Andrew S Chiang1, D Andrew Loblaw1, Vibhuti Jethava1, Perakaa Sethukavalan1, Liying Zhang2, Danny Vesprini1, Alexandre Mamedov3, Robert Nam4, Laurence Klotz4. 1. Department of Radiation Oncology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON; 2. Department of Biostatistics, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON; 3. Department of Clinical Trials and Epidemiology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON; 4. Division of Urology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON.
Abstract
INTRODUCTION: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha-reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable-risk prostate cancer. METHODS: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. RESULTS: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. CONCLUSION: 5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancer-related DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.
INTRODUCTION: This retrospective review compares prostate-specific antigen (PSA) doubling time (DT) prior to the initiation of a 5-alpha-reductase inhibitor (pre-5-ARI) to after the PSA nadir (post-nadir) has been reached for patients on active surveillance for favourable-risk prostate cancer. METHODS: Between 1996 and 2010, a total of 100 men with a history of 5-ARI use were captured from our active surveillance database. Twenty-nine patients had a sufficient number of PSA values to determine both pre-5-ARI and post-nadir DTs. PSADT was calculated using the general linear mixed-model method. RESULTS: The median follow-up was 69.5 months. The median pre-5-ARI PSADT was 55.8 (range: 6-556.8) months, while the post-nadir value was 25.2 (range: 6-231) months (p = 0.0081). Six patients were reclassified after an average of 67.7 (range: 59-95) months, due to progression in PSADT (n = 2) or Gleason score (n = 4). The median pre-5-ARI and post-nadir DTs for this group were 42.3 (range: 32.4-91.1) and 21.1 (range: 6-44.3) months, respectively. CONCLUSION:5-ARIs significantly decreased PSADT compared to prior to their initiation. This effect may be due to preferential suppression of benign tissue following PSA nadir. The resulting PSADT would then represent a more accurate depiction of the true cancer-related DT. If validated with a larger cohort, 5-ARIs may enhance the utility of PSADT as a biomarker of disease progression in active surveillance.
Authors: Neil E Fleshner; M Scott Lucia; Blair Egerdie; Lorne Aaron; Gregg Eure; Indrani Nandy; Libby Black; Roger S Rittmaster Journal: Lancet Date: 2012-01-24 Impact factor: 79.321
Authors: Claus G Roehrborn; Gerald L Andriole; Timothy H Wilson; Ramiro Castro; Roger S Rittmaster Journal: Eur Urol Date: 2010-11-04 Impact factor: 20.096
Authors: Gerald L Andriole; David G Bostwick; Otis W Brawley; Leonard G Gomella; Michael Marberger; Francesco Montorsi; Curtis A Pettaway; Teuvo L Tammela; Claudio Teloken; Donald J Tindall; Matthew C Somerville; Timothy H Wilson; Ivy L Fowler; Roger S Rittmaster Journal: N Engl J Med Date: 2010-04-01 Impact factor: 91.245
Authors: James Mohler; Robert R Bahnson; Barry Boston; J Erik Busby; Anthony D'Amico; James A Eastham; Charles A Enke; Daniel George; Eric Mark Horwitz; Robert P Huben; Philip Kantoff; Mark Kawachi; Michael Kuettel; Paul H Lange; Gary Macvicar; Elizabeth R Plimack; Julio M Pow-Sang; Mack Roach; Eric Rohren; Bruce J Roth; Dennis C Shrieve; Matthew R Smith; Sandy Srinivas; Przemyslaw Twardowski; Patrick C Walsh Journal: J Natl Compr Canc Netw Date: 2010-02 Impact factor: 11.908
Authors: Pär Stattin; Erik Holmberg; Jan-Erik Johansson; Lars Holmberg; Jan Adolfsson; Jonas Hugosson Journal: J Natl Cancer Inst Date: 2010-06-18 Impact factor: 13.506
Authors: Philip M Arlen; Fernando Bianco; William L Dahut; Anthony D'Amico; William D Figg; Stephen J Freedland; James L Gulley; Philip W Kantoff; Michael W Kattan; Andrew Lee; Meredith M Regan; Oliver Sartor Journal: J Urol Date: 2008-04-18 Impact factor: 7.450
Authors: Yael C Cohen; Kenneth S Liu; Norman L Heyden; Alexandra D Carides; Keaven M Anderson; Anastasia G Daifotis; Peter H Gann Journal: J Natl Cancer Inst Date: 2007-09-11 Impact factor: 13.506