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Brachytherapy‐based radiotherapy with androgen deprivation for management of high‐risk prostate cancer – time to reverse the declining trend?

2018; Wiley; Volume: 122; Issue: S5 Linguagem: Inglês

10.1111/bju.14487

1464-410X

Wee Loon Ong, John Yaxley, Jeremy Millar,

Advanced Radiotherapy Techniques

BJU InternationalVolume 122, Issue S5 p. 5-6 CommentFree Access Brachytherapy-based radiotherapy with androgen deprivation for management of high-risk prostate cancer – time to reverse the declining trend? Wee Loon Ong, Corresponding Author Wee Loon Ong weeloonong@cantab.net Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, Heidelberg, Vic., Australia Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia School of Clinical Medicine, University of Cambridge, Cambridge, UK Correspondence: Wee Loon Ong, Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, 145 Studley Road, Heidelberg, Vic. 3084 Australia. e-mail: weeloonong@cantab.netSearch for more papers by this authorJohn W. Yaxley, John W. Yaxley Wesley Urology Clinic Brisbane, Brisbane, Qld., Australia Department of Medicine, University of Queensland, Brisbane, Qld., Australia Royal Brisbane and Women's Hospital, Brisbane, Qld., AustraliaSearch for more papers by this authorJeremy L. Millar, Jeremy L. Millar Alfred Health Radiation Oncology Services, Prahran, Vic., Australia Central Clinical School, Monash University, Melbourne, Vic., AustraliaSearch for more papers by this author Wee Loon Ong, Corresponding Author Wee Loon Ong weeloonong@cantab.net Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, Heidelberg, Vic., Australia Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Vic., Australia School of Clinical Medicine, University of Cambridge, Cambridge, UK Correspondence: Wee Loon Ong, Department of Radiation Oncology, Olivia Newton-John Cancer Centre, Austin Health, 145 Studley Road, Heidelberg, Vic. 3084 Australia. e-mail: weeloonong@cantab.netSearch for more papers by this authorJohn W. Yaxley, John W. Yaxley Wesley Urology Clinic Brisbane, Brisbane, Qld., Australia Department of Medicine, University of Queensland, Brisbane, Qld., Australia Royal Brisbane and Women's Hospital, Brisbane, Qld., AustraliaSearch for more papers by this authorJeremy L. Millar, Jeremy L. Millar Alfred Health Radiation Oncology Services, Prahran, Vic., Australia Central Clinical School, Monash University, Melbourne, Vic., AustraliaSearch for more papers by this author First published: 19 October 2018 https://doi.org/10.1111/bju.14487Citations: 3AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Brachytherapy (BT), in the form of low-dose-rate (LDR) or high-dose-rate (HDR) BT, in combination with external beam radiotherapy (EBRT) is an excellent treatment option for men with high-risk prostate cancer (PCa). Earlier randomized trials have shown better disease control outcomes with EBRT + BT compared with EBRT alone. The recent randomized ASCENDE-RT trial, which compared dose-escalation EBRT alone to a total dose of 78 Gy vs EBRT + BT in men with intermediate- to high-risk PCa, showed that those treated with EBRT + BT were half as likely to develop biochemical failure at a median follow-up of 6.5 years 1. The significant difference in biochemical failure-free survival, we believe, may lead to improved metastatic-free survival and overall survival with longer follow-up. More recently, two non-randomized studies added further weight to the oncological benefits of EBRT + BT over ERBT alone. In a population-based retrospective study involving 42 576 men in the National Cancer Database, Ennis et al. 2 reported that there were no differences in overall survival between men with high-risk PCa treated with RP and those treated with EBRT + BT plus ADT, but men treated with EBRT plus ADT had significantly lower overall survival. In a separate retrospective study pooling 1 809 men with Gleason 9–10 PCa across 12 tertiary institutions in the USA and Norway, Kishan et al. 3 reported that men treated with EBRT + BT plus ADT had significantly lower PCa-specific mortality and longer time to distant metastasis than men treated with EBRT plus ADT. EBRT + BT plus ADT was still associated with lower risk of distant metastases when compared with subset of men treated with dose-escalated EBRT to a total dose of ≥78 Gy plus ADT 3. This new evidence has the weaknesses typical of retrospective studies. Case ascertainment may be biased, or not representative of the population of men actively treated for PCa. There are many unknown confounding or biasing factors that could affect the observed results. Men treated with EBRT + BT, for example, were probably fitter and more suitable for a (relatively minor) procedure, compared with men treated with EBRT alone. Nonetheless, there are laudable aspects of these two studies: they are large population-based or multi-institution, rather than single-institution studies, and they add weight to not just the ASCENDE-RT trial, but earlier randomized studies which showed the oncological benefits of