Testicular cancer

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**Testicular cancer**
*Classification & external resources*
OMIM	273300
DiseasesDB	12966
eMedicine	med/2250 med/3232
MeSH	C04.588.322.762

Testicular cancer is a type of cancer that develops in the testicles, a part of the male reproductive system. In the United States, about 8,000 to 9,000 diagnoses of testicular cancer are made each year. Over his lifetime, a man's chance of getting testicular cancer is roughly 1 in 250 (four tenths of one percent, or 0.4%). It is most common among males aged 15-40 years. Testicular cancer has one of the highest cure rates of all cancers: in excess of 90%; essentially 100% if it has not spread. Even for the relatively few cases in which the cancer has spread widely, chemotherapy offers a cure rate of at least 85% today.

[edit] Symptoms and early detection

Because testicular cancer is curable (stage I can have a success rate of >95%) when detected early, experts recommend regular monthly testicular self-examination after a hot shower or bath, when the scrotum is looser. Men should examine each testicle, feeling for pea-shaped lumps. Symptoms may include one or more of the following:

a lump in one testis or a hardening of one of the testicles
pain and tenderness in the testicles
build-up of fluid in the scrotum
a dull ache in the lower abdomen or groin
an increase, or significant decrease, in the size of one testis
blood in semen [1]

Men should report any of these to a doctor as soon as possible.

The presence and of testicular cancer is ascertained by ultrasound (of the testicles), the extent of the disease is evaluated by CT scans and X-rays, which are used to locate metastases. Blood tests are also used to identify and measure tumor markers that are specific to testicular cancer. A biopsy should not be performed, as it raises the risk of migrating cancer cells into the scrotum.

[edit] Differential diagnosis

An incorrect diagnosis is made at the initial examination in up to 25% of patients with testicular tumors and may result in delay in treatment or a suboptimal surgical approach (scrotal incision) for exploration.

Epididymitis or epididymoorchitis
Hematocele
Hydrocele
Spermatocele
Granulomatous orchitis

[edit] Prevalence and distribution

Testicular cancer is most common among white males and rare among African Americans. Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand. Testicular cancer is uncommon in Asia and Africa.

Incidence among African Americans doubled from 1988 to 2001 with a bias towards seminoma. The lack of any significant increase in the incidence of early-stage testicular cancer during this timeframe suggests that the overall increase was not due to heightened awareness of the disease.

Although testicular cancer is most common among men aged 15-40 years, it has three peaks: infancy, ages 25-40 years, and age 60 years.

[edit] Pathology, staging, and genetics

Testicular cancer can be caused by any type of cell found in the testes, but more than 95% of all testicular cancers originate in germ cells. (Germ cells produce sperm. They are not pathogenic; i.e., they are not to be confused with the "germs" (viruses, bacteria) that cause illness.) In general, the remainder of this article discusses germ-cell testicular cancer.

Germ-cell tumors are classified as either seminomas or nonseminomas (which may be called teratomas in the UK). Seminomas are slow-growing. Seminomas, when found, tend to be localized (i.e., only in the testicles), simply because they spread relatively slowly. Nonseminomas, on the other hand, tend to spread more quickly. Nonseminomas are further classified into four subtypes; embryonal carcinomas, choriocarcinomas, yolk sac tumors, teratomas and mixed tumors. Their appearance under the microscope and also their gene expression is rather distinguished from each other, their rate of spread varies somewhat, but they are nevertheless treated similarly. When seminomas and nonseminomas are both present (which is not unusual), the cancer is classified as nonseminoma.

[edit] Tumor markers

Blood markers for testicular tumors include the beta subunit of human chorionic gonadotropin (βhCG), lactate dehydrogenase (LDH), and alpha-fetoprotein (AFP). Seminomatous tumors never present elevated AFP levels. Placental alkaline phosphatase and other markers are sometimes used by the pathologist to differentiate between seminoma and nonseminomatous tumors.

