Abstract

Simple SummaryAmong patients with prostate cancer who have been operated on, a subset harboring high-risk features will present with a biochemical recurrence (BCR). Adjuvant radiotherapy (aRT) was proven to significantly reduce the risk of BCR when compared to salvage radiotherapy (SRT) but suffered from several limitations: a lack of patient selection criteria, a higher treatment-related morbidity and an uncertain benefit for long-term clinical endpoints. In the same clinical setting, early SRT (eSRT) appears as non-inferior to aRT with a lower morbidity, replacing aRT as the preferred option. In this review, we insist on the need for multidisciplinary discussions to fully comprehend the individual characteristics of each patient and propose the best treatment strategy for every patient.Despite three randomized trials indicating a significant reduction in biochemical recurrence (BCR) in high-risk patients, adjuvant radiotherapy (aRT) was rarely performed, even in patients harboring high-risk features. aRT is associated with a higher risk of urinary incontinence and is often criticized for the lack of patient selection criteria. With a BCR rate reaching 30–70% in high-risk patients, a consensus between urologists and radiation oncologists was needed, leading to three different randomized trials challenging aRT with early salvage radiotherapy (eSRT). In these three different randomized trials with event-free survival as the primary outcome and a planned meta-analysis, eSRT appeared as non-inferior to aRT, answering, for some, this never-ending question. For many, however, the debate persists; these results raised several questions among urologists and radiation oncologists. BCR is thought to be a surrogate for clinically meaningful endpoints such as overall survival and cancer-specific survival but may be poorly efficient in comparison with metastasis-free survival. Imaging of rising prostate-specific antigen (PSA), post-operative persistent PSA and BCR was revolutionized by the broader use of MRI and nuclear imaging such as PET-PSMA; these imaging modalities were not analyzed in the previous randomized trials. A sub-group of very high-risk patients could possibly benefit from an adjuvant radiotherapy; but their usual risk factors such as high Gleason score or invaded surgical margins mean they are unable to be selected. More precise biomarkers of early BCR or even metastatic-relapse were developed in this setting and could be useful for the patients’ stratification. In this review, we insist on the need for multidisciplinary discussions to fully comprehend the individual characteristics of each patient and propose the best treatment strategy for every patient.

Highlights

  • 30% of operated on prostate cancer (PCa) patients will experience biochemical recurrence (BCR), this rising to 50–70% in very high-risk patients [1,2,3]

  • Despite a significant benefit for biochemical-free recurrence, the only trial in favor of a significant benefit on metastasis-free survival (MFS) and overall survival (OS) was criticized for its design [4]. These debates resulted in a low use of adjuvant radiotherapy (aRT), clinicians fearing the higher genitourinary morbidity associated with aRT when compared to salvage radiotherapy (SRT)

  • Given the possible lack of benefit on OS and its higher toxicity profile, aRT was challenged by early SRT in three recently published RCTs [6,7,8] pooled in a preplanned meta-analysis [9] that proved early salvage radiotherapy (eSRT) to be non-inferior to aRT when considering event-free survival (EFS harmoniously defined as the time from randomization until the first evidence of either biochemical progression (prostate-specific antigen (PSA) ≥ 0.4 ng/mL

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Summary

Introduction

30% of operated on prostate cancer (PCa) patients will experience biochemical recurrence (BCR), this rising to 50–70% in very high-risk patients [1,2,3]. Given the possible lack of benefit on OS and its higher toxicity profile, aRT was challenged by early SRT (eSRT) in three recently published RCTs [6,7,8] pooled in a preplanned meta-analysis [9] that proved eSRT to be non-inferior to aRT when considering event-free survival (EFS harmoniously defined as the time from randomization until the first evidence of either biochemical progression (prostate-specific antigen (PSA) ≥ 0.4 ng/mL and rising after completion of any post-operative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer or a PSA level of at least 2.0 ng/mL at any time after randomization) with a toxicity profile in favor of eSRT over aRT. These trials closed the discussion between aRT and (e)SRT

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