The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating 'trials within cohorts' (TwiCs) for the evaluation of interventions for prostate cancer

Frederik R Teunissen, Thomas Willigenburg, Richard P Meijer, Harm H E van Melick, Helena M Verkooijen, Jochem R N van der Voort van Zyp, Frederik R Teunissen, Thomas Willigenburg, Richard P Meijer, Harm H E van Melick, Helena M Verkooijen, Jochem R N van der Voort van Zyp

Abstract

Purpose: To describe the development and first outcomes of the Utrecht Prostate Cohort (UPC): the first 'trials within cohorts' (TwiCs) platform for prostate cancer (PCa).

Methods: All non-metastasized, histologically proven PCa patients who are planned to receive standard of care are eligible for inclusion in UPC. Patients provide informed consent for the collection of clinical and technical patient data, physician-reported outcomes, and patient-reported outcomes (PROs) up to 10 years post-treatment. Additionally, patients may provide broad consent for future randomization for experimental-intervention trials (TwiCs). Changes in PROs (EPIC-26 questionnaire domains) of the participants who received standard of care were analyzed using Wilcoxon signed-rank tests.

Results: In two years, 626 patients were enrolled, 503 (80.4%) of whom provided broad consent for future randomization. Among these, 293 (46.8%) patients underwent magnetic resonance-guided adaptive radiotherapy (MRgRT), 116 (18.5%) CT-guided external beam radiation therapy (EBRT), 109 (17.4%) robot-assisted radical prostatectomy (RARP), and 65 (10.4%) patients opted for active surveillance. Patients treated with MRgRT and CT-guided EBRT showed a transient but significant decline in urinary irritative/obstructive and bowel domain scores at 1-month follow-up. RARP patients showed a significant deterioration of urinary incontinence domain scores between baseline and all follow-up moments and significant improvement of urinary irritative/obstructive domain scores between baseline and 9- and 12-month follow-up. All radical treatment groups showed a significant decline in sexual domain scores during follow-up. Active surveillance patients showed no significant deterioration over time in all domains.

Conclusion: The first results from the UPC study show distinct differences in PROs between treatment options for PCa.

Registration no: NCT04228211.

Keywords: Cohort studies; Patient-reported outcome measures; Prostatic neoplasms; Quality of life; Treatment outcome.

Conflict of interest statement

HV receives research funding from Elekta. The remaining authors declare no potential competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
EPIC-26 domain scores for the four largest patient groups at baseline and 1, 3, 6, 9, and 12 months follow-up (numbers at risk in supplementary material). BL baseline, M month, AS active surveillance, EBRT external beam radiation therapy, MRgRT magnetic resonance-guided adaptive radiotherapy, RARP robot-assisted radical prostatectomy

