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.
Background: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. Objective: To develop consensus statements for all domains of DAT. Design, setting, and participants: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed. Results and limitations: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion. Conclusions: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials. Patient summary: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.
Biochemical recurrence (BCR) after primary treatment of localized prostate cancer (PCa) does not necessarily lead to clinically apparent progressive disease. To aid prognostication, the EAU Prostate Cancer Guideline Panel undertook a systematic review and successfully developed a novel BCR risk stratification system based on disease and PSA characteristics (i.e. EAU Low-risk BCR and High-risk BCR risk groups).
Context. The optimal treatment for men with high-risk localized or locally advanced prostate cancer (PCa) remains unknown. Objective. To perform a systematic review of the existing literature on the effectiveness of the different primary treatment modalities for high-risk localized and locally advanced PCa. The primary oncological outcome is the development of distant metastases at ≥5 years of follow-up. Secondary oncological outcomes are prostate cancer specific mortality (PCSM), overall mortality (OM), biochemical recurrence and need for salvage treatment with ≥5 years of follow-up. Non-oncological outcomes are quality of life (QoL), functional outcomes and treatment-related side effects reported. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Randomized Controlled Trials were searched. All comparative (randomized and non-randomized) studies published between January 2000 and May 2019 with at least 50 participants in each arm were included. Studies reporting on high-risk localized PCa (ISUP grade 4-5 [GS 8-10] or PSA >20 ng/mL or ≥cT2c) and/or locally advanced PCa (any PSA, cT3-4 or cN+, any ISUP grade/ GS score) or where subanalyses were performed on either group were included. The following primary local treatments were mandated: radical prostatectomy (RP), external beam radiotherapy (EBRT) (≥64 Gy), brachytherapy (BT) or multimodality treatment combining any of the local treatments above (+/-any systemic treatment). Risk of Bias (RoB) and confounding factors were assessed for each study. A narrative synthesis was performed. Evidence synthesis. Overall, 90 studies met the inclusion criteria. RoB and confounding factors revealed high RoB for selection, performance and detection bias and low RoB for correction of initial PSA and biopsy GS. When comparing RP to EBRT, retrospective series suggested an advantage for RP, although with a low level of evidence. Both RT and RP should be seen as part of a multimodal treatment plan with possible addition of (post-operative) RT and/or ADT respectively. High levels of evidence exist for EBRT treatment with several RCTs showing superior outcome for adding long-term ADT or BT to EBRT. No clear cutoff can be proposed for RT dose but higher RT doses by means of dose escalation schemes result in an improved biochemical control. Twenty studies reported data on QoL, with RP resulting mainly in GU toxicity and sexual dysfunction, and EBRT in bowel problems. Conclusion. Based on the results of this systematic review, both RP as part of multimodal treatment and EBRT + long-term ADT can be recommended as primary treatment in high-risk and locally advanced PCa. For high-risk PCa, also EBRT + BT can be offered, despite more grade 3 toxicity. Interesting, for selected patients, e.g. with higher comorbidity, a shorter duration of ADT might be an option. For locally advanced PCa, EBRT + BT shows promising result but still needs further validation. In this setting, it is important that patients are aware that the offered therapy will be mos...
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