Fitch DL et al. (2006) Unification of a common biochemical failure definition for prostate cancer treated with brachytherapy or external beam radiotherapy with or without androgen deprivation. Int J Radiat Oncol Biol Phys 66: 1430–1439

Various definitions of biochemical failure are used to assess prostate cancer recurrence after radiotherapy. Debate continues over which definitions provide optimal reproducibility and correlate best with clinical outcomes; Fitch and colleagues, therefore, retrospectively analyzed data from 2,376 patients with localized, T1–3N0M0 prostate cancer treated at a single center, to determine an optimal definition for biochemical failure.

In total, 1,201 men received conventional-dose (median 66.6 Gy) external-beam radiotherapy (EBRT), 465 received high-dose (median 75.6 Gy) adaptive EBRT, 416 received EBRT and brachytherapy, and 294 received brachytherapy only. Overall, 21% (496 men) also received neoadjuvant androgen deprivation. Patients were followed up 1 month after radiotherapy and every 3–6 months thereafter (median 4.5 years).

The authors assessed multiple definitions of biochemical failure for their positive and negative predictive values and sensitivity and specificity, in predicting local or distant metastasis and survival. Most definitions outperformed the American Society for Therapeutic Radiation and Oncology criteria for biochemical failure (three consecutive PSA rises); however, those that performed best were a PSA threshold of ≥3 ng/ml at or after nadir—which appeared to be optimal—and a PSA rise of ≥2 ng/ml above nadir. The authors call for further studies to confirm their results.

Surprisingly, all definitions performed better in brachytherapy-treated patients than in those treated with EBRT only. The authors attribute this finding to the particularly low PSA nadir values of brachytherapy-treated patients.