Prostate Cancer: Further Tests, Biopsy and Confirmation

When you've had a digital rectal exam (DRE) and probably a couple of rounds of prostate-specific antigen (PSA) tests, your medical team has only begun to scratch the surface of the required testing. There's still a tremendous amount of work involved in figuring out the problem and determining if it requires treatment.

Though your primary care physician has likely asked you a number of questions about your medical and family history, and general health, a urologist will likely dig even deeper.

"We're going to take our own focused history and physical," said Aditya Bagrodia, M.D., a urologic oncologist with the University of California San Diego Health. "That will largely touch on family history, specifically prostate cancer, breast cancer, endometrial cancer, lymphoma, leukemia or pancreatic cancer, because that may suggest you have hereditary cancer predisposition syndrome."

Bagrodia said a urologist might also request information on urinary parameters, such as urinary frequency, urgency, straining to void and waking up at night. Additionally, expect to be asked about your sexual history, ability to maintain an erection, sexual activity and so forth.

Testing in the wake of a suspicious DRE or PSA test is varied, gets better by the year and ranges from more simple blood tests to an invasive biopsy.

PSA test

First things first: When you see a specialist about a worrying preliminary prostate exam, you'll probably undergo another blood draw to measure PSA again. Prostate-specific antigen is a protein produced by both cancerous and noncancerous cells in the prostate gland, and elevated levels can indicate the presence of cancer. But there are tons of variables involved that can affect the results of the PSA test, which hinders the ability to confirm one or even two separate tests as conclusive. You can think of the PSA test as a warning sign pointing out potential danger ahead, but certainly not a determination of what's to come.

"The PSA is a nonspecific test," Bagrodia said. "It can be elevated from sexual activity, bike riding, inflammation without infection and person-specific variations. We may want to verify it, then basically the options are manifold. If it's a very sick patient with a relatively low PSA, we may say this is something that we're never going to need to fool with or we'll check it again in a period of time."

4Kscore test

The second line of testing may involve looking for even more specific blood markers for prostate cancer. While the PSA test is a solid starting point, further tests, such as the 4Kscore test, are considered reliable indicators of the potential for a man to develop an aggressive type of prostate cancer.

The 4Kscore test is actually the amalgamation of four separate blood tests for proteins produced by the prostate:

1. Total PSA: PSA molecules in the blood that are attached to proteins.
2. Free PSA: PSA molecules that are freely floating in the blood.
3. Intact PSA: PSA molecules in the blood that are currently inactive.
4. Human kallikrein 2 (or hK2): Another marker that's related to PSA.

Using the 4Kscore data—along with other factors, including the man's age, family history, genetic background, DRE results and whether he's had a prior biopsy—medical providers can determine the percentage of likelihood that the man's cancer is a fast-growing type and likely to spread.

MRI

Next up would probably be an MRI. Magnetic resonance imaging technology takes 3D images of body parts to determine the presence of disease or damage. Studies show that MRI in the hands of a skilled technician is quite effective at predicting higher-grade prostate cancer, as well as eliminating the need for biopsy for men with abnormal PSA levels but no tumor growth.

"The MRI gives you a lot of information on the size of the prostate, the anatomy of the prostate, are there any lesions that are targetable," Bagrodia said. "So we can actually index the PSA to the size of the prostate. Suffice to say, a huge prostate is a little more likely to be associated with a benign prostate-making [excess] PSA. And then, of course, there could be targetable lesions."

However, even with as much valuable information as the MRI provides, it can still miss something.

"If the prostate MRI is stone-cold clear, there's still a 10 to 15 percent chance there's a lesion," Bagrodia said. "MRIs are good—they're not perfect. That's a conversation between a patient and his urologist, again taking in age, size, density, family history, anxiety, age, all of it—and making a decision if we just do a standardized random sampling [biopsy] to put this to rest or do we just follow the PSA."

Biopsy

Providing better, more precise information for the patient and his medical provider is the goal of MRI and tests such as the 4Kscore. They provide pieces of the puzzle that were unavailable less than a generation ago.

Crucially, this information can mean the difference between needing to undergo a biopsy or not.

However, once the die has been cast and a biopsy is on the menu, here's what you can expect.

There is a newer procedure called a transperineal biopsy, in which the prostate gland is reached via a needle inserted into a small incision between your testicles and anus, whereas the typical method is transrectal, when a small probe inserted into your rectum delivers a set of numbing shots to the affected area before the doctor takes samples from the prostate.

"We can do it in the office, we can do it with local anesthetic or we can give you mild sedation, like a colonoscopy-type of twilight sedation," said Jayram Krishnan, D.O., a urologist with the Cleveland Clinic. "So you come in, we numb up your prostate and we take 12 small samples transrectally."

It's not a pleasant sensation, having a needle jabbed into your prostate a dozen times through your rectum wall, which is why the development of the 4Kscore and MRI technology is welcome, as it allows a high percentage of men who might otherwise be subjected to a biopsy to avoid it.

One study looking at an experimental new urine test to predict aggressive prostate cancer found only 22 percent of men who had a biopsy following an elevated PSA level had cancers of grade 2 or higher—those are the types that warrant immediate intervention. The remainder would probably be candidates for active surveillance and periodic PSA level tests.

"There's a lot of discomfort while you're doing [the biopsy]," Krishnan said. "We try to minimize that by doing a lot of local anesthesia right around the prostate. But you have to understand there's a lot of psychological barriers. First of all, we're going in through the rectum and we're taking about 15 minutes, so it's not done in a minute."

Even when every other avenue has been exhausted and a biopsy seems necessary, you can rest assured the techniques developed in recent years make the experience as effective as possible. By combining MRI and ultrasound technology, trained healthcare providers can hone in on the precise areas that look suspicious.

"The gold standard would probably be an MRI-ultrasound fusion biopsy," Bagrodia said. "It just makes sure that you're hitting the areas that are likely to be cancer. That's just 101: that you're not just missing a lesion. You could go straight to a biopsy, but generally, that's not going to be as effective."

While a biopsy is uncomfortable, the silver lining is it doesn't have any lasting effects, just some temporary if slightly distressing visual ones.

"You don't really have much pain or discomfort afterward," Krishnan said. "The biggest thing is there could be blood in the urine, blood in the stool or blood in the semen, and they can last up to one week. Sometimes, the blood in the semen can last a little longer."

But if the price for a precise indication of the type and location of cancerous cells in the prostate is a bit of harmless blood afterward, it's probably worth it.