PURPOSE: For prostate cancer that is thought to be locally recurrent after prostatectomy, the optimal timing, dose and techniques for salvage radiotherapy (SRT) have not been established. Here we perform a systematic review of published reports including regression meta-analysis and radiobiologic modelling to identify predictors of biochemical disease control and late toxicity. METHODS: We performed a review of published series reporting treatment outcomes following SRT. Studies with at least 30 patients, median PSA before SRT of less than 2.0 ng/mL, and median follow-up of greater than 36 months were identified. Univariate and multivariate analyses were performed to test Gleason Score, SRT dose, SRT timing, pre-SRT PSA, whole pelvic irradiation and androgen deprivation therapy as predictors of 5-year biochemical progression-free survival (bPFS) and severe (grade≥3) late GI and GU toxicity. bPFS and toxicity data were fit to tumour control probability and normal tissue complication probability models, respectively. RESULTS: Twenty-five articles met the inclusion criteria for this analysis. Five-year bPFS ranged from 25% to 70%. Severe late GI toxicity rates were 0% to 9%, and severe late GU toxicity rates were 1-11%. On multivariate analysis, bPFS increased with SRT dose by 2.5% per Gy and decreased with pre-SRT PSA by 18.3% per ng/mL (p<0.001). Late GI and GU toxicity increased with SRT dose by 1.2% per Gy (p=0.012) and 0.7% per Gy (p=0.010), respectively. Radiobiological models demonstrate the interaction between pre-SRT PSA, SRT dose and bPFS. For example, an increase in pre-SRT PSA from 0.4 to 1.0 ng/mL increases the SRT dose required to achieve a 50% bPFS rate from 60 to 70Gy. This could increase the rate of severe late toxicity by approximately 10%. CONCLUSION: Biochemical control rates following SRT increase with SRT dose and decrease with pre-SRT PSA. Severe late GI and GU toxicity rates also increase with SRT dose. Radiobiological models suggest that the therapeutic ratio of SRT may be improved by initiating treatment at low PSA levels.
PURPOSE: For prostate cancer that is thought to be locally recurrent after prostatectomy, the optimal timing, dose and techniques for salvage radiotherapy (SRT) have not been established. Here we perform a systematic review of published reports including regression meta-analysis and radiobiologic modelling to identify predictors of biochemical disease control and late toxicity. METHODS: We performed a review of published series reporting treatment outcomes following SRT. Studies with at least 30 patients, median PSA before SRT of less than 2.0 ng/mL, and median follow-up of greater than 36 months were identified. Univariate and multivariate analyses were performed to test Gleason Score, SRT dose, SRT timing, pre-SRT PSA, whole pelvic irradiation and androgen deprivation therapy as predictors of 5-year biochemical progression-free survival (bPFS) and severe (grade≥3) late GI and GU toxicity. bPFS and toxicity data were fit to tumour control probability and normal tissue complication probability models, respectively. RESULTS: Twenty-five articles met the inclusion criteria for this analysis. Five-year bPFS ranged from 25% to 70%. Severe late GI toxicity rates were 0% to 9%, and severe late GU toxicity rates were 1-11%. On multivariate analysis, bPFS increased with SRT dose by 2.5% per Gy and decreased with pre-SRT PSA by 18.3% per ng/mL (p<0.001). Late GI and GU toxicity increased with SRT dose by 1.2% per Gy (p=0.012) and 0.7% per Gy (p=0.010), respectively. Radiobiological models demonstrate the interaction between pre-SRT PSA, SRT dose and bPFS. For example, an increase in pre-SRT PSA from 0.4 to 1.0 ng/mL increases the SRT dose required to achieve a 50% bPFS rate from 60 to 70Gy. This could increase the rate of severe late toxicity by approximately 10%. CONCLUSION: Biochemical control rates following SRT increase with SRT dose and decrease with pre-SRT PSA. Severe late GI and GU toxicity rates also increase with SRT dose. Radiobiological models suggest that the therapeutic ratio of SRT may be improved by initiating treatment at low PSA levels.
Authors: Michael S Cookson; Gunnar Aus; Arthur L Burnett; Edith D Canby-Hagino; Anthony V D'Amico; Roger R Dmochowski; David T Eton; Jeffrey D Forman; S Larry Goldenberg; Javier Hernandez; Celestia S Higano; Stephen R Kraus; Judd W Moul; Catherine Tangen; J Brantley Thrasher; Ian Thompson Journal: J Urol Date: 2007-02 Impact factor: 7.450
Authors: Axel Heidenreich; Gunnar Aus; Michel Bolla; Steven Joniau; Vsevolod B Matveev; Hans Peter Schmid; Filliberto Zattoni Journal: Eur Urol Date: 2007-09-19 Impact factor: 20.096
Authors: O Kenneth Macdonald; Anthony V D'Amico; Natalia Sadetsky; Dennis C Shrieve; Peter R Carroll Journal: Urol Oncol Date: 2007-12-03 Impact factor: 3.498
Authors: Gordon W Wong; Kerrin L Palazzi-Churas; David F Jarrard; David R Paolone; Andrew K Graf; Sean P Hedican; John D Wegenke; Mark A Ritter Journal: Int J Radiat Oncol Biol Phys Date: 2007-09-14 Impact factor: 7.038
Authors: Laurent Quero; Pierre Mongiat-Artus; Vincent Ravery; Claude Maylin; François Desgrandchamps; Christophe Hennequin Journal: BMC Cancer Date: 2008-01-29 Impact factor: 4.430
Authors: Dmitry Koulikov; Maura C Mohler; Diana C Mehedint; Kristopher Attwood; Gregory E Wilding; James L Mohler Journal: J Urol Date: 2014-05-21 Impact factor: 7.450
Authors: Nitin Ohri; Xinglei Shen; Robert B Den; Adam P Dicker; Edouard J Trabulsi; Timothy N Showalter Journal: Cancer Biol Ther Date: 2012-09-06 Impact factor: 4.742
Authors: A Hervás; A Gómez-Caamaño; M Casaña; A Gómez-Iturriaga; J Pastor; J Jove; J L Mengual; C Gónzalez-San Segundo; J Muñoz Journal: Clin Transl Oncol Date: 2017-06-30 Impact factor: 3.405
Authors: Michael Pinkawa; Carolin Schubert; Nuria Escobar-Corral; Richard Holy; Michael J Eble Journal: Strahlenther Onkol Date: 2014-10-23 Impact factor: 3.621
Authors: Gunnar Lohm; Jörg Lütcke; Basil Jamil; Stefan Höcht; Konrad Neumann; Wolfgang Hinkelbein; Thomas Wiegel; Dirk Bottke Journal: Strahlenther Onkol Date: 2014-02-28 Impact factor: 3.621
Authors: Berrend G Muller; Aradhana Kaushal; Sandeep Sankineni; Elena Lita; Anthony N Hoang; Arvin K George; Soroush Rais-Bahrami; Jochen Kruecker; Pingkun Yan; Sheng Xu; Jean J de la Rosette; Maria J Merino; Bradford J Wood; Peter A Pinto; Peter L Choyke; Baris Turkbey Journal: Urol Oncol Date: 2015-08-08 Impact factor: 3.498