How to Determine if a Rising PSA after Radiation is from Cancer

Detecting a cancer relapse at an early stage after radiation can be challenging.  Certainly, progressive rises of PSA greater than 10 or 15 are an obvious sign of cancer relapse.  But delaying therapy and allowing such substantial increases in PSA before starting therapy is undesirable.  It’s much more preferable to initiate treatment at an earlier stage when the chance for cure is better. 

PSA monitoring after radiation is less accurate than PSA monitoring after surgery because the prostate gland (which produces PSA) continues to be present.

 PSA from the prostate gland creates background noise that has nothing to do with recurrent cancer.  I tell patients that a “normal” PSA after radiation will generally be less than 1.0 in men who are cured.  However, the PSA level can be above 1.0 after radiation in men that have unusually large prostate glands and in men who develop delayed radiation prostatitis, called the “PSA Bump (see below).”  Clearly, expertise is required for the interpretation of PSA levels after radiation.

Assessing an elevated PSA after radiation should initially lean on prostate imaging with color Doppler ultrasound or multi-parametric MRI.  Scanning accomplishes two things.  One, the prostate size can be determined.  Bigger prostates make more PSA, providing a benign explanation for a modest elevation of PSA levels.  Two, suspicious cancer lesions may also be detected by scanning.  However, interpreting scans after radiation can be challenging.

 Evaluating a suspicious lesion by doing a needle biopsy can also be problematic, especially within the first two years after radiation.  Cancer that is dying may still remain detectable on a biopsy during this time period.  Therefore, prostate biopsies performed within two years of radiation that indicate “cancer,” need to be interpreted with a grain of salt.

  Many of them will eventually disappear over time without further therapy.  

The pattern of PSA decline after radiation can be variable.  While PSA levels drop quickly in men receiving hormone therapy with the radiation, without hormone therapy it may take a couple of years for the PSA to drop to its nadir (nadir is defined as the lowest PSA attained after therapy).  As noted above, most men who are cured with radiation achieve a nadir of less than 1.0.

The “official” method for defining a cancer relapse that is used in clinical trials is having a PSA that increases more than 2 points above the nadir.  Caution needs to be exercised, however, in relying on any single ironclad rule.  While most, but not all PSA Bumps tend to be less than 2 points, it is possible for a Bump to drive up the PSA more than 2 points.  And please recall, a Bump is not a relapse.  In fact, a Bump may actually indicate a lower risk of relapse in the future.  When considering whether or not a PSA rise is due to a Bump or a cancer recurrence, several factors should be considered.

1.     The likelihood of recurrence is influenced by the original cancer profile at the time of the first treatment.  For purely statistical reasons, since men with high-risk disease are more likely to have a relapse a PSA rise due to a Bump is less likely.  Since men with low-risk disease are less likely to have a relapse, are rise in PSA is therefore more likely to be due to a Bump.

2.     When PSA levels are graphed out sequentially over time, cancer relapse tends to shows a smooth, steady unremitting upward curve.  Conversely, a PSA Bump is an inflammatory condition.  PSA levels tend to fluctuate up and down in a zig zag pattern.

3.     Particular care needs to be exercised in interpreting PSA levels in men with recovering testosterone levels after hormone therapy.  Hormone therapy almost always lowers PSA to less than 0.1.  When testosterone recovers, PSA originating from the prostate gland usually rises to some degree.  Small rises in PSA that occur when the hormone therapy is wearing off should not be interpreted as a cancer relapse!

Usually the best course of action, when there is doubt about the cause of a PSA rise, should be to continue monitoring with frequent PSA testing.  Over time the situation will declare itself one way or the other.  As is the case for men with newly-diagnosed prostate cancer, I am not a fan of using a 12-core random biopsy to search for recurrent cancer.  Some of problems with biopsy after radiation, particularly within two years of completing radiation, have already been discussed above.

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