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A Critical Analysis Of the Interpretation Of Biochemical Recurrence In Surgically Treated Patients Using the Revised ASTRO Criterion (“Nadir + 2”)
Matthew E. Nielsen, Danil V. Makarov, Elizabeth Humphreys, Leslie Mangold, Alan W. Partin, Patrick C. Walsh
Johns Hopkins, Baltimore, MD
Introduction: A combined ASTRO/RTOG consensus conference was convened in 2005 to address shortcomings of the 1997 consensus definition of biochemical failure after radiation therapy for prostate cancer. The updated recommendation is that failure after radiation be defined as a PSA ≥ absolute nadir PSA plus 2 ng/ml. We evaluated the effects of this definition on the interpretation of failure when applied to radical prostatectomy.
Methods: We reviewed data from 2,570 men who underwent radical prostatectomy from 1985 to 2004. Biochemical failure was defined as any measurable PSA ≥0.2 ng/ml. We evaluated how the nadir+2 definition affected the failure rate when applied to this series.
Results: The actuarial 5-, 10- and 15-year biochemical recurrence-free survival probabilities with failure defined as PSA>0.2 ng/ml and PSA≥2 ng/ml were 88.6%, 81.2% and 78.1%, and 94.6%, 89.4%, and 84.3%, respectively (p<0.0001). Median time to biochemical progression was 2.8 years for the >0.2 ng/ml definition and 7.9 years for the ≥ 2 ng/ml definition. The nadir+2 definition systematically overestimated cure, even after stratifying patients into standard prognostic risk groups, especially in men who developed local recurrence.
Conclusions: When applied to a mature series of surgically treated patients with localized prostate cancer, the ASTRO “nadir+2”definition of biochemical failure results in a systematic overestimation of cure, relative to the standard surgical definition. This was particularly evident for men who developed local progression. Caution must be exercised when comparing outcomes between series due to inherent differences in the definition of biochemical failure.
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