Adding high-dose radiotherapy to long-term androgen deprivation therapy boosts survival in high-risk prostate cancer

Radiotherapy in combination with androgen deprivation therapy improves survival for patients with prostate cancer. In the GETUG-AFU 18 study, the efficacy and safety of radiotherapy dose escalation (80 Gy vs. 70 Gy) in combination with long-term androgen deprivation therapy was evaluated in high-risk prostate cancer patients. Dose escalation was found to increase not only progression-free survival but also specific survival and overall survival, without worsening long-term toxicity.

Long-term androgen deprivation therapy is a standard of care for patients with high-risk prostate cancer and seems to be required even when high-dose radiotherapy is administered. Although high-dose radiotherapy is generally well tolerated, it is accompanied by a higher rate of grade 3 or 4 toxicities than standard-dose radiotherapy. Furthermore, androgen deprivation therapy may increase radiotherapy-related toxicity. Therefore, it is unclear whether high-dose (80 Gy) radiotherapy improves survival and patient-reported outcomes compared with standard-dose (70 Gy) radiotherapy in patients with high-risk prostate cancer who receive long-term androgen deprivation therapy. This was further investigated in the phase III GETUG-AFU 18 study.

Methods

GETUG-AFU 18 is a randomised phase III study performed in 25 French centres. Eligible patients had a high-risk (cT3-T4 or PSA ≥20 ng/ml or Gleason score ≥8) adenocarcinoma of the prostate without positive lymph nodes on CT or MRI and no distant metastasis. Patients who received prior pelvic radiotherapy or surgical treatment for prostate cancer, except transurethral resection at least 3-4 months before enrolment, were excluded. Participants were randomised 1:1 to receive high-dose (80 Gy) radiotherapy or standard-dose (70 Gy) radiotherapy with 3 years of androgen deprivation therapy in both groups. The primary endpoint was the 5-year biochemical or clinical progression-free survival (bcPFS) based on the ASTRO-Phoenix definition. Secondary endpoints were prostate cancer-specific survival, overall survival (OS), late toxicity, and quality of life (EORTC CLQ-C30 and EORTC CLQ-PR25).

Results

In total, 505 patients were randomised to receive high-dose radiotherapy (n=250) or standard-dose radiotherapy (n=250). Median age of the patients was 71.0 years, 37.5% had a PSA value ≥20 ng/ml and 16.4% had a lymph node dissection. After a median follow-up of 114.2 months, high-dose radiotherapy significantly improved bcPFS versus standard-dose radiotherapy (HR [95% CI]: 0.56 [0.40-0.76], p= 0.0005). The 5-year bcPFS was 91.4% and 88.1%, and the 10-year bcPFS 83.6% and 72.2% in the high-dose and standard-dose group, respectively. Prostate cancer-specific survival (HR [95% CI]: 0.48 [0.27-0.83], p= 0.0090) and OS (HR [95% CI]: 0.61 [0.44-0.85], p= 0.0039) were also significantly in favour of the high-dose group. No significant differences were observed in late grade ≥2 genito-urinary (20.6% vs. 19.9%) and digestive toxicity (6.9% vs. 8.8%) between the high-dose and standard-dose group. Furthermore, quality of life did not differ over time between treatment groups.

Conclusions

Long-term follow-up data from the phase III GETUG-AFU 18 study show that high-dose (80 Gy) radiotherapy in combination with long-term ADT is effective and safe, increasing not only bcPFS but also prostate-cancer specific and overall survival in high-risk prostate cancer patients without increasing late toxicity.

Reference

Hennequin C, 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 GU 2024; Abstract LBA259.