The Early Prostate Cancer Trial (EPC) was the largest prostate cancer (CaP) study ever undertaken. It evaluated adjuvant bicalutamide in patients across the world that still had their standard care primary therapy: whether watchful-waiting, radiotherapy or radical prostatectomy.

The original study was published in 2001, and two analyses followed; one in 2004 with 5.4 years follow-up and most recently in 2006 with 7.4 years follow-up. The study design, outcomes and conclusions remain controversial, and thus two substantial commentaries were published in the March 2006 issue of the BJU International.

The first commentary is from Dr. Cora Sternberg, a medical oncologist in Rome Italy. She critiques the fact that the EPC study was actually 3 trials around the world that had different participant mix with regard to CaP stage and distribution of treatments selected.

She notes that there was no improvement in overall survival in patients receiving bicalutamide. As such, she is concerned about the usage of subset analysis to define smaller populations of patients who benefited. For example, bicalutamide plus standard care improved objective progression-free survival (PFS) by 21% compared with standard care alone.

However, this was noted in only two of the three international trials and in her opinion questions the validity of broad interpretation that PFS is improved irrespective of the standard treatment rendered. Also, if patients in the placebo arm were treated with early salvage therapy for a PSA level increase they might have done equally well, but this was not done. Finally, Dr. Sternberg notes that initial reports suggested benefit from bicalutamide for even localized CaP, but now this is presented to benefit only those with locally advanced disease.

In his commentary, the study principal investigator Dr. Peter Iverson, Copenhagen Denmark points out that the EPC was designed to pool the 3 trials. He emphasizes that the sequential data analyses and reporting are a tribute to the integrity of the data set and permit identification of sub-populations of patients that benefit.

Dr. Iverson comments that adjuvant bicalutamide is not for every patient, but has benefit in some and significantly less toxicity than LHRH therapy. He admits that the large scope of the EPC trial and range of patients has damaged its impact, but hypothesizes that had an LHRH agonist been used in the EPC trial, its risks would have outweighed its benefit. This, of course is not known and the EPC continues to spark controversy and reinforce that optimal trial design is paramount to ascertaining data that is universally accepted and applicable.

BJU Int 2006; 97:435-39

By Christopher P. Evans, M.D.

Link Here.
Sternberg CN

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