Progression-directed Therapy for Oligoprogression in Castration-refractory Prostate Cancer

Berghen, Charlien; Joniau, Steven; Ost, Piet; Everaerts, Wouter; Decaestecker, Karel; Haustermans, Karin; Devos, Gaëtan; Meerleer, Gert De

doi:10.1016/j.euo.2019.08.012

Cited by 49 publications

(41 citation statements)

References 10 publications

(9 reference statements)

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“…Additionally some patients presented with progression among ADT at PSMA ligand staging and must be considered as early castration-resistant. Data about RT as MDT on this oncological situation are rare, although Berghen et al recently yielded first information that RT substantially postponed next-line systemic treatment [32]. In general the definition of oligometastases for prostate cancer is controversial and there is no general agreement between different experts panels [13,33].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy

Oehus¹,

Kroeze²,

Schmidt-Hegemann³

et al. 2020

BMC Cancer

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Background: A substantial number of patients will develop further biochemical progression after radical prostatectomy (RP) and salvage radiotherapy (sRT). Recently published data using prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET) for re-staging suggest that those recurrences are often located outside the prostate fossa and most of the patients have a limited number of metastases, making them amenable to metastasis-directed treatment (MDT). Methods: We analyzed 78 patients with biochemical progression after RP and sRT from a retrospective European multicenter database and assessed the biochemical recurrence-free survival (bRFS; PSA < nadir + 0.2 ng/ml or no PSA decline) as well as the androgen deprivation therapy-free survival (ADT-FS) using Kaplan-Meier curves. Logrank test and multivariate analysis was performed to determine influencing factors. Results: A total of 185 PSMA-PET positive metastases were detected and all lesions were treated with radiotherapy (RT). Concurrent ADT was prescribed in 16.7% (13/78) of patients. The median PSA level before RT was 1.90 ng/mL (range, 0.1-22.1) and decreased statistically significantly to a median PSA nadir level of 0.26 ng/mL (range, 0.0-12.25; p < 0.001). The median PSA level of 0.88 ng/mL (range, 0.0-25.8) at the last follow-up was also statistically significantly lower (p = 0.008) than the median PSA level of 1.9 ng/mL (range, 0.1-22.1) before RT. The median bRFS was 17.0 months (95% CI, 14.2-19.8). After 12 months, 55.3% of patients were free of biochemical progression. Multivariate analyses showed that concurrent ADT was the most important independent factor for bRFS (p = 0.01). The median ADT-FS was not reached and exploratory statistical analyses estimated a median ADT-FS of 34.0 months (95% CI, 16.3-51.7). Multivariate analyses revealed no significant parameters for ADT-FS. Conclusions: RT as MDT based on PSMA-PET of all metastases of recurrent prostate cancer after RP and sRT represents a viable treatment option for well-informed and well-selected patients.

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Section: Discussionmentioning

confidence: 99%

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy

Oehus¹,

Kroeze²,

Schmidt-Hegemann³

et al. 2020

BMC Cancer

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“…Preliminary data support this hypothesis [8][9][10][11][12][13][14][15][16][17][18][19]. Our research group recently published promising results on the use of PDT in this setting, with a next-line systemic treatment-free survival (NEST-FS) of 21 months [20].…”

Section: Introductionmentioning

confidence: 85%

“…Based on the number of eligible patients we expect to recruit 18 patients in one year, for which a follow-up of at least 24 months will be necessary (median NEST-FS in the PDT group was 21 months in our retrospective trial [20].…”

