ASTRO 2024: Short-Term Androgen Deprivation Therapy and High-Dose Radiotherapy in Intermediate- and High-Risk Localized Prostate Cancer: Results from the GETUG 14 Randomized Phase III Trial

(UroToday.com) The 2024 American Society for Radiation Oncology (ASTRO) Annual Meeting held in Washington, DC between September 29^th and October 2^nd, 2024, was host to a clinical trials session. Dr. Nicolas Demogeot presented the results of GETUG 14, a randomized phase III trial of short-term androgen deprivation therapy (ADT) plus high-dose radiotherapy in intermediate- and high-risk localized prostate cancer patients.

Dr. Demogeot noted that high-dose radiotherapy improves local control and biochemical failure-free survival outcomes in intermediate- and high-risk prostate cancer patients. However, to date, there has been no documented overall survival benefit. In the MARCAP consortium study, the addition of short-term androgen deprivation therapy (ST-ADT) to standard-dose radiotherapy improved all clinical outcomes.1-8 Dr. Demogeot and colleagues hypothesized that adding ST-ADT to high-dose radiotherapy (80 Gy) would improve survival outcomes in patients with localized prostate cancer. 

This was a multicenter, randomized phase III trial of prostate cancer patients with intermediate- or high-risk, localized prostate cancer, PSA <30 ng/ml, and without evidence of clinical seminal vesicle involvement. Eligible patients were randomized to either:

• Arm A: High-dose radiotherapy (80 Gy)
• Arm B: High-dose radiotherapy (80Gy) + monthly triptorelin + daily flutamide for a total duration of 4 months, starting 2 months prior to radiotherapy

The primary study endpoint was disease-free survival. Key secondary endpoints included:

• Biochemical failure, per the Phoenix definition
• Metastatic failure
• Overall survival
• Acute and late toxicities 

Between September 2003 and June 2010, 376 patients were enrolled (Arm A: 191; Arm B: 185). In Arm B, 6 patients were not treated (5 withdrew consent; 1 experienced an acute coronary event). The modified intention-to-treat cohort thus included 179 patients in Arm B.

The patient characteristics are summarized below. The median patient age was 69–70 years. Overall, 12% of patients had cT3a disease (remainder ≤cT2). 40% of patients had Grade Group 3 disease. Notably ~34% had Grade Group 1 disease. 65% of patients had D’Amico intermediate-risk disease, whereas~30% had high-risk disease. 70% of patients received three-dimensional conformal radiotherapy, and 30% received intensity-modulated radiotherapy.

The addition of ST-ADT to radiotherapy was associated with a 36% relative improvement in disease-free survival (5-year disease-free survival: 84% versus 76%; HR: 0.64, 95% CI: 0.43–0.94, p=0.02).
When analysis was limited to the intermediate-risk subgroup, there was a significant improvement in disease-free survival outcomes:
However, there was no significant disease-free survival benefit to the addition of ST-ADT to high-dose radiotherapy in the high-risk subgroup (HR: 0.76, p=0.40).
On multivariable analysis adjusted for grade and PSA level, the addition of ST-ADT to high-dose radiotherapy was found to be associated with significant disease-free survival benefits (HR: 0.66, p=0.038).
Patients who received ST-ADT were significantly less likely to experience biochemical failure (10% versus 21%; HR: 0.45, 95% CI: 0.28–0.72, p=0.001).
There were no significant metastasis-free or overall survival benefits.

With respect to adverse events, there were no significant differences in the proportions of patients with early or late grade ≥2 gastrointestinal or genitourinary events. Patients in the ST-ADT arm had an increased frequency of early grade ≥2 erectile dysfunction (31% versus 6%; p<0.001). There were no differences in the frequency of late grade ≥2 erectile dysfunction events.
Dr. Demogeot concluded as follows:

• Short-term ADT improves disease-free survival in intermediate- and high-risk prostate cancer patients receiving high-dose (80 Gy) radiotherapy
• Short-term ADT addition to high-dose radiotherapy does not increase the frequency of early/late genitourinary or gastrointestinal toxicities
• Limitations to this study included the following:
  • Heterogenous population that included low-risk patients, in addition to intermediate- and high-risk
  • Short term follow-up
  • Low power for detecting differences between intermediate- and high-risk patients
  • Low power for assessing metastasis-free and overall survivals
  • Short-term ADT regimen was likely not long enough for high-risk patients
• Short-term ADT should be added to high-dose radiotherapy regimens

Presented by: Nicolas Demogeot, MD, Radiation Oncology, Hopitaux de Nancy, Institut Cancerologie Lorraine, Nancy, Lorraine, France

Written by: Rashid Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the 2024 ASTRO Annual Congress held in Washington, DC between September 29th and October 2nd, 2024

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