[edit] Staging

After removal, a testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging. [2] In broad terms, tesicular cancer is staged as follows:

Stage I: the cancer remains localized to the testis.
Stage II: the cancer involves the testis and metastasis to retroperitoneal and/or Paraaortic lymph nodes (lymph nodes below the diaphragm).
Stage III: the cancer involves the testis and metastasis beyond the retroperitoneal and Paraaortic lymph nodes. Stage III is further subdivided into nonbulky stage III and bulky stage III. [3]

[edit] Genetics

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Most germ cell tumors have a chromosome count in the hypo to hyper triploid range (i.e. 60-70 chromosomes per cell nucleus in stead of the normal 46). About 80 % of these tumors also have a specific marker chromosome called isochromosome 12p. This is a chromosome where the shortest "arm" of chromosome 12 (12p) is present on both sides of the same centromer. Among germ cell tumors not having the isochromosome 12p, almost all have increased DNA copy number of 12p through other means. Thus, in tumors with unknown origin, increased DNA copy number of 12p is used as a marker for germ cell origin. The general gene expression patterns are clearly distinguishing the various histological subtypes of germ cell tumors. For example, in embryonal carcinomas, the same genes are overexpressed as are found highly expressed in embryonic stem cells. Further, AFP is a gene specifically expressed from yolk sac tumor, and CGB (encoding HCG) and other "pregnancy related genes" are specifically expressed from choriocarcinomas.

[edit] Germ cell tumors of the testis and their rates of occurrence

Seminoma (35%)
Embryonal carcinoma (20%)
Teratoma (5%)
Choriocarcinoma (<1%)
Mixed Cell Type (40%)
Carcinoma in Situ [4]

[edit] Non-germ cell tumors of the testis

Leydig cell tumors
Sertoli cell tumors
Gonadoblastomas [5]

[edit] Secondary tumors of the testis

Lymphoma
Leukemic infiltration of the testis
Metastatic tumors [6]

[edit] Treatment

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

Surgery is performed by urologists; radiation therapy is administered by radiation oncologists; and chemotherapy is the work of medical oncologists.

[edit] Surgery

[edit] Orchiectomy

While it may be possible, in some cases, to remove testicular cancer tumors from a testis while leaving the testis functional, this is almost never done, as more than 95% of testicular tumors are malignant. Since only one testis is typically required to maintain fertility, hormone production, and other male functions, the afflicted testis is almost always removed completely in a procedure called inguinal orchiectomy. (The testicle is almost never removed through the scrotum; an incision is made beneath the belt line in the inguinal area.) Most notably, since removing the tumor alone does not eliminate the precancerous cells that exist in the testis, it is usually better in the long run to remove the entire testis to prevent another tumor. A plausible exception could be in the case of the second testis later developing cancer as well.

[edit] Retroperitoneal Lymph Node Dissection (RPLND)

In the case of nonseminomas that appear to be stage I, surgery may be done on the retroperitoneal/Paraaortic lymph nodes (in a separate operation) to accurately determine whether the cancer is in stage I or stage II and to reduce the risk that malignant testicular cancer calls that may have metastasised to lymph nodes in the lower abdomen. This surgery is called Retroperitoneal Lymph Node Dissection (RPLND). However, this approach, while standard in many places, especially the United States, is falling out of favor due to costs and the high level of expertise required to perform the surgery.

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

Lymph node surgery may also be performed after chemotherapy to remove masses left behind, particularly in the cases of advanced initial cancer or large nonseminomas.

[edit] Radiation therapy

Radiation may be used to treat stage II seminoma cancers, or as adjuvant (preventative) therapy in the case of stage I seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is never used as a primary therapy for nonseminoma because a much higher dose is required and chemotherapy is far more effective in that setting.

[edit] Chemotherapy

As an adjuvant treatment, use of chemotherapy as an alternative to radiation therapy is increasing, because radiation therapy appears to have more significant long-term side effects (for example, internal scarring, increased risks of secondary malignancies, etc.). Two doses of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy.

