Prognostic Factors for Prostate Cancer Endpoints Following Biochemical Failure: A Review of the Literature

Abstract

Purpose: In the setting of biochemical failure (BCF) following primary treatment for prostate cancer, additional discrimination between clinically significant and non-clinically significant biochemical recurrence is critical in defining robust surrogate endpoints for prostate cancer and guiding salvage management decisions. We reviewed the literature to determine which prognostic factors are most significant for predicting prostate cancer-specific survival (PCSS), metastases-free survival (MFS), and/or overall survival (OS) after BCF.Materials and Methods: A search of PubMed from 1980 to 2013 yielded 999 studies that examined prognostic factors predictive for PCSS, MFS, and/or OS in prostate cancer patients with BCF following primary treatment. Eligibility criteria for inclusion were: 1) examined a prostate cancer population in the setting of BCF without overt clinical relapse following primary treatment with radical prostatectomy or radiotherapy; 2) based analyses on patient parameters obtained prior to the initiation of salvage therapies; and 3) determined clinical prognostic factors that were significant prognostic measures for at least one of three clinically relevant endpoints: OS, PCS, or MFS.Results: Nineteen eligible studies reported on 8,040 patients that experienced BCF from 1981-2013. The initial primary therapy was variable: radical prostatectomy alone (n=8), radiotherapy alone (n=4), radiotherapy/radical prostatectomy ± adjuvant therapy (n=5), and multiple treatment arms (n=2). There was also heterogeneity in which outcomes were assessed: PCSS (n=14), MFS (n=7), and OS (n=5). The prognostic factors most commonly found to be significant on multivariate analyses were PSA doubling time (PSADT), time to biochemical failure (TTBF), pathological Gleason score (pGS), and age. Conclusions: Risk stratification in prostate cancer post-BCF is challenging because of limited predictive modeling that can determine which patients will optimally benefit from salvage therapy. Our systematic literature review has identified PSADT, TTBF, pGS, and age as the leading prognostic factors for the prediction of PCSS, MFS, and OS after BCF. We plan to leverage the Canadian ProCaRS database to perform predictive modeling using the putative findings in the present study in order to propose potential evidence-based surrogate endpoints for prostate cancer in the setting of BCF.

High expression of SLCO2B1 is associated with prostate cancer recurrence after radical prostatectomy

“…Radical prostatectomy (RP) is the gold standard treatment for localized PCa, however, approximately 30% of the cases develop recurrence after RP despite advances in surgical techniques [ 2 ]. Several pathological features such as positive surgical margins, extracapsular invasion, or seminal vesicle invasion were found to be associated with recurrence after RP [ 3 , 4 ]. Pathological Gleason score (GS) has also been recognized as one of the most reliable prognostic factors predicting recurrence after RP [ 4 – 7 ].…”

Expression of epithelial-mesenchymal transition-related genes in prostate tumours

“…Prostate cancer is one of the most commonly diagnosed cancers among men in the world. It is highly heterogeneous and complicated cancer type, when taking into account a wide variety of multiple genetic and demographic factors that affect cell transformation, as well as the different origins of cancerous cells [1,2]. One of the critical molecular process for tumor progression is epithelial-to-mesenchymal cell transition (EMT), i.e.…”

Classifying high-risk versus very high-risk prostate cancer: is it relevant to outcomes of conformal radiotherapy and androgen deprivation?

“…Although several different CRT treatment techniques were used during the study period and moderate hypo-fractionation and IGRT were instituted only after 2009, univariate and multivariate analysis were unable to demonstrate differences in outcome based on treatment technique. Although most BFs occur within 5 years of treatment [33], longer duration of follow-up is needed to verify our findings.…”