Is Biochemical Response More Important Than Duration of Neoadjuvant Hormone Therapy Before Radiotherapy for Clinically Localized Prostate Cancer? An Analysis of the 3- Versus 8-Month Randomized Trial

Alexander, Abraham; Crook, Juanita; Jones, Stuart; Malone, Shawn; Bowen, Julie; Truong, Pauline; Pai, Howard; Ludgate, Charles

doi:10.1016/j.ijrobp.2009.01.030

« Previous Next »International Journal of Radiation Oncology * Biology * Physics
Volume 76, Issue 1 , Pages 23-30, January 2010

Is Biochemical Response More Important Than Duration of Neoadjuvant Hormone Therapy Before Radiotherapy for Clinically Localized Prostate Cancer? An Analysis of the 3- Versus 8-Month Randomized Trial

Presented at the 50th Annual American Society of Therapeutic Radiology Oncology Meeting, September 21–25, 2008, Boston, MA, and the 22^nd Annual Canadian Association of Radiation Oncology Scientific Meeting, Montreal, PQ, Canada.

Abraham Alexander, M.D., F.R.C.P.C.
- Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC, Canada
- Reprint requests to: Abraham Alexander, M.D., BC Cancer Agency, Vancouver Island Centre, 2410 Lee Avenue, Victoria, BC, Canada, V8R 6V5. Tel: (250) 519-5575; Fax: (250) 519-2018
Juanita Crook, M.D., F.R.C.P.C.
- Department of Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada
Stuart Jones, B.Sc.
- Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC, Canada
Shawn Malone, M.D., F.R.C.P.C.
- Department of Radiation Oncology, Ottawa Regional Cancer Center, Ottawa, ON, Canada
Julie Bowen, M.D., F.R.C.P.C.
- Department of Radiation Oncology, Northeastern Ontario Regional Cancer Center, Sudbury, ON, Canada
Pauline Truong, M.D., F.R.C.P.C.
- Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC, Canada
Howard Pai, M.D., F.R.C.P.C.
- Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC, Canada
Charles Ludgate, M.D., F.R.C.P.C.
- Radiation Therapy Program, British Columbia Cancer Agency, Vancouver Island Centre, University of British Columbia, Victoria, BC, Canada

Received 18 June 2008; received in revised form 15 January 2009; accepted 27 January 2009. published online 22 April 2009.

Purpose

To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) ≤0.1 ng/ml vs those >0.1 ng/ml.

Methods and Materials

From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA ≤0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome.

Results

Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA ≤0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome.

Conclusion

Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

Prostate cancer, Neoadjuvant androgen-deprivation therapy (ADT), Prostate radiotherapy, Prostate specific antigen (PSA)