Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localized or locally advanced prostate cancer: An analysis of two randomized trials
The Lancet Oncology, 11/23/2011
Clinical Article
D'Amico AV et al. – After radiotherapy and 6 months of androgen suppression, men with PSA end values exceeding 0·5 ng/mL should be considered for long-term androgen suppression and those with localised or locally advanced prostate cancer with PSA nadir values exceeding 0·5 ng/mL should be considered for inclusion in randomized trials investigating the use of drugs that have extended survival in castration-resistant metastatic prostate cancer.
Methods- Systematically reviewed randomized controlled trials that showed improved overall and prostate cancer-specific survival with radiotherapy and 6 months of androgen suppression compared with radiotherapy alone and measured lowest PSA concentrations (PSA nadir) and those immediately after treatment (PSA end)
- Cohort of 734 men with localised or locally advanced prostate cancer from 2 eligible trials in USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001
- Used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0·5 ng/mL were surrogates for PCSM
- Men treated with radiotherapy and 6 months of androgen suppression in both trials were significantly less likely to have PSA end and PSA nadir values of more than 0·5 ng/mL than were those treated with radiotherapy alone (p<0·0001)
- Presence of candidate surrogates (ie, PSA end and PSA nadir values >0·5 ng/mL) alone and when assessed in conjunction with the randomised treatment group increased risk of PCSM in the US trial (PSA nadir p=0·0016; PSA end p=0·017) and Australasian trial (PSA nadir p<0·0001; PSA end p=0·0012)
- In both trials, randomized treatment group was no longer associated with PCSM (p≥0·20) when the candidate surrogates were included in the model
- Both PSA metrics satisfied Prentice criteria for surrogacy
