Clinical implications of a prostate-specific antigen bounce after radiation therapy for prostate cancer

After receiving local treatment, many patients will develop a biochemical recurrence (BCR) in the absence of detectable distant disease (cM0) and comprise a significant proportion (20.1%) of prostate cancer disease states. The natural history of patients with BCR ranges from those with indolent, nonprogressive, slow prostate-specific antigen (PSA)-only progression to those ultimately destined to develop metastases and progress to a cancer-specific death. Pathologic predictors of BCR, clinical progression, and cancer-specific mortality are well established in the literature, although multiple novel predictors are emerging, which are highlighted. Traditional imaging cannot reliably distinguish local versus distant microscopic metastasis at the PSA levels that have been shown to confer survival advantage for salvage radiation therapy. We review past and present imaging standards and discuss novel imaging modalities, which may improve staging and offer opportunity for novel salvage therapies, including salvage lymph node dissection and stereotactic beam radiation therapy. With an emphasis on BCR after radical prostatectomy, both curative and palliative treatments are reviewed. This review contains 7 figures, 6 tables and 73 references Key words: biochemical recurrence, clinically undetectable metastases, molecular imaging, monitoring treatment response, prostate cancer, radical prostatectomy, rising prostate-specific antigen, salvage lymph node dissection, salvage radiation

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Event-Free Survival, a Prostate-Specific Antigen–Based Composite End Point, Is Not a Surrogate for Overall Survival in Men With Localized Prostate Cancer Treated With Radiation

Journal of Clinical Oncology ◽

10.1200/jco.19.03114 ◽

2020 ◽

Vol 38 (26) ◽

pp. 3032-3041 ◽

Cited By ~ 3

Author(s):

Wanling Xie ◽

Meredith M. Regan ◽

Marc Buyse ◽

Susan Halabi ◽

Philip W. Kantoff ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Prostate Specific Antigen ◽

Specific Antigen ◽

Event Free Survival ◽

Free Survival ◽

Patient Level ◽

End Point

PURPOSE Recently, we have shown that metastasis-free survival is a strong surrogate for overall survival (OS) in men with intermediate- and high-risk localized prostate cancer and can accelerate the evaluation of new (neo)adjuvant therapies. Event-free survival (EFS), an earlier prostate-specific antigen (PSA)–based composite end point, may further expedite trial completion. METHODS EFS was defined as the time from random assignment to the date of first evidence of disease recurrence, including biochemical failure, local or regional recurrence, distant metastasis, or death from any cause, or was censored at the date of last PSA assessment. Individual patient data from trials within the Intermediate Clinical Endpoints in Cancer of the Prostate–ICECaP–database with evaluable PSA and disease follow-up data were analyzed. We evaluated the surrogacy of EFS for OS using a 2-stage meta-analytic validation model by determining the correlation of EFS with OS (patient level) and the correlation of treatment effects (hazard ratios [HRs]) on both EFS and OS (trial level). A clinically relevant surrogacy was defined a priori as an R2 ≥ 0.7. RESULTS Data for 10,350 patients were analyzed from 15 radiation therapy–based trials enrolled from 1987 to 2011 with a median follow-up of 10 years. At the patient level, the correlation of EFS with OS was 0.43 (95% CI, 0.42 to 0.44) as measured by Kendall’s tau from a copula model. At the trial level, the R2 was 0.35 (95% CI, 0.01 to 0.60) from the weighted linear regression of log(HR)-OS on log(HR)-EFS. CONCLUSION EFS is a weak surrogate for OS and is not suitable for use as an intermediate clinical end point to substitute for OS to accelerate phase III (neo)adjuvant trials of prostate cancer therapies for primary radiation therapy–based trials.

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