RESUMEN
Radical prostatectomy in high-risk prostate cancer patients has long been followed by immediate adjuvant radiotherapy (IART) to increase biochemical relapse-free survival. However, the increased urinary and digestive radio-induced toxicities have raised questions about the safety of delaying radiotherapy until the occurrence of biochemical or clinical relapse. Recently, early salvage radiotherapy (ESRT) has been compared to IART, and results found equivalence in terms of efficiency outcomes, but increased toxicity was noted in patients receiving IART, leading to the proposal of ESRT as the new standard of care in high-risk patients after surgery. However, several confounding points are discussed in the present review regarding the methodology and results of these recent trials. Further follow-up is necessary to detect possible long-term advantages of one radiotherapy timing over the other.
RESUMEN
Background: The presence of adverse pathological features like extraprostatic extension, seminal vesicle involvement, or positive margins at radical prostatectomy incurs a high risk of postoperative recurrence. Currently, adjuvant radiotherapy (ART) is the standard of care in these patients, while early salvage radiotherapy (eSRT) is a potential alternative strategy. Aims: The purpose of this paper is to review the latest evidence comparing outcomes of adjuvant versus early SRT in this clinical scenario. Materials and Methods: A systematic review of Google Scholar, PubMed/Medline, and EMBASE was done to identify relevant studies published in the English language, regarding outcomes of adjuvant radiotherapy and early SRT in post radical prostatectomy patients. Twelve studies, including six randomized trials, four retrospective studies, one systematic review, and one metanalysis were included in the final analysis. Results: We found that initial randomized trials demonstrated better event-free survival with adjuvant radiotherapy when compared to observation alone. However, ART was associated with increased risk of overtreatment and thus increased radiation-related toxicity rates. Conclusion: Preliminary evidence from recently reported RCTs suggests that eSRT may provide equivalent oncological outcomes to ART in prostate cancer patients with adverse pathology on radical prostatectomy while decreasing unnecessary treatment and radiation-related toxicity in a significant proportion of patients. However, the final verdict would be delivered after the long-term metastasis-free survival and overall survival outcomes are available.
Asunto(s)
Neoplasias de la Próstata , Vesículas Seminales , Humanos , Masculino , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Radioterapia Adyuvante/efectos adversos , Estudios Retrospectivos , Terapia Recuperativa , Vesículas Seminales/patologíaRESUMEN
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.
RESUMEN
BACKGROUND AND PURPOSE: Salvage radiotherapy (SRT) is the main potentially curative treatment option for prostate cancer patients with post-prostatectomy PSA progression. Improved diagnostics by positron emission tomography/computed tomography (PET/CT) can lead to adjustments in treatment procedures (e.g. target volume of radiotherapy, androgen deprivation therapy). We analyzed the impact of 68Ga-PSMA-11-PET/CT on the target volume in early biochemical recurrence (PSA up to 0.5 ng/ml). PATIENTS AND METHODS: We retrospectively analyzed 76 patients with biochemical recurrence after radical prostatectomy in whom SRT was planned after 68Ga-PSMA-11-PET/CT. All patients had a PSA ≤0.5 ng/ml. An experienced radiation oncologist determined the radiotherapy concept, first with consideration of the PET/CT, second hypothetically based on the clinical and pathological features excluding PET/CT results. RESULTS: Without considering the PET/CT, all 76 patients would have been assigned to RT, 60 (79%) to the bed of the prostate and seminal vesicles alone, and 16 (21%) also to the pelvic lymph nodes because of histopathologic risk factors. Uptake indicative for tumor recurrence in 68Ga-PSMA-11-PET/CT was found in 54% of the patients. The median pre-PET/CT PSA level was 0.245 ng/ml (range 0.07-0.5 ng/ml). The results of the PET/CT led to a change in the radiotherapeutic target volume in 21 patients (28%). There were major changes in the target volume including the additional irradiation of lymph nodes or the additional or exclusive irradiation of bone metastases in 13 patients (17%). Minor changes including the additional irradiation of original seminal vesicle (base) position resulted in eight patients (11%). CONCLUSION: Using 68Ga-PSMA-11-PET/CT for radiation planning, a change in the treatment concept was indicated in 28% of patients. With PET/CT, the actual extent of the tumor can be precisely determined even with PSA values of ≤0.5 ng/ml. Thus, the treatment concept can be improved and individualized. This may have a positive impact on progression free survival. Our results warrant further prospective studies.
RESUMEN
CONTEXT: Depending on the pathologic tumour stage, up to 60% of prostate cancer patients who undergo radical prostatectomy will develop biochemical relapse and require further local treatment. OBJECTIVES: We reviewed the results of early salvage radiation therapy (RT), defined as prostate-specific antigen (PSA) values prior to RT ≤ 0.5 ng/ml in the setting of lymph node-negative disease. EVIDENCE ACQUISITION: Ten retrospective studies, including one multicentre analysis, were used for this analysis. Among them, we received previously unpublished patient characteristics and updated outcome data from five retrospective single-centre trials to perform a subgroup analysis for early salvage RT. EVIDENCE SYNTHESIS: Patients treated with early salvage RT have a significantly improved biochemical recurrence-free survival (BRFS) rate compared with those receiving salvage RT initiated after PSA values are >0.5 ng/ml. Similarly, within the cohort of patients with pre-RT PSA values <0.5 ng/ml, improved BRFS rates were noted among those with lower rather higher pre-RT PSA levels. It is possible that higher RT dose levels and the use of adjunctive androgen-deprivation therapy improve biochemical control outcomes in the salvage setting. CONCLUSIONS: Based on a literature review, improved 5-yr BRFS rates are observed for patients who receive early salvage RT compared with patients treated with salvage RT with a pre-RT PSA value >0.5 ng/ml. Whether the routine application of early salvage RT in patients with initially undetectable PSA levels will be associated with demonstrable clinical benefit awaits the results of ongoing prospective trials.