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    Curative-intent metastasis-directed therapies for molecularly-defined oligorecurrent prostate cancer: a prospective phase ii trial testing the oligometastasis hypothesis

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    Authors
    Glicksman, R. M.
    Metser, U.
    Vines, D.
    Valliant, J.
    Liu, Z.
    Chung, P. W.
    Bristow, Robert G
    Finelli, A.
    Hamilton, R.
    Fleshner, N. E.
    Perlis, N.
    Zlotta, A. R.
    Green, D.
    Bayley, A.
    Helou, J.
    Raman, S.
    Kulkarni, G.
    Catton, C.
    Lam, T.
    Chan, R.
    Warde, P.
    Gospodarowicz, M.
    Jaffray, D. A.
    Berlin, A.
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    Affiliation
    University of Toronto, Department of Radiation Oncology, 149 College Street, Unit 504, Toronto, Ontario, M5T 1P5, Canada.
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    Background: The hypothesis of a curable oligometastatic prostate cancer (PCa) state remains to be clinically-proven. Conventional imaging often fails to localize early recurrences, hampering the potential for radical approaches. Objective: We hypothesize that prostate-specific membrane antigen (PSMA)-targeted PET-MR/CT allows for earlier detection and localization of oligorecurrent-PCa, unveiling a molecularly-defined state amenable to curative-intent metastasis-directed treatment (MDT). Design/setting/participants: Single-institution single-arm phase-two study. Patients with rising PSA (0.4-3.0 ng/mL) after maximal local therapy (radical prostatectomy and post-operative radiotherapy), negative conventional staging, and no prior salvage hormonal therapy (HT) were eligible. Interventions: All patients underwent [18F]DCFPyL PET-MR/CT. Patients with molecularly-defined oligorecurrent-PCa had MDT (stereotactic ablative body radiotherapy [SABR] or surgery) without HT. Outcome measurements/statistical analysis: Primary endpoint was biochemical response (complete, i.e. biochemical 'no evidence of disease' [bNED], or partial response [100% or ≥50% PSA decline from baseline, respectively]) after MDT. Simon's two-stage design was employed (null and alternate hypotheses <5% and >20% response rate, respectively), with α and β of 0.1. Results: Seventy-two patients were enrolled (May/2017-July/2019). Thirty-eight (53%) had PSMA-detected oligorecurrent-PCa amenable for MDT. Thirty-seven (51%) agreed to MDT: 10 and 27 underwent surgery and SABR, respectively. Median follow-up was 15.9 months (IQR 9.8-19.1). Of patients receiving MDT, the overall response rate was 60%, including 22% rendered bNED. One (2.7%) grade 3 toxicity (intra-operative ureteric injury) was observed. Conclusions: PSMA-defined oligorecurrent-PCa can be rendered bNED, a necessary step towards cure, in 1 of 5 patients receiving MDT alone. Randomized trials are justified to determine if MDT +/- systemic agents can expand the curative therapeutic armamentarium for PCa. Patient summary: We studied men treated for prostate cancer with rising PSA. We found PSMA imaging detected recurrent cancer in three-quarters of patients, and targeted treatment to these areas significantly decreased PSA in half of patients.
    Citation
    Glicksman RM, Metser U, Vines D, Valliant J, Liu Z, Chung PW, et al. Curative-intent Metastasis-directed Therapies for Molecularly-defined Oligorecurrent Prostate Cancer: A Prospective Phase II Trial Testing the Oligometastasis Hypothesis. Eur Urol. 2021.
    Journal
    European Urology
    URI
    http://hdl.handle.net/10541/623828
    DOI
    10.1016/j.eururo.2021.02.031
    PubMed ID
    33685838
    Additional Links
    https://dx.doi.org/10.1016/j.eururo.2021.02.031
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.eururo.2021.02.031
    Scopus Count
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    All Paterson Institute for Cancer Research

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