ADT Sequencing With Radiotherapy for Nonmetastatic Prostate Cancer

A pooled analysis of 12 randomized trials found that when delivering short-term androgen-deprivation therapy (ADT) with radiotherapy for prostate cancer, the sequencing of ADT (concurrent/adjuvant vs neoadjuvant/concurrent) exhibits a significant interaction with the size of the radiotherapy field, which can have an impact on multiple oncological outcomes.

The study identified an association between concurrent/adjuvant ADT with prostate-only radiotherapy and significantly improved metastasis-free survival, prostate cancer-specific mortality, and overall survival (OS). When using whole-pelvic radiation however, neither neoadjuvant/concurrent nor concurrent/adjuvant ADT sequencing had a clear benefit.

This study analyzed patient data from 12 randomized trials included in the Meta-Analysis of Randomized Trial in Cancer of Prostate Consortium. In total, 7409 patients were included, who received either neoadjuvant/concurrent (n = 6325) or concurrent/adjuvant (n = 1084) short-term ADT, delivered with radiotherapy for localized prostate cancer.

The primary end point was metastasis-free survival, with OS, distant metastasis, prostate-cancer specific mortality, among the other end points assessed. All outcomes were also analyzed independently for patients receiving prostate-only radiation (n = 4355) compared with patients receiving whole-pelvic radiotherapy (n = 3049).

The median follow-up duration was 10.2 years. There was a significant interaction found between ADT sequencing and radiotherapy field size for all end points (P interaction < .02 for all), aside from OS.

For patients who underwent prostate-only radiotherapy, concurrent/adjuvant ADT was associated with improved metastasis-free survival (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.54 to 0.79; P <.0001), distant metastasis (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate-cancer specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P <.0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; I = .0001), when compared to neoadjuvant/concurrent ADT. In patients who underwent whole-pelvic radiotherapy, there was no significant difference in any end points when it came to ADT sequencing. Though, there was an association between concurrent/adjuvant ADT and worse distant metastasis (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) in this subgroup.

The authors concluded for patients undergoing prostate-only radiotherapy with short-term ADT, which is the recommendation for patients with intermediate-risk disease, the standard of care for ADT sequencing should be concurrent/neoadjuvant. They also stated, while the effects were less clear for patients undergoing whole-pelvic radiotherapy, “neoadjuvant/concurrent [short-term ADT] sequencing may be preferred, given its [distant metastasis] benefit.”

Source:

Ma TM, Sun Y, Malone S, et al. Sequencing of androgen-deprivation therapy of short duration with radiotherapy for nonmetastatic prostate cancer (SANDSTORM): A pooled analysis of 12 randomized trials. Published online October 21, 2022. doi:10.1200/JCO.22.00970