Phase I/IIa trial of androgen deprivation therapy, external beam radiotherapy, and stereotactic body radiotherapy boost for high-risk prostate cancer (ADEBAR)

Yeon Joo Kim, Hanjong Ahn, Choung-Soo Kim, Young Seok Kim, Yeon Joo Kim, Hanjong Ahn, Choung-Soo Kim, Young Seok Kim

Abstract

Background: To evaluate the clinical outcomes of combination of androgen deprivation therapy (ADT), whole pelvic radiotherapy (WPRT), and stereotactic body radiotherapy (SBRT) boost in high-risk prostate cancer patients.

Methods: This prospective phase I/IIa study was conducted between 2016 and 2017. Following WPRT of 44 Gy in 20 fractions, patients were randomized to two boost doses, 18 Gy and 21 Gy, in 3 fractions using the Cyberknife system. Primary endpoints were incidences of acute toxicities and short-term biochemical recurrence-free survival (BCRFS). Secondary endpoints included late toxicities and short-term clinical progression-free survival (CPFS).

Results: A total of 26 patients were enrolled. Twelve patients received a boost dose of 18 Gy, and the rest received 21 Gy. The Median follow-up duration was 35 months. There were no grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicities. Sixty-one and 4% of patients experienced grade 1-2 acute GU and GI toxicities, respectively. There were 12% late grade 1-2 GU toxicities and 8% late grade 1-2 GI toxicities. Patient-reported outcomes of urinary symptoms were aggravated after WPRT and SBRT boost. However, they resolved at 1 month and returned to the baseline level at 4 months. Three-year BCRFS was 88.1%, and CPFS was 92.3%.

Conclusions: The present study protocol demonstrated that the combination of ADT, WPRT, and SBRT boosts for high-risk prostate cancer is safe and feasible, and may reduce total treatment time to 5 weeks. Boost dose of 21 Gy in 3 fractions seems appropriate.

Trial registration: ClinicalTrials.gov, ID; NCT03322020 - Retrospectively registered on 26 October 2017.

Keywords: Prostate neoplasms; Quality of life; Radiosurgery; Radiotherapy; Toxicity.

Conflict of interest statement

The authors report no conflicts of interest.

Figures

Fig. 1
Fig. 1
Treatment for ADEBAR trial
Fig. 2
Fig. 2
Results of patient-reported outcomes utilizing International Prostate Symptom Score (IPSS) and Overactive Bladder Symptom Score (OABSS) questionnaires in 25 patients. a IPSS total score, b IPSS voiding score, c IPSS storage score, d OABSS total score, and e IPSS Quality of Life [*Numbers on y-axis represent Delighted (0), Pleased (1), Mostly satisfied (2), Mixed (3), Mostly dissatisfied (4), and unhappy (5)]. Abbreviation = M months
Fig. 3
Fig. 3
Graphs of biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS)

