Previous studies indicate that the benefit of short-term androgen deprivation therapy (ADT) with radiotherapy (RT) for prostate cancer depends on competing risks.
To determine whether a quantitative method to stratify patients by risk for competing events (omega score) could identify subgroups that selectively benefit from ADT.
An ancillary analysis of NRG/RTOG 9408 phase 3 trial (NCT00002597) involving 1945 prostate cancer patients was conducted.
Short-term ADT.
We applied generalised competing event regression models incorporating age, performance status, comorbidity, T category, Gleason score (GS), and prostate-specific antigen (PSA), to stratify patients according to relative hazards for primary cancer-related events (distant metastasis or prostate cancer death) versus competing noncancer mortality. We tested interactions between ADT and subgroups defined by standard risk criteria versus relative risk (RR) using the omega score.
T2b, higher GS, and higher PSA were associated with an increased RR for cancer-related versus competing mortality events (a higher omega score); increased age and comorbidity were associated with a decreased omega score. Of 996 patients with low-risk/favourable intermediate-risk (FIR) disease, 286 (28.7%) had a high omega score (≥0.314). Of 768 patients with unfavourable intermediate-risk disease, 175 (22.8%) had a low omega score. The overall discordance in risk classification was 26.1%. Both standard criteria and omega score identified significant interactions for the effect of ADT on cancer-related events and late mortality in low- versus high-risk subgroups. Within the low-risk/FIR subgroup, a higher omega score identified patients in whom ADT significantly reduced cancer events and improved event-free survival. Limitations are the need for external/prospective validation and lower RT doses than contemporary standards.
Stratification based on competing event risk is useful for identifying prostate cancer patients who selectively benefit from ADT.
We analysed the effectiveness of androgen deprivation therapy (ADT) for localised prostate cancer among patients, defined by the relative risk (RR) for cancer versus noncancer events. Among patients with traditional low-risk/favourable intermediate-risk disease, those with a higher RR benefitted from short-term ADT.
European urology. 2023 Jan 27 [Epub ahead of print]
Loren K Mell, Stephanie L Pugh, Christopher U Jones, Tyler J Nelson, Kaveh Zakeri, Brent S Rose, Kenneth L Zeitzer, Elizabeth M Gore, Jean-Paul Bahary, Luis Souhami, Jeff M Michalski, Alan C Hartford, Mark V Mishra, Mack Roach, Matthew B Parliament, Kwang N Choi, Thomas M Pisansky, Siraj M Husain, Shawn C Malone, Eric M Horwitz, Felix Feng
University of California San Diego, Moores Cancer Center, San Diego, CA, USA. Electronic address: ., NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA., Sutter Medical Center Sacramento, Sacramento, CA, USA., University of California San Diego, Moores Cancer Center, San Diego, CA, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Einstein Medical Center Philadelphia, Philadelphia, PA, USA., Froedtert and the Medical College of Wisconsin, Milwaukee, WI, USA., CHUM - Centre Hospitalier de l'Universite de Montreal, Montreal, QC, Canada., The Research Institute of the McGill University Health Centre (MUHC), Montreal, QC, Canada., Washington University School of Medicine, Saint Louis, MO, USA., Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH, USA., University of Maryland/Greenebaum Cancer Center, Baltimore, MD, USA., UCSF Medical Center-Mount Zion, San Francisco, CA, USA., Cross Cancer Institute, Edmonton, AB, Canada., State University of New York Downstate Medical Center, Brooklyn, NY, USA., Mayo Clinic, Rochester, MN, USA., Tom Baker Cancer Centre, Calgary, AB, Canada., Ottawa Hospital and Cancer Center, Ottawa, ON, Canada., Fox Chase Cancer Center, Philadelphia, PA, USA.