Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial

BACKGROUND - The relative effects of radiation dose escalation (RDE) and androgen suppression (AS) duration on local prostatic progression (LP) remain unclear.

METHODS - We addressed this in the TROG 03.04 RADAR trial by incorporating a RDE programme by stratification at randomisation. Men were allocated 6 or 18months AS±18months zoledronate (Z). The main endpoint was a composite of clinically diagnosed LP or PSA progression with a PSA doubling time ⩾6months. Fine and Gray competing risk modelling with adjustment for site clustering produced cumulative incidence estimates at 6.5years for each RDE group.

RESULTS - Composite LP declined coherently in the 66, 70 and 74Gy external beam dosing groups and was lowest in the high dose rate brachytherapy boost (HDRB) group. At 6.5years, adjusted cumulative incidences were 22%, 15%, 13% and 7% respectively. Compared to 6months AS, 18months AS also significantly reduced LP (p<0.001). Post-radiation urethral strictures were documented in 45 subjects and increased incrementally in the dosing groups. Crude incidences were 0.8%, 0.9%, 3.8% and 12.7% respectively.

CONCLUSIONS - RDE and increasing AS independently reduce LP and increase urethral strictures. The risks and benefits to the individual must be balanced when selecting radiation dose and AS duration.

Radiother Oncol. 2015 Jun;115(3):301-7. doi: 10.1016/j.radonc.2015.05.016. Epub 2015 Jun 10.

Denham JW1, Steigler A2, Joseph D3, Lamb DS4, Spry NA3, Duchesne G5, Atkinson C6, Matthews J7, Turner S8, Kenny L9, Tai KH5, Gogna NK10, Gill S3, Tan H3, Kearvell R3, Murray J4, Ebert M3, Haworth A5, Kennedy A5, Delahunt B11, Oldmeadow C12, Holliday EG12, Attia J12.

1 School of Medicine and Public Health, University of Newcastle, Australia.
2 School of Medicine and Public Health, University of Newcastle, Australia.
3 Sir Charles Gairdner Hospital, Perth, Australia.
4 Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.
5 Peter MacCallum Cancer Centre, Melbourne, Australia.
6 St Georges Cancer Care Centre, Christchurch, New Zealand.
7 Auckland Hospital, New Zealand.
8 Westmead Hospital, Sydney, Australia.
9 Royal Brisbane and Women's Hospital, Australia.
10 Mater Radiation Oncology Centre, Princess Alexandra Hospital, Brisbane, Australia.
11 Wellington School of Medicine and Health Sciences, University of Otago, New Zealand.
12 School of Medicine and Public Health, University of Newcastle, Australia; Hunter Medical Research Institute, Newcastle, Australia