Brachytherapy Boost May Allow for Shorter ADT With EBRT

NEW YORK (Reuters Health) – In patients with high-risk prostate cancer undergoing external beam radiotherapy (EBRT) alone, androgen deprivation therapy (ADT) may be needed for more than 18 months, versus 18 months or “possibly less” with a brachytherapy boost, researchers say.

“The duration of ADT with EBRT has been looked at very extensively in multiple randomized trials, but the duration of ADT with EBRT+BT (extremely high dose radiation) has not,” Dr. Amar Kishan of the University of California, Los Angeles told Reuters Health by email. “In this analysis, we were able to use a different statistical approach with our data from several centers. I was surprised to see the suggestion that an 18-month duration may not be enough with dose-escalated EBRT. This has not been clearly suggested before.”

“We recently formed a group, MARCAP (Meta-Analysis of Randomized Trials in Cancer of the Prostate), that pools data from multiple trials that have already been run and hope to use those data to compare different durations in men getting EBRT in a more direct fashion,” he said. “Specifically, we will be able to compare 6 versus 18 versus 36 months, and also bring in other standard durations, such as 4 months and 28 months. This work is ongoing.”

As reported in JAMA Oncology, Dr. Kishan and colleagues investigated the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving EBRT or EBRT+BT.

The team reviewed data from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) clinical trial; and a cross-trial comparison of RADAR versus the randomized Androgen Deprivation and Radiation Therapy trial 01/05 (2005-2010).

Overall, the three studies included 3,410 men with a mean age of 68: 1,827 patients treated with EBRT and 1,108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. Race/ethnicity data were lacking.

The primary outcome was DMFS.

A significant interaction was found between the treatment type (EBRT vs. EBRT+BT) and ADT duration: <6 months, 6 to <18, and 18 or more.

For an optimal effect on DMFS, the analysis identified minimum ADT duration thresholds of 26.3 months for EBRT and 12 months for EBRT+BT.

In RADAR, prolonging ADT for those receiving only EBRT was not associated with significant DMFS improvements (hazard ratio, 1.01); however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (HR, 0.56).

For those receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (HR, 0.37).

“Additional studies are needed to determine more precise minimum durations,” the authors conclude.

Dr. Scott Glaser, chief of brachytherapy and gynecological radiotherapy at City of Hope in Duarte, California, commented on the study in an email to Reuters Health, “The two primary findings seem plausible and reasonable based on the overall body of literature and clinical practice.”

However, he said, “This trial used fairly complex statistical methodology and relied upon cross-trial comparison to strengthen conclusions. The suggestion that if optimal duration of ADT for EBRT patients is 26 months, then there would be small-to-no benefit from going from 6 months to 18 months, is debatable, as there could be a either a linear relationship between duration of therapy and degree of benefit or a threshold effect where a benefit is realized only after a certain duration.”

“This concept wasn’t fully explored, given the low number of patients in the intermediate range of ADT duration,” he noted.

“Rather than recommending a universal optimal duration of ADT based on risk group, I believe the field will move toward more personalized recommendations,” he added. “How this personalization will be guided (genomics, cardiovascular risk, more advanced imaging, etc.) will be the next wave of research.”

SOURCE: https://bit.ly/34n1pM6 JAMA Oncology, online January 20, 2022.

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