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Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence.

ABSTRACT: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT).Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events.With a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13-25 mo) with 75% of recurring patients having ?3 metastases. A 2nd and 3rd course of SBRT was delivered in 19 and 6 patients respectively. This results in a median ADT-FS of 25 months (20-30 mo). On univariate analysis, only a short PSA doubling time was a significant predictor for both PFS (HR: 0.90, 95% CI: 0.82 - 0.99) and ADT-FS (HR: 0.83; 95% CI: 0.71 - 0.97). Ten patients (20%) developed toxicity following treatment, which was classified as grade I in 7 and grade II in 3 patients.Repeated SBRT for oligometastatic prostate cancer postpones palliative androgen deprivation therapy with 2 years without grade III toxicity.

SUBMITTER: Decaestecker K

PROVIDER: S-EPMC4066290 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence.

Decaestecker Karel K De Meerleer Gert G Lambert Bieke B Delrue Louke L Fonteyne Valérie V Claeys Tom T De Vos Filip F Huysse Wouter W Hautekiet Arne A Maes Gaethan G Ost Piet P

Radiation oncology (London, England) 20140612

<h4>Purpose</h4>To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT).<h4>Methods</h4>Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractio ...[more]

PMID: 24920079

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Project description:BackgroundAndrogen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated.MethodsPatients with ≤5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS).ResultsFifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤1 ng/ml (p = 0.03).ConclusionFor patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS.

Project description:Prostate cancer is the most common non-cutaneous cancer in males. There are a number of options for patients with localized early stage disease, including active surveillance for low-risk disease, surgery, brachytherapy, and external beam radiotherapy. Increasingly, external beam radiotherapy, in the form of dose-escalated and moderately hypofractionated regimens, is being utilized in prostate cancer, with randomized evidence to support their use. Stereotactic body radiotherapy, which is a form of extreme hypofractionation, delivered with high precision and conformality typically over 1 to 5 fractions, offers a more contemporary approach with several advantages including being non-invasive, cost-effective, convenient for patients, and potentially improving patient access. In fact, one study has estimated that if half of the patients currently eligible for conventional fractionated radiotherapy in the United States were treated instead with stereotactic body radiotherapy, this would result in a total cost savings of US$250 million per year. There is also a strong radiobiological rationale to support its use, with prostate cancer believed to have a low α/β ratio and therefore being preferentially sensitive to larger fraction sizes. To date, there are no published randomized trials reporting on the comparative efficacy of stereotactic body radiotherapy compared to alternative treatment modalities, although multiple randomized trials are currently accruing. Yet, early results from the randomized phase III study of HYPOfractionated RadioTherapy of intermediate risk localized Prostate Cancer (HYPO-RT-PC) trial, as well as multiple single-arm phase I/II trials, indicate low rates of late adverse effects with this approach. In patients with low- to intermediate-risk disease, excellent biochemical relapse-free survival outcomes have been reported, albeit with relatively short median follow-up times. These promising early results, coupled with the enormous potential cost savings and implications for resource availability, suggest that stereotactic body radiotherapy will take center stage in the treatment of prostate cancer in the years to come.

Project description:Prostate is the most common non-cutaneous cancer diagnosed among men in North America. Fortunately most prostate cancers are screen detected and non-metastatic on diagnosis. Treatment options for men with localized prostate cancer include surgery ± postoperative radiation or radiation ± androgen deprivation therapy (ADT). Brachytherapy ± external beam radiation treatment (EBRT) appears to have superior long-term disease control over EBRT alone likely because of higher biologic effective dose delivered. Stereotactic ablative body radiation (SABR) is a novel, non-invasive, high-precision EBRT technique that allows safe delivery of biologic doses similar to brachytherapy with similar or lower side effects [measured using toxicity or quality of life (QOL) scales]. Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2-3 years post treatment, biochemical failure (BF) rates out to 10-year and incidence of metastases. SABR dose escalation reduces biopsy positivity and prostate-specific antigen (PSA) nadirs but increases genitourinary (GU) and gastrointestinal (GI) toxicity-no effect on BF has been realized yet. The overall treatment time (OTT) varies in many protocols. Phase 2 randomized data shows that QOL is better in the acute setting with a weekly course of treatment compared to an every other day treatment regimen with no difference in late setting. Follow-up data are immature and likely underpowered to determine efficacy differences. SABR is cheaper and uses less resource than any other radiation technique. Given the healthcare resource challenges (including financial resources), SABR would be a welcomed addition if studies show non-inferiority to other radiation techniques. For patients with de novo or metastatic disease on relapse, there is much enthusiasm regarding the use of SABR in the setting of oligometastatic prostate cancer. SABR appears to be feasible to deliver, well tolerated and may delay the next line of therapy. However, until adequately powered randomized studies confirm a benefit, such an approach cannot be considered standard of care treatment at this time. Enrollment of eligible prostate cancer patients onto SABR clinical trials should be encouraged.

Project description:ObjectiveIn contrast to traditional views of incurability, patients with oligometastatic disease present with an opportunity for disease eradication with aggressive treatment. There is mounting evidence in support of the role of stereotactic body radiotherapy (SBRT) in oligometastatic prostate cancer (OMPC).MethodsMEDLINE and EMBASE were queried for prospective cohort studies reporting the outcomes of metachronous OMPC treated with SBRT. The primary outcome was overall local control. Secondary outcomes included androgen deprivation therapy-free survival (ADTFS), biochemical recurrence free survival (BCFS), and progression-free survival (PFS). When appropriate, these endpoints were combined in a meta-analysis.ResultsWe screened 356 abstracts and identified 10 studies to include in our analysis, with a total of 653 patients and 1,111 lesions. The maximum number of lesions included in any single study ranged from 3 to 5. PET-CT staging occurred in 92.4% of all patients. SBRT dose varied, with BED1.5 ranging from 152 to 408. Only one Grade 3 bone toxicity was observed. Meta-analysis reported an overall local control rate of 97% (95% CI, 94-100). Median ADTFS was 24.7 months (95% CI, 20.1-29.2 months). Two-year BCFS, PFS, and ADTFS were 33% (95% CI, 11-55), 39% (95% CI, 24-54), and 52% (95%CI, 41-62), respectively. Patients treated with SBRT were half as likely to experience PSA progression than those on observation when looking at randomized control trial data alone.ConclusionSBRT appears to be effective in controlling overall disease burden in metachronous OMPC patients and is associated with minimal significant toxicity. The current prospective literature is scarce, and further prospective data are needed to guide treatment recommendations.Advances in knowledgeThis study provides a comprehensive summary of the prospective evidence reporting the outcomes of SBRT in the management of OMPC patients. We quantify the rates of local control, biochemical-free recurrence, progression-free survival, and ADT-free survival through meta-analysis.

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Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence.

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Repeated stereotactic body radiotherapy for oligometastatic prostate cancer recurrence.

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