News | Prostate Cancer | November 02, 2020

MFS Is a Strong Surrogate Endpoint for OS for Men Receiving Salvage RT

Metastasis-free survival is a strong surrogate endpoint for overall survival over biochemical failure for men receiving salvage radiotherapy for recurrent prostate cancer

Metastasis-free survival is a strong surrogate endpoint for overall survival over biochemical failure for men receiving salvage radiotherapy for recurrent prostate cancer

Getty Images

November 2, 2020 — An analysis of the phase III NRG Oncology clinical trial RTOG 9601 on men receiving salvage radiotherapy (SRT) following prostatectomy for recurrent prostate cancer indicated that, while biochemical failure (BF) was not a strong surrogate endpoint to determine overall survival (OS), metastasis-free survival (MFS) was in this patient population. These findings are consistent with data in the intact prostate primary radiation treatment setting. The analysis results were presented at the virtual edition of the American Society for Radiation Oncology's (ASTRO) Annual Meeting in October 2020.

Previously, the Intermediate Clinical Endpoints in Cancer of the Prostate (ICECaP) working group identified MFS as a valid surrogate for OS in men treated with localized prostate cancer, however, only 8% of the men in the ICECaP analysis were treated with prostatectomy and this included no trials that employed SRT. Prior to the analysis of NRG-RTOG 9601, the performance of intermediate clinical endpoints (ICEs) to serve as surrogate endpoints were unknown in a SRT setting. The NRG-RTOG 9601 analysis surveyed two types of BF including PSA nadir +0.3-0.5 ng/mL or initiation of salvage hormone therapy as defined by the NRG-RTOG 9601 study and PSA nadir + 2ng/mL as defined by the NRG-RTOG 0534 study. Researchers also assessed DM and MFS endpoints. Endpoints were all assessed for surrogacy using two approaches; the Prentice Criteria, and a two-stage meta analytic approach in which two conditions had to be met for surrogacy including that the ICE had to be correlated to OS and the treatment effect on the ICE and OS had to be correlated.

Although BF, MFS, and distant metastasis (DM) each satisfied the four Prentice Criteria for OS, there were differences with the two-condition approach that was used to determine surrogacy. In the two-stage, meta-analytic approach, MFS was strongly correlated with OS (τ = 0.86). Other endpoints were not significantly associated with OS. DM was only moderately correlated with OS (τ = 0.66) and BF weakly correlated to OS on both the RTOG 9601-defined BF (τ = 0.25) and RTOG 0534-defined BF (τ = 0.40) endpoints. Biochemical failure was considered prognostic in this analysis; however, PSA-based ICEs as well as the treatment effect of antiandrogen therapy were only weakly correlated with OS and, therefore, would be considered a poor surrogate endpoint.

"From this analysis, we believe that researchers should be cautious when inferring clinical benefit from studies utilizing biochemical failure as a surrogate for overall survival," stated William Jackson, M.D., of the University of Michigan and lead author of the NRG-RTOG 9601 analysis abstract. "These findings highlight that the two-stage meta analytic approach should be the preferred method when assessing surrogacy."

These findings can be further validated as data is collected from current, ongoing salvage radiotherapy trials in this patient population.

For more information: www.nrgoncology.org

Related Content

A single image of a human brain using a magnetic resonance imaging (MRI) machine. Image courtesy of Dr Leon Kaufman. University Of California, San Francisco

A single image of a human brain using a magnetic resonance imaging (MRI) machine. Image courtesy of Dr Leon Kaufman. University Of California, San Francisco

News | Ultrasound Imaging | March 03, 2021
March 3, 2021 — A type of ultrasound scan can detect
F-18 FES PET images of patients with ER+/PR+/HER2- invasive ductal carcinoma. Left panel: Progressive disease seen at the 8-week time-point in a patient on sequential therapy. Right panel: Stable disease through all 3 time-points, remaining on study therapy for 6.7 months until disease progression on combined vorinostat aromatase inhibitor therapy. Image created by Lanell M Peterson, Research Scientist, University of Washington Medical Oncology, Seattle WA.

F-18 FES PET images of patients with ER+/PR+/HER2- invasive ductal carcinoma. Left panel: Progressive disease seen at the 8-week time-point in a patient on sequential therapy. Right panel: Stable disease through all 3 time-points, remaining on study therapy for 6.7 months until disease progression on combined vorinostat aromatase inhibitor therapy. Image created by Lanell M Peterson, Research Scientist, University of Washington Medical Oncology, Seattle WA.

News | Molecular Imaging | February 22, 2021
February 22, 2021 — Molecular imaging
Immunotherapy-based precision medicine clinical trials being developed

Getty Images

News | Prostate Cancer | February 16, 2021
February 16, 2021 — Black men die more often of prostate cancer yet, paradoxically, have greater survival benefits fr
Phase III clinical trial of men with a clinical suspicion of prostate cancer finds MRI with targeted biopsies to be more accurate at diagnosis and less intrusive than current standard
News | Magnetic Resonance Imaging (MRI) | February 08, 2021
February 8, 2021 — The results of a Phase III randomized clinical trial have shown that when it comes to detecting cl

Chart courtesy of the American Cancer Society

News | Breast Imaging | February 08, 2021
February 8, 2021 — Cancer ranks as a leading cause of death in every country in the world, and, for the first time,

Images in 69-year-old man with biopsy-confirmed Gleason score 7 (3+4) prostate cancer. (a) Pretreatment axial T2-weighted fast spin-echo MRI scan (repetition time msec/echo time msec, 3820/97) shows tumor in midline anterior transition zone (arrow). (b) Intraoperative MRI scan shows contoured rectal wall (red line), prostate margin (blue outline), and region of interest (orange outline). Because the urethra was included in planned treatment volume, a suprapubic catheter was placed for continuous bladder drainage during treatment. (c) Intraoperative MRI scan shows focused ultrasound beam path (blue) overlaid on treatment plan. Rectangles illustrate each sonication spot. (d) Thermal map image obtained during treatment with heat deposition color coded in red overlaid on sonication spot. (e) Axial gadopentetate dimeglumine-enhanced MRI scan (230/2.97) obtained immediately after treatment shows devascularized ablated volume (arrows). (f) Corresponding T2-weighted fast spin-echo MRI scan (3820/97) at 5 months after ablation shows complete involution of transition zone. All seven cores from treatment area margins were negative for cancer at biopsy. Image courtesy of the Radiological Society of North America

News | Prostate Cancer | February 05, 2021
February 5, 2021 — A technique that delivers...