Concurrent/adjuvant ADT sequencing appears optimal in patients receiving prostate-only RT

“To our knowledge, this study represents the first time a significant association has been demonstrated between concurrent and adjuvant ADT sequencing and overall survival rates among prostate cancer patients," says Amar Kishan, MD.

Androgen deprivation therapy (ADT) sequenced during and after radiotherapy (RT) has clinical benefits for patients undergoing treatment for prostate cancer, according to investigators at the University of California, Los Angeles (UCLA) Jonsson Comprehensive Cancer Center.1 The study analyzed ADT in combination with prostate-only radiotherapy (PORT) and whole-pelvis radiotherapy (WPRT).

“To our knowledge, this study represents the first time a significant association has been demonstrated between concurrent and adjuvant ADT sequencing and overall survival rates among prostate cancer patients. For patients receiving prostate-only RT, concurrent/adjuvant sequencing is associated with optimal outcomes,” said Amar Kishan, MD, chief of genitourinary oncology for Radiation Oncology at UCLA, in a news release about the findings.2

Although ADT has been shown to improve survival for localized prostate cancer when in combination with RT in past studies, its sequencing has remained controversial. In clinical practice, patients have typically been placed on ADT prior to beginning RT. This study now shows that concurrent/adjuvant sequencing of ADT for RT optimally causes the period of having low testosterone to be “backloaded” after radiation is complete.

The study cohort consisted of 7409 participants across 12 randomized trials who were treated with short-term ADT (4-6 months) with RT for localized prostate cancer. Patient data were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. A total of 6325 patients received ADT before and during RT (neoadjuvant/concurrent) and 1084 received ADT during and after RT (concurrent/adjuvant). The median follow-up period across both groups was 10.2 years.

Findings showed that there was a significant interaction between ADT sequencing and RT field size for all study end points except overall survival (OS). Concurrent/adjuvant ADT sequencing showed improved outcomes for metastasis-free survival (MFS), which was the primary end point of this study (P = .0015).

For men receiving PORT, concurrent/adjuvant ADT sequencing was associated with improvements in multiple oncologic end points, including MFS (P < .0001), distant metastasis (DM) (P = .0046), prostate cancer-specific mortality (P < .0001), and OS (P = .0001). For men receiving WPRT, no significant difference was seen in any end point when comparing neoadjuvant/concurrent sequencing with concurrent/adjuvant except for worse DM (P = .0009) with concurrent/adjuvant sequencing.

According to Kishan, these results should be “considered practice-changing with regards to how ADT is sequenced with radiation for patients getting short courses of ADT with prostate radiation.”

Investigators concluded that when PORT is delivered with short-term ADT (as is recommended for men with intermediate-risk disease), concurrent/adjuvant ADT sequencing should be the standard of care. When WRPT is delivered with short-term ADT, neoadjuvant/concurrent ADT may be better for patients given its DM benefit, although this is less consistent than the benefit seen with concurrent/adjuvant ADT with PORT.

References

1. 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. J Clin Oncol. Published online October 21, 2022. Accessed October 25, 2022. doi/full/10.1200/JCO.22.00970

2. News analysis led by UCLA Jonsson Comprehensive Care Center finds timing androgen-deprivation therapy with radiation therapy improves outcomes in localized prostate cancer. News release. University of California, Los Angeles (UCLA). October 21, 2022. Accessed on October 25, 2022. https://www.newswise.com/articles/new-analysis-led-by-ucla-jonsson-comprehensive-cancer-center-finds-timing-androgen-deprivation-therapy-with-radiation-therapy-improves-outcomes-in-localized-prostate-cancer?sc=mwhr&xy=10016681