KEY TAKEAWAYS
- The GETUG-AFU 18 study aimed to investigate the efficacy and safety of dose escalation in combination with ADT in high-risk prostate cancer pts.
- The primary endpoint is to determine bcPFS.
- Researchers noticed that dose-escalation RT with long-term ADT is not only effective and safe but also improves bcPFS rate, and OS in high-risk prostate cancer pts.
Radiotherapy (RT) combined with androgen deprivation therapy (ADT) has demonstrated enhanced survival outcomes in prostate adenocarcinoma. While 80 Gy RT is generally well-tolerated, its association with increased grade 3-4 toxicities compared to 70 Gy raises concerns. Additionally, ADT may exacerbate RT-related toxicity.
In this study, Christophe Hennequin and his team aimed to assess the impact of dose escalation with long-term ADT on survival outcomes and toxicity in high-risk prostate cancer.
The GETUG-AFU 18 phase III study involved eligible patients (pts) diagnosed with high-risk prostate adenocarcinoma (cT3-T4 or PSA≥ 20 ng/ml or Gleason score ≥ 8-10) with negative lymph-node status on CT-scan or MRI. The randomized assignment included dose-escalated RT (80 Gy) or conventional-dose (70 Gy), coupled with 3 years of ADT in both arms. Randomization (1:1) was stratified based on pelvic lymph-node dissection (PLND; yes or no) and institution. Pelvic nodal irradiation (46 Gy) was administered to all pts except in cases of negative PLND.
The primary endpoint focused on biochemical or clinical progression-free survival (bcPFS) at 5 years, according to ASTRO-Phoenix definition. Secondary endpoints encompassed overall survival (OS), acute and late toxicity (CTCAE v3), and quality of life. To achieve an improvement in bcPFS from 65% to 75% (Hazard Ratios [HR] = 0.67), the study performed an inclusive analysis requiring 500 pts (α= 5% and 1-β= 80%) with 197 events at 5 years.
About 505 pts were enrolled in the study from June 2009 to January 2013, exhibiting a median age of 70.6 years (range 52-80). Among them, 268 (53.1%) had a Gleason score ≥ 8, and the median PSA value was 13.8 ng/ml (range 0.4-109.9). Notably, 62.3% of pts presented with cT3, and 16.4% underwent PLND. There were no discernible imbalances in major prognostic factors between the dose-escalated RT and conventional RT arms.
The study revealed a significant improvement in biochemical or clinical progression-free survival (bcPFS) in the dose-escalated RT arm compared to conventional RT (HR = 0.56, [95% CI, 0.40-0.76], p = 0.0005). The 5-year bcPFS rates were 91.4% (95% CI, 87.0-94.4) and 88.1% (95% CI, 83.2-91.6) for dose-escalated RT and conventional RT, respectively, while the 7-year bcPFS rates were 88.1% (95% CI, 83.1-91.7) and 79.2% (95% CI, 73.1-84.0).
Significant differences were observed in prostate cancer-specific survival (HR = 0.48 [95% CI, 0.27-0.83], p = 0.0090) and OS (HR = 0.61 [95% CI, 0.44-0.85], p = 0.0039), favoring the dose-escalated RT arm. Notably, no prognostic factors were identified for bcPFS. Regarding late toxicities, no significant difference was found between arms, with 78.2% and 76.1% experiencing ≥Grade 2 toxicity with dose-escalated RT and conventional RT, respectively.
The study concluded that dose-escalation RT, when combined with long-term ADT, proves to be effective and safe in high-risk prostate cancer pts. This approach not only enhances the bcPFS rate but also improves specific survival and OS outcomes, all achieved without an increase in long-term toxicity.
The study is sponsored by UNICANCER
Source: https://meetings.asco.org/abstracts-presentations/230309
Clinical Trial: https://clinicaltrials.gov/study/NCT00967863
Hennequin C, Sargos P, Roca L, et al. (2023). “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 (Abstract LBA259).
