CONTEXT: In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological outcomes. OBJECTIVE: To perform a systematic review of the existing literature on BCR after treatment with curative intent for nonmetastatic 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 patient and tumor characteristics in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies tool. Both a narrative synthesis and a meta-analysis were undertaken. EVIDENCE SYNTHESIS: Overall, 77 studies were included for analysis, of which 14 addressed objective 1, recruiting 20 406 patients. Objective 2 was addressed by 71 studies with 29 057, 11 301, and 4272 patients undergoing RP, RT, and a mixed population (mix of patients undergoing RP or RT as primary treatment), respectively. There was a low risk of bias for study participation, confounders, and statistical analysis. For most studies, attrition bias, and prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with short prostate-specific antigen doubling time (PSA-DT) and a high final Gleason score after RP, or a short interval to biochemical failure (IBF) after RT and a high biopsy Gleason score. CONCLUSIONS: BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. Short PSA-DT and a high final Gleason score after RP, and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival. These factors may form the basis of new BCR risk stratification (European Association of Urology BCR Risk Groups), which needs to be validated formally. PATIENT SUMMARY: This review looks at the risk of death in men who shows rising prostate-specific antigen (PSA) in the blood test performed after curative surgery or radiotherapy. For many men, rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term. Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death. These factors may form the basis of new risk stratification (European Association of Urology biochemical recurrence Risk Groups), which needs to be validated formally.

Academic Urology Unit University of Aberdeen Aberdeen UK; Department of Urology Aberdeen Royal Infirmary Aberdeen UK

Academic Urology Unit University of Sheffield Sheffield UK

Charite Universitätsmedizin Berlin Germany; Department of Urology Medical University of Vienna Vienna Austria

Department of Medicine McMaster University Hamilton ON Canada

Department of Pathology Erasmus Medical Centre Rotterdam The Netherlands

Department of Radiation Oncology University Hospital Ulm Ulm Germany

Department of Radiology and Nuclear Medicine Erasmus MC University Medical Center Rotterdam The Netherlands

Department of Surgery Central Clinical School Monash University Caulfield North Victoria Australia

Department of Urology Hospital Saint Luc Saint Joseph Lyon France

Department of Urology Leto Hospital Athens Greece

Department of Urology Netherlands Cancer Institute Amsterdam The Netherlands

Department of Urology University Hospital Groningen Groningen The Netherlands

Department of Urology University Hospital St Etienne France

Department of Urology University Hospitals Leuven Leuven Belgium; Laboratory of Molecular Endocrinology KU Leuven Leuven Belgium

Department of Urology University of Bern Inselspital Bern Switzerland

Department of Urology Wrightington Wigan and Leigh NHS Foundation Trust Wigan UK

Division of Cancer and Genetics School of Medicine Cardiff University Velindre Cancer Centre Cardiff UK

Division of Cancer Sciences University of Manchester and The Christie Manchester UK; Department of Oncology and Haematology Cantonal Hospital St Gallen St Gallen Switzerland; University of Bern Bern Switzerland

Hasselt Belgium

Hospices Civils de Lyon Radiology Department Edouard Herriot Hospital Lyon France

Leeds Cancer Centre St James's University Hospital and University of Leeds Leeds UK

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany; Department of Urology University Hospital Hamburg Eppendorf Hamburg Germany

Nuclear Medicine Division Policlinico S Orsola University of Bologna Italy

Pecanka Consulting Services Prague Czech Republic; Department of Biomedical Data Sciences University Medical Center Leiden The Netherlands

Royal Liverpool and Broadgreen Hospitals NHS Trust Liverpool UK

Unit of Urology Division of Oncology URI IRCCS Ospedale San Raffaele Milan Italy; Università Vita Salute San Raffaele Milan Italy

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Eur Urol. 2019 Jul;76(1):e15. doi: 10.1016/j.eururo.2019.03.028. PubMed

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Eur Urol. 2019 Jun;75(6):896-900. doi: 10.1016/j.eururo.2019.03.016. PubMed

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Eur Urol. 2019 Jul;76(1):e16. doi: 10.1016/j.eururo.2019.03.027. PubMed

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Eur Radiol. 2023 Feb;33(2):748-751. doi: 10.1007/s00330-022-09095-6. PubMed

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