Supiot Stephane, Shubbar Shubber, Fleshner Neil, Warde Padraig, Hersey Karen, Wallace Kris, Cole Heather, Sweet Joan, Tsihlias John, Jewett Michael A S, Klotz Laurence, Bristow Robert G
Princess Margaret Hospital (University Health Network), Toronto, Ont., Canada.
Radiother Oncol. 2008 Jul;88(1):53-60. doi: 10.1016/j.radonc.2008.03.019. Epub 2008 Apr 16.
Selected patients undergoing radical prostatectomy for localized prostate cancer can be at high-risk for pT3 disease and require subsequent radiotherapy. In a phase I trial, we investigated the feasibility of pre-operative radiotherapy for this patient subset.
Eligibility criteria were: T1/T2N0M0 tumors plus (i) Gleason >or=7, PSA>10 ng/ml and <35 ng/ml, or (ii), PSA >15 ng/ml and less <35 ng/ml (any Gleason). Patients received 25 Gy in five fractions of radiotherapy followed by radical prostatectomy. Trial endpoints included intra-operative morbidity and late toxicity following combined treatment. We also stained pre- and post-radiotherapy prostate samples for DNA damage response proteins.
Between 2001 and 2004, 15 patients were entered on trial. Thirteen patients completed combined-modality treatment. Only one patient had signs of intra-operative inflammation. No patient had post-operative complication. There was no severe late gastrointestinal toxicity. Late genitourinary toxicity consisted of severe urinary incontinence in 2 of 13 patients. From a translational standpoint, irradiated prostate tumor tissues had long-term activation of the CDK-inhibitor p21(WAF) associated with reduced cell proliferation.
Intra-operative morbidity is low following short-course, pre-operative radiotherapy. A phase II trial is planned to fully document biochemical response with this combined-modality approach.
