The term “biochemical failure” means the presence of a rising PSA after any prostate cancer treatment. In fact, a rising PSA is the gold standard for suspecting prostate cancer recurrence (the cancer has come back). However, a precise, universal standard for defining biochemical failure is difficult because prostatectomy and radiation therapy have different aftereffects. Successful surgery creates a drop in PSA to zero because no prostate tissue is left behind to produce PSA. In this case, any rise in PSA is assumed to indicate biochemical failure, so the question then becomes its location and extent.
On the other hand, after radiation treatment the meaning of a rising PSA is less clear, especially in the early stages of cancer recurrence. This is because radiation destroys cancer over a period of months by interfering with the DNA of the cancer cells in such a way that they can’t reproduce and they gradually die off. Thus, the pre-treatment PSA continues to drop, or even bounce around, until it reaches its nadir or lowest point. PSA blood tests will be more frequent during the post-radiation period in order to track when nadir is reached, and stays put. But experts asked at what point after nadir would a rise, however small, suggest the treatment had failed? In 1996, the American Society for Therapeutic Radiology and Oncology (ASTRO) convened a special consensus conference to define that point. Agreement was reached that three consecutive rises in PSA after nadir indicated that the cancer was progressing. This was called the “ASTRO definition” of biochemical failure, but it proved unsatisfactory because it made comparing survival estimates based on different follow-up periods confusing. A second conference (held in Phoenix, AZ) redefined biochemical failure after radiation as a PSA increase of 2 ng/mL after nadir. This “Phoenix definition” formed the standard for clinical studies that examined the probability of mortality based on how early biochemical failure occurred following treatment.
At the 2009 annual ASTRO meeting, one such study was presented based on data from more than 2100 men whose localized prostate cancer was treated with radiation. The investigators reported that 19% of the men experienced biochemical failure at 18 months or sooner, and were 25% more likely to die from prostate cancer within 5 years. Specifically, according to a news release at that time, the “five-year cancer-specific survival for these men was 69.5% compared with 89.8% for men who developed biochemical failure after 18 months.”[i].
PSA testing as a way to monitor for biochemical failure is relatively inexpensive. Typically, however, when failure is evident (according to the Phoenix definition) many doctors either put such patients on hormone ablation, or simply hold off on treatment until the PSA climbs even higher. A huge advantage of multiparametric MRI over PSA is its ability to give visual definition to localized recurrence, assisting with an effective treatment plan—especially during an early stage when a salvage treatment such as focal ablation may still be curative. For more information on mpMRI detection of localized recurrence, see my article at https://sperlingprostatecenter.com/detection-localized-cancer-recurrence-using-mpmri/.