Biochemical failure in prostate cancer

«The definition of biochemical recurrence following radiation therapy is complicated by the incomplete ablation of all functioning prostatic epithelium, which creates difficulty in establishing a meaningful absolute nadir and the phenomenon of “prostate-specific antigen (PSA) bounce”» [4]. Biochemical failure after primary radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer by 2005 RTOG-ASTRO Phoenix Consensus Conference is: 1) PSA rise by 2 ng/mL or more above the nadir PSA; and 2) a recurrence evaluation should be considered when PSA has been confirmed to be increasing after radiation even if the rise above nadir is not yet 2 ng/mL, especially in candidates for salvage local therapy who are young and healthy [1]. The rise has to be at least 25% over nadir [5]. «This definition accepts some limitation on sensitivity in the interest of increased specificity for detecting failures associated with clinical outcomes other than cure» [4].
Following radical prostatectomy, a cutoff of 0.2 ng/mL has been associated with a high likelihood of subsequent PSA progression [2]. More recently, 0.4 ng/mL and rising has been proposed as a definition associated more closely with the development of distant metastases [3]. However, according to the ASTRO/AUA (American Urological Association) guidelines [6], «biochemical (PSA) recurrence after surgery is defined as detection of PSA concentration at 0.2 ng/mL, with a second confirmatory level detected at 0.2 ng/mL.»
Following salvage radiotherapy, biochemical recurrence is «defined as a rise in PSA ≥ 0.2 ng/ml above the PSA nadir followed by a sequentially equal or higher value [7].»

Bibliographic references:

[1] Roach M 3rd, Hanks G, Thames H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):965-74. Available at: https://doi.org/10.1016/j.ijrobp.2006.04.029.
[2] Freedland SJ, Sutter ME, Dorey F, Aronson WJ. Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology. 2003 Feb;61(2):365-9. Available at: http://dx.doi.org/10.1016/S0090-4295(02)02268-9.
[3] Amling CL, Bergstralh EJ, Blute ML, et al. Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point? J Urol. 2001 Apr;165(4):1146-51. Available at: http://dx.doi.org/10.1016/S0022-5347(05)66452-X.
[4] Nielsen ME, Partin AW. The Impact of Definitions of Failure on the Interpretation of Biochemical Recurrence Following Treatment of Clinically Localized Prostate Cancer. Rev Urol. 2007 Spring;9(2):57-62.
[5] Lowrance WT, Roth BJ, Kirkby E, Murad MH, Cookson MS. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015. J Urol. 2016 May;195(5):1444-52. Available at: https://doi.org/10.1016/j.juro.2015.10.086.
[6] Valicenti RK, Thompson I Jr, Albertsen P, et al. Adjuvant and salvage radiation therapy after prostatectomy: American Society for Radiation Oncology/American Urological Association guidelines. Int J Radiat Oncol Biol Phys. 2013 Aug 1;86(5):822-8. Available at: https://doi.org/10.1016/j.ijrobp.2013.05.029.
[7] Jackson WC, Suresh K, Tumati V, et al. Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure. Eur Urol Oncol. 2018 Sep;1(4):276-282. Available at: https://doi.org/10.1016/j.euo.2018.04.014.