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.

Keywords: biochemical failure; biochemical recurrence; clinical endpoints; clinical outcomes; predictor; prognostic factor; prostate cancer; psa; survival.

Figure 1. Search Strategy

Figure 2. Increasing Age

Number of studies showing age as a significant predictor for PCM, DM, and ACM on multivariate analyses. One study (not represented in the figure) found younger age to be associated with worse PCM and ACM

Figure 3. TNM Staging

Number of studies showing TNM staging as a significant predictor for PCM, DM, and ACM on multivariate analyses.

Figure 4. Gleason Score

Number of studies showing GS as a significant predictor for PCM, DM, and ACM on multivariate analyses.

Figure 5. PSA Doubling Time

Number of studies showing PSADT as a significant predictor for PCM, DM, and ACM on multivariate analyses.

Figure 6. Time to Biochemical Failure

Number of studies showing TTBF as a significant predictor for PCM, DM, and ACM on multivariate analyses.

Figure 7. Initial PSA

Number of studies showing iPSA as a significant predictor for PCM, DM, and ACM on multivariate analyses.