The Long Haul: Facing the Long-Term Side Effects of Testicular Cancer

Jonny Imerman hadn’t seen a doctor in five years. He was 26 years old. He woke up feeling great every day. He felt invincible.

By the time he noticed the lump on his testicle, the cancer had spread to his lymph nodes, his abdomen and the area behind his kidneys. He lost his left testicle to cancer, banked some sperm at the local fertility clinic and began the combination chemo­therapy that would, hopefully, cure him — but would also elevate his lifetime risk of everything from stroke to hearing loss.

Despite an early recurrence that necessitated a second surgery just two years later, Imerman has now lived 15 cancer-free years. Odds are, he will remain cancer-free for decades, but the risk of both recurrence and long-term side effects means that he’ll always need extra checkups and face extra dangers.

“Like a lot of young adults, I very foolishly took my health for granted. Now I do everything I can to keep myself healthy. I never smoked, but I quit drinking soon after my initial diagnosis. I eat vegan, I go to the gym every day, and I walk over to the nearest hospital every six months for blood tests and other diagnostic work,” says Imerman, who started a cancer support group called Imerman Angels and runs ClozTalk, a company that designs and sells apparel that promotes various advocacy organizations.

“I guess I could be mad that the cancer and the chemo­therapy have put me at risk,” he says, “but I’m actually just grateful that I survived the initial experience, that I can minimize the risks with a healthy lifestyle, and that I have an opportunity to give back by helping people who are just receiving their initial diagnoses.”

Testicular cancer is a relatively rare type, expected to account for just 9,300 of the 1.74 million new cancers diagnosed in the United States this year. It is also a highly treatable type. The five-year survival rate is more than 95 percent, far higher than the overall five-year adult cancer survival rate (68 percent).

^{“Like a lot of young adults, I very foolishly took my health for granted. Now I do everything I can to keep myself healthy.” — JONNY IMERMAN, survivor and patient advocate}

For patients who receive a diagnosis when the tumor remains confined to a single testicle — and most patients do — the long-term effects of the disease tend to be minimal. Recurrence is rare, and the lifetime risk of a new cancer in the second testicle is 2 to 5 percent. Most of those patients always retain a single working testicle, which in many cases can produce enough testosterone and sperm to keep them healthy and fertile for many years.

The chances of long-term problems are far greater for patients who, at diagnosis, have metastatic cancer that has already spread beyond a single testicle and its immediate environs. Such patients naturally face a higher risk of death from their initial cancer and a higher risk of recurrence, but specialists say the biggest risks stem less from the cancer than from the chemicals used to treat it.

The most common treatment for metastatic testicular cancer is surgery followed by a chemotherapy combina­tion of bleomycin, etoposide and cisplatin. This powerful combination routinely produces all the harsh side effects associated with chemotherapy, but it can also lead to a litany of long-term side effects: infertility, low testosterone, lung scarring, hypertension, coronary artery disease, metabolic syndrome and secondary cancers.

These treatment-related conditions are relatively rare in patients who get chemotherapy for other tumor types. Most cancers tend to strike people who are beyond an age when they might worry either about fertility or problems that take decades to develop. The average age of a typical patient with cancer upon initial diagnosis is 67.

Long-term effects pose a much greater risk to the survivors of testicular cancer because they tend to be much younger. The average age of a man who receives that diag­nosis is 33, so men who undergo treatment today could live with its consequences for more than four decades.

“The long-term issues associated with testicular cancer are serious, and they do require lifelong monitoring, but it’s important to see them in perspective. Metastatic testicular cancer used to be fatal in most patients, and now it’s mostly curable. The development of the cisplatin-based treat­ment regimen, despite its very real toxicities, was a major breakthrough,” says Darren R. Feldman, M.D., a medical oncologist who studies and treats testicular cancer at Memorial Sloan Kettering Cancer Center in New York City.

Researchers have yet to definitively determine why the chemotherapy given to patients with metastatic testicular cancer causes so many long-term effects, but the problems seem to stem both from damage done during the initial treatment and the fact that patients’ bodies never fully eliminate the chemicals. “You can still detect low levels of platinum in patients decades after they receive cisplatin treatment, and one hypothesis is that the initial intense exposure followed by the ongoing low-level presence of this heavy metal eventually damages the vascular system and other parts of the body,” Feldman says.

“The problem is, we haven’t discovered any effective substitute for cisplatin in testicular cancer treatment,” he says. “Several studies have tried to substitute carbo­platin, which is closely related to cisplatin and less toxic to nerves and hearing, but that was unable to produce the same cure rates.” One study showed that higher levels of platinum more than 20 years after treatment are associated with more hearing impairment and less gonadal function.

The most immediate and serious side effect of chemo­therapy for testicular cancer is often the inability to have children. The chemical cocktail obliterates sperm produc­tion in nearly all men throughout the course of treatment and during its immediate aftermath.

