Interval to biochemical failure as a biomarker for cause‐specific and overall survival after dose‐escalated external beam radiation therapy for prostate cancer

Abstract

BACKGROUND:After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of <18 months has been proposed as a surrogate for cause‐specific survival. Because EBRT dose influences biochemical failure, the authors investigated the interval to biochemical failure in a cohort of patients treated with dose‐escalated EBRT.METHODS:From 1998 to 2008, 710 patients were treated with EBRT (≥75 grays) ± androgen deprivation therapy (ADT) at the University of Michigan. Biochemical failure was defined using the Phoenix consensus definition (nadir + 2 ng/mL). A short interval to biochemical failure was defined as <18 months after completing radiotherapy and/or ADT. The associations between biochemical failure, the interval to biochemical failure, and clinical factors with cause‐specific survival (CSS) and overall survival (OS) were evaluated.RESULTS:There were 149 biochemical failures (21%), and short interval to biochemical failure accounted for 14% and 40% of biochemical failures in those with intermediate‐risk or high‐risk disease, respectively. Biochemical failure impacted CSS (P < .0001) but not OS (P = .36). However, a short interval to biochemical failure predicted decreased CSS (P < .0001; hazard ratio [HR], 5.6; 95% confidence interval [CI], 2.4‐13.0) and OS (P < .0001; HR, 4.8; 95% CI, 2.3‐10.3) when compared with a long interval to biochemical failure. The 8‐year OS was 78% without biochemical failure, compared with 87% with a long interval to biochemical failure (P = .1; HR, 0.7; 95% CI, 0.4‐1.1) and 38% with a short interval to biochemical failure (P < .0001; HR, 3.7; 95% CI, 2.3‐5.9). On multivariate analysis, a short interval to biochemical failure increased the risk of prostate cancer death (P < .0001; HR, 18.1; 95% CI, 8.4‐39) and all cause mortality (P = .0027; HR, 1.5; 95% CI, 1.2‐2.1), whereas a long interval to biochemical failure did not.CONCLUSIONS:The relation between the interval to biochemical failure, CSS, and OS was independently validated in patients treated with dose‐escalated EBRT. Further evaluation of the interval to biochemical failure as a surrogate endpoint is warranted. Cancer 2012. © 2011 American Cancer Society.

Does prostate-specific antigen nadir predict longer-term outcomes of prostate cancer after neoadjuvant and adjuvant androgen deprivation therapy in conjunction with brachytherapy?

“…Nevertheless, the role of treatment effect in our study can be extrapolated from previous findings after EBRT with or without hormone use (6,12,13,17,18). Most recently, Kapadia et al (21) and Ray et al (12) demonstrated a short interval to biochemical failure after completing EBRT that correlated with a significantly increased rate of biochemical failure and DM as compared with a longer interval to biochemical failure or lack of biochemical failure. Ray et al (12) also noted that dose higher than 70 Gy was associated with not only a lower nPSA level but also a longer TnPSA, and that greater dose was significantly associated with greater PSA-DFS and distant metastasis-free survival (12).…”

“…The use of HDR brachytherapy is now widely used and accepted in the United States and worldwide (22). The PDR brachytherapy combined with EBRT is emerging as a potentially advantageous modality as it has a lesser source strength and hence lower requirements for surrounding shielding, yet potentially provides equivalent cancericidal effects and normal tissue sparing to other brachytherapy modalities (20,21). In our study, PDR brachytherapy equipment was used in an HDR technique, in which a 1 Ci 192 Ir source delivered dose in three large fractions rather than multiple small fractions, the rationale of which is outlined in our previous reports (19,20).…”

Prognostic Value of Biochemical Recurrence Following Treatment with Curative Intent for Prostate Cancer: A Systematic Review

“…For cancer-related outcomes, all four studies investigating DM or PCSM as outcome showed a significant negative impact of BCR with varying impact. In contrast, the impact of BCR on OM is less clear, but still five out of eight studies report an impact of BCR on OM rates [16,17,79,87,88] while the other three studies do not show this effect [15,18,19].…”

Impact of biochemical failure classification on clinical outcome: A secondary analysis ofRadiationTherapyOncologyGroup 9202 and 9413

“…In addition to metastasis, which could have influenced A2 failures and led to worse clinical outcomes, early BF (with a short interval to BF) has also been identified as carrying a significantly increased risk of death from prostate cancer 24,25 or death overall. 26 and it may have been captured in the A2 definition, particularly for those men who had continually rising PSA after RT or recurrence even during ADT.…”