Advertisement

After ASCENDE-RT: Biochemical and survival outcomes following combined external beam radiotherapy and low-dose-rate brachytherapy for high-risk and unfavourable intermediate-risk prostate cancer, a population-based analysis

  • Author Footnotes
    # Author responsible for statistical analysis.
    Justin Oh
    Footnotes
    # Author responsible for statistical analysis.
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • W. James Morris
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Ingrid Spadinger
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Medical Physics, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Scott Tyldesley
    Correspondence
    Corresponding author. Department of Radiation Oncology, BC Cancer, 600 West 10th Avenue, Vancouver, BC, Canada, V5Z 4E6.
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Mira Keyes
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Ross Halperin
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Juanita Crook
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Vincent Lapointe
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Tom Pickles
    Affiliations
    Department of Radiation Oncology, British Columbia Cancer Agency Vancouver Centre, Vancouver, British Columbia, Canada

    Department of Surgery, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
    Search for articles by this author
  • Author Footnotes
    # Author responsible for statistical analysis.

      Abstract

      PURPOSE

      To evaluate the outcomes of unfavorable intermediate-risk (UIR) and high-risk (HR) prostate cancer patients treated with combined external beam radiation therapy (EBRT) and low-dose-rate prostate brachytherapy (LDR-PB).

      METHODS AND MATERIALS

      A population-based cohort of 568 prostate cancer patients treated with combined EBRT and LDR-PB from 2010 to 2016 was analyzed. All patients received EBRT followed by LDR-PB boost. Outcomes were compared with the results for the brachytherapy arm of the ASCENDE-RT trial.

      RESULTS

      The median followup was 4.5 years. Sixty-nine percent (N = 391) had HR disease. Ninety-four percent of the HR and 57% of UIR were treated with androgen deprivation therapy (ADT) with a median duration of 12 months. The 5-year K-M biochemical progression-free survival (b-PFS), metastasis-free survival (MFS), and overall survival (OS) were 84 ± 2%, 90 ± 2%, and 88 ± 2%, similar to 89 ± 5%, 94 ± 4%, and 92 ± 4% for the ASCENDE-RT LDR-PB arm. The likelihood of achieving a PSA ≤0.2 ng/mL at 4 years was 88%, similar to 86% in the ASCENDE-RT LDR-PB arm. Thirty-three men (5.8%) would have been ineligible for ASCENDE-RT due to high-risk features. The 5-year K-M b-PFS, MFS and OS estimates were 86 ± 2%, 92 ± 1% and 89 ± 2% for the ASCENDE-RT eligible versus 56 ± 10% (p < 0.001), 73 ± 8% (p < 0.001), and 77 ± 9% (p = 0.098) for the ineligible patients.

