Testicular cancer: fact or fiction?

Fiction

You might think that the disease is more common because the Netherlands is aging, but that is not the reason. In fact, especially men younger than 45 suffer from testicular cancer. It is even the most common type of cancer in men aged between 18 and 39. This is remarkable because cancer is usually an aging disease: slow accumulation of cell mutations will eventually lead to cancer. “But testicular cancer arises in the first phase of life. That’s why the patients are still relatively young,” Leendert says.

How exactly does that work? In development (embryogenesis), each person is created from an egg and sperm cell. These cells fuse together, and cell division begins, resulting in different types of cells. One of these cells is the precursor of the germ cell. In the early embryo, these early germ cells travel from the tailbone to where the testes or ovaries will be formed. They receive signals from the developing gonads (testicle and ovary in disposition) to move and divide. Eventually, they will mature in a particular direction: boy or girl. Germ cells will eventually develop into sperm cells in men, and eggs in women.

But at birth, there is a clear difference in how far the germ cells have matured. In girls, all the germ cells are present when they are born, and they all have already matured into eggs. Starting at puberty, with each menstrual cycle, the number of eggs will decrease due to ovulation. This will continue until there are almost no eggs left, with women entering menopause.

Boys, however, are born with immature germ cells. Once they reach puberty (around 11-12 years of age), the precursor germ cells will grow into sperm cells, under the influence of testosterone. And it is at this early stage that something goes wrong: the primitive germ cells are disturbed in their maturation, start dividing at some point, culminating into testicular cancer.

“It’s actually a childhood cancer. You need puberty for the disease to develop: the hormonal drive urges the cells to divide,” Leendert explains. “Because of that, it’s the most common cancer in young men. When men grow older, the number of patients declines. Once you get past that age peak, you’ll have (almost) no chance of getting this type of cancer.”

Fact

It’s good to check your balls once a month. “Try to do so every month at a set time. Checking under the hot shower works well because then the scrotum will feel  loose and relaxed,” Richard says.

Check successively for:

• an enlargement, hardening or lump.
• a noticeable difference between the two balls, in size and feel.
• changes.

“Don’t hesitate to go to your GP if something feels suspicious of if you have any questions. And ask for a referral to the urologist for an ultrasound, if necessary. It would be great if boys start self-examining when they enter adolescence.”

Fiction

Testicular cancer is rare, but it is the most common cancer in young men. In 2023, 900 men and boys in the Netherlands were diagnosed with it. Remarkably, the number of patients has more than doubled in the last 30 years.

“We recognize even more that the number of patients is increasing fast because of the centralization of testicular cancer care to our Center of Expertise,” Richard says. What is causing this nationwide increase is not yet known exactly. It probably has to do with a combination of genetic and environmental factors, doctors and scientists suspect.

Fact

Most patients do not have the illness in their family background. However, if a direct family member does have testicular cancer, it is indeed a risk factor. For example, if your grandfather, father, brother, cousin or uncle has (had) testicular cancer, you’ll have a 1 to 4 percent chance of getting the condition. By comparison, that risk is normally 0.6 percent. How this is possible, we don’t know yet, because no precise gene abnormality has yet been discovered that can be directly linked to testicular cancer.

“A lot of research has already been done on this, however, and there are numerous genetic variants that seem to give a higher chance of testicular cancer,” Leendert explains. “We know, for example, that the disease occurs mainly in white men, and much less in Asia and Africa. And that doesn’t change if men have emigrated to Europe from Asia or Africa: they don’t suddenly have a higher chance of getting testicular cancer.”

Even within Europe, striking variations can be found. “We see that the disease is less prevalent in Finnish men than in Swedish men. But when Finnish young boys move to Sweden, they suddenly, remarkably enough, do seem to be more at risk.” This also appears to be the case for boys who have not yet been born, thus the ones who move to Sweden when their mothers are still pregnant with them. Here, genetic factors seem to play less of a role than with the Asian and African men. “The combination of DNA and the environment is decisive, we think. But unfortunately, we don’t yet know which factors precisely are involved”, Leendert says.

Fiction

Prevention is incredibly difficult, because the disease arises at a very early stage, in those early germ cells. Furthermore, we don’t yet know which environmental factors might be harmful. “We do have ideas, of course,” Leendert says. “It probably involves (a combination of) factors suppressing the male hormones. Very strikingly, in Eastern European countries, testicular cancer is more prevalent since they became part of the Western community. So, there seems to be a connection with industrialization.”

But exactly which substances or other factors are harmful remains difficult to determine during scientific research. Leendert: “You can’t use animal models to mimic the situation in a laboratory. It has been tried, of course, but studies in mice, for example, have not given any useful results. This is not a surprise, because mice only live for two years, and the disease only reveals itself within men after 18 to 35 years. All the expected outcomes have not been found in lab studies.”

Long-term, epidemiological scientific studies will have to conducted, but even then it will be almost impossible to pinpoint the exact environmental causes “You’ll have to go all the way back to a person’s early development, because between birth and the first years of life something seems to go wrong. And you’ll also have to figure out the mother’s habits because she may have already been exposed to certain substances during pregnancy. And on top of this, you’ll have to do all this for large groups of men and their mothers. While you don’t even know what exactly you would like to measure.”