Section: Data Analysis Sample Size Calculationmentioning

confidence: 99%

Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial

et al. 2020

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Background: Patients diagnosed with metastatic castration-refractory prostate cancer (mCRPC) rely on a limited number of therapeutic agents resulting in a median survival of 2-3 years. A subgroup of those patients with mCRPC presents with oligoprogressive disease, with a limited number of progressive lesions while other metastases are still controlled by ongoing systemic treatment. Methods: In this single arm prospective phase II trial, we aim to include 18 patients with oligoprogressive mCRPC (1-3 metastases and/or local recurrence) who will be treated with metastasis-directed therapy to all visible progressive lesions. Progression is based on conventional imaging, as the use of PSMA PET-CT is considered investigational. However all patients will undergo PSMA PET-CT and the images will be blinded until progression. Primary endpoint is the postponement of the start of next-line systemic treatment (NEST) and the additional clinical value of PSMA PET-CT. Recruitment of patients for this trial started in January 2020 and will be completed approximately by December 2020. Discussion: In this phase 2 trial on oligoprogressive mCRPC, we will investigate the benefit of progression-directed therapy while continuing ongoing systemic treatment. We hypothesize that progression-directed therapy (PDT) with surgery or stereotactic body radiation therapy for these oligoprogressive lesions will postpone the start of next-line systemic treatment and therefore serve as a new or add-on therapy in the spectrum of treatments available for mCRPC. The results of this trial will serve as guidance for a later randomized phase 3 trial. All participants are given an information sheet and are required to give written informed consent. Results will be published in a peer-reviewed journal. Trial registration: This study is registered at ClinicalTrials.gov: NCT04222634 (December 18th 2019).

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“…In contrast, cRT for mCRPC seems less attractive because the value of local therapy at such a late stage is questionable. Several retrospective studies show that radiotherapy to oligoprogressive sites could delay disease progression in mCRPC [22,24,28]. In the study by Yildirim et al, prolonged abiraterone use was also observed in mCRPC patients receiving prostate-directed therapy, but no signi cant improvement of OS was found (24.1 vs. 21.4 months; P = 0.08) [23].…”

Section: Discussionmentioning

confidence: 99%

Cytoreductive Radiotherapy Combined with Abiraterone in Metastatic Castration-Resistance Prostate Cancer: A Single Center Experience

Liu

Long

Zhang

et al. 2020

Preprint

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Abstract Background: To investigate the potential benefit of cytoreductive radiotherapy (cRT) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving abiraterone.Methods: From February 2014 to February 2019, 149 mCRPC patients treated with abiraterone were identified. Patients receiving cRT before abiraterone failure (AbiRT group) were matched by one-to-two propensity score to patients without cRT before abiraterone failure (non-AbiRT group).Results: The median follow-up was 23.5 months. Thirty patients (20.1%) were in the AbiRT group, whereas 119 patients (79.9%) were in the non-AbiRT group. The 2-year overall survival (OS) of patients managed by AbiRT, cRT after abiraterone failure, and no cRT was 89.5%, 72.0% and 72.0%, respectively (P = 0.001). On multivariate analysis, only AbiRT (HR, 0.17; 95%CI, 0.05–0.58; P = 0.004) and prognostic index (HR 2.71; 95% CI, 1.37–5.35; P = 0.004) were significant factors. After matching, AbiRT continued to be associated with improved OS (median OS not reached vs. 44.0 months, P = 0.009). Subgroup analysis revealed that patients aged ≤65 years (HR, 0.09; 95%CI, 0.01–0.65; P = 0.018), PSA ≤20 ng/mL (HR 0.29; 95% CI, 0.09–0.99; P = 0.048), chemotherapy-naïve upon abiraterone treatment (HR 0.20; 95% CI, 0.06–0.66; P = 0.008) and in intermediate prognosis groups (HR 0.13; 95% CI, 0.03-0.57; P = 0.007) had improved OS with AbiRT. Conclusions: cRT before resistance to abiraterone may improve survival in selected mCRPC patients: relatively young, chemotherapy-naïve, with a relatively low PSA level at the diagnosis of mCRPC.

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Progression-directed Therapy for Oligoprogression in Castration-refractory Prostate Cancer

Cited by 49 publications

References 10 publications

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy

Efficacy of PSMA ligand PET-based radiotherapy for recurrent prostate cancer after radical prostatectomy and salvage radiotherapy

Metastasis-directed therapy in castration-refractory prostate cancer (MEDCARE): a non-randomized phase 2 trial

Cytoreductive Radiotherapy Combined with Abiraterone in Metastatic Castration-Resistance Prostate Cancer: A Single Center Experience

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