Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202

Kimberley S Mak; Molly Scannell Bryan; James J Dignam; William U Shipley; Yue Lin; Christopher A Peters; Elizabeth M Gore; Seth A Rosenthal; Kenneth L Zeitzer; David P D'Souza; Eric M Horwitz; Thomas M Pisansky; Jordan M Maier; Susan M Chafe; Tyler P Robin; Mack Roach 3rd; Phuoc T Tran; Luis Souhami; Jeff M Michalski; Alan C Hartford; Felix Y Feng; Howard M Sandler; Jason A Efstathiou

doi:10.1016/j.euf.2024.01.008

Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-term Update of NRG/RTOG 9202

Eur Urol Focus. 2024 Feb 1:S2405-4569(24)00011-7. doi: 10.1016/j.euf.2024.01.008. Online ahead of print.

Authors

Kimberley S Mak¹, Molly Scannell Bryan², James J Dignam³, William U Shipley⁴, Yue Lin⁵, Christopher A Peters⁶, Elizabeth M Gore⁷, Seth A Rosenthal⁸, Kenneth L Zeitzer⁹, David P D'Souza¹⁰, Eric M Horwitz¹¹, Thomas M Pisansky¹², Jordan M Maier¹³, Susan M Chafe¹⁴, Tyler P Robin¹⁵, Mack Roach 3rd¹⁶, Phuoc T Tran¹⁷, Luis Souhami¹⁸, Jeff M Michalski¹⁹, Alan C Hartford²⁰, Felix Y Feng¹⁶, Howard M Sandler²¹, Jason A Efstathiou⁴

Affiliations

¹ Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA. Electronic address: kimberley.mak@bmc.org.
² University of Illinois Cancer Center, Chicago, IL, USA.
³ University of Chicago, Chicago, IL, USA; NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
⁴ Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁵ Boston Medical Center, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
⁶ Northeast Radiation Oncology Center, Dunmore, PA, USA.
⁷ Medical College of Wisconsin and the Zablocki Veteran Affairs Medical Center, Milwaukee, WI, USA.
⁸ Sutter Cancer Centers, Roseville, CA, USA.
⁹ Albert Einstein Medical Center, Philadelphia, PA, USA.
¹⁰ London Regional Cancer Program, London, ON, Canada.
¹¹ Fox Chase Cancer Center, Philadelphia, PA, USA.
¹² Mayo Clinic, Rochester, MN, USA.
¹³ Wayne State University-Karmanos Cancer Institute, Detroit, MI, USA.
¹⁴ Cross Cancer Institute, Edmonton, AB, USA.
¹⁵ University of Colorado Hospital, Aurora, CO, USA.
¹⁶ University of California San Francisco, San Francisco, CA, USA.
¹⁷ University of Maryland, Baltimore, MD, USA.
¹⁸ The Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
¹⁹ Washington University School of Medicine, Saint Louis, MO, USA.
²⁰ Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, Lebanon, NH, USA.
²¹ Cedars-Sinai Medical Center, Los Angeles, CA, USA.

PMID: 38307806
DOI: 10.1016/j.euf.2024.01.008

Abstract

Background: Androgen deprivation therapy (ADT) has been associated with coronary heart disease and myocardial infarction (MI) in prostate cancer patients, but controversy persists regarding its effects on cardiovascular mortality (CVM).

Objective: We assessed the long-term relationship between ADT and CVM in a prostate cancer randomized trial (NRG Oncology/Radiation Therapy Oncology Group 9202).

Design, setting, and participants: From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-T4, prostate-specific antigen <150 ng/ml) received radiotherapy with 4 mo (short-term [STADT]) versus 28 mo (longer-term [LTADT]) of ADT.

Outcome measurements and statistical analysis: Using the Fine-Gray and Cox regression models, the relationship between ADT and mortality was evaluated.

Results and limitations: With a median follow-up of 19.6 yr, LTADT was associated with improved overall survival (OS) versus STADT (adjusted hazard ratio [HR] 0.88; p = 0.03) and prostate cancer survival (subdistribution HR [sHR] 0.70, p = 0.003). Comparing LTADT with STADT, prostate cancer mortality improved by 6.0% (15.6% [95% confidence interval 13.0-18.3%] vs 21.6% [18.6-24.7%]) at 15 yr, while CVM increased by 2.2% (14.9% [12.4-17.6%] vs 12.7% [10.4-15.3%]). In multivariable analyses, LTADT was not associated with increased CVM versus STADT (sHR 1.22 [0.93-1.59]; p = 0.15). An association between LTADT and MI death was detected (sHR 1.58 [1.00-2.50]; p = 0.05), particularly in patients with prevalent cardiovascular disease (CVD; sHR 2.54 [1.16-5.58]; p = 0.02).

Conclusions: With 19.6 yr of follow-up, LTADT was not significantly associated with increased CVM in men with locally advanced prostate cancer. Patients may have increased MI mortality with LTADT, particularly those with baseline CVD. Overall, there remained a prostate cancer mortality benefit and no OS detriment with LTADT.

Patient summary: In a long-term analysis of a large randomized prostate cancer trial, radiation with 28 mo of hormone therapy did not increase the risk of cardiovascular death significantly versus 4 mo of hormone therapy. Future studies are needed for patients with pre-existing heart disease, who may have an increased risk of myocardial infarction death with longer hormone use.

Keywords: Androgen deprivation therapy; Cardiovascular mortality; Hormonal therapy; Prostate cancer; Radiation therapy.

Abstract

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