And what about  lifestyle advice for pregnant women? Should they avoid specific possible risk factors? “Some research has been done, but those studies were problematic because there were few participants,” Leendert answers. “The only recurrent factor the researchers were confronted with is that a very low or very high birth weight might affect testicular development.” What causes this is not yet known. Smoking during pregnancy, for example, is known to cause a lower birth weight with babies. “In terms of prevention, the best advice for now is that boys should start checking their balls from the age of 12 or so,” Richard adds.

Fiction

The HPV virus is a sexually transmitted disease. It is more likely to cause cancer in those areas where there is ‘frictional contact’, and the virus can directly be transmitted internally. This is not the case with the testicles. The HPV virus may lead to cancer of the penis, cervix, mouth and throat, anus, vagina and labia.

Fiction

Of course, damage may occur when you are kicked or hit in your scrotum (for example, during ball games or martial arts). But this does not involve testicular cancer, because that illness has already originated earlier, in those early germ cells. “Such a blow, however, might be the first trigger for men and boys to examine their own balls more closely. If abnormalities are then felt, that may be the reason to see a doctor,” Richard says.

Fiction

The disease originates well before a person will become sexually active, so this has no impact.

Fiction

“Anything that impacts testicular development may have predictive value and should be monitored,” Leendert advises.

Such as these risk factors:

• failure of the testicle(s) to descend.
• an atrophied testicle (testis atrophy).
• hypospadia: a urethra with an opening at the bottom or halfway down the penis (instead of at the apex).
• fertility problems (no, few or abnormal sperm).
• congenital disorders in sex development, such as when people are less sensitive to male sex hormones.
• – previous testicular cancer: after a few years, a tumor may develop in the other testicle.

Fiction

Of course, the type and duration of treatment must ultimately be considered on a patient-by-patient basis and depends on the type of testicular cancer and whether there are metastases.

Usually, the affected testicle will indeed have to be surgically removed. This is necessary because germ cell tumors grow rapidly and often more evenly spread in the testicle: it is then safer to remove the entire testicle as soon as possible to prevent metastases.

But other treatments that are less invasive could sometimes be possible. “We could opt for partial removal of the testicle (partial orchiectomy – ed.) if possible. We then remove only the tumor from the testicle. Unfortunately, this is only possible in a minority of patients, when a small tumor is found lying on the outer edge of the ball,” Richard says.

Other treatments for testicular cancer, such as chemotherapy and radiation, are used when the disease has already spread, not to save a testicle. “Urologists may, however, be able to place a testicular prosthesis, which makes it no longer visible that a testicle has been removed. This, of course, is purely cosmetic: sperm production will not be regenerated int the prosthetic ball.”

Fact

It depends, of course, on how advanced the disease is, and on the type and duration of treatment. At the Center of Expertise, various research is taking place on how to protect fertility as much as possible. “First of all, semen preservation is offered to the patients,” Richard says. Patients then collect sperm themselves during ejaculation. After the sperm is examined, it will be frozen and stored. Later, it can be used for artificial insemination or in-vitro fertilization in order to have children.

“When semen preservation is not successful (because too few fertile sperm cells have been collected – ed.), Onco-TESE, for example, is performed in collaboration with our andrologist Jetske van Breda and the fertility team,” Richard adds. “Then, we try to isolate and freeze sperm cells from the tissue of the affected testicle. We do so during the same surgery in which the testicle is being removed.”

Of course, the above two interventions only work when boys/men have already reached puberty: the germ cells will have matured by then, and sperm production has already started. The Princess Máxima Center and the UMC Utrecht are now investigating whether fertility can be protected at an earlier stage. “The PRINCE study focuses on prepubertal boys whose treatment puts them at high risk of becoming infertile,” Leendert explains. “We offer to remove a small piece of the testicle, during an already scheduled surgery. So, they won’t have to undergo an extra surgical session. The material is stored, and in the lab, we’ll try to multiply the unique germ cells and make them suitable for reassignment. If the child is cured and will later on prove to be infertile, we will be able to transfer the material back after adolescence. We hope that the germ cells will then start to mature and sperm production will take off.

Fiction

Patients have a high chance to survive testicular cancer: about 95 percent. “With metastases, men are treated with chemotherapy or radiotherapy, and even then there is still a high chance that they will be cured. This is quite different from, for example, metastatic breast, colon or prostate cancer. Then, we can no longer talk about curing,” Richard says.

Despite the good prognosis, there are long-term effects that (former) patients should be aware of. Chemotherapy may lead to persistent neuropathy and tinnitus, for instance. And after chemotherapy, patients will have an increased risk of developing cardiovascular disease and other cancers.

The intensive treatment and the patients’ young age often implicate that the consequences will be severe: unique milestones appropriate to young adulthood will be delayed or not even achieved. These include, for instance, creating one’s own (sexual) identity, getting a steady job and reaching social and financial independence.

“The TIGER study is now investigating whether an alternative treatment could be given for germ cell tumors that do not respond to standard chemotherapy. With about 10 percent of men, chemo does not work. We suspect that this results from chromosomal abnormalities in the cancer cells,” Leendert explains. These patients may then suffer from the long-lasting side effects of chemo when that treatment would not have been necessary. “Finding the cause for this insensitivity will give us the opportunity to develop successful alternative treatments without unpleasant side effects. We are now working on this in the laboratory in close cooperation with the clinic.”

Despite the good survival rate, it remains important to recognize the disease at an early stage. This is precisely why it is important for men and boys to check their own balls regularly. This will reduce the risk of metastases, making treatment less invasive and reducing long-term symptoms and side effects.