By David Feder, RD

For John Fender, an associate art and design professor at Drake University in Des Moines, Iowa, the only symptom was an abnormal enlargement of a testicle.

“I never did any sort of regular self-check, but one morning in the shower I noticed that my right testicle was much bigger than the left,” recalls Fender. “The increase in size was noticeable. But there wasn’t any sort of prominent bump and it wasn’t really sore.”

Testicular cancer has the distinction of being a cancer that has seen a dramatic increase in the number of patients who can say the word cured—among them one of the country’s premiere athletes, Lance Armstrong.

Testicular cancer only accounts for 1 percent of all cancers seen in American men, but it is the most common cancer seen in men between the ages of 15 and 34. There was a gradual but steady increase in the overall occurrence rate of testicular cancer in previous decades, but these numbers have plateaued in the past decade or so.

The American Cancer Society says just below 9,000 new cases of testicular cancer will be diagnosed in 2004. But only about 360 patients are expected to die from testicular cancer as advances in diagnosis, surgery and chemotherapy have dramatically increased the cure rate of this disease, which is now greater than 90 percent for most patients. For reasons as yet unknown, Caucasian men are four times more likely to develop testicular cancer than non-Caucasian men.

Testicular cancer most commonly comes to attention when the patient notices a lump on the testicle. Some patients complain of a dull ache, although testicular pain may be entirely absent. Breast tenderness or growth is occasionally reported by men whose tumors secrete a hormone called HCG (human chorionic gonadotropin), which is usually found only in pregnant women. Patients with more advanced disease can develop symptoms like shortness of breath and cough. It must be remembered that many benign conditions like injury to the testicle or inflammation of the testicle or the epididymis can also cause painful swelling of the testicle, and these symptoms need to be brought to the attention of your physician.

Types of Testicular Tumors

“Testicular tumors nearly always begin in the sperm-forming cells called germ cells,” explains Walter Stadler, MD, associate professor and director of genitourinary oncology at the University of Chicago. “The tumors can be either seminomatous or nonseminomatous. These tumors may have somewhat different clinical courses in patients, but they both likely arise from the same germ cell precursor.”

Dr. Stadler says that approximately 40 percent of testicular tumors are the slower-growing seminomas, while the rest make up the more aggressive nonseminomatous germ cell tumors.

An ultrasound examination of the testicle is the first diagnostic test used to confirm the presence of a testicular mass. This can differentiate a solid testicular mass (which may be malignant) from other benign conditions.

If testicular cancer is suspected, the patient undergoes a series of blood tests to check levels of two tumor markers that are elevated in testicular cancer. These are AFP (alpha-fetoprotein), which is normally not seen in adults, and HCG, both of which can be elevated in patients with nonseminomatous testicular cancer. Very high levels of these tumor markers usually portend a higher risk of spread and may predict for a somewhat poorer outcome.

“Since the cancer cells can break loose into the bloodstream (hematogenous metastasis) and spread to the lungs, bones or liver, most assessment procedures involve an X-ray or CAT scan of the chest and abdomen,” says Dr. Stadler. Once these initial evaluations are complete, the patient is usually scheduled for an orchiectomy (removal of the testicle). Evaluation of the removed testicle by a pathologist finalizes the diagnosis and determines the type of testicular tumor.

Staging the Cancer

To decide the optimal combination of surgery, chemotherapy and/or radiation, each patient undergoes a series of tests to help decide the extent of disease. This process is called “staging.” Stage 1 testicular cancer is contained within the affected testicle, while stage 2 cancer has spread to the lymph nodes in the abdomen. Stage 3 indicates that the cancer has metastasized to other areas of the body, such as the lungs or brain.

Fender discovered his cancer by accident in January 2000 at age 34. The father of two with a third on the way had the testicle removed in an outpatient procedure. “I also had a chest X-ray plus a CAT scan of the lower abdomen to ensure there were no other tumors.” Fender says when those tests came back negative, he was told he had stage 1 seminoma and met with an oncologist.

As Fender’s tumor was still in the earliest stages, the oncologist did not feel he would need chemotherapy but did recommend adjuvant radiation therapy in the lower right abdomen to target the retroperitoneal lymph nodes, which are the first part of the body to which testicular tumors spread.

Fender received a relatively low dose of radiation therapy during a course of 17 treatments over 21 days. The use of radiation therapy “insurance” used to be standard for increasing the already high cure rate for early stages of testicular cancer. The lower dosage of radiation therapy generates fewer reported side effects, and Dr. Stadler points out that stage 1 seminoma can also be treated with orchiectomy followed by observation without the need for radiation therapy. These patients then need to be followed fairly closely as they would need immediate treatment if their cancer did recur.

“It comes down to whether the patient wants to accept the side effects and risks of radiation,” says Dr. Stadler. “Some patients may develop a bowel obstruction or radiation-induced malignancy years later. However, the probability for either complication is less than one in 1,000.”

“The radiation was not a problem,” Fender says, “although toward the end I felt tired. I only experienced slight nausea and had a diminished appetite. But I didn’t have any problems keeping food down.” And other than the week for surgery and recovery, Fender says he didn’t need to take time off work.

Fender says he sometimes feels strange calling himself a cancer survivor. “We found the cancer early and took care of it soon. There was no spreading, and although I still have to pass the five-year mark, it’s four years later and I’m cancer-free.”

