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

Abstract

Context. In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological patient outcomes. Objective. To perform a systematic review of the existing literature on BCR after treatment with curative intent for non-metastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic features in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies (QUIPS) tool. Both a narrative synthesis and meta-analysis were undertaken. Evidence synthesis. Overall, 77 studies were included for analysis, of which 14 studies addressed objective 1, recruiting 20406 patients. Objective 2 was addressed by 71 studies with 29057, 11301 and 4272 patients undergoing RP, RT or a mixed population (mix of patients undergoing RP or RT as primary treatment) respectively. There was low risk of bias for study participation, confounders and statistical analysis. For most studies, attrition bias, prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with a short PSA Doubling Time (PSA-DT) and high final Gleason score after RP or a short Interval to Biochemical Failure (IBF) after RT and high biopsy Gleason score. Conclusion. BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. A short PSA-DT and high final Gleason score after RP and a short IBF after RT and high biopsy Gleason score are the main factors which have a negative impact on survival. Patient summary. This review looks at the risk of dying in men who have a rising PSA blood test after curative surgery or radiotherapy. For many men a rising PSA does not mean they are at a higher risk of dying from prostate cancer in the longer term. Men with a PSA that rises shortly after they were treated with radiotherapy or a rapidly rising PSA after surgery and a high tumor-grade for both treatment modalities are at the highest risk of dying.

SIRT7 depletion inhibits cell proliferation and androgen-induced autophagy by suppressing the AR signaling in prostate cancer

“…As a target gene of AR, PSA is mainly regulated by an upstream promoter and enhancer androgen response element [35]. A rapidly rising PSA indicates activation of AR signaling pathways [36] and predicts the poor prognosis [37]. As androgen-independent PCa cell lines, DU145 and PC3 are much more invasive than LNCaP and 22Rv1 cells.…”

Identification and validation of a prognostic 5-protein signature for biochemical recurrence following radical prostatectomy in prostate cancer

“…The majority of patients with early BCR will develop clinical recurrence and require timely intervention [2].…”

“…Prostate cancer (PCa) is the second leading cause of tumor death among American male, accounting for 20% newly-diagnosed cancer with 31,620 deaths in 2019 [1]. Although radical prostatectomy (RP) is considered to be an effective therapy for PCa patients, recent work reveals that approximately 20%-40% patients suffered from biochemical recurrence (BCR) after RP [2]. BCR is de ned as recurrent prostate speci c antigen (PSA) more than 0.2 µg/L and an indicator for distant metastasis or PCa-speci c mortality [2,3].…”

“…Although radical prostatectomy (RP) is considered to be an effective therapy for PCa patients, recent work reveals that approximately 20%-40% patients suffered from biochemical recurrence (BCR) after RP [2]. BCR is de ned as recurrent prostate speci c antigen (PSA) more than 0.2 µg/L and an indicator for distant metastasis or PCa-speci c mortality [2,3]. 32%-45% among BCR patients with post-RP would die from PCa within 15 years [4].…”

Elevated miR-615-3p Expression Predicts Adverse Clinical Outcome and Promotes Proliferation and Migration of Prostate Cancer Cells

“…BCR is a surrogate end point for outcome after RP and is not necessarily associated with PC mortality. 46 Unfortunately, other more optimal end points, such as metastasis, CSS, and overall survival, require long follow-up time (>15 years). 47 Nevertheless, when cohorts 1 to 3 were merged, high miR-615-3p expression was a significant predictor of CSS in both univariate (HR Z 3.75; P < 0.001) and multivariate (HR Z 2.66; P Z 0.01) analysis beyond routinely available postoperative clinicopathologic factors.…”