For patients with high-risk prostate cancer, treatment with long-term androgen deprivation therapy (ADT) and high-dose radiation was associated with significantly better progression-free, cancer-specific, and overall survival compared with ADT and standard-dose radiation.
The investigators also found that the patients taking long-term ADT and high-dose radiation did not experience additional late urinary tract or gastrointestinal toxicities. Christophe Hennequin, MD, PhD, reported these and other findings of the Radiation Therapy in Treating Patients Receiving Hormone Therapy for Prostate Cancer (GETUG-AFU 18) trial, at the 2024 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.
Among 505 patients randomly assigned to be treated with radiation therapy (RT) at either the standard 70 Gy dose or a high, 80 Gy dose followed by 3 years of adjuvant ADT, the 10-year progression-free survival (PFS) rate was 83.6% for patients who had received the 80 Gy dose, vs. 72.2% for patients who had received the 70 Gy dose. This translated into a hazard ratio (HR) for biochemical or clinical progression of 0.56 (P=.0005).
This PFS advantage for high-dose radiation was also reflected by an overall survival (OS) advantage, with 10-year OS rates of 77% vs. 65.9%, respectively, translating into a 39% reduction in risk of death (HR 0.61, P=.0039) for patients who had received the higher radiation dose, reported Dr. Hennequin, of the Hospital Saint Louis in Paris, France.
“We have now Level 1 evidence that high-dose RT with long-term ADT must be the standard of care in high-risk prostate cancer patients,” he said at the meeting.
Dr. Hennequin noted that significantly more patients assigned to high-dose RT were treated with intensity modulated radiation therapy (IMRT) rather than conventional beam radiation, and emphasized that the superior results seen with the higher dose is likely due to the use of IMRT.
Prior evidence
Dr. Hennequin pointed to a meta-analysis published in The Lancet in 2022 which showed that among nearly 11,000 patients with a median follow-up of 11.4 years the addition of ADT to RT significantly improved metastasis-free survival, and that longer ADT reduced the risk of metastases by 16% compared with standard schedule ADT.
He also cited the DART 01/05 trial results, which were published in 2022 in The Lancet: Oncology, which found a clinically relevant benefit for 24 months vs. 4 months of adjuvant ADT following a minimum of 76 Gy radiation in patients with high-risk disease, but not among patients with intermediate-risk disease.
The GETUG-AFU 18 trial was designed to address the question of whether 80 Gy of radiation could improve outcomes compared with 70 Gy in patients treated with long-term ADT.
Study details and results
The investigators enrolled men with high-risk prostate cancer defined as either a prostate-specific antigen (PSA) level 20 ng/ml or greater, Gleason score 8 or higher, or clinical stage T3 or T4 disease, and after stratification by treatment center and lymph node resection randomly assigned them to receive either 70 Gy or 80 Gy RT followed by 3 years of ADT.
Approximately two-thirds of the patients in each study arm had one risk factor and about one-fourth had two risk factors. The remaining patients had all three high-risk defining factors.
Approximately 16.5% of patients in each arm had undergone lymph node dissection.
The median ADT duration was 33.4 months. In all, 82.9% of patients underwent pelvic lymph node radiation; lymph node radiation was not performed in those patients who had negative node dissection results.
Significantly more patients assigned to the 80 Gy dose were treated with IMRT (80.6% vs. 58.6%, P <.001>
The cancer-specific survival rate was also higher for the group receiving the 80 Gy dose, with a 10 year rate of 95.6% vs. 90% for patients treated with 70 Gy. This difference translated into a HR of 0.48 (P=.0090).
Comparable safety
The safety analysis, which included 248 patients who received 80 Gy and 251 who received 70 Gy, showed that the incidence rates of both late genitourinary and gastrointestinal toxicities were low and comparable between the groups. Grade 3 or greater late genitourinary toxicities were seen in 2.0% of patients treated with 80 Gy and 3.2% of those treated with 70 Gy. In both arms, only 1.6% of patients had grade 3 or greater later GI toxicities.
There were also no differences between the study arms in patient-reported quality of life measures related to either bowel or urinary symptoms.
Invited discussant Neha Vapiwala, MD, FACR, from Penn Medicine in Philadelphia commented that the results of the GETUG-AFU 18 trial suggest that “if you had even lower-dose systemic therapy that the radiation control at the local level – local-regional level in this case – can in fact contribute to the prevention of distant metastases and can contribute to cancer-specific survival.”
She said that with the efficacy results and the comparable toxicity and quality of life measures, dose-escalated radiation therapy and long-term ADT appear to offer a synergistic benefit.
The results are “practice-affirming for many, perhaps practice-changing for some if you’re not already offering this,” she said.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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