Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial

Denham, James W.; Steigler, Allison; Joseph, David; Lamb, David; Spry, Nigel; Duchesne, Gillian; Atkinson, Callum; Matthews, John; Turner, Sandra; Kenny, Lizbeth; Tai, Keen‐Hun; Gogna, Nirdosh Kumar; Gill, Suki; Tan, Hendrick; Kearvell, Rachel; Murray, Janice; Ebert, Martin; Haworth, Annette; Kennedy, Angel; Delahunt, Brett; Oldmeadow, Christopher; Holliday, Elizabeth G.; Attia, John

doi:10.1016/j.radonc.2015.05.016

Cited by 53 publications

(51 citation statements)

References 27 publications

(30 reference statements)

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“…18 months of ADT had a positive effect on the PSA and local control outcome on all EBRT dose levels with greater benefit is seen in lower doses, and had almost no effect for patients treated with HDR boost (absolute difference 3%). This data suggest minimal if any benefit to longer ADT with the use of PB, however it does not answer the question of whether ADT in needed with PB at all (122). Three other completed Brachytherapy RCTs do not provide information on the role of ADT with dose-escalated radiation using PB (22,23)(24).…”

Section: Randomized Controlled Trials: Adt and Brachytherapy (Table 6)mentioning

confidence: 82%

“…Patients in LR and IR most often received ADT to downsize the prostate, and in some IR and most HR studies, ADT was given for high risk features, as described above. While optimal duration of ADT cannot be determined from this review, TROG 03.04 RADAR has provided some evidence that duration of ADT together with HDR-BP has less impact on bPFS and local control than when combined with EBRT (122). As most of the studies, even those with HR PCa limited ADT to median 12 months; one may consider shorted duration of ADT if PB boost is to be used (up to 12 months).…”

Section: Discussionmentioning

confidence: 99%

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American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

et al. 2017

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Introduction Prostate Brachytherapy (PB) has well-documented excellent long-term outcomes in all risk groups. There are significant uncertainties regarding the role of Androgen Deprivation Therapy (ADT) with brachytherapy. The purpose of this report is to review systemically the published literature and summarize present knowledge regarding the impact of ADT on Biochemical Progression Free Survival (bPFS), Cause Specific Survival (CSS) and Overall Survival (OS). Material and Methods A literature search was conducted in Medline and Embase covering the years 1996-2016. Selected were articles with >100 patients, minimum follow-up 3 years, defined risk stratification and directly examining the role and impact of ADT on bPFS, CSS and OS. The studies were grouped to reflect disease risk stratification. We also reviewed the impact of ADT on OS, cardiovascular morbidity, mortality, and ongoing brachytherapy Randomized Controlled Trials (RCTs). Results 52 selected studies (43,303 patients) were included in this review; 7 HDR (High Dose Rate), and 45 LDR (Low Dose Rate). Twenty-five studies were multi-institutional and 27 single institution, (retrospective review or prospective data collection) and two were RCTs. The studies were heterogeneous in patient population, risk categories, risk factors, follow-up time, and treatment administered, including ADT administration and duration (median 3-12 months). Seventy one percent of the studies reported a lack of benefit, while 28% show improvement in bPFS with addition of ADT to PB. The lack of benefit was seen in LR and favourable IR disease, as well as the majority of HDR studies. A bPFS benefit of up to 15% was seen with ADT use in: patients with suboptimal dosimetry, those with multiple adverse risk factors (unfavourable IR) and most HR studies. Four studies reported very small benefit to CSS (2%). None of the studies showed OS advantage, however 3 studies reported an absolute 5-20% OS detriment with ADT. Literature suggests OS detriment is more likely in older patients or those with pre-existing cardiovascular disease (CVD). Four RCTs with an adequate number of patients and well defined risk stratification are in progress. One RTC will answer the question regarding the role of ADT with PB in favourable IR patients, and the other 3 RTCs will focus on optimal duration of ADT in the unfavourable IR and favourable HR population. Conclusions Patients treated with brachytherapy have excellent long-term disease outcomes. Existing evidence shows no benefit of adding ADT to PB in LR and favourable IR patients. Unfavourable IR, HR patients and those with suboptimal dosimetry may have up to 15% improvement in bPFS with addition of 3-12 months of ADT, with uncertain impact on CSS and a potential detriment on OS. In order to minimize morbidity one should exercise caution in prescribing ADT together with PB, in particular to older men and those with existing CVD. Due to the retrospective nature of this evidence, significant selection and treatment bias, no definitive conclusions a...

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Section: Randomized Controlled Trials: Adt and Brachytherapy (Table 6)mentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

et al. 2017

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“…The radiotherapy consisted of HDR‐BT commencing 2–5 weeks after the completion of EBRT. Patient criteria and treatment methodology were as specified for the Trans‐Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) trial . The standard HDR‐BT treatment has previously been described .…”

Section: Methodsmentioning

confidence: 99%

Accumulation of rectum dose‐volume metrics for prostate external beam radiotherapy combined with brachytherapy: Evaluating deformably registered dose distribution addition using parameter‐based addition

et al. 2017

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“…These patients were treated as part of the Trans-Tasman Radiation Oncology Group (TROG) 03.04 Randomized Androgen Deprivation and Radiotherapy (RADAR) trial [14,15]. The patient criteria and treatment methodology for the RADAR trial have previously been detailed [14,15].…”

Section: Patient Datamentioning

confidence: 99%

Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications

et al. 2016

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Background: Derivation of dose-volume correlated with toxicity for multi-modal treatments can be difficult due to the perceived need for voxel-by-voxel dose accumulation. With data available for a single-institution cohort with long follow-up, an investigation was undertaken into rectal dose-volume effects for gastrointestinal toxicities after deformably-registering each phase of a combined external beam radiotherapy (EBRT)/high-dose-rate (HDR) brachytherapy prostate treatment.

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Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial

Cited by 53 publications

References 27 publications

American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

American Brachytherapy Society Task Group Report: Use of androgen deprivation therapy with prostate brachytherapy—A systematic literature review

Accumulation of rectum dose‐volume metrics for prostate external beam radiotherapy combined with brachytherapy: Evaluating deformably registered dose distribution addition using parameter‐based addition

Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications

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