Kupelian PA et al. (2006) Use of different definitions of biochemical failure after external beam radiotherapy changes conclusions about relative treatment efficacy for localized prostate cancer. Urology 68: 593–598

Biochemical failure is defined differently for patients with localized prostate cancer treated with radical prostatectomy or radiotherapy, which has confounded comparison of these treatment modalities. In radiotherapy-treated patients, the standard definition of biochemical failure requires three successive PSA increases after a nadir, but a PSA increase of 2 ng/ml above nadir has been proposed as an alternative. Biochemical failure after radical prostatectomy is defined as PSA >0.2 ng/ml.

Kupelian et al. evaluated the effect of these different definitions on the estimation of biochemical relapse-free survival in 2,516 consecutive patients treated for localized prostate cancer with radical prostatectomy (n = 1,467) or external-beam radiotherapy (n = 1,049). In radiotherapy-treated patients, the alternative definition gave a 13% greater biochemical relapse-free survival estimate at 5 years, but a 12% lower estimate at 10 years, compared with the standard definition. Higher radiotherapy doses were associated with better outcomes irrespective of the definition used. After adjustment for confounding variables, radical prostatectomy was associated with better biochemical relapse-free survival than radiotherapy only with the standard definition.

Kupelian and colleagues note that the alternative definition could delay initiation of salvage therapy, because it underestimates early treatment failures compared with the standard definition. The observation that these definitions reached different conclusions on the relative efficacies of radiotherapy and radical prostatectomy could confuse clinicians and patients who are considering treatment options. Ultimately, data on mortality and distant metastases will be required to determine which definition is most accurate.