Out of sequence.

Top Line: Does the sequence of short-course ADT and radiation matter when treating prostate cancer?

The Study: In 2020, a meta-analysis of two clinical trials stirred debate about the sequencing of ADT with definitive radiation for localized prostate cancer. Historically, many of us gave ADT and waited several months before starting radiation, but the meta-analysis suggested that ADT during radiation and the duration of ADT after radiation (but not before) drove improvements in treatment outcomes. SANDSTORM is the latest meta-analysis from the MARCAP Consortium that tackles the question of short-course ADT sequencing in the setting of prostate only or prostate + pelvis radiation. They assembled individual patient data from 7409 patients treated in 12 randomized trials of radiation and either neoadjuvant/concurrent (85.4%) or concurrent/adjuvant ADT (14.6%). In contrast to the prior meta-analysis, which only included patients who received prostate-only RT, they also included patients who received pelvic nodal RT (22%). Among all patients, concurrent and adjuvant ADT was associated with a higher rate of 10-year metastasis free survival (64.9% v 61.4%) and a lower risk of biochemical recurrence (27.5% v 33.7%) and prostate cancer mortality (6.5% v 7.7%) compared to neoadjuvant and concurrent ADT. They even found a possible improvement in OS with concurrent and adjuvant ADT (68.8% v 64.7%). However, these outcomes were driven by the group of patients who received prostate only radiation. Among those treated with pelvic RT, concurrent and adjuvant ADT did not improve outcomes. In fact, distant metastasis risk was lower with neoadjuvant ADT in the setting of pelvic RT. The important takeaways are that the duration of adjuvant ADT is important when delivering prostate-only radiation. It isn’t that neoadjuvant ADT is bad, it’s just that when you are giving a fixed duration of ADT, the longer duration after RT is better. The second takeaway is that there is an incompletely understood interaction between pelvic nodal radiation and the sequencing of ADT. Put simply, sequencing doesn’t appear as important with pelvic radiation, but with neoadjuvant ADT reducing DM risk in this group there may be more to the story. 

TBL: The sequencing of concurrent and adjuvant ADT is associated with better treatment outcomes when delivering prostate only radiation, but this is not the case when also treating the pelvic lymph nodes. | Ma, J Clin Oncol 2022