References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–249. doi: 10.3322/caac.21660.
    1. Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–1424. doi: 10.1056/nejmoa1606220.
    1. McPartlin AJ, Li XA, Kershaw LE, Heide U, Kerkmeijer L, Lawton C, et al. MRI-guided prostate adaptive radiotherapy – a systematic reviewMRI-linac and prostate motion review. Radiother Oncol. 2016;119:371–380. doi: 10.1016/j.radonc.2016.04.014.
    1. Alongi F, Rigo M, Figlia V, Cuccia F, Giaj-Levra N, Nicosia L, et al. 1.5 T MR guided and daily adapted SBRT for prostate cancer: feasibility, preliminary clinical tolerability, quality of life and patient-reported outcomes during treatment. Radiat Oncol. 2020 doi: 10.1186/s13014-020-01510-w.
    1. van der Poel HG, van den Bergh RCN, Briers E, Cornford P, Govorov A, Henry AM, et al. Focal therapy in primary localised prostate cancer: the European association of urology position in 2018. Eur Urol. 2018;74:84–91. doi: 10.1016/j.eururo.2018.01.001.
    1. Young RC. Cancer clinical trials — a chronic but curable crisis. N Engl J Med. 2010;363:306–309. doi: 10.1056/nejmp1005843.
    1. Song F, Altman DG, Glenny AM, Deeks JJ. Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. Br Med J. 2003;326:472–475. doi: 10.1136/bmj.326.7387.472.
    1. Kennedy-Martin T, Curtis S, Faries D, Robinson S, Johnston J. A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results. Trials. 2015 doi: 10.1186/s13063-015-1023-4.
    1. Sedgwick P. Controlled trials: allocation concealment, random allocation, and blinding. BMJ. 2015;350:h2633. doi: 10.1136/bmj.h2633.
    1. Relton C, Torgerson D, O’Cathain A, Nicholl J. Rethinking pragmatic randomised controlled trials: introducing the “cohort multiple randomised controlled trial” design. BMJ. 2010;340:963–967. doi: 10.1136/bmj.c1066.
    1. Young-Afat DA, Verkooijen HAM, Van Gils CH, Van Der Velden JM, Burbach JP, Elias SG, et al. Staged-informed consent in the cohort multiple randomized controlled trial design. Epidemiology. 2016;27:389–392. doi: 10.1097/eDe.0000000000000435.
    1. van der Velden JM, Verkooijen HM, Ayoung-Afat D, Burbach JPM, van Vulpen M, Relton C, et al. The cohort multiple randomized controlled trial design: a valid and efficient alternative to pragmatic trials? Int J Epidemiol. 2017;46:96–102. doi: 10.1093/ije/dyw050.
    1. Szymanski KM, Wei JT, Dunn RL, Sanda MG. Development and validation of an abbreviated version of the expanded prostate cancer index composite instrument for measuring health-related quality of life among prostate cancer survivors. Urology. 2010;76:1245–1250. doi: 10.1016/j.urology.2010.01.027.
    1. Fayers P, Aaronson N, Bjordal K. EORTC QLQ-C30 scoring manual. Eortc. 2001 doi: 10.2001/6136/001.
    1. Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Peñ BM. Development and evaluation of an abridged, 5-item version of the international index of erectile function (IIEF-5) as a diagnostic tool for erectile dysfunction. Int J Impot Res. 1999;11:319–326. doi: 10.1038/sj.ijir.3900472.
    1. Herdman M, Gudex C, Lloyd A, Janssen M, Kind P, Parkin D, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20:1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. Barry MJ, Fowler FJ, O’Leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, et al. The American urological association symptom index for benign prostatic hyperplasia. J Urol. 1992;148:1549–1557. doi: 10.1016/S0022-5347(17)36966-5.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67:361–370. doi: 10.1111/j.1600-0447.1983.tb09716.x.
    1. Tuomi K, Ilmarinen J, Jahkola A, Katajarinne L, Tulkki A (1998) Work Ability Index. 2nd revised edn. Finnish Inst Occup Health, Helsinki
    1. Skolarus TA, Dunn RL, Sanda MG, Chang P, Greenfield TK, Litwin MS, et al. Minimally important difference for the expanded prostate cancer index composite short form. Urology. 2015;85:101–105. doi: 10.1016/j.urology.2014.08.044.
    1. Martin NE, Massey L, Stowell C, Bangma C, Briganti A, Bill-Axelson A, et al. Defining a standard set of patient-centered outcomes for men with localized prostate cancer. Eur Urol. 2015;67:460–467. doi: 10.1016/j.eururo.2014.08.075.
    1. Verkooijen HM, Kerkmeijer LGW, Fuller CD, Huddart R, Faivre-Finn C, Verheij M, et al. R-IDEAL: a framework for systematic clinical evaluation of technical innovations in radiation oncology. Front Oncol. 2017 doi: 10.3389/fonc.2017.00059.
    1. Hoffman KE, Penson DF, Zhao Z, Huang LC, Conwill R, Laviana AA, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA - J Am Med Assoc. 2020;323:149–163. doi: 10.1001/jama.2019.20675.
    1. Mazariego CG, Egger S, King MT, Juraskova I, Woo H, Berry M, et al. Fifteen year quality of life outcomes in men with localised prostate cancer: population based Australian prospective study. BMJ. 2020 doi: 10.1136/bmj.m3503.
    1. Lardas M, Liew M, van den Bergh RC, De Santis M, Bellmunt J, Van den Broeck T, et al. Quality of life outcomes after primary treatment for clinically localised prostate cancer: a systematic review. Eur Urol. 2017;72:869–885. doi: 10.1016/j.eururo.2017.06.035.
    1. Downing A, Wright P, Hounsome L, Selby P, Wilding S, Watson E, et al. Quality of life in men living with advanced and localised prostate cancer in the UK: a population-based study. Lancet Oncol. 2019;20:436–447. doi: 10.1016/S1470-2045(18)30780-0.
    1. Teunissen FR, Wortel RC, Hes J, Willigenburg T, de Groot-van Breugel EN, de Boer JCJ, et al. Adaptive magnetic resonance-guided neurovascular-sparing radiotherapy for preservation of erectile function in prostate cancer patients. Phys Imaging Radiat Oncol. 2021;20:5–10. doi: 10.1016/j.phro.2021.09.002.
    1. EREctile Function Preservation for Prostate Cancer Radiation Therapy (ERECT). identifier: NCT04861194. Updated August 25, 2021. Accessed 5 Feb 2022
    1. Kim SYH, Flory J, Relton C. Ethics and practice of trials within cohorts: an emerging pragmatic trial design. Clin Trials. 2018;15:9–16. doi: 10.1177/1740774517746620.
    1. Young-Afat DA, Gal R, Gerlich S, Burbach JPM, van der Velden JM, van den Bongard DHJG, et al. Oncology patients were found to understand and accept the trials within cohorts design. J Clin Epidemiol. 2021 doi: 10.1016/j.jclinepi.2020.10.015.

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