Results of the Randomized Phase 3 AFU-GETUG-20 Trial Evaluating Adjuvant Leuprorelin Acetate after Radical Prostatectomy in Men with High-risk Localized Prostate Cancer - Beyond the Abstract
These findings contribute important randomized evidence to a previously controversial field, in which data on adjuvant ADT after RP have been limited and inconsistent. While clear survival benefits have been established for immediate long-term ADT in combination with external beam radiotherapy and in patients with substantial nodal involvement, such benefits have not been consistently observed in predominantly node-negative populations. The present study, which included mainly pN0 (69%) and pT3 (77%) patients, reinforces earlier reports showing a lack of survival advantage from postoperative ADT in high-risk patients without lymph node involvement, and for the first time extends these conclusions to a GnRH receptor agonist.
Although PSA levels were persistently lower in the leuprorelin arm than in the observation arm, PSA values remained very low in both groups. This sustained biochemical control likely reflects the favorable prognosis of the study population after RP and may partly explain the absence of downstream effects on metastatic progression or survival. The low number of metastatic events further underscores this good prognosis and represents a limitation in terms of statistical power. However, additional analyses suggest that even with the initially planned sample size, clinically meaningful differences between treatment arms would have been unlikely.
From a safety perspective, leuprorelin was generally well tolerated, with low rates of permanent or temporary treatment discontinuation due to toxicity. The most common adverse events were consistent with known ADT-related effects, including hot flashes, fatigue, and pain, as well as vascular and gastrointestinal disorders among severe events. Importantly, the trial identified a substantially higher incidence of psychiatric disorders in leuprorelin-treated patients compared with observation, including clinically diagnosed depression and anxiety, an association that remains debated in the literature for GnRH agonists specifically.
In addition to clinical adverse events, longitudinal quality-of-life analyses revealed a significant and persistent deterioration across multiple domains in the leuprorelin arm, notably social and role functioning, insomnia, pain, and global health status. These findings highlight the long-term functional and psychosocial burden associated with prolonged postoperative ADT.
In conclusion, the AFU-GETUG 20 trial demonstrates that immediate long-term leuprorelin administration after RP does not improve survival outcomes in non-metastatic, high-risk prostate cancer patients without lymph node involvement and with undetectable PSA levels, while exposing patients to increased toxicity and sustained quality-of-life impairment. In the absence of a demonstrated survival benefit, a strategy of observation appears appropriate in this setting. Future perioperative trials may need to focus on therapeutic intensification using androgen receptor pathway inhibitors in patients with more aggressive or advanced disease to achieve meaningful clinical benefit.
Written by: François Rozet, MD, Department of Urology, Institut Mutualiste Montsouris, Paris, France
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