Daniel Gimpel, a California “dot-commer,” was also one of the lucky ones whose cancer was caught early.

“By coincidence, a few months before my diagnosis, my general practitioner was describing how cancerous tumors feel. He was explaining how a tumor feels like a rock and the description stuck in my mind. When I checked myself months later, that’s exactly what my left testicle felt like. I had no sensation of a node or a change in size. No pain or discomfort. In my case, it was simply a density change. It turned out to be stage 1 seminoma.”

For the 47-year-old, orchiectomy was followed by three weeks of low-dose radiation therapy. But Gimpel’s brother David had a different experience.

For the More Advanced

“My brother David was diagnosed with both stage 2 seminomatous and nonseminomatous testicular cancers when he was 24,” says Gimpel. “This was almost four years before I got it at age 32.”

David Gimpel noticed an abnormality shortly before his 24th birthday in 1984 but ignored it for six months. By the time he saw a doctor it was the size of a grapefruit and he was admitted to the hospital immediately. After an orchiectomy and biopsy, it was determined to be stage 2 cancer. He received standard chemotherapy and his cancer went into remission for nearly five years before a new tumor was discovered in his remaining testicle at age 30. After chemotherapy for what was now stage 3 cancer, a recurrence and additional chemotherapy, the cancer eventually spread to David’s lungs, bones and other organs. David was 38 when he succumbed to the disease.

“[My brother and I] are a study in contrasts,” says Daniel Gimpel. “I had cancer the easiest way possible by catching it early and getting the best treatment at the right point in time. Sometimes, a matter of days can make all the difference in the world. I guess that’s the lesson for any cancer: If anything changes—if you suspect anything is wrong—you must present it to your doctor immediately.”

Chemotherapy for Advanced Cancer

Chemotherapy for testicular cancer produces cure rates ranging from more than 90 percent for stage 2 to more than 70 percent for advanced-stage tumors, a success rate achieved in the past two decades as the result of work initiated by Lawrence Einhorn, MD, distinguished professor of medicine at Indiana University Medical Center in Indianapolis.

When testing a new platinum-based combination therapy in the mid-’70s, Dr. Einhorn and colleagues saw remarkable responses. Within weeks of treating the initial patients, Dr. Einhorn says they knew something was happening. Patients with multiple pulmonary metastases came back for the second treatment and the tumors had already begun melting away.

“Our radiologist actually called us and asked what we were doing. He was amazed to see them before and after,” Dr. Einhorn says. But, while the initial dramatic resolution of tumor was very gratifying, Dr. Einhorn says the bigger moment came when these remissions were durable.

“At one year out we had about a dozen who remained in complete remission, which, because of how fast the metastases grow, was remarkable. We knew then that even if there were a few people, it was doing something incredible.”

Dr. Einhorn and his team became internationally known in 1996 when they treated American cyclist Lance Armstrong, who was diagnosed and treated for advanced testicular cancer that had spread to his lungs, abdomen and brain. Three years later, Armstrong won the first of five consecutive Tour de France competitions, with a sixth possible victory to come in July.

Individualizing Treatment by Stage

Chemotherapy, which has been shown to be remarkably effective against testicular cancer, is typically reserved as treatment for advanced testicular cancer and large stage 2 tumors (bulky disease). Current standard chemotherapy regimens for testicular cancer involve a combination of two or three drugs that may include Platinol® (cisplatin), VePesid® (etoposide), Blenoxane® (bleomycin), Ifex® (ifosfamide) or Velban® (vinblastine). The whole may truly be greater than the sum of its parts in that the drugs accentuate each other’s activity.

“For stage 1 testes cancer, after observation and surgery to remove lymph nodes, there’s also a third option of adjuvant chemotherapy,” says Dr. Stadler, “but that’s not standard. This modality has been discussed over the past five years. However, most doctors are uncomfortable with the idea of giving chemotherapy to patients who are essentially cured. They don’t want to expose them to the toxicity—including the capacity to induce mutations—of chemotherapy.” However, chemotherapy is increasingly being considered for patients with stage 1 nonseminomatous tumors whose blood levels of tumor marker proteins (AFP and HCG) remain elevated after surgical removal of the testicle, suggesting residual cancer in the patient.

The standard options for stage 2 cancer are surgery to remove the testicles followed by chemotherapy for nonseminomatous tumors (or radiation if it is a seminoma).

Treatment for stage 3 is naturally more aggressive and varies more than treatment for stages 1 and 2, Dr. Stadler explains. “Not all stage 3 tumors are the same,” he says. “It all depends on the details—how big the lymph nodes are, how high the blood markers have risen. At stage 3, chemo is the main thing and radiation is not much of an option. Chemotherapy, sometimes followed by surgical resection of any residual masses, is the standard.”

The most common chemotherapy combinations are BEP (bleomycin, etoposide and Platinol), which is given every three weeks for a total of three cycles, and VIP (VePesid, Ifex and Platinol). More aggressive chemotherapy with VIP and stem cell transplant (see “Inside Stem Cells,”) is used as second-line therapy, and sometimes VIP is used instead of BEP if there is a need to avoid bleomycin’s rare potential of pulmonary side effects.

Dr. Einhorn says finding the platinum-based treatment helped the drive for cancer research, proving that cure was possible for advanced disease, and all the money and time that goes into research pays off.

“If only all cancers could have the same story,” he says.