Intergroup randomized controlled phase III trial of Androgen Deprivation Therapy (ADT) +/- Radiation Therapy (RT) in locally advanced prostate cancer (CaP) (NCIC-CTG, SWOG, MRC, INT: T94-0110; NCT00002633)


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Padraig R Warde2, Matthew R Sydes3, Keyue Ding8, Mary K Gospodarowicz2, Gregory P Swanson4, Peter Kirkbride5, Ed Kostashuk6, John Hetherington7, Andrea Hiltz8, Karen Sanders3, John Anderson5, Jim Barber1, Mahesh KB Parmar3, Wendy Parulekar8
2Princess Margaret Hospital and University of Toronto, Canada,3MRC Clinical Trials Unit, London, UK,4University of Texas Health Science Center, San Antonio, USA,5Weston Park Hospital, Sheffield, UK,6British Columbia Cancer Agency, Surrey, Canada,7Castle Hill Hospital, Hull, UK,8NCIC Clinical Trials Group, Kingston, Canada

Background

The impact of RT on overall survival (OS) in men with locally advanced prostate cancer (CaP) is unclear. SPCG-7 [1] showed a benefit for adding RT to anti-androgens in terms of for diseasespecific survival (DSS). We assessed the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP.

Method

Eligible patients had T3/T4 CaP (n=1057) or T2 with high-risk features(PSA>40μg/l (n=119) or PSA>20μg/l plus Gleason≥8 (n=25)); all were N0 /NX, M0. Men were randomised to lifelong ADT (bilateral orchiectomy or LHRH agonist) +/- RT (65-69Gy to prostate +/- 45Gy to pelvic nodes). The primary outcome measure was OS; secondary outcome measures included DSS

Results

Between 1995 and 2005,1205 patients were randomized in Canada, the UK and elsewhere, 602 ADT-alone, 603 ADT+RT. These were well balanced with respect to baseline characteristics. A protocol-specified 2nd interim analysis was performed with data cut-off at 31-Dec-2008. The independent data monitoring committee recommended release and presentation of these results. Median follow-up is 6.0 years and 320 patients have died. 10% of patients had no follow-up data beyond 2006. Addition of RT to ADT significantly reduced the risk of death (hazard ratio (HR) 0·77, 95%CI 0·61--0·98, p=0·033). 140 patients died of disease and/or treatment (89 ADT-alone, 51 ADT+RT). For DSS, the HR was 0·57 (95%CI 0·41--0.81, p=0.001) favouring ADT+RT. 10-year DSS was estimated at 15% for ADT+RT and 23% for ADT-alone. Grade ≥2 late gastro-intestinal toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT).

Conclusion

These results indicate a substantial benefit for ADT+RT in terms of OS and DSS with no clear evidence of an increase in late treatment toxicity. ADT+RT should now be the standard treatment approach for these patients. Acknowledgements Submitted on behalf of the NCIC CTG PR.3, MRC PR07 and SWOG JPR3 investigators. Supported by grants from NCI-US, CCSRI and MRC