How should biochemical recurrence be defined after external beam radiation therapy?

The authors aimed to evaluate if a new definition of biochemical recurrence is appropriate in prostate cancer treated with radical external beam radiation.

Prostate-specific antigen is a protein that is found at higher levels in the blood when prostate cancer is present. After prostatectomy (surgery to remove the prostate), prostate-specific antigen production ceases and its level in the blood approaches zero. Therefore, a detectable prostate-specific antigen level is considered to be due to local recurrent (returning) disease, or biochemical failure. Biochemical failure is typically defined as prostate-specific antigen levels rising more than 2 ng/ml above the lowest level of prostate-specific antigen previously experienced.

Radical external beam radiation is a type of radiation that is directed at the prostate gland from outside the body, and is the standard treatment for men with organ-confined prostate cancer. However, after radical external beam radiation cells that produce prostate-specific antigen may survive, meaning that prostate-specific antigen levels won’t immediately drop to zero but will typically decline slowly before increasing again (bounce). This means that following radical external beam radiation, prostate-specific antigen is less reliable in determining tumor activity. A new definition of biochemical failure (the Kamat definition) suggests that biochemical failure be defined as an increase in prostate-specific antigen level – measured at least 24 months after external beam radiation therapy – of greater than 1.5 ng/ml above the lowest level of prostate-specific antigen previously experienced.  

The aim of this study was to determine the reliability of the Kamat definition of biochemical recurrence.   

The records of 193 prostate cancer patients who were treated with radical external beam radiation and hormone therapy, which blocks the testosterone tumors need for growth, were studied. The average follow-up was 7.4 years.

Overall, cancer-specific survival for prostate cancer patients treated with external beam radiation and hormone therapy was 92.5% at 5 years and 76% at 10 years. Overall survival at 5 years was 87% and 60% at 10 years.

By the traditional definition of biochemical recurrence the 5-year biochemical failure-free survival rate was 83% compared to 92% when the Kamat definition was used. By the traditional definition the 10-year biochemical failure-free survival rate was 22% compared to 60% when the Kamat definition was used.

When analyzed in comparison to alternative definitions of biochemical recurrence, the Kamat definition was found to be more accurate in predicting clinical outcomes.

The authors suggest that future definitions of biochemical recurrence should take into account that prostate-specific antigen levels in the first two years after external beam radiation are not a reliable indicator of biochemical recurrence.  

The backwards-looking (retrospective) nature of the study means that therapy was not prescribed due to strict study guidelines, which may have influenced the results.