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.
Highlights
In 2014, an estimated 23,600 men will be diagnosed with prostate cancer in Canada, resulting in approximately 4,000 prostate cancer-specific deaths [1]
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, and age
Risk stratification in prostate cancer post-biochemical failure (BCF) is challenging because of limited predictive modeling that can determine which patients will optimally benefit from salvage therapy
Summary
In 2014, an estimated 23,600 men will be diagnosed with prostate cancer in Canada, resulting in approximately 4,000 prostate cancer-specific deaths [1]. Of the men who are successfully treated with radical prostatectomy, about 35% will have a biochemical failure (BCF) [2]. The AUA defines BCF as two successive measurements of a serum PSA ≥ 0.2 ng/mL after undetectable PSA levels had been reached, which typically occurs at least six weeks postoperatively [3]. In 2005, the American Society for Therapeutic Radiation and Oncology (ASTRO) Consensus Committee convened in Phoenix, Arizona, and proposed a definition for BCF following primary treatment with radiotherapy as an increase in PSA by ≥ 2 ng/mL above the treatment nadir [4]. The ASTRO definition for BCF was three consecutive rises after a treatment nadir had been established [5]. There is a dichotomy amongst the definitions of BCF used which needs to be considered when comparing studies published before and after the 2005 amendment
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