Surrogate endpoints for prostate cancer-specific mortality after radiotherapy and androgen suppression therapy in men with localised or locally advanced prostate cancer: an analysis of two randomised trials

• Published in: The lancet oncology 2012-02, Vol.13 (2), p.189-195
• Main Authors: D'Amico, Anthony V, Prof, Chen, Ming-Hui, Prof, de Castro, Mario, ScD, Loffredo, Marian, RN, Lamb, David S, Prof, Steigler, Allison, BMath, Kantoff, Philip W, Prof, Denham, James W, Prof
• Format: Article
• Language: English
• Subjects: Aged; Androgen Antagonists - therapeutic use; Androgens; Androgens - metabolism; Antigens; Antineoplastic Agents, Hormonal - therapeutic use; Australia; Biomarkers - analysis; Cancer therapies; Combined Modality Therapy; Hematology, Oncology and Palliative Medicine; Humans; Male; Meta-Analysis as Topic; Metastasis; Mortality; Prognosis; Prostate cancer; Prostate-Specific Antigen - analysis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - mortality; Prostatic Neoplasms - radiotherapy; Prostatic Neoplasms - therapy; Radiation therapy; Randomized Controlled Trials as Topic; Survival Analysis; United States
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(11)70295-9

Summary Background Androgen suppression therapy and radiotherapy are used to treat locally advanced prostate cancer. 3 years of androgen suppression confers a small survival benefit compared with 6 months of therapy in this setting, but is associated with more toxic effects. Early identification of men in whom radiotherapy and 6 months of androgen suppression is insufficient for cure is important. Thus, we assessed whether prostate-specific antigen (PSA) values can act as an early surrogate for prostate cancer-specific mortality (PCSM). Methods We systematically reviewed randomised 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). We assessed a cohort of 734 men with localised or locally advanced prostate cancer from two eligible trials in the USA and Australasia that randomly allocated participants between Feb 2, 1996, and Dec 27, 2001. We used Prentice criteria to assess whether reported PSA nadir or PSA end concentrations of more than 0·5 ng/mL were surrogates for PCSM. Findings 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 (p0·5 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