Nonsurgical Salvage Local Therapies for Radiorecurrent Prostate Cancer: A Systematic Review and Meta-analysis
Introduction
Radiotherapy (RT) plays a pivotal role in the radical therapeutic approach for locally confined prostate cancer. The development of advanced radiation treatment technologies has led to the possibility of achieving dose escalation limited to the gland while avoiding the surrounding structures [1]. However, biochemical recurrence (BCR) occurs within 5 yr after treatment in nearly one-third of patients treated with radical RT for localized disease [2]. In 2006, the American Society for Radiation Oncology updated its definition of BCR after radical RT, describing it as a rise by 2 ng/ml or more above the prostate-specific antigen nadir (nPSA) [3]. However, PSA fluctuations are common, especially in the first 2 yr after RT, and a post-RT PSA increase could be expression from either malignant or benign prostate tissue [4]. Prostate biopsies and diagnostic imaging are helpful in identifying true local recurrence. In an editorial in European Urology, Jones [5] stresses the importance of executing prostate biopsy, despite its limitations in the setting of previously irradiated tissues, to determine the need for local salvage procedures. More specifically, the correlation between histologic findings and PSA could help in recognition of truly localized recurrence, which would most likely benefit from local treatment, and unrecognized metastatic disease. While the aid of conventional anatomic magnetic resonance imaging (MRI) has traditionally been limited by the glandular atrophy and fibrosis induced by RT, evidence regarding the role of multiparametric MRI (mpMRI) in the detection of radiorecurrent disease is slowly growing [6]. Choline positron emission tomography (PET)/computed tomography (CT), fluciclovine PET and, more recently, 68Ga-labeled PSMA ligand PET/CT have shown more efficacy than conventional imaging in restaging patients with BCR [7], [8].
Different therapeutic strategies can be adopted for local relapses, including re-irradiation (with brachytherapy [BT] or external beam RT [EBRT]) and other focal therapies such as high-intensity focused ultrasound (HIFU) and cryotherapy (CRYO). However, according to the CAPSURE report [9] only a small proportion of patients with radiorecurrent prostate cancer (between 15% and 20%) undergo local salvage therapy, and androgen deprivation therapy (ADT) and observation currently represent the preferred option for therapeutic management of these patients.
One of the main issues to consider when choosing local therapies is the possibility of significant genitourinary toxicity, which can have a detrimental effect on the quality of life of patients who have previously undergone prostate RT. At the same time, indiscriminately offering only ADT to patients who still have the potential for cure has been strongly criticized [5], taking into account the spectrum of systemic side effects associated with androgen ablation (eg, higher risk of metabolic syndrome and cardiovascular events).
The aim of this review was to conduct a comprehensive analysis of the role of nonsurgical salvage modalities in radiorecurrent prostate cancer and the associated clinical outcomes and toxicity profiles.
Section snippets
Evidence acquisition
A review of the literature according to the Preferred Reporting Items and Meta-analyses statement was independently performed by two authors (A.L. and C.B.) using a formal computer-assisted search of the Medline, Scopus, and ClinicalKey databases from January 1, 2000 through February 1, 2018. Keywords used were “salvage radiotherapy”, “recurrent prostate cancer”, “re-irradiation prostate”, “radio-recurrent prostate cancer”, “hifu”, “high-intensity focused ultrasound”, “brachytherapy”,
Evidence synthesis
Overall, 221 studies were identified. After duplicate exclusion, initial screening, and eligibility evaluation, 64 case-series studies were included in the final analysis, corresponding to a cohort of 5585 patients [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60],
Conclusions
Overall, results from the current analysis showed promising outcomes in terms of biochemical control for nonsurgical therapeutic options in the local recurrence setting, especially for BT and EBRT using modern stereotactic body RT techniques. Our systematic review is based on case series and because of the lack of a control group and the limited follow-up for the majority of the studies, it is not possible to draw conclusions with a high level of evidence. In addition, it should be noted that
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