For most men, sperm production gradually recovers over months and years. Studies suggest that up to 30 percent of all testicular cancer patients who undergo chemotherapy never become fertile again, but as much as 80 percent of the patient population that was fertile initially and then underwent chemotherapy will recover their fertility within five years of treatment.

Although some men may recover their fertility sooner, their oncologists often advise them to delay conception for a least a year after treatment ends. The results of a few studies suggest a tiny increased risk of birth defects when men conceive very shortly after completing chemotherapy, Feldman said, but no evidence of problems beyond the one-year mark.

Given that there’s no way to predict which men will become fertile again and which won’t — and that recovery can take at least two years — the best solution is often to bank sperm before treatment. Among currently fertile men, the primary drawback to this option is the cost: Fees for collection and annual storage typically run several hundred dollars each, and the costs of artificial assisted reproduction may reach thou­sands of dollars. Insurance rarely covers the costs of fertility preservation or assisted reproduction. Much depends on state law and the comprehensiveness of different policies.

Another potential problem with sperm banking: Many testicular cancer patients are infertile before they find out they have the disease or get treated. Indeed, infertility at a young age (along with a family history or an undescended testicle) is a risk factor for testicular cancer and can be lifelong, even when one testicle remains after treatment. (Uncertainty about how many patients were infertile before treatment is one reason it isn’t clear how many men are rendered permanently infertile by treatment.)

“There’s no way to know in advance which patients will and won’t recover their fertility, so banking sperm is like taking out an insurance policy, and the best time to do that is before the patient receives any treatment at all, including surgery, radiation or chemotherapy,” says Matthew Coward, M.D., director of male reproductive medicine and surgery at University of North Carolina Fertility in Raleigh. “The understandable desire to minimize the time between diagnosis and surgery leads many to delay fertility preservation until after the initial surgery, but if you wait that long, the patient may have already lost some of his sperm production.”

Treatment for testicular cancer can cause other side effects, too. For example:

Chemotherapy for metastatic testicular cancer reduces the production of hormones such as testosterone. Production levels generally recover over time, but not always.

Bleomycin can harm the lungs. A nine-dose course causes lung damage in about 5 percent of recipients (and can be fatal in less than 1 percent of cases).

Bleomycin also leads to Raynaud’s phenomenon in about 10 percent of all patients. In this condition, the blood vessels narrow and the skin turns white, then blue and finally red when exposed to triggers such as cold.

Cisplatin can cause kidney damage — though this is rare now that fluids are given during chemotherapy — and nerve damage that leaves many patients with pins and needles in their extremities. The feeling gener­ally goes away but can persist for months or even years. Cisplatin can also cause mild to profound hearing loss.

Like most cancers, testicular cancer demands frequent follow-ups immediately after treatment and then progressively fewer appointments as patients remain cancer-free. Patients who show no sign of recurrence after five years typically see their oncologists just once a year. These follow-ups are called for even though the vast majority of such patients never have a recurrence or develop a new cancer.

Testicular cancer survivors who receive chemotherapy without experiencing immediate lung damage tend to maintain normal cardiovascular health in the years just after treatment, but they face an elevated risk of serious problems decades later. Compared with men who have not had this type of cancer, they are more likely to develop not just hypertension but also high cholesterol and diabetes. They are also more likely than other men to develop low testosterone, even if their levels bounce back to within normal limits after their initial treatment.

“Normal testosterone levels are approximately 300 to 800 nanograms per deciliter. A testicular cancer patient who starts with testosterone around 700 nanograms per deciliter might fall to 400 nanograms per deciliter after surgery, which is high enough to preclude the weight gain, fatigue, loss of libido and other symptoms that come with low testosterone,” Coward says. “But testicular function also naturally declines with aging, so there could be a much higher chance that a testicular cancer survivor could eventually fall below the threshold for symptoms. It’s just that it often takes years before that might happen.”

Metabolic side effects combine with the cardio­vascular side effects to increase the risk of a range of problems, including hypertension, stroke, heart attacks, hyperlipidemia and obesity. “It is very important for testicular cancer survivors, especially those who underwent chemotherapy, to always continue making regular visits to an oncologist and/or a primary care provider who understands testicular cancer survivorship issues. They do not have the luxury of letting medical care slide a bit while they’re still young, because they are starting off with a potentially serious cardio­vascular risk factor,” says David J. Vaughn, M.D., vice chief for clinical affairs in the hematology/oncology department at Penn Medicine in Philadelphia.

The other key strategy for improving long-term outcomes is one that patients must use at the very beginning: See a doctor who treats a significant number of patients with testicular cancer and has experi­ence with the disease.

“This is a rare cancer, and most oncologists might only see one or two cases a year, but several different studies clearly show that outcomes are better at institu­tions that see a high volume of these patients — e.g., more than 20 cases per year,” says Christian Kollmannsberger, M.D., a clinical professor of medicine in the division of oncology at the University of British Columbia in Vancouver. “It’s very difficult to be good at something if you don’t do it regularly.”