Tough DARTs.

Top Line: Is 24 months of ADT superior to 4 months in men with intermediate and high risk prostate cancer?

The Study: DART 01/05 was a randomized phase 3 trial that compared short term and long term ADT along with radiation for localized prostate cancer. The importance of DART 01/05 is that it explored the question of ADT duration in the setting of dose-escalated radiation (minimum 76 Gy). 354 men with intermediate and high risk (just over half) prostate cancer received radiation and 4 months total of neoadjuvant (2 months) and concurrent (2 months) ADT. ADT consisted of oral flutamide or bicalutamide plus goserelin. They were randomized to no further ADT or 24 months of goserelin. The original results showed a significant improvement in biochemical disease free survival at 5 years with 24 months ADT (90% v 81%) as well as overall survival (95% v 86%) and metastasis free survival (94% v 83%). This benefit was more notable in those with high risk disease. Here we have long-term results of DART 01/05. At 10 years, these differences largely disappeared with no difference in bDFS (70.2% v 62.3%), OS (78.4% v 73.3%), or MFS (76.0% v 70.9%). Even among high risk patients, the benefit of 24 months ADT dissipated. bDFS, OS, and MFS were still numerically superior with >10% absolute improvement in each, but the differences were no longer statistically significant given the relatively limited size of the trial. In contrast, those with intermediate risk disease didn’t even have a numeric benefit in bDFS, OS, or MFS with long term ADT. With prostate cancer, more time means more competing risks of mortality. In fact, only 3% of patients died from prostate cancer compared to 9% from other malignancies and 6% from cardiovascular disease.

TBL: In the setting of dose-escalated radiation, men with high risk disease likely derive a clinically meaningful benefit from adjuvant long-term ADT, however the statistical significance of that benefit has diminished over time. Men with intermediate risk disease did not benefit from long-term ADT. | Zapatero, Lancet Oncol 2022