Long-Term, High-Dose Radiation, ADT Boosts Survival in Prostate Cancer

A higher dose of radiation plus long-term androgen deprivation therapy (ADT) improved long-time survival in patients with high-risk prostate cancer without causing significant decreases in quality of life, according to findings from the GETUG-AFU 18 trial presented at the 2024 ASCO Genitourinary Cancers Symposium.

“Even if we use a long-term ADT, high-dose radiotherapy improves progression-free survival, cancer-specific survival, and overall survival, compared to a (standard dose of) 70 Gy, in (patients with) high-risk prostate cancer without increasing toxicity,” Dr. Christophe Hennequin, Department of Radiation Oncology, Saint-Louis Hospital, Paris, said during a presentation of the data.

After a median follow-up of 114.2 months, the five-year biochemical or clinical progression-free survival (PFS; time from treatment until disease progression or death) rates in the 80 Gy (dose escalation) and 70 Gy (control) groups were 91.4% and 88.1%, respectively, while the 10-year rates were 83.6% and 72.2%. The dose-escalation of radiotherapy reduced the risk of disease progression by 44%.

Study Highlights:

  • Higher doses of radiation, combined with long-term androgen deprivation therapy (ADT), improved long-term survival in patients with high-risk prostate cancer without significant impacts on their quality of life.
  • The GETUG-AFU 18 trial revealed that the dose-escalation of radiotherapy to 80 Gy demonstrated better progression-free survival, cancer-specific survival and overall survival compared to the standard 70 Gy, reducing the risk for disease progression and death.
  • After a median follow-up of 114.2 months, the 80 Gy group showed higher five-year and 10-year rates for progression-free survival, cancer-specific survival, and overall survival, with a 44% reduction in the risk for disease progression.
  • There were no significant differences in toxicity and quality of life between the higher dose and standard dose arms of the trial, with both showing similar rates of late toxicities.
  • The study suggests that high-dose radiotherapy, particularly using intensity-modulated radiation therapy, in combination with long-term ADT should be considered the standard of care for high-risk prostate cancer patients.

When evaluating cancer-specific survival in the dose escalation and control groups, the five-year and 10-year rates continued to demonstrate superiority with the 80-Gy.

Lastly, the dose-escalation arm showed a five-year overall survival (OS; time from treatment until death of any cause) rate of 93.4%, compared with 88.7% with the control arm, as well as 10-year OS rates of 77.0% and 65.9%, respectively, reducing the risk of death by 39%.

Hennequin noted that there was no difference between arms regarding toxicity and quality of life. Grade 3 or higher late genitourinary toxicities occurred in 20.6% of the high-dose arm, versus 19.9% in the control arm, while 1.6% of patients in each arm experienced a grade 3 or higher late digestive toxicity.

Hennequin noted that a variety of randomized trials have been conducted to evaluate the role of de-escalation in prostate cancer.

“Most of them demonstrated an improvement in biochemical control, but no demonstrated benefit in overall survival. However, most of these trials included a low number of high-risk patients, and most of (the patients) did not choose long-term ADT. They used no ADT or short-term ADT,” he added, also acknowledging that long-term ADT is the standard of care in this patient population.

“The question remains: Is it necessary to increase the dose of radiotherapy in case of long-term ADT, or is the standard dose good enough for these patients?” Hennequin said.

Therefore, in the randomized phase 3 trial, high-risk patients were randomized to receive either dose-escalated (80 Gy) or conventional-dose (70 Gy) radiotherapy plus three years of ADT to determine the efficacy and safety of dose escalation in combination with long-term ADT.

Investigators stratified patients by lymph node resection and institution.

PFS served as the trial’s primary endpoint, while secondary endpoints included cancer-specific survival, OS and late toxicity. In the updated evaluation of the trial, six-year biochemical or clinical PFS was the primary endpoint; OS, specific survival, acute and delayed toxicities, and quality of life were the secondary endpoints; and exploratory endpoints included clinical relapse-free survival and metastasis-free survival.

In total, 505 patients from across 25 French centers were recruited from June 4, 2009, to Jan. 24, 2013. Patients were a median age of 71 years (range, 52-80), with the majority reporting just one high-risk disease factor (64.6%). Further, 16.4% of patients received lymph node dissection.

The median duration for ADT was 33.4 months, while 82.9% of patients underwent pelvic lymph node radiation, and 6 patients did not have radiotherapy performed. Interestingly, according to Hennequin, 80.6% of the dose-escalation arm received intensity-modulated radiation therapy (IMRT) in addition to ADT.

“Obviously IMRT is required to obtain these results. So, we have now level 1 evidence that high-dose (radiotherapy) with long-term ADT must be the standard of care in high-risk prostate cancer patients,” Hennequin concluded.

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