Radiation oncology

Studies confirm optimal ADT strategy in prostate cancer


The optimal duration of androgen-deprivation therapy (ADT) may be  more than 18 months for prostate cancer patients receiving high-dose external beam radiotherapy (EBRT) but less for those receiving EBRT with a brachytherapy boost (EBRT+BT).

A patient-level cohort study from three cohorts, including the Trans-Tasman Radiation Oncology Group’s RADAR trial, compared distant metastasis-free survival (DMFS) benefit in 2,935 patients with high-risk prostate cancer receiving either EBRT or EBRT+BT.

Data from a single retrospective cohort showed that among patients treated with EBRT, six to less than 18 months of ADT was not associated with DMFS (hazard ratio [HR], 0.90; 95% CI, 0.61-1.31; P = .58) or OS (HR, 0.90; 95% CI, 0.58-1.38; P = .62) compared with less than six months of ADT.

However, receiving ADT for 18 months or more was associated with improved outcomes compared with ADT for less than six months (DMFS HR, 0.44; 95% CI, 0.31-0.63; P < .001; OS HR, 0.45; 95% CI, 0.30-0.68; P < .001).

ADT for 18 months or more was also associated with improved outcomes compared with ADT of six to less than 18 months (DMFS HR, 0.49; 95% CI, 0.39-0.62; P < .001; OS HR, 0.50; 95% CI, 0.39-0.65; P < .001).

“In contrast, among patients receiving EBRT+BT, six to less than 18 months of ADT was associated with improved DMFS (HR, 0.34; 95% CI, 0.25-0.45; P < .001) and OS (HR, 0.30; 95% CI, 0.22-0.41; P < .001) compared with less than six months.”

As well, receiving ADT for 18 months or more was associated with improved DMFS and OS compared with less than six months (DMFS HR, 0.42; 95% CI, 0.32-0.54; P < .001; OS HR, 0.43; 95% CI, 0.33-0.56; P < .001).

“However, the analyses did not detect an association between receiving ADT for 18 months or more and improved DMFS compared with six to less than 18 months (HR, 1.23; 95% CI, 0.91-1.66; P = .17) and the longer duration was associated with inferior OS (HR, 1.44; 95% CI, 1.04-1.99; P = .03).”

The study, published in JAMA Oncology, found that for patients receiving EBRT, the optimal ADT duration was 26.3 months and 12 months for those receiving EBRT+BT.

“The thresholds for ADT duration that were identified by the spline analysis from retrospective data are supported by analysis of individual patient data from the 2 RCTs,” the authors said.

They noted that ADT was commonly underused in practice given its adverse effects.

“Ongoing and future trials will help clarify whether predictive biomarkers can aid in selecting optimal ADT durations; in the interim, individual patient meta-analyses that consider ADT duration data from various relevant trials may be the best available guidance on optimal ADT duration,” the article concluded.

Meanwhile, a study published in The Lancet Oncology has confirmed the role of various androgen deprivation therapy (ADT) intensification strategies in improved metastasis-free survival in men

The individual patient data meta-analysis of 12 eligible trials published between 1962 and 2020 found the addition of ADT to radiotherapy significantly improved metastasis-free survival (HR 0·83 [95% CI 0·77–0·89], p<0·0001), as did adjuvant ADT prolongation (0·84 [0·78–0·91], p<0·0001), but not neoadjuvant ADT extension (0·95 [0·83–1·09], p=0·50).

The number-needed-to-treat was 8–18 patients treated to prevent one distant metastasis event at 10 years.

“Finally, the treatment effects of each intensification strategy were not significantly affected by radiotherapy dose, NCCN risk group, or patient age,” the researchers said.

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