      CONCLUSIONS

      In this population-based cohort, combining LDR-PB with pelvic EBRT (+/- ADT) achieves very favorable b-PFS that compares to the LDR-PB arm of the ASCENDE-RT, supporting the generalizability of those results. Men ineligible for ASCENDE-RT, based on prognostic features, have a much higher risk of biochemical recurrence and metastatic relapse.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Brachytherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Brenner DR
        • Weir HK
        • Demers AA
        • et al.
        Projected estimates of cancer in Canada in 2020.
        CMAJ. 2020; 192: E199-E205
        • Mohler JL
        • Antonarakis ES
        • Armstrong AJ
        • et al.
        Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.
        J Natl Compr Canc Netw. 2019; 17: 479-505
        • Morris WJ
        • Tyldesley S
        • Rodda S
        • et al.
        Androgen suppression combined with elective nodal and dose escalated radiation therapy (the ASCENDE-RT Trial): an analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 275-285
        • Morris WJ
        • Tyldesley S
        • Rodda S
        • et al.
        Androgen suppression combined with elective nodal and dose escalated radiation therapy (the ASCENDE-RT Trial): an analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 275-285
        • Rodda S
        • Tyldesley S
        • Morris WJ
        • et al.
        ASCENDE-RT: an analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer.
        Int J Radiat Oncol Biol Phys. 2017; 98: 286-295
        • Pickles T
        • Morris WJ
        • Keyes M.
        High-intermediate prostate cancer treated with low-dose-rate brachytherapy with or without androgen deprivation therapy.
        Brachytherapy. 2017; 16: 1101-1105
        • Pickles T
        • Tyldesley S
        • Hamm J
        • Virani SA
        • Morris WJ
        • Keyes M.
        Brachytherapy for intermediate-risk prostate cancer, androgen deprivation, and the risk of death.
        Int J Radiat Oncol Biol Phys. 2018; 100: 45-52
        • Crook JM
        • Tang C
        • Thames H
        • et al.
        A biochemical definition of cure after brachytherapy for prostate cancer.
        Radiother Oncol. 2020; 149: 64-69
        • Lo AC
        • Morris WJ
        • Lapointe V
        • et al.
        Prostate-specific antigen at 4 to 5 years after low-dose-rate prostate brachytherapy is a strong predictor of disease-free survival.
        Int J Radiat Oncol Biol Phys. 2014; 88: 87-93
        • Jones CU
        • Hunt D
        • McGowan DG
        • et al.
        Radiotherapy and short-term androgen deprivation for localized prostate cancer.
        N Engl J Med. 2011; 365: 107-118
        • Zapatero A
        • Guerrero A
        • Maldonado X
        • et al.
        High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial.
        Lancet Oncol. 2015; 16: 320-327
        • Krauss DJ
        • Karrison TG
        • Martinez AA
        • et al.
        Dose escalated radiotherapy alone or in combination with short-term androgen suppression for intermediate risk prostate cancer: outcomes from the NRG Oncology/RTOG 0815 randomized trial.
        Int J Radiat Oncol Biol Phys. 2021; 111: Supp: S1
        • Joseph D
        • Denham JW
        • Steigler A
        • et al.
        Radiation dose escalation or longer androgen suppression to prevent distant progression in men with locally advanced prostate cancer: 10-year data from the TROG 03.04 RADAR trial.
        Int J Radiat Oncol Biol Phys. 2020; 106: 693-702
        • Potters L
        • Cao Y
        • Calugaru E
        A comprehensive review of CT-based dosimetry parameters and biochemical control in patients treated with permanent prostate brachytherapy.
        Int J Radiat Oncol Biol Phys. 2001; 50: 605-614
        • Stock RG.
        Counterpoint: there is a dose-response relationship in the low-dose rate brachytherapy management of prostate cancer.
        Brachytherapy. 2010; 9 (discussion 299): 293-296
        • Zelefsky MJ
        • Kuban DA
        • Levy LB
        • et al.
        Multi-institutional analysis of long-term outcome for stages T1-T2 prostate cancer treated with permanent seed implantation.
        Int J Radiat Oncol Biol Phys. 2007; 67: 327-333
        • Spadinger I
        • Chu J
        • Afsari Golshan M
        • et al.
        Regional dose metrics as predictors of biochemical failure and local recurrence after low-dose-rate prostate brachytherapy.
        Brachytherapy. 2015; 14: 350-358
        • Morris WJ
        • Spadinger I
        • Keyes M
        Whole prostate D90 and V100: a dose-response analysis of 2000 consecutive (125)I monotherapy patients.
        Brachytherapy. 2014; 13: 32-41
        • Keyes M
        • Miller S
        • Pickles T
        • et al.
        Late urinary side effects 10 years after low-dose-rate prostate brachytherapy: population-based results from a multiphysician practice treating with a standardized protocol and uniform dosimetric goals.
        Int J Radiat Oncol Biol Phys. 2014; 90: 570-578
        • Zheng J
        • Bachand F
        • Halperin R
        • et al.
        After ASCENDE-RT: outcomes of androgen deprivation, external beam radiation and LDR brachytherapy boost for high-tier intermediate and high risk prostate cancer treated at BC cancer Kelowna.
        Radiother Oncol. 2021; 163: S32-S33
        • Rahman S
        • Cosmatos H
        • Dave G
        • et al.
        Predicting pelvic lymph node involvement in current-era prostate cancer.
        Int J Radiat Oncol Biol Phys. 2012; 82: 906-910
        • Roach 3rd, M
        • Marquez C
        • Yuo HS
        • et al.
        Predicting the risk of lymph node involvement using the pre-treatment prostate specific antigen and Gleason score in men with clinically localized prostate cancer.
        Int J Radiat Oncol Biol Phys. 1994; 28: 33-37
        • Attard G
        • Murphy L
        • Clarke NW
        • et al.
        Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol.
        Lancet (London, England). 2022; 399: 447-460
        • Hofman MS
        • Lawrentschuk N
        • Francis RJ
        • et al.
        Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.
        Lancet. 2020; 395: 1208-1216
        • Maurer T
        • Gschwend JE
        • Rauscher I
        • et al.
        Diagnostic Efficacy of (68)Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer.
        J Urol. 2016; 195: 1436-1443
        • Feng FY
        • Huang HC
        • Spratt DE
        • et al.
        Validation of a 22-gene genomic classifier in patients with recurrent prostate cancer: an ancillary study of the NRG/RTOG 9601 randomized clinical trial.
        JAMA Oncol. 2021; 7: 544-552