BY MARK SCHOLZ, MD
PSA testing is an essential part of prostate cancer treatment, and it is done at various stages in a patient’s journey. Initial PSA screening of healthy men to detect prostate cancer is controversial. It has a marked propensity to drive thousands of men toward unnecessary prostate surgery. However, PSA screening also saves lives.
In a different role, using PSA to detect a cancer relapse in men who have had previous surgery or radiation is a totally different matter. In this context, PSA is the undisputed King of the Hill. None of the other major cancers—colon, lung, breast or pancreas—has a similar blood marker that accurately detects cancer relapse at such an early stage. PSA is truly great for signaling relapse. But it offers little help in determining where in the body the recurrent cancer is located.
The Implications of a PSA Relapse
PSA has been on the market for over 30 years, and we have learned several important things about what a rising PSA after surgery or radiation means:
- As noted above, PSA does not indicate where in the body the recurrent cancer is located. Traditional bone and CT scans (which have been the only technology available until just recently) are also unable to show where the prostate cancer located. These scans can detect the cancer’s location after the PSA has risen above 20 or 30. Unfortunately, at these high levels any chance for curing the cancer will have passed.
- The rate of PSA rise (called the PSA doubling time) is an excellent indicator of the seriousness of the relapse. Fast doubling times, those that are under 3 months for example, indicate a cancer that is behaving aggressively. This knowledge about the cancer’s behavior can be very helpful to guide the doctor in selecting treatment.
- Interpreting a PSA relapse in men who have had surgery versus those who have had radiation requires different methodologies. For surgery, almost any degree of PSA elevation indicates a relapse. After radiation, patients may see a rise in PSA for a variety of noncancerous reasons, including residual PSA from the prostate gland, post-radiation prostatitis (the PSA bump) and erratic testosterone levels after hormonal therapy. Determining the cause of a slightly elevated PSA after radiation—PSA levels between one and three for example—can be very difficult.
What We Know About Treating PSA Relapse
Over the last 30 years there has been notable progress in the way doctors manage men with rising PSA levels after surgery or radiation:
- We now know that salvage therapy with testosterone inactivating pharmaceuticals (TIP) results in PSA regression, usually back to undetectable levels, and offers cancer control for over 10 years, on average. TIP, however, is not curative. If TIP is stopped (and testosterone production resumes) the PSA will again rise.
- Sometimes men with relapsing PSA after surgery can still be cured with radiation targeted to where the prostate used to be. Sometimes men with relapsing PSA after radiation can be cured with cryotherapy to the residual prostate gland. These salvage therapies are more likely to succeed when treatment is administered to men with relatively low PSA: Under one in men who had surgery and less than three or four in men who have had radiation. Salvage treatment is more likely to be successful while the PSA is low because the likelihood of cancer spreading to other parts of the body is increases as the PSA increases.
- Recently there have been some astounding advancements in radiation therapy. High radiation doses can now be safely and accurately directed to locations of the body outside where the prostate used to be located. This opens up the possibility of curing cancer after it has spread!
- The Axumin PET scan, which was approved by the FDA in 2017, is the newest and possibly biggest game-changer for men with PSA relapse since the approval of PSA screening itself. For the first time we have a commercially-available scan that can detect the location of the cancer outside the prostate at a much earlier stage than what was possible with standard bone scans and CT scans. Axumin can detect the cancer’s location while PSA is in the one to five range, rather than in the 10 to 30 range.
The Need for a Cure
At this point we need to ask, “Why do we need to pursue a cure?” After all, many men facing PSA relapse are older, perhaps in their 70s or 80s. If TIP can control the disease for over ten years, why not simply rely on TIP? TIP is so effective that most men will live a normal life expectancy and ultimately die of other natural causes, not prostate cancer. Why try for a cure with salvage radiation or cryotherapy? The appeal for achieving a cure is obvious when you consider the attractiveness of avoiding TIP-related side effects: muscle loss, fatigue, impotence, low libido, depression, osteoporosis, memory problems, weight gain, hot flashes, breast enlargement, arthritis, liver problems and possibly an increased incidence of cardiovascular problems. Men who can be cured are spared from the need for lifelong TIP and enjoy a vastly improved quality of life.
How Does Axumin Work?
In light of the opportunity to avoid lifelong TIP, the Axumin PET scan is especially thrilling. Axumin can point to the location of the cancer at a much earlier stage so the chances of curing it are greatly increased. Axumin works by exploiting a discovery that prostate cancer cells have a big appetite for protein—prostate cancer “feeds” preferentially on amino acids, which are the building blocks of protein. Patients are given an intravenous injection a radioactive type of amino acid called FACBC. Due to the cancer’s predilection for amino acids, the prostate cancer cells rapidly suck up FACBC out of the blood stream. The patient is then placed immediately in a scanner. The location of the cancer in the body is demonstrated by the areas of concentrated radiation, AKA, “hot spots” of radioactivity.
Why Don’t Older Scans Work?
Prostate cancer, when it spreads, tends to spread sequentially, first to the lymph nodes in the pelvis then, as the PSA rises higher and higher, to the bones. With standard CT and MRI scans, detecting lymph node enlargement required tumors more than a half-inch in diameter. Axumin works by detecting the metabolic activity of the cancer rather than the tumor’s size. As such, it can detect tumors as small as a quarter-of-an-inch.
The Axumin PET scan is a spectacular technological advancement. In light of the recent advancements in radiation, which can now target lymph nodes safely with minimal side effects, Axumin provides the missing information the radiation therapist needs to accurately target the cancer.