Post-Treatment PSA Nadir Heralds Increased Mortality After Localised Unfavourable-Risk Disease

Prostate-specific antigen nadir at the end of treatment for unfavourable localised prostate cancer but before biochemical failure identifies men with an increased risk of all-cause mortality

  • Date: 16 Jan 2017
  • Author: By Lynda Williams, Senior medwireNews Reporter
  • Topic: Prostate Cancer

medwireNews: Trial results from men with unfavourable-risk localised prostate cancer indicate that a prostate-specific antigen (PSA) nadir above 0.5 ng/mL after treatment with radiation alone or alongside 6 months of androgen deprivation therapy (ADT) is an early warning sign of a high risk of death.

“The clinical importance of this finding is that it provides an opportunity for patient selection for clinical trial entry at a time when the patient is still responding to but has not yet [been] declared as having failed primary therapy”, write Trevor Royce, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-workers.

They believe this would allow such patients to “be considered for entry on to clinical trials at the time of PSA nadir investigating standard of care (conventional ADT with [a] luteinizing hormone-releasing hormone agonist) with or without novel forms of hormonal therapy (eg, enzalutamide or abiraterone ) or cytotoxic chemotherapy (eg, docetaxel ) that have been shown to prolong survival in men with metastatic and castrate-resistant prostate cancer.”

The researchers collated data from a subgroup of 157 men with unfavourable-risk localised prostate cancer, defined as a PSA greater than 10 ng/mL but below 40 ng/mL, or a Gleason score of at least 7, or evidence of extracapsular extension and/or seminal vesicle invasion. The patients, all of whom had minimal or no comorbidity, took part in a randomised clinical trial comparing radiation therapy with or without ADT and were followed-up for a median of 16.5 years.

This allowed the team to use the Prentice criteria for surrogacy to assess four possible surrogate endpoints for all-cause mortality: PSA failure; PSA nadir above 0.5 ng/mL; PSA doubling time of less than 9 months, and a time to PSA failure of less than 30 months.

All but the PSA failure marker met the criteria for surrogacy, giving adjusted hazard ratios for all-cause mortality of 1.72 for PSA nadir, 2.06 for PSA doubling time and 1.76 for interval to PSA failure.

And for these three surrogates, the corresponding proportion of treatment effect values, denoting what proportion of the treatment effect can be explained by the surrogate endpoint, were 103.86%, 43.09% and 41.26%.

Thus, PSA nadir greater than 0.5 ng/mL, with the value closest to 100%, was determined to be the “optimal surrogate” for all-cause mortality, the researchers explain.

Noting that PSA failure was not a surrogate endpoint for all-cause mortality even among these men in otherwise good health, the authors say this has “potential implications” for the management of patients with moderate-to-severe comorbidity after PSA failure. 

Such patients might therefore be “optimal candidates for surveillance” rather than salvage ADT, they suggest, “[p]articularly given the known cardiometabolic adverse effects of ADT, which can at the very least lessen quality of life and perhaps quantity of life in such men.”


Royce TJ, Chen M-H, Wu J, et al. Surrogate end points for all-cause mortality in men with localized unfavorable-risk prostate cancer treated with radiation therapy vs radiation therapy plus androgen deprivation therapy. A secondary analysis of a randomized clinical trial. JAMA Oncol; Advance online publication 12 January 2017. doi:10.1001/jamaoncol.2016.5983

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