BACKGROUND: The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). METHODS: A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen. RESULTS: BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM. CONCLUSIONS: The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.
BACKGROUND: The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). METHODS: A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen. RESULTS: BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM. CONCLUSIONS: The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.
Authors: Mira A Patel; Marisa Kollmeier; Sean McBride; Daniel Gorovets; Melissa Varghese; Luanna Chan; Andrea Knezevic; Zhigang Zhang; Michael J Zelefsky Journal: Radiother Oncol Date: 2019-06-06 Impact factor: 6.280
Authors: Michele Billia; Khurram M Siddiqui; Susanne Chan; Fan Li; Ali Al-Zahrani; Jose A Gomez; Joseph L Chin Journal: Can Urol Assoc J Date: 2016 Nov-Dec Impact factor: 1.862
Authors: Nicholas G Zaorsky; Thomas M Churilla; Karen Ruth; Shelly B Hayes; Mark L Sobczak; Mark A Hallman; Marc C Smaldone; David Yt Chen; Eric M Horwitz Journal: Am J Clin Nutr Date: 2016-10-26 Impact factor: 7.045
Authors: Nicholas G Zaorsky; Nitin Ohri; Timothy N Showalter; Adam P Dicker; Robert B Den Journal: Cancer Treat Rev Date: 2013-03-01 Impact factor: 12.111
Authors: S P Rowe; M A Gorin; M E Allaf; K J Pienta; P T Tran; M G Pomper; A E Ross; S Y Cho Journal: Prostate Cancer Prostatic Dis Date: 2016-05-03 Impact factor: 5.554
Authors: Marijo Bilusic; David J Einstein; Fatima H Karzai; William L Dahut; James L Gulley; Jeanny B Aragon-Ching; Ravi A Madan Journal: Urol Clin North Am Date: 2020-11 Impact factor: 2.241