Abstract
Purpose. Survival following biochemical failure is highly variable. Using a randomized trial dataset, we sought to define a risk stratification scheme in men with locally advanced prostate cancer (LAPC). Methods. The TROG 96.01 trial randomized 802 men with LAPC to radiation ± neoadjuvant androgen suppression therapy (AST) between 1996 and 2000. Ten-year follow-up data was used to develop three-tier post-biochemical failure risk stratification schemes based on cutpoints of time to biochemical failure (TTBF) and PSA doubling time (PSADT). Schemes were evaluated in univariable, competing risk models for prostate cancer-specific mortality. The performance was assessed by c-indices and internally validated by the simple bootstrap method. Performance rankings were compared in sensitivity analyses using multivariable models and variations in PSADT calculation. Results. 485 men developed biochemical failure. c-indices ranged between 0.630 and 0.730. The most discriminatory scheme had a high risk category defined by PSADT < 4 months or TTBF < 1 year and low risk category by PSADT > 9 months or TTBF > 3 years. Conclusion. TTBF and PSADT can be combined to define risk stratification schemes after biochemical failure in men with LAPC treated with short-term AST and radiotherapy. External validation, particularly in long-term AST and radiotherapy datasets, is necessary.
Highlights
Biochemical failure is a very common problem in the treatment of prostate cancer
time to biochemical failure (TTBF) and PSA doubling time (PSADT) can be combined to define risk stratification schemes after biochemical failure in men with locally advanced prostate cancer (LAPC) treated with short-term androgen suppression therapy (AST) and radiotherapy
Three-tier post-Biochemical failure (BF) risk categorization (BFRC) schemes based on low, intermediate, and high risk groups were derived in two stages: (1) 12 “cut point range-finding” schemes were identified and evaluated using combinations of TTBF and PSADT cutpoints regularly cited in the literature as being predictive of outcome following BF and (2) new “candidate” BFRC schemes were derived based on the most prognostic ranges identified in the range-finding schemes
Summary
Biochemical failure is a very common problem in the treatment of prostate cancer. Klotz has estimated that approximately 40% of men treated curatively by prostatectomy or radiotherapy will develop biochemical failure [1]. Clinical signs of local or distant progression can follow within months but may take years to become evident, and five year prostate cancer-specific survival probability has been shown to vary between 35% and 100% [3]. An important breakthrough in the management of prostate cancer is the emergence of effective new options for the treatment of castrate-resistant prostate cancer (CRPC) [4]. These options are routinely withheld until castration-resistant tumour growth develops; many clinicians believe that earlier intervention may Prostate Cancer be beneficial. The identification of subgroups of men with unfavourable outcomes after biochemical failure, needing immediate treatment and/or new therapeutic agents, is a high priority in clinical prostate cancer research
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