Recognizing False Biochemical Failure Calls After Radiation With or Without Neo-Adjuvant Androgen Deprivation for Prostate Cancer
Received 17 June 2008; received in revised form 5 August 2008; accepted 13 August 2008. published online 27 January 2009.
Purpose
We studied prostate-specific antigen (PSA) changes after radiation with or without neoadjuvant androgen deprivation to determine posttreatment PSA scenarios in which false-positive biochemical failures (FPBF) are most likely to occur.
Methods and Materials
In the Trans-Tasman Radiation Oncology 96.01 Group trial, patients with T2b, 2c, 3, 4 N0 prostate cancer were randomized to 3 or 6 months goserelin and flutamide (STAD) before and during 66 Gy to the prostate and seminal vesicles (XRT) or to XRT alone. Piecewise longitudinal changes in PSA before relapse were characterized and quantified to determine which might cause FPBF calls.
Results
Between 1996 and 2000, 802 eligible patients were randomized. Of these, 492 met the criteria for American Society for Therapeutic Radiology and Oncology (ASTRO) failure and 467 for Phoenix failure. Seventy-seven ASTRO fails and 39 Phoenix fails were deemed false positives (FPs). The majority of FPBFs were associated with the “plateauing” in PSA values that follow posttreatment nadir. FPBFs were particularly common in men treated with STAD, in whom small, consecutive PSA rises before or during this phenomenon triggered 56 FP ASTRO fail calls. In these men, the Phoenix fail criteria triggered only 15 FPBF calls. However, the Phoenix criteria were more vulnerable than ASTRO to short-term isolated PSA rises during plateau, which resulted in 15 Phoenix fail calls but only 3 FP ASTRO fails.
Conclusions
The Phoenix definition avoided 50% of FPBF calls that occurred with the ASTRO definition. Failures should be confirmed by further PSA rises before investigation and treatment is considered.
‡‡Westmead Hospital, Sydney, New South Wales, Australia
§§School of Physical and Mathematical Sciences, University of Newcastle, Newcastle, New South Wales, Australia
¶¶Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, New South Wales, Australia
Reprint requests to: Prof. James W. Denham, Calvary Mater Newcastle, Locked Bag 7, Hunter Region Mail Centre New South Wales 2310 Australia. Tel: (+61) 2-4921-1174; Fax: (+61) 2-4921-1465
Supported by the Australian Government National Health and Medical Research Council (Project Grant Applications 9936572, 209801, 455520); Hunter Medical Research Institute (Newcastle, Australia); AstraZeneca Pty Ltd (Sydney, Australia); and Schering-Plough Pty Ltd (Sydney, Australia).
Conflict of interest: David Lamb—support to attend meetings from AstraZeneca. David Joseph—honoraria associated with membership of AstraZeneca's Breast Cancer Medical Advisory Board. John Matthews—support to attend Australasian meetings by AstraZeneca and Schering Plough. Keen-Hun Tai—received a FROGG-AstraZeneca educational grant in 2003 and was supported by AstraZeneca to attend two Casodex Investigators Meetings in 2001 and 2004. Nigel Spry—honararia associated with AstraZeneca and Schering Plough; research funding from Schering Plough. David Christie—partial sponsorship to attend ASCO 2007 by AstraZeneca. Allison Steigler—support from AstraZeneca to attend one meeting. James Denham, Mahesh Kumar, Paul Gleeson, Chris Atkinson, Sandra Turner, Peter Greer, and Catherine D'Este have no disclosures to make.
ABSTRACT