Chemotherapy is the standard treatment, with or without radiation, when the cancer has spread to other parts of the body (that is, stage II or III). The standard chemotherapy protocol is three to four rounds of Bleomycin-Etoposide-Cisplatin (BEP). This treatment was developed by Dr. Lawrence Einhorn at Indiana University. An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP).

While treatment success depends on the stage, the average survival rate after five years is around 95%, and stage I cancers cases (if monitored properly) have essentially a 100% survival rate (which is why prompt action, when testicular cancer is a possibility, is extremely important).

[edit] Actions after treatment

[edit] Surveillance

For stage I cancers that have not had any adjuvant (preventive) therapy, close monitoring for at least a year is important, and should include blood tests (in cases of nonseminomas) and CT-scans (in all cases), to ascertain whether the cancer has metastasized (spread to other parts of the body). For other stages, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) will vary on the basis of the circumstances, but normally should be done for five years (with decreasing intensity).

[edit] Fertility

A man with one remaining testis can lead a normal life, because the remaining testis takes up the burden of testerone production and will generally have adequate fertility.[7] However, it is worth the (minor) expense of measuring hormone levels before removal of a testicle, and sperm banking may be appropriate for younger men who still plan to have children, since fertility may be lessened by removal of one testicle^{[citation needed]}, and can be severely affected if extensive chemotherapy and/or radiotherapy is done.

Less than five percent of those who have testicular cancer will have it again in the remaining testis. A man who loses both testicles will normally have to take hormone supplements (in particular, testosterone, which is created in the testicles), and will be infertile, but can lead an otherwise normal life.

[edit] Famous survivors

Decorated cyclist Lance Armstrong
American actor Richard Belzer
Canadian comedian Tom Green was diagnosed with testicular cancer in 2000 and made a widely acclaimed documentary about his treatment.
In 1997, figure-skater Scott Hamilton survived a bout with testicular cancer.
Four English footballers (soccer players): England's World Cup winning captain Bobby Moore was treated for testicular cancer in 1962, soon after his international debut. More recently, Alan Stubbs, Jason Cundy, and Neil Harris have also survived the condition.
Jos Francisco Molina , Spanish football goalkeeper from Real Club Deportivo de la Corua, in 2001, UEFA player page
Bulgarian footballer Luboslav Penev, from Valencia, in 1994
English Snooker player Jimmy White
British drummer Philly Morris survived testicular cancer in 2003. Afterwards, he created checkemlads.com, Europe's biggest testicular cancer web site, with Mick Riley and Tim Stollery.
Former Major League Baseball player John Kruk, who played for the Philadelphia Phillies when they won the 1993 National League Pennant, but lost to the Toronto Blue Jays in the World Series. Kruk was diagnosed during spring training in 1994.
Steve Scott, an American miler who currently holds the American Mile Record (3:47.69). He also attempted to be the first cancer survivor to run a sub 4:00 after completing treatment; however, his best time following treatment was a 4:02.
Mike Lowell, Boston Red Sox third baseman was diagnosed during spring training of his rookie year.
Christopher Arena, National Basketball Association and co-founder of ArenaTilton Golf
Australian politician Mark Latham
Former Hereford United Exeter City and Shrewsbury Town physiotherapist and television actor Simon Shakeshaft
Hockey player Phil Kessel of the Boston Bruins, diagnosed during his rookie season in 2006-07

[edit] Famous victims

Brian Piccolo, an American football player in the late 1960s with the Chicago Bears, died of a germ cell tumor that was not detected until it had metastasized into his lungs. Piccolo would be a major subject of teammate and friend Gale Sayers's autobiography, I Am Third; Sayers's story of their friendship and of Piccolo's struggle with cancer was adapted into the legendary TV movie Brian's Song.

Peter Crimmins, an Australian rules football player in the 1970s with the Hawthorn Hawks, suffering from the cancer was forced to stand down as captain in 1976. An emotional coach inspired the team to do it for the little feller, with the Hawks taking out the 1976 VFL premiership for the courageous small rover. Crimmins died just a few days after the victory. [8]