According to results from the phase 3 GETUG-AFU-18 study, the combination of dose-escalated radiotherapy with long-term androgen-deprivation therapy (ADT) was found to improve the biochemical or clinical progression-free survival (bcPFS) as well as specific survival and overall survival among patients with high-risk prostate cancer, without increasing any long-term toxicities.

These results were first presented by Christophe Hennequin, MD, Saint-Louis Hospital, Paris, France, at the 2024 ASCO Genitourinary Cancers Symposium in San Francisco, California.

According to Dr Hennequin and coauthors, radiotherapy at a dose of 80 Gy “is generally well tolerated but the occurrence of grade 3/4 toxicities is significantly more frequent than at a dose of 70 Gy. Furthermore, ADT has been reported to increase [radiotherapy]-related toxicity.”

In this trial, 505 patients with high-risk prostate adenocarcinoma with negative lymph-node status were randomized on a 1-to-1 basis to receive either dose-escalated radiotherapy at 80 Gy or conventional dosing at 70 Gy. Patients in both arms also received 3 years of ADT. All patients additionally received pelvic nodal radiation at 46 Gy, unless they had a negative pelvic lymph-node dissection. The primary end point in this study was bcPFS at 5 years, with secondary end points including overall survival, acute and late toxicity, and quality of life.  

There was a significant improvement of bcPFS seen in the dose-escalation arm compared with the conventional dosing arm (hazard ratio [HR], 0.56; 95% [confidence interval] CI, 0.40 to 0.76; P = .0005). The 5-year bcPFS in the dose-escalation arm was 91.4% vs 88.1% in the conventional dosing arm. The 7-year bcPFS was 88.1% vs 79.2%, respectively. There were also significant differences in prostate cancer-specific survival (HR, 0.48; P = .0090) and overall survival (HR, 0.61; P = .0039) between the arms. There was no significant difference in the rate of grade ≥2 late toxicities between the 2 arms.

Dr Hennequin et al concluded, “Dose-escalation [radiotherapy] in combination with long-term ADT is effective and safe, increasing not only the bcPFS rate but also specific survival and overall survival in high-risk prostate cancer patients without increasing long-term toxicity.”

Source:

Hennequin C, Sargos P, Roca L, et al. Long-term results of dose escalation (80 vs 70 Gy) combined with long-term androgen deprivation in high-risk prostate cancers: GETUG-AFU 18 randomized trial. Presented at ASCO Genitourinary Cancers Symposium; January 25 – 27, 2024; San Francisco, California. Abstract LBA 259