EBRT + BT over EBRT alone. It would seem that, for men with high-risk PCa who opted for radiotherapy (RT), EBRT + BT is at least comparable, if not a better option than EBRT alone. Notwithstanding the level 1 evidence supporting improved oncological outcomes for EBRT + BT, this treatment seems to be increasingly less frequently used in practice. For example, the publicly available Medicare Benefits Schedules data showed a significant decline in the use of BT over the last 10 years 4, and the population-based PCa registry data showed that only 8% of men with high-risk PCa treated with EBRT received BT boost 4. Similarly, ADT also appeared to be under-utilised, with large institutional variations, despite multiple level 1 evidence showing its benefits in men with high-risk PCa 5. The reasons for the decline in BT utilisation are most likely multifactorial. The proportion of all men diagnosed with PCa going on to have active treatment has fallen; and this decrease is larger in the proportion managed with any form of RT. The advent of EBRT technology with volumetric modulated arc therapy or stereotactic technique, along with hypofractionated schedules, are very widely available in most RT facilities, routinely as a general technique that can be applied to the prostate. By contrast, prostate BT radiation oncologists are much less common and not all RT facilities have BT services. Hence, BT is less likely to be offered as an option to men with high-risk PCa. In a survey among radiation oncologists in North America, there was dramatic polarization in opinion regarding the use of BT boost with EBRT between BT expert vs non-BT expert radiation oncologists 6. To improve access to BT services, there should be effort and government support to set up BT services in regional RT facilities. Finally, the reported complication rate with BT boost is higher than that of EBRT alone, including the risk of urethral strictures and incontinence. As is the case with surgery, complication rates decrease with increasing clinicians' experience, and the risk of urethral strictures with BT among modern experienced BT clinicians has been reported to be <5% 7. In fit men with high-risk PCa, surgery may be the preferred treatment option. Among the men who opt for RT, not all are suitable for BT boost because of pre-existing urethral strictures, significant BOO, previous TURP, or large prostate volume; these men will be more appropriately treated with EBRT alone. However, with an increasing body of evidence supporting improved oncological outcomes with EBRT + BT over EBRT alone 1-3, the addition of BT boost, in the form of HDR or LDR therapy, to EBRT should be considered in all men with high-risk PCa who opt for RT. In fact, it may be considered suboptimal care to not refer these patients for discussion and evaluation for BT boost, particularly the younger cohort. Not only is it incumbent on clinicians to educate our patients about the potential oncological benefits of BT boost, but we also need to liaise with the government and funding and policy bodies to increase funding for more BT programmes and specialist training opportunities to improve access to BT training. Conflict of Interest None declared. References 1Morris 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– 85 2Ennis RD, Hu L, Ryemon SN, Lin J, Mazumdar M. Brachytherapy-based radiotherapy and radical prostatectomy are associated with similar survival in high-risk localized prostate cancer. J Clin Oncol 2018; 36: 1192– 8 3Kishan AU, Cook RR, Ciezki JP et al. Radical prostatectomy, external beam radiotherapy, or external beam radiotherapy with brachytherapy boost and disease progression and mortality in patients with Gleason score 9-10 prostate cancer. JAMA 2018; 319: 896– 905 4Ong WL, Evans SM, Millar JL. Under-utilisation of high-dose-rate brachytherapy boost in men with intermediate-high risk prostate cancer treated with external beam radiotherapy. J Med Imaging Radiat Oncol 2018; 62: 256– 61 5Ong WL, Foroudi F, Evans S, Millar J. Large institutional variations in use of androgen deprivation therapy with definitive radiotherapy in a population-based cohort of men with intermediate- and high-risk prostate cancer. BJU Int 2017; 120(Suppl. 3): 35– 42 6McClelland S 3rd, Sandler KA, Degnin C, Chen Y, Mitin T. Dramatically polarized opinion on the role of brachytherapy boost in management of high-risk prostate cancer: a survey of North American genitourinary expert radiation oncologists. Clin Genitourin Cancer 2018; 16: e543– 5 7Yaxley JW, Lah K, Yaxley JP, Gardiner RA, Samaratunga H, MacKean J. Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years. BJU Int 2017; 120: 56– 60 Abbreviations BT brachytherapy EBRT external beam radiotherapy HDR high-dose-rate LDR low-dose-rate PCa prostate cancer RT radiotherapy Citing Literature Volume122, IssueS5Special Issue: Urological Society of Australia and New Zealand. The Urological Society of Australia and New Zealand and Wiley have published this supplement with no financial support.November 2018Pages 5-6 ReferencesRelatedInformation