Jim, a 57-year-old Boston businessman, climbs up on an examining room table at Brigham and Women's Hospital for a procedure that's high on most men's list of dreads: a prostate biopsy.
A doctor will push an eight-inch ultrasound wand into his backside, then insert a spring-loaded gun that shoots a dozen needles through the rectum into Jim's prostate gland. Each needle grabs a tiny piece of tissue that will be examined for evidence of cancer.
Ask him how he got to this point and Jim — who didn't want us to use his last name — gives an answer like one many men would: "The acceleration of my PSA level was quite rapid — more than doubled over the course of a year."
Doctors call it "PSA velocity," the change in the level of a chemical in the blood called prostate-specific antigen. In recent years, many doctors have come to rely on it as the best indicator for when it's time for an initial biopsy to check for prostate cancer.
But PSA velocity has come under challenge. A recent article in the Journal of the National Cancer Institute concludes that a rising PSA is no better sign of incipient prostate cancer than the old signal — a PSA level over a specific threshold. That's often 4 nanograms of PSA in a thousandth of a liter of blood. (A healthy man's PSA level can range from zero to 10 and beyond.)
"We found out that in many cases, to our complete surprise, [PSA velocity] didn't really tell us very much at all," says Andrew Vickers, a biostatistician at Memorial Sloan-Kettering Cancer Center in New York and lead author of the study.
"Once you knew what somebody's PSA level was, their change in PSA, or PSA velocity, was essentially uninformative," Vickers says of his results, "particularly for the aggressive cancers, the ones we should really be worrying about."
De-Emphasize The PSA Velocity Test?
Vickers and his colleagues say they think PSA velocity should be removed from guidelines as an indicator for first-time biopsies. The American Urological Association and the National Comprehensive Cancer Network endorse the use of PSA velocity in their guidelines.
Dr. Michael Barry agrees. He's a primary care doctor at Massachusetts General Hospital and president of the Foundation for Informed Medical Decision-Making.
"I think the guidelines should be rewritten to de-emphasize PSA velocity in making an upfront decision about whether to have a biopsy or not," Barry says. "I think Dr. Vickers' study is the strongest data yet."
But other experts remain convinced in the value of a rising PSA level as a trigger for biopsy.
"If you are under the age of 60 and you've had a PSA rise of more than half-a-point in a year, your likelihood of having prostate cancer is markedly increased and you should have a prostate biopsy," says Dr. Anthony D'Amico, a prostate-cancer expert at Harvard Medical School. For men over 60, the trigger should be a rise of more than three-quarters of a point in a year, he says.
D'Amico says Vickers' study has an important flaw — it cannot guarantee that many of the 5,519 men whose prostate biopsies it considered did not have elevated PSAs for reasons having nothing to do with cancer. They might have done a lot of bike riding, or they might have had sex shortly before their PSA test, or a recent colonoscopy. All can increase PSA.
The debate is not merely academic. Well over a million American men have prostate biopsies every year.
Most of these are "unnecessary," Vickers says. "It's a biopsy done in a man who does not have prostate cancer."
Why Doctors Turned To PSA Velocity
PSA velocity emerged over the past decade as a strategy to cut down on unnecessary biopsies that are an inevitable problem when a biopsy is ordered on the basis of a given PSA threshold.
Barry explains the problem: For most of the past two decades, he says, doctors assumed "there wasn't much prostate cancer south of a PSA threshold of about four."
But a 2003 study called the Prostate Cancer Prevention Trial, which biopsied nearly all participants, whatever their PSA level, discovered that 15 percent of men with PSAs less than four had prostate cancer — and about 15 percent of those were aggressive, potentially lethal cancers.
At the same time, most men who had PSA levels "north" of four didn't have detectable prostate cancer, and many of those who did had low-grade cancers that probably didn't need to be treated because they grow so slowly that they wouldn't cause a problem.
But many of these cancers get treated anyway, because it's hard for both doctors and patients to stand by and do nothing after cancer is found. (Lately, many experts have been advocating a strategy of watchful waiting — or "active surveillance" — of these low-grade tumors. But Barry notes that this approach hasn't caught on much among activist Americans.)
The findings that a "raw" PSA number as an indicator for biopsy missed many cancers and "over-diagnosed" others shook up experts. They sought to find a better way, and it looked like measuring increases in PSA over time would fit the bill.
It seemed like "an absolutely great idea," Vickers says. "When you think about it, the thing about cancer is it's a growth process. What really matters is how fast it's growing, not its current size. So with PSA, the thought was, 'Well, let's see how it's changing.' The initial evidence was promising. But it didn't turn out that way."
PSA Numbers Still Important
If Vickers is right, the only current alternative is a return to the imperfect use of a PSA threshold number — perhaps using a lower threshold of three or even less for younger men who have many more potential years of life, and a higher threshold for older men with shorter life spans and also higher PSA levels due to benign enlargement of the prostate, a very common occurrence among older men.
It's important to note, by the way, that a rapidly rising PSA is still a very important sign for some men.
For instance, for men who have already had a negative biopsy, perhaps because of a higher PSA due to enlarged prostate, an increase in PSA velocity is probably a more reliable indicator of cancer. And for men being treated for known prostate cancer, a rising PSA can signal recurrence of cancer in organs outside the prostate.
And what about Jim, the Boston businessman who bravely let us watch his biopsy? Well, his procedure is over in the time it took you to read this article.
"Really, it wasn't bad at all," he says. "I would say if you're told to get a biopsy, you should do it. It's not painful and it could save your life, ultimately, if there's a problem there."
And by the way, there's no question Jim needed his biopsy — whether or not you believe in PSA velocity. That's because his PSA recently spiked to 10.
"This is enough of a rise that you have to explain it," says O'Leary, the urologist who did Jim's biopsy. "It could well turn out to be benign disease and that will be great. But I think the responsibility is on us to prove that this is benign disease."
Once a man's PSA level gets that high — and is confirmed by more than one test — O'Leary says there's little choice: A doctor has to find cancer or rule it out — if he can.