Objectives: The new American Society for Therapeutic Radiology and Oncology/Radiation Therapy Oncology Group consensus definition of biochemical failure after radiotherapy for prostate cancer is defined as a prostate-specific antigen level at or greater than the absolute nadir PSA level plus 2 ng/mL. Because this definition inevitably will be used to compare cancer control rates after radiotherapy to those after surgery, this study examined the effect of this comparison. Methods: We reviewed the data from 2570 men who had undergone radical prostatectomy from 1985 to 2004. Biochemical failure was defined as any measurable PSA level of 0.2 ng/mL or greater. 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 probability with failure defined as a PSA level of 0.2 ng/mL or more and a PSA level of 2 ng/mL or more was 88.6%, 81.2%, and 78.1% and 94.6%, 89.4%, and 84.3%, respectively (P <0.0001). The median time to biochemical progression was 2.8 years for the greater than 0.2 ng/mL definition and 7.9 years for the 2 ng/mL or more definition. The nadir+2 definition systematically overestimated the biochemical recurrence-free survival, 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 American Society for Therapeutic Radiology and Oncology "nadir+2" definition resulted in a systematic delay in the determination of biochemical failure. Because patients in this series who experienced a detectable PSA level took more than 5 years to progress to a PSA level of 2 ng/mL or greater, the 5-year biochemical control rates with the definition of 0.2 ng/mL or more should be compared with the 10-year biochemical control rates using the nadir+2 definition.
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