Eur Urol 2020 Dec 10
A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER).
Abstract
Context
Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.
Objective
To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.
Evidence acquisition
We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.
Evidence synthesis
A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.
Conclusions
Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.
Patient summary
In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
Related Questions
Is salvage SBRT an option for focal recurrence of PCa after prior proton therapy for intermediate-risk disease?
Yes, it is an option. There is a great need for randomized trials in the setting of local-only recurrence after definitive RT, and we do not know the optimal approach. The MASTER systematic review and meta-analysis is a good summary (Valle et al., PMID 33309278). I do not think that protons vs. phot...
Would you offer re-irradiation for a prostate local recurrence after I-125 seed implant >10 years ago in a healthy young patient with life expectancy >15 years?
While I think salvage re-irradiation does have the potential to become a routine option in such situations, I think further study is required to define both the efficacy and toxicity profile prior to establishing it as such. The current state of knowledge is based on limited information, as Dr. @Dr....
What urethral dose constraints would you use off-trial for reirradiating the prostate using SBRT?
The short answer to this question is that there is no evidence-based answer. Below is a review for anyone interested. Background: The recognition of local recurrence as a pattern of failure seems to be growing, perhaps in part due to the increased utilization of advanced imaging (as previously discu...
Is there evidence that prostatectomy improves overall survival in local recurrence of prostate cancer post-definitive radiation?
I am not aware of any prospective clinical trial data to suggest that salvage prostatectomy for locally recurrent prostate cancer improves overall survival as compared to any other comparator. Such evidence would be very difficult to generate given that historically, most prospective studies have fo...
Would you recommend prostate re-irradiation using SBRT?
Yes, we offer it for patients who had prostate cancer, underwent definitive radiation, have failed by Phoenix criteria, and have a PSMA PET confirming no metastatic disease.We obtain an MRI of the prostate and our Urologists perform a full TP biopsy + biopsy of ROI to identify areas of active diseas...
How do you approach a local failure with a rising PSA following prostate SBRT?
I would obtain an MRI if not already done to help delineate local disease extent. A variety of salvage options are available (RP; HIFU; cryotherapy; and re-irradiation with brachytherapy or focal SBRT). A recent systematic review and meta-analysis of local salvage therapies was published by a group ...
What dose constraints would you use if reirradiating the prostate using SBRT?
This is a difficult question to answer in this forum due to the limited availability of prospective data on which to define optimal OAR tolerance. The answer would depend on the dose, fractionation, treatment volume (GTV vs. whole gland), and technique which would be employed (CK vs. IMRT/VMAT). The...
Would you offer SBRT for intraprostatic recurrence after definitive RT in a patient with contraindications to ablation and brachytherapy?
This is a very nice review on this topic, highlighting brachytherapy and SBRT for salvage after previous EBRT - A Systematic Review and Meta-analysis of Local Salvage Therapies After Radiotherapy for Prostate Cancer (MASTER) - ScienceDirect.