Faculty Collaboration Database

Biochemical Failure Is Not a Surrogate End Point for Overall Survival in Recurrent Prostate Cancer: Analysis of NRG Oncology/RTOG 9601. J Clin Oncol 2022 Sep 20;40(27):3172-3179

Date

06/24/2022

Pubmed ID

35737923

Pubmed Central ID

PMC9514834

DOI

10.1200/JCO.21.02741

Scopus ID

2-s2.0-85138447340 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

PURPOSE: Metastasis-free survival (MFS), but not event-free survival, is a validated surrogate end point for overall survival (OS) in men treated for localized prostate cancer. It remains unknown if this holds true in biochemically recurrent disease after radical prostatectomy. Leveraging NRG/RTOG 9601, we aimed to determine the performance of intermediate clinical end points (ICEs) as surrogate end points for OS in recurrent prostate cancer.

MATERIALS AND METHODS: NRG/RTOG 9601 randomly assigned 760 men with recurrence after prostatectomy to salvage radiation therapy with 2 years of placebo versus bicalutamide 150 mg daily. ICEs assessed were biochemical failure (BF) per NRG/RTOG 9601 (prostate-specific antigen nadir + 0.3-0.5 ng/mL or initiation of salvage hormone therapy; [BF1]) and NRG/RTOG 0534 (prostate-specific antigen nadir+2 ng/mL; [BF2]), distant metastasis (DM), and MFS (DM or death). Surrogacy was assessed by the Prentice criteria and a two-stage meta-analytic approach (condition one assessed at the patient level with Kendall's τ and condition two assessed by randomly dividing the entire trial cohort into 10 pseudo trial centers and calculating the average R² between treatment hazard ratios for ICE and OS).

RESULTS: BF1, BF2, DM, and MFS satisfied the four Prentice criteria. However, with the two-condition meta-analytic approach, there was strong correlation between MFS and OS (τ = 0.86), moderate correlation between DM and OS (τ = 0.66), and weaker correlation between BF1 (τ = 0.25) or BF2 (τ = 0.40) and OS. Similarly, for condition two, the treatment effect of antiandrogen therapy on MFS and OS were correlated (R² = 0.67), but this was not true for BF1 (R² = 0.09), BF2 (R² = 0.12), or DM (R² = 0.18) and OS.

CONCLUSION: MFS is also a strong surrogate for OS in men receiving salvage radiation therapy for recurrence after prostatectomy. Caution should be used when inferring survival benefit from effects on BF in biochemically recurrent prostate cancer. Lack of comorbidity data did not allow us to assess whether BF in men with no/minimal comorbidity could serve as a surrogate for OS.

Author List

Jackson WC, Tang M, Schipper MJ, Sandler HM, Zumsteg ZS, Efstathiou JA, Shipley WU, Seiferheld W, Lukka HR, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Hall WA, Dess RT, Lovett RD, Balogh AG, Feng FY, Spratt DE

Author

William Adrian Hall MD Professor in the Radiation Oncology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Androgen Antagonists
Biomarkers
Hormones
Humans
Male
Neoplasm Recurrence, Local
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms