Burden of Proof -- At 32, a Decision:
Is Cancer Small Enough to Ignore?

December 20 2004. Two years ago, John MacMahon went in for a routine physical. During his checkup, his doctor drew blood and sent it out to have his prostate specific antigen level, or PSA, measured to screen for prostate cancer. Mr. MacMahon was 29, in great shape and had no family history of prostate cancer. His doctor said he just wanted to see what was normal for Mr. MacMahon, to measure future tests against.

Mr. MacMahon's test came back showing an elevated PSA level -- higher than what is considered normal for a man his age. But because many things, including increased sexual activity, inflammation, or even bike riding, can elevate a man's PSA, the doctor told him not to worry.

In January 2004, a new doctor decided to redo the PSA test, and once again, Mr. MacMahon's level was elevated. It is extremely rare for a man that young to have prostate cancer. Just to be on the safe side, Mr. MacMahon was advised to undergo a biopsy, in which six samples of cells from his prostate were removed and tested for cancer. Five samples came back normal. One was deemed "suspicious," but the pathologist wasn't certain enough to call it cancer.

A few days later, Mr. MacMahon moved from his hometown of Houston to New York City, to take a job as an analyst at a hedge fund. He worked long hours, then went to the gym to lift weights. On weekends, he went on 10-mile runs. But the unusual finding worried him. In May, he went to Memorial Sloan-Kettering Cancer Center in New York and got tested again.

This time, 12 samples of his prostate were removed. Eleven came back normal. One, however, didn't. "It was frustrating," says Mr. MacMahon, who is now 32. "I was so confused."

Did he have cancer?

The pathology report from Memorial Sloan-Kettering said yes. But the experts he consulted in the six months following his diagnosis were divided about whether he needed to be treated immediately. Prostate cancer is often a slow-growing disease, and in older men, some doctors recommend waiting when the amount of cancer is small. Mr. MacMahon's dilemma was different. His cancer was found at such an early stage, and in such a tiny amount, that it wasn't clear what he should do.

His predicament reflects a startling new idea suggested by a growing number of researchers: Almost everyone harbors cells in their body that could be called cancer.

Because detection methods have greatly improved in recent years, more people are being diagnosed with cancer at its earliest stages. This is creating new questions. When is cancer the kind that can kill you and needs to be treated -- with all the toxic therapies and damaging side effects that go along with that decision? And when is it too small to matter?

Autopsy studies have shown that people who died of other causes sometimes have cancer in their bodies. Researchers at Wayne State University in Detroit found 8% of 1,027 men in their 20s, who died of other causes, had small amounts of prostate cancer. In its study of 1,500 men, which lasted more than a decade, the percentage of those with cancer rose during each decade of a man's life. Fully 80% of men in their 70s were found to have microscopic cancers in their prostates during autopsies.

Other autopsy studies have found microscopic amounts of cancer in the lungs, breasts, and thyroids of people who have died of other causes and weren't known to have cancer.

People may live their entire lifetime with trace amounts of some cancers without ever knowing it was there, some doctors now say. In a paper published earlier this year by Judah Folkman of Children's Hospital Boston and Raghu Kalluri of Beth Israel Deaconess Medical Center in Boston, the researchers coined a term for this phenomenon. They called it "cancer without disease."

The National Cancer Institute says the idea is gaining attention, but more research is needed. Yet some are convinced. Says Ian M. Thompson, chairman of the urology department at the University of Texas Health Science Center at San Antonio: "Everyone has cancer growing somewhere in their body."

The number of people living five years or more after being diagnosed with cancer continues to rise and now is an estimated 10 million. New drugs can hold some tumors in check, making cancer more like a manageable chronic illness, such as diabetes. But if nearly everyone has traces of the disease, then "what is meant by having 'cancer'?" asks H. Gilbert Welch, a professor at Dartmouth Medical School who has researched issues surrounding early detection.

In one study, Dr. Welch and his colleague William C. Black looked at an early form of breast cancer, confined within a single milk duct, and how its diagnosis has skyrocketed, thanks to powerful imaging machines that detect the tiniest abnormalities. The cancer was found so early in some patients that doctors weren't sure which would spread to the rest of the breast and turn lethal, and which wouldn't. In such situations, more women are being forced to decide whether to undergo treatment.

Increasingly, cancer tests are being given to younger people by doctors who, like Mr. MacMahon's physician, want to establish a "baseline" -- to see what is normal for a specific patient. But if these tests find anything unusual, they can force an agonizing decision.

In Mr. MacMahon's job at the hedge fund, he sits on a trading floor in front of four screens, tracking the stock market and developments in companies he covers. He often has to make decisions, he says, "in the face of ambiguity and conflicting information." When it came to his cancer, at first, he didn't feel any ambiguity. He wanted whatever was there, no matter how small, out of his body immediately.

"Then I started telling people about it," he says, "and realized surgery was a bigger deal than I thought."

The most established way to treat prostate cancer is to have the prostate removed. Some men opt for radiation treatments, which seek to eradicate the tumor.

Mr. MacMahon's doctors urged him to have surgery. They worried the effects of radiation might not last his entire life. If the cancer came back in 20 years, surgery on a prostate that had already undergone radiation was risky. Removing the entire prostate offered him the best chance for life-long freedom from the disease, they contended.

But surgery has huge risks -- including impotence, incontinence and infertility. Mr. MacMahon, who is single, says he would like to have children someday. The walnut-sized prostate sits near the nerves that control bladder function as well as the ability to have an erection.

He went to discuss his concerns with Peter T. Scardino, chairman of urology at Memorial Sloan-Kettering. Dr. Scardino told him the vast majority of men in their mid-40s to age 70 will, within two years of surgery, be able to have an erection "good enough for intercourse." Men under 50 recover sooner than other patients, he said. But 5% to 10% of patients don't recover erections, even with the help of drugs, he said, "and why this is, we don't fully know."

The statistics frightened him, Mr. MacMahon says. "It is not like 90% in this case is an A," he says. "Anything short of perfection is an F."

Second Opinion

Mr. MacMahon went for a second opinion at New York University School of Medicine. He asked a specialist if he could wait until he was 35 to get treated. The doctor told him his odds of a full cure were never better than if he had the surgery now -- but he probably could delay treatment for years. "It made me think that some people were looking at the same pattern and weren't seeing the same things," Mr. MacMahon says.

This year, more than 240,000 men will be diagnosed with prostate cancer, according to the Prostate Cancer Foundation. Nearly 30,000 will die from it. But the rate of survival five years after diagnosis is excellent -- 98% -- because it is a slow-growing cancer, and often caught early enough to be treated.

In July, Mr. MacMahon flew back to Houston, to consult with Christopher J. Logothetis, director of the Genitourinary Cancer Center at M.D. Anderson Cancer Center in Houston. Mr. MacMahon's father, Andrew, a pediatrician, went with him. "I was on the fence about what he should do," Dr. MacMahon says.

Dr. Logothetis was blunt in analyzing the decision that had to be made.

"John can wait and expose himself to the risk that the disease gets out from under us," Dr. Logothetis recalls telling them. "Or we can operate on him before he may need it," taking the risk of making him infertile and impotent. "He has two awful choices and unfortunately he has to pick one."

Dr. Logothetis told Mr. MacMahon he might want to wait a year, with careful monitoring, to see if the tumor grew in size, before making a decision.

There was no guarantee that surgery would actually find cancer. Memorial Sloan-Kettering says it looked at 2,000 patients whose prostates were removed during the last four years, after biopsies said they had cancer. But in more than 30% of the cases, the prostate removed either had microscopic amounts that weren't life-threatening, or no cancer at all. Dr. Scardino says that in some cases, cells removed in biopsies were cancerous, but the rest of the prostate appeared cancer-free.

Ten years ago, the number of people who had their prostates removed -- only to learn the amount of cancer wasn't life-threatening -- was between 10% to 15%. The rate has risen because more men are having biopsies that indicate they may need treatment, Dr. Scardino says.

Mr. MacMahon says his confusion only deepened. He underwent a test called endorectal magnetic resonance imaging, or eMRI. Using probes put in the rectum, the test takes an image of the inside of the prostate, trying to determine the extent and location of the cancer. Doctors told Mr. MacMahon they saw a spot that hadn't turned up in his two biopsies. They thought it could be an additional tumor.

This was his greatest fear, Mr. MacMahon says -- that the biopsies had missed a more-extensive tumor growing somewhere else. But when he read research papers about the technique, they noted the eMRI test, a nascent technology, had a high false-positive rate. Dr. Scardino acknowledged the spot it found could just be a shadow.

"Now they're talking about surgery based on something that could be a tumor or could be a shadow, they didn't really know," Mr. MacMahon says. On the other hand, he thought, "here was another test coming up on the wrong side. How many more tests did I have to do before I decided what to do?"

Mr. MacMahon's insurer covered most of the costs of his testing. But he estimates he spent $10,000 out-of-pocket this year on his share of test and consultation costs, nutritional supplements, and $2,000 for a DNA test to insure that the Memorial Sloan-Kettering tissue sample was his and hadn't been inadvertently mixed up with someone else's tissue.

Dr. Scardino told Mr. MacMahon he had operated on only one prostate-cancer patient as young as him, a 32-year-old who had also survived testicular cancer. In August, while Mr. MacMahon was taking a train to Baltimore for another medical consultation, the patient called him.

The man reassured Mr. MacMahon he had made a full recovery -- and, using sperm he had banked before his operation, had fathered two children since the surgery. The conversation left him "feeling optimistic," Mr. MacMahon recalls.

In Baltimore, he met with Patrick C. Walsh, who for three decades led the Department of Urology at the Johns Hopkins Hospital and pioneered radical prostatectomy surgery. Dr. Walsh felt Mr. MacMahon's PSA test results were a signal something was going wrong. He thought Mr. MacMahon should have surgery. "In a man his age, no matter how much cancer there is, it's going to progress," says Dr. Walsh. "If we wait too long to treat it, we may overshoot and miss the window of curability."

But Dr. Walsh wanted the Hopkins pathologist to look at the slides from Mr. MacMahon's biopsy before he arrived at a final conclusion. When Mr. MacMahon got the Hopkins pathologist's report a few weeks later, "It sent me through the roof," he says.

Mr. MacMahon's voice had a note of frustration as he read what he refers to as "the disclaimer" paragraph in the report. In cases similar to his, the report stated, about 50% of the prostates removed had minuscule amounts of cancer. "They're basically saying that they might take out my prostate," Mr. MacMahon concluded, "and find nothing."

Dr. Walsh says that could happen. But he felt that in Mr. MacMahon's case, it was more likely that they would find more cancer than the trace amounts that had shown up in his biopsies.

John MacMahon on one of his favorite running routes around Manhattan

Mr. MacMahon's younger brother, Doug, advised him to take his time before deciding about surgery. Against the wishes of their mother, Doug MacMahon refused to take a PSA test after his brother was diagnosed. He says he didn't want to find himself in a similar dilemma.

The brothers had grown up down the street from four cousins, who Mr. MacMahon said were so close he considered them like sisters. They spent every summer together at their grandmother's beach house in Galveston. Every year, they traveled as a group to a ranch overlooking a national park in Texas and went hiking.

At the age of 19, one of the cousins was diagnosed with advanced Hodgkin's disease after finding a lump in her neck. Mr. MacMahon, who was spending his junior year abroad at the time, flew back from Spain immediately to accompany her to chemotherapy treatments. After she finished treatment, she gave Mr. MacMahon a picture of the two of them, taken right before she cut off her hair and started chemotherapy. Today, it sits prominently on a table in his apartment. As he weighed his own options, he looked frequently at that picture. His cousin survived, and now has a child of her own.

"With my sister, the path was so clear," says Stephanie Teleki, another of Mr. MacMahon's cousins. "But with John, I'm ambivalent. When all this started, I was really in the camp of 'you're young, let's change your diet and watch it and not rush because it seems like there isn't enough information about cancers caught this early.' " But, she adds, "little by little, fear eats away at you."

Mr. MacMahon says knowing he had cancerous cells inside his body, even in a tiny amount, prompted him to make changes. He increased his workouts to six times a week, including weight training with a personal trainer. He went running several times a week. His cousin recommended a nutritionist who worked with cancer patients, and he started carrying a tackle box filled with 30 vitamins he took throughout the day. He drank green tea, ate more soy, fruits, and vegetables, and drank fruit smoothies at his desk. Even as it proved difficult to understand what was happening inside his body, he could see the changes on the outside, as his upper body became more muscular.

'Life Moves On'

Last month, he decided to get a third biopsy. His mother, Candace, questioned the choice. From the start, she thought that he should get surgery right away. At the age of 34, she had a hysterectomy. "Life moves on," she says.

She felt postponing surgery until the disease became active wouldn't allow her son to ever put it behind him. "I wanted John to think in terms of the greater picture of his life," she says. "I don't believe in centering your life on illness."

