What`s new in testicular cancer research and treatment?

Important research into testicular cancer is being done in many university hospitals, medical centers, and other institutions around the country. Each year, scientists find out more about what causes the disease, how to prevent it, and how to improve treatment.

Recently, researchers have found inherited variations in two genes called c-KIT ligand (KITLG) and sprouty 4 (SPRY4) that appear to increase a man’s risk of developing testicular cancer. Another study found that variants of 3 other genes, DMRT1, TERT, and ATF71P, may also increase the risk of testicular cancer. These findings may help identify men at higher risk, but they need to be studied much more.

Scientists are also studying the changes in DNA of testicular cancer cells to learn more about the causes of this disease. Their hope is that improved understanding will lead to even more effective treatment. Certain gene mutations found in the testicular cancer cells have been linked to resistance to chemotherapy and predict poor outcomes. These findings may help individualize treatment better and help find new drugs to treat testicular cancer that can target these gene mutations. A better understanding of the genetic changes will help doctors decide which patients need further treatment and which can be safely treated with surgery alone.

Clinical trials have refined doctors’ approaches to treating these cancers and are expected to answer additional questions. For example, studies have identified factors to help predict which patients have a particularly good prognosis and may not need lymph node surgery or radiation therapy. Studies also have found unfavorable prognostic factors that suggest certain patients may benefit from more intensive treatment.

A large amount of work is being done to try to limit the long-term toxicities of treatment while maintaining the cure rate. Doctors want to be able to predict better whose cancer is more likely to recur and then base the amount of therapy on this, thereby not under- or over- treating anyone. One study reported good results by individualizing treatment in men with metastatic testicular cancer based on the decline of tumor marker (AFP and HCG) levels after chemo, giving more intense treatment to those with a slower decline.

New drugs and new drug combinations are being tested for patients with recurrent cancer. Stem cell transplantation is being studied as a strategy for helping men who have tumors with a poor prognosis tolerate more intensive chemo. And chemo combinations are being refined to see if eliminating certain drugs, replacing them with others, or lowering doses can reduce side effects for some men without reducing the effectiveness of treatment.

As more and more young men are surviving testicular cancer, fertility has become an increasingly important consideration. Advances in assisted reproduction methods such as in vitro fertilization have made fatherhood possible for testicular cancer survivors, even if their sperm counts are extremely low. In some cases, sperm cells removed from a testicular biopsy specimen can be successful when other options have failed.

Last Medical Review: 05/04/2012
Last Revised: 05/14/2012

Pesticide Linked to Testicular Cancer Risk

Posted: 04/30/2008

Adapted from the  NCI Cancer Bulletin .

Males exposed to a byproduct of the pesticide DDT may have an increased risk of testicular cancer, according to research published online in the Journal of the National Cancer Institute on April 29, 2008. Blood levels of DDE, the main persistent  metabolic  product of  DDT , were higher in a sample of American men with testicular  germ cell tumors  (TGCT) than in other men. This relatively rare cancer is often treatable, especially when detected early.

The U.S.  banned  DDT in 1973, but the pesticide continues to be used elsewhere. The chemical and its metabolites are stored in fat tissue and can accumulate, for instance, in humans and in fish. “While levels have declined in the population since the 1970s, DDE remains detectable in the majority of Americans,” said lead investigator Dr. Katherine A. McGlynn of the National Cancer Institute’s  Division of Cancer Epidemiology and Genetics . “This study suggests that chemicals that persist in the environment may have effects years after their usage ceases.”

A link between pesticides and testicular cancer was proposed decades ago, but testing the hypothesis has been a challenge because the disease is rare. The researchers studied 739 U.S. servicemen with TGCT and 915 healthy men who had provided blood samples to the Department of Defense, on average, 14 years before the current analysis.

The men in the group with the highest blood levels of DDE were 1.7 times more likely to develop TGCT than men with the lowest concentrations. If the risk estimates are correct, then DDT exposure could account for 15 percent of TGCT cases in the study.

DDT belongs to a family of organochlorine pesticides that may disrupt the body’s endocrine system. “Because evidence suggests that TGCT is initiated in very early life, it is possible that exposure to these [pesticides] during fetal life or via breast feeding may increase the risk of TGCT in young men,” the researchers write.

Study Links Marijuana Use to Testicular Cancer

Article date: September 12, 2012

By Stacy Simon

Researchers in California have found a possible link between using marijuana and developing testicular cancer. Conducting a case-control study in Los Angeles County, they found that men who had testicular germ cell tumors were about twice as likely to report having ever used marijuana as men without these tumors.

Testicular cancer is expected to be diagnosed in 8,590 men in 2012. It is often highly treatable, and usually curable. More than 90% of these cancers are germ cell tumors. The rate of testicular cancer has been increasing for several decades, but experts are not sure why. The study, published online Sept. 10, 2012 in the American Cancer Society journal Cancer, speculates that environmental causes, including recreational drug use, may play a role.

In the study, 163 men diagnosed with testicular germ cell tumors and 292 men not diagnosed with the tumors were interviewed about their recreational drug use. The researchers found that men with these tumors were about twice as likely to have a history of using marijuana. Most of the increased risk was found in men with a germ cell tumor sub-type called non-seminomas. This type of tumor is harder to treat and usually occurs in men between their late teens and early 30s.

Case-control studies such as this compare a group of people with a certain disease to a group of similar people without it, to look for factors that may contribute to the disease. However, this type of study cant prove that a factor actually causes the disease. Other types of studies are needed for this.

Study author Victoria K. Cortessis, MSPH, PhD, of the University of Southern California in Los Angeles said her team based its hypothesis on research that shows the active ingredient in marijuana may interfere with normal hormone signaling between the brain and the testicles. Cortessis and her team plan to conduct research that will look at those processes.

Cortessis said, Three studies have now found the same specific result a history of marijuana use associated with double the risk of non-seminoma testicular cancer. This is a more dangerous type of testicular cancer that requires chemotherapy treatment. We have to take it seriously.

The researchers also found that men with a history of cocaine use actually had a reduced risk of testicular cancer. Cortessis speculates this might be because cocaine destroys testicular germ cells, whether they are healthy or not. Destroying the cells prevents them from becoming cancerous, but also leads to infertility because germ cells produce sperm.

Len Lichtenfeld, MD, deputy chief medical officer for the American Cancer Society cautioned that the studys findings are preliminary, and the number of men studied was small. Lichtenfeld said, The study is interesting, but the findings are not conclusive. More research needs to be done to form a firmer conclusion that this is a definite relationship (between marijuana use and testicular cancer risk).

Citation: Population-Based Case-Control Study of Recreational Drug Use and Testis Cancer Risk Confirms an Association Between Marijuana Use and Nonseminoma Risk. Published online Sept. 10, 2012 in Cancer. First author: Victoria K. Cortessis MSPH, PhD, University of Southern California, Los Angeles.