Refining the Definition of Biochemical Failure in the Era of Stereotactic Body Radiation Therapy for Prostate Cancer: the Phoenix Definition and Beyond.

Abstract Background and purpose The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA)+2ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs. Materials and methods PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA18month/PSA6month) and timing of reaching nPSA+2 with BCF. Results Median follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16ng/mL. False positivity of nPSA+2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA+1.5, nPSA+1.0, and nPSA+0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA+threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p Conclusion The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA≥2.6 or time to nPSA+2≥18 months).