References

    1. Zietman AL, DeSilvio ML, Slater JD, Rossi CJ, Jr, Miller DW, Adams JA, et al. Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA. 2005;294(10):1233–1239.
    1. Peeters ST, Heemsbergen WD, Koper PC, van Putten WL, Slot A, Dielwart MF, et al. Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol. 2006;24(13):1990–1996.
    1. Brenner DJ, Hall EJ. Fractionation and protraction for radiotherapy of prostate carcinoma. Int J Radiat Oncol Biol Phys. 1999;43(5):1095–1101.
    1. King MT, Yang DD, Muralidhar V, Mahal B, Butler S, Devlin PM, et al. A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer. Brachytherapy. 2019;18(2):186–191.
    1. Morton GC. High-dose-rate brachytherapy boost for prostate cancer: rationale and technique. J Contemp Brachytherapy. 2014;6(3):323.
    1. Fuller DB, Naitoh J, Lee C, Hardy S, Jin HJ. Virtual HDRSM CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. Int J Radiat Oncol Biol Phys. 2008;70(5):1588–1597.
    1. Mercado C, Kress M-A, Cyr RA, Chen LN, Yung TM, Bullock EG, et al. Intensity-modulated radiation therapy with stereotactic body radiation therapy boost for unfavorable prostate cancer: the Georgetown University experience. Front Oncol. 2016;6:114.
    1. Katz A, Kang J. Stereotactic body radiotherapy with or without external beam radiation as treatment for organ confined high-risk prostate carcinoma: a six year study. Radiat Oncol. 2014;9(1):1.
    1. Anwar M, Weinberg V, Seymour Z, Hsu IJ, Roach M, Gottschalk AR. Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer. Radiat Oncol. 2016;11(1):8.
    1. Lin Y-W, Lin L-C, Lin K-L. The early result of whole pelvic radiotherapy and stereotactic body radiotherapy boost for high-risk localized prostate cancer. Front Oncol. 2014;4:278.
    1. Kim HJ, Phak JH, Kim WC. Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer. Asia Pac J Clin Oncol. 2017;13(5):e342–e3e7.
    1. Pasquier D, Peiffert D, Nickers P, Maingon P, Pommier P, Lacornerie T, et al. A Multicenter Phase 2 study of Hypofractionated Stereostatic Boost in Intermediate Risk Prostate Carcinoma: A 5-Year Analysis of the CKNO-PRO Trial. Int J Radiat Oncol Biol Phys. 2020;106(1):116–123.
    1. Kim YJ, Ahn H, Kim C-S, Lee J-L, Kim YS. Stereotactic body-radiotherapy boost dose of 18 Gy vs 21 Gy in combination with androgen-deprivation therapy and whole-pelvic radiotherapy for intermediate-or high-risk prostate cancer: a study protocol for a randomized controlled, pilot trial. Trials. 2018;19(1):212.
    1. Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff R-O, Storme G, et al. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010;11(11):1066–1073.
    1. Lee SU, Cho KH. Multimodal therapy for locally advanced prostate cancer: the roles of radiotherapy, androgen deprivation therapy, and their combination. Radiat Oncol J. 2017;35(3):189–197.
    1. Siddiqui ZA, Krauss DJ. Adjuvant androgen deprivation therapy for prostate cancer treated with radiation therapy. Transl Androl Urol. 2018;7(3):378.
    1. Joseph D, Denham JW, Steigler A, Lamb DS, Spry NA, Stanley J, 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(4):693–702.
    1. Pryor D, Sidhom M, Arumugam S, Bucci J, Gallagher S, Smart J, et al. Phase 2 Multicentre Study of Gantry-Based Stereotactic Radiotherapy Boost for Intermediate and High Risk Prostate Cancer (PROMETHEUS) Front Oncol. 2019;9:217.
    1. Tritschler S, Roosen A, Füllhase C, Stief CG, Rübben H. Urethral stricture: etiology, investigation and treatments. Dtsch Arztebl Int. 2013;110(13):220–226.
    1. Pommier P, Chabaud S, Lagrange J-L, Richaud P, Le Prise E, Wagner J-P, et al. Is there a role for pelvic irradiation in localized prostate adenocarcinoma? Update of the long-term survival results of the GETUG-01 randomized study. Int J Radiat Oncol Biol Phys. 2016;96(4):759–769.
    1. Tharmalingam H, Tsang Y, Choudhury A, Alonzi R, Wylie J, Ahmed I, et al. External beam radiation therapy (EBRT) and high-dose-rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: The impact of EBRT volume. Int J Radiat Oncol Biol Phys. 2020;106(3):525–533.
    1. Morris WJ, Tyldesley S, Rodda S, Halperin R, Pai H, McKenzie M, 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(2):275–285.
    1. Miralbell R, Roberts SA, Zubizarreta E, Hendry JH. Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: alpha/beta = 1.4 (0.9-2.2) Gy. Int J Radiat Oncol Biol Phys. 2012;82(1):e17–e24.
    1. Mitin T, Henry A, Choudhury A, Chen RC, Pinkawa M, Spratt DE. SBRT for Localized Prostate Cancer: Is it Ready for Take-Off? Int J Radiat Oncol Biol Phys. 2019;105(3):618–620.
    1. King CR. The dose–response of salvage radiotherapy following radical prostatectomy: A systematic review and meta-analysis. Radiother Oncol. 2016;121(2):199–203.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다