Paradoxical metastatic progression following 3months of neo-adjuvant androgen suppression in the TROG 96.01 trial for men with locally advanced prostate cancer
Denham JW, Steigler A, Tai KH, Joseph D, Matthews J, Atkinson C, Spry NA, Turner S, North J, Christie D, Wynne C, Lamb DS. Radiother Oncol. 2013 Apr 22. pii: S0167-8140(13)00155-2. doi: 10.1016/j.radonc.2013.03.025. [Epub ahead of print]

Source

School of Medicine and Public Health, The University of Newcastle, Australia. Electronic address: Jim.Denham@newcastle.edu.au.

Abstract

PURPOSE:

In the TROG 96.01 trial 6month neo-adjuvant androgen suppression (NAS) and radiotherapy (RT) for locally advanced prostate cancer prevented distant progressions (DPs) when compared to RT alone, but 3months did not. We ask why?

METHODS:

Between 1996 and 2000, 802 men with T2-4 N0 M0 prostate cancers received RT alone (0month NAS) to 66Gy, 3months or 6months NAS before RT. Interval hazards and cumulative incidences of DP were compared using competing risks methodology.

RESULTS:

In the first 4 follow-up years 39, 40 and 26 DPs were diagnosed in subjects treated with 0, 3 and 6month NAS, respectively. Compared with 0month, significant reductions in PSA doubling time in subjects with DP occurred following 3month NAS (p=0.01), but a significant reduction (p=0.01) and a near significant delay in DPs (p=0.06) occurred after 6month NAS. Subsequently 25, 20 and 11 DPs occurred in the three trial arms. After early secondary therapy for PSA or local progression 34, 19 and 12 DPs were diagnosed after median delays of almost 4years.

CONCLUSIONS:

The data are consistent with the failure of 3month NAS to prevent the progression of sub-clinical metastatic deposits already present before treatment.