrow) which will kill the patient if the marrow is not replaced. The step of giving high dose chemotherapy is commonly called “ablation”. They then have the stored marrow “reinfused” into a a vein (it makes it own way into the bones) and hopefully “takes” (“engrafts”) and starts growing there, producing its own life-sustaining cells. The procedure can only be done it the patient’s bone marrow is free of cancer cells; otherwise it would just be re-implanting the cancer. Alternatively, the patient can get matching bone marrow from another individual-- typically a sibling or other close relative. This is called “allogeneic” transplant and is less successful and has more complications than the autologous type, which is generally much safer.
Bone Marrow transplant has advanced dramatically in the past 2 decades and is even being done in some Community Hospitals (instead of just Academic Hospitals). The risk of death from the procedure is less than 10% for the commoner autologous transplant, but as high as 50% from the allogeneic variety. The main problem with getting slightly mismatched bone marrow is the risk of “Graft versus Host” or “GVH” for short, which means that the transplanted marrow actually rejects the patient it is being put into. CancerAnswers.com has an In-Depth Transcript describing Bone Marrow transplant available via our website. The overall success rate for Bone Marrow transplant in patients with advanced disease is about 40%, and offers hope in saving the lives of patients with advanced or relapsed testicular cancer who were previously incurable. This therapy continues to advance by the month.
Conclusion:
For the patient diagnosed with testicular cancer, it is important not to rely on a single pill or ray, but utilize a “combination” approach. This means utilizing a program for improved nutrition, exercise and spiritual renewal. It is worthwhile to select a safe, affordable Alternative Therapy that the patient can believe in.
This is the full transcript, offered freely in the spirit of internet sharing, of CancerAnswers' report on Testicle Cancer. Much more, including latest
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ADDITIONAL TOPICS
Acute Leukemia
Anal Cancer
Bladder Cancer
Bone Cancer
Brain Cancer
Breast Cancer: Early
Breast Cancer: Advanced
Cartilage Cancer
Cervical Cancer
Chronic Leukemia
Colo-rectal Cancer
Esophagus Cancer
Fat Cancer
Gall-Bladder Cancer
Hodgkin's disease
Kidney Cancer
Larynx Cancer
Liver Cancer
Lung Cancer
Lung "small cell" Cancer
Lymphoma
Melanoma
Mesothelioma
Mouth Cancer
Multiple Myeloma
Muscle Cancer
Muscle and Fat Tumors
Nasal Cavity Cancer
Nasopharynx Cancer
Ovarian Cancer
Pancreas Cancer
Penile Cancer
Plasmacytomia
Prostate Cancer
Skin Cancer
Stomach Cancer
Testicle Cancer
Thyroid Cancer
Tongue Base and Tonsil
Cancer of Unknown Origin
Uterine Cancer
Vaginal Cancer
Vulvar Cancer
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