Prostate-specific antigen nadir and testosterone level at prostate-specific antigen failure following radiation and androgen suppression therapy for unfavorable-risk prostate cancer and the risk of all-cause and prostate cancer–specific mortality Journal Article


Authors: Bitterman, D. S.; Chen, M. H.; Wu, J.; Renshaw, A. A.; Loffredo, M.; Kantoff, P. W.; Small, E. J.; D'Amico, A. V.
Article Title: Prostate-specific antigen nadir and testosterone level at prostate-specific antigen failure following radiation and androgen suppression therapy for unfavorable-risk prostate cancer and the risk of all-cause and prostate cancer–specific mortality
Abstract: BACKGROUND: Although both PSA nadir (PSAn) and testosterone levels at PSA failure are known prognostic factors in men undergoing radiation therapy (RT) and androgen deprivation therapy (ADT) for unfavorable-risk prostate cancer (PC), it is unclear whether their prognostic significance is independent or overlapping. METHODS: Seventy-five men treated with RT with or without 6 months of ADT for unfavorable-risk nonmetastatic PC enrolled in 2 prospective clinical trials between 1986 and 2001 formed the study cohort. Competing risks and Cox multivariable regression were used to assess whether low versus normal serum testosterone at the time of PSA failure and higher PSAn after initial therapy were independently associated with the risk of PC-specific (PCSM) and all-cause mortality (ACM) adjusting for PC prognostic factors. RESULTS: After a median follow-up of 15.34 years (interquartile range, 6.66-16.88 years), there were 53 deaths (73.3%): 30 (56.6%) were from PC. Low testosterone at PSA failure was significantly associated with an increased risk of PCSM (adjusted HR [AHR], 7.77; 95% CI, 1.14-52.99; P =.04) and ACM (AHR, 3.01; 95% CI, 1.01-8.96; P =.05), as was higher PSAn (PCSM AHR, 1.03; 95% CI, 1.01-1.05; P <.01; ACM AHR, 1.04; 95% CI, 1.02-1.07; P <.01), although the prognostic significance of PSAn was only noted in men with a normal testosterone at PSA failure. CONCLUSIONS: Low testosterone level at PSA failure in high-risk patients with PC treated with RT is associated with increased PCSM and ACM risk. In men with normal testosterone levels at the time of PSA failure, an elevated PSAn was associated with worse PCSM and ACM risk. LAY SUMMARY: This study investigates whether the prostate-specific antigen (PSA) nadir and normal versus low testosterone at the time of PSA failure provide mutually exclusive or overlapping prognostic information following treatment with radiation and androgen deprivation therapy for unfavorable-risk patients with prostate cancer using data from 2 prospective clinical trials. It was found that both provided prognostic information; however, higher PSA nadir was only found to be of prognostic significance in men with normal testosterone levels at PSA failure. © 2021 American Cancer Society
Keywords: radiotherapy; prostate cancer; prostate-specific antigen; death; biochemical failure; testosterone; prostate-specific antigen (psa) failure; prostate-specific antigen (psa) nadir
Journal Title: Cancer
Volume: 127
Issue: 15
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2021-08-01
Start Page: 2623
End Page: 2630
Language: English
DOI: 10.1002/cncr.33543
PUBMED: 33823065
PROVIDER: scopus
PMCID: PMC9436009
DOI/URL:
Notes: Article -- Export Date: 2 August 2021 -- Source: Scopus
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  1. Philip Wayne Kantoff
    197 Kantoff