I have written numerous times over the years about the term biochemical recurrence. In case it’s not familiar, it’s only used for prostate cancer patients who have had a whole gland treatment for localized prostate cancer (PCa). Treating the entire gland can be done by surgically removing it (prostatectomy). It can also be accomplished non-surgically by treating the gland inside the body using beam radiation, seed implants (brachytherapy), freezing (cryotherapy) or HIFU (high intensity focused ultrasound).

Urologists refer to whole-gland procedures as definitive treatments, a term that most patients take to mean no further treatment will be necessary.^[i] However, that’s not always the case. In fact, PCa can come back after whole gland treatment for either of two reasons:

1. If PCa comes back after prostatectomy, it’s because undetected cancer cells had already left the gland and are growing somewhere else, or
2. Some cancer was missed, or survived nonsurgical treatments (radiation, brachytherapy, cryotherapy, HIFU).

Biochemical recurrence

In almost all cases of recurrence, the first warning is a rise in PSA. This is a biological substance that can be measured in the blood, called a biomarker. It’s like a whisper that active PCa might be present.

If the entire gland is removed, there is nothing to produce PSA so it is expected that PSA will fall to zero after prostatectomy and remain there for the rest of the patient’s life. If the entire gland is radiated, or has seed implants, it is expected that within a certain time period (usually 12-18 months, since PCa does not die all at once during radiation) the PSA will bottom out (called the nadir, or lowest point) at near zero and stay there for the rest of the patient’s life.

After any PCa treatment, it is vital to track each patient’s PSA over time. Especially after a definitive treatment, this is so important because a rise in PSA signals suspicion that PCa is back. This is exactly what biochemical recurrence means. Since PCa cells emit PSA just like healthy prostate cells, it is presumed that tumor activity somewhere in the body is causing the rising number. Then what? Well, the detective work begins. Imaging and other tests are used to locate the bad actors, and to determine the best strategy for treatment. There are rare occurrences of false positives, in which PSA rises but no cancer can be found. However, in most cases, a rise in PSA is a red flag and must be addressed.

Until recently, there were generally accepted PSA thresholds to alert doctors to probable biochemical recurrence. After surgery or whole gland ablation (cryotherapy or HIFU), a PSA that shows up at 0.2 ng/ml signifies the culprit is back. After radiation or seed implants, after nadir is reached a change in PSA greater than 0.2 ng/ml from two consecutive measurements is considered likely biochemical recurrence.

Thus, it is essential that PCa patients who have had a whole gland treatment comply fully with their doctor’s schedule for post-treatment PSA tests. It is reasonable that men who were diagnosed with higher grade (more aggressive) or larger tumors be tested more frequently.

PSA tracking during Active Surveillance

Keeping in mind that a PSA test only whispers that PCa is present, what about patients on Active Surveillance (AS)? They are men with low-to-favorable-intermediate-risk PCa whose doctors have cleared them to hold off on any treatment until their cancer enlarges and/or becomes more aggressive. For them, there are two main ways to monitor. The first, of course, is scheduled PSA tests; if there’s no change, AS may continue. The second is multiparametric MRI (mpMRI); this may be routinely done on an annual basis, but more often it’s done only if there’s an upward change in PSA. If the mpMRI reveals significant PCa, a targeted biopsy must be done, and the result determines if treatment is now needed.

PSA tracking after focal therapy

Just as after definitive whole gland treatment, a patient who has had a focal treatment like Focal Laser Ablation or TULSA for localized PCa should monitor PSA regularly. Today’s focal therapies that are guided by MRI have low recurrence rates comparable to whole gland treatments. However, if PSA rises after focal treatment, it usually means one of two things:

1. Either a new tumor is starting in the untreated part of the gland, implying that the patient’s disease was multifocal—as many prostate cancers are—but the tiny scattered cells were too microscopic to be picked up initially by mpMRI, or
2. Some PCa cells survived in the zone of ablation if the lethal temperature was not evenly distributed or the extent of the ablation wasn’t quite large enough.

However, note that rising PSA after focal treatment does not necessarily indicate cancer. For example, an infection or other condition that stimulates the prostate gland can raise PSA. Again, other tests including mpMRI are warranted to identify the exact cause, which may be noncancerous.

Rising PSA? Don’t panic        

Generally, routine PSA tests after their treatment cause at least a tinge of anxiety. This is normal, because there’s always a little worry that it means recurrence. However, detecting recurrence early is the key to outliving one’s cancer. There are excellent treatments, including focal therapy, customized to the patient’s needs. The important thing is, don’t be caught off guard. Stick to your doctor’s PSA follow up schedule and don’t rationalize that you can skip it this time because it’s been steady so far.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Soloway, MS et al. The Fallacy of “Definitive Therapy” for Prostate Cancer. European Urology, Volume 78, Issue 5, 650 – 651