Mr. MacMahon recognized he was delaying a decision by having another biopsy. Dr. Walsh warned that scar tissue forms after each biopsy, which can make it more difficult to separate the prostate from surrounding nerves if he pursued surgery. The biopsy, which involves having a needle inserted through the rectum to get tissue samples, is painful. He would have to wait at least six weeks for his prostate to heal before he could have surgery, if he chose that route.

He also consulted a colleague of his father's, Thomas M. Wheeler, interim chair of the pathology department at Houston's Baylor College of Medicine. When Dr. Wheeler read the slides, he didn't just give his assessment of the amount of cancer he saw, but set the results in the wider context of his life. "John is in the marketplace for a suitable mate, and this is going to have a bearing on whether he is considered damaged goods," Dr. Wheeler says. "He may be more appealing to a woman who knows he's cured of prostate cancer than if he keeps his prostate and has to say, 'by the way, I have prostate cancer, but we don't think it's threatening.' "

Mr. MacMahon says he realized cancer would be a topic in any future relationship, and a successful surgery "would make that conversation easier." Still, sometimes it seemed impossible to imagine he had cancer. He felt great. The night before the third biopsy, he lifted weights, then went for a run.

"I just want to see if there's more in there, if more than one of the 12 samples comes back positive for cancer," he said after returning from his workout.

Late last month, Mr. MacMahon and his parents gathered in Dr. Scardino's office to discuss the biopsy results. Coming directly from work, Mr. MacMahon wore a blue shirt, a tie, khaki pants, and loafers. His parents, who are divorced, sat across from him. His mother refused to take off her coat, her arms tightly clenched around her purse.

Dr. Scardino opened up Mr. MacMahon's file, and said, "We have what is so often troubling -- conflicting data."

The latest biopsy didn't reveal much that was new. He had a small amount of low-grade cancer in one of the samples. It did result in a bit of good news: the MRI result turned out to be a false positive. "The area we were worried about was probably not cancer, but a shadow," Dr. Scardino said.

The real issue was that Mr. MacMahon's PSA level in his blood test was still elevated. That indicated the possibility of more cancer than the trace amount they had found in the biopsies. For a man his age, a PSA score of less than 1 is normal, Dr. Scardino says. Mr. MacMahon's level in January when he got sent for his first biopsy was 3.1.

There were signs of some pre-malignant changes in another area of his prostate, but the cluster of cells was so small the pathologist couldn't make a definite diagnosis. "We're dealing with a very, very early cancer," he told the family.

Dr. Scardino said there were two options. "You can say you have cancer and it won't go away. If you're going to operate, pick a time, do it, and move on. Or you can say it's cancer, but it's small, you're young, and if we could wait three or five years without treating, great, you've had a chance to live through another phase of life."

Mr. MacMahon sat without speaking for a moment. "So it's up to me to decide," he finally said.

His father, taking notes, looked up and asked about the risks of waiting. Dr. Scardino estimated that if Mr. MacMahon postponed treatment for five years, there was a 5% reduction in the chance that surgery would cure him. "The wisest thing to do is be treated," he said.

His mother strongly favored surgery. Even if he could bank sperm for future use, she was sad that surgery might leave her son infertile. "It's a door that will close, and it's a pretty final door," she says. But when he asked the doctor about the possibility of delaying treatment until he was 40, she didn't wait for the answer. "There is no way you are waiting until you are 40," she told her son.

After the meeting, Dr. MacMahon continued to agonize. He thought the chances of the cancer harming his son in the next five years were small. If the decision had been about him, he says he would wait. But he felt differently about his son. "I don't want him to take the chance," he said.

Dr. Scardino and other researchers recently published a risk-assessment profile to help men decide whether to delay treatment. According to that profile, there was an 80% likelihood Mr. MacMahon had a small cancer that wasn't life-threatening at the moment. "The problem is you want to be 99% sure before you recommend that someone his age do nothing," Dr. Scardino says. "The price you pay for being wrong is very high."

After listening to the doctor tick off the information they had, Mr. MacMahon said, "I wish I had more data." But when he went back to work, he says it struck him that he made choices based on limited data every day.

Since his diagnosis, "I have been living every day like it might be my last," he says. He wanted to find a way to make cancer as normal a part of his life as possible.

The day after Thanksgiving, he went for a run. Later, he joined his parents, his brother and his sister-in-law at a Manhattan restaurant. At the table, he told his family what he had decided. That morning, he said, he signed up to compete in a triathlon to be held in New York City in June. Then he called Dr. Scardino to tell him he would have surgery in August.