TY - JOUR
T1 - Veterans Affairs Cooperative Studies Program Study #553
T2 - Chemotherapy After Prostatectomy for High-risk Prostate Carcinoma: A Phase III Randomized Study
AU - Lin, Daniel W.
AU - Shih, Mei Chiung
AU - Aronson, William
AU - Basler, Joseph
AU - Beer, Tomasz M.
AU - Brophy, Mary
AU - Cooperberg, Matthew
AU - Garzotto, Mark
AU - Kelly, W. Kevin
AU - Lee, Kelvin
AU - McGuire, Valerie
AU - Wang, Yajie
AU - Lu, Ying
AU - Markle, Vivian
AU - Nseyo, Unyime
AU - Ringer, Robert
AU - Savage, Stephen J.
AU - Sinnott, Patricia
AU - Uchio, Edward
AU - Yang, Claire C.
AU - Montgomery, R. Bruce
N1 - Publisher Copyright:
© 2020 European Association of Urology
PY - 2020/5
Y1 - 2020/5
N2 - Background: The Veterans Affairs Cooperative Studies Program study #553 was designed to evaluate the efficacy of adjuvant chemotherapy added to the standard of care (SOC) for patients who are at high risk for relapse after prostatectomy. Objective: To test whether addition of chemotherapy to surgery for high-risk prostate cancer improves progression-free survival (PFS). Design, setting, and participants: Eligible patients after prostatectomy were randomized to the SOC group with observation or to the chemotherapy group with docetaxel and prednisone administered every 3 wk for six cycles. Randomization was stratified for prostate-specific antigen, Gleason, tumor stage, and surgical margin status. Outcome measurements and statistical analysis: The primary endpoint was PFS. Secondary endpoints included overall, prostate cancer–specific, and metastasis-free survival, and time to androgen deprivation therapy. Results and limitations: A total of 298 of the planned 636 patients were randomized. The median follow-up was 59.1 mo (0.2–103.7 mo). For the primary endpoint, the two groups did not statistically differ in PFS (median 55.5 mo in the chemotherapy group and 42.2 mo in the SOC group; test adjusted for site via gamma frailty p = 0.21; adjusted hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.58–1.11; p = 0.18). Prespecified subgroup analyses showed benefit in PFS for patients with tumor stage ≥T3b (HR 0.54, 95% CI 0.32–0.92; p = 0.022) and patients with Gleason score ≤7 (HR 0.65, 95% CI 0.43–0.99; p = 0.046). Secondary endpoint analyses are hampered by low event rates. The most common adverse events (≥grade 3 related or possibly related to chemotherapy) included neutropenia (43%), hyperglycemia (20%), and fatigue (5%), with febrile neutropenia in 2%. Conclusions: Adjuvant chemotherapy in high-risk prostate cancer using docetaxel and prednisone did not lead to statistically significant improvement in PFS for the intention-to-treat population as a whole. The analysis was challenged by lower power