TY - JOUR
T1 - Cardiovascular Mortality and Duration of Androgen Deprivation in Locally Advanced Prostate Cancer
T2 - Long-term Update of NRG/RTOG 9202
AU - Mak, Kimberley S.
AU - Scannell Bryan, Molly
AU - Dignam, James J.
AU - Shipley, William U.
AU - Lin, Yue
AU - Peters, Christopher A.
AU - Gore, Elizabeth M.
AU - Rosenthal, Seth A.
AU - Zeitzer, Kenneth L.
AU - D'Souza, David P.
AU - Horwitz, Eric M.
AU - Pisansky, Thomas M.
AU - Maier, Jordan M.
AU - Chafe, Susan M.
AU - Robin, Tyler P.
AU - Roach, Mack
AU - Tran, Phuoc T.
AU - Souhami, Luis
AU - Michalski, Jeff M.
AU - Hartford, Alan C.
AU - Feng, Felix Y.
AU - Sandler, Howard M.
AU - Efstathiou, Jason A.
N1 - Publisher Copyright:
© 2024 European Association of Urology
PY - 2024/3
Y1 - 2024/3
N2 - 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.
AB - 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.
KW - Androgen deprivation therapy
KW - Cardiovascular mortality
KW - Hormonal therapy
KW - Prostate cancer
KW - Radiation therapy
UR - http://www.scopus.com/inward/record.url?scp=85184044805&partnerID=8YFLogxK
U2 - 10.1016/j.euf.2024.01.008
DO - 10.1016/j.euf.2024.01.008
M3 - Article
C2 - 38307806
AN - SCOPUS:85184044805
SN - 2405-4569
VL - 10
SP - 271
EP - 278
JO - European Urology Focus
JF - European Urology Focus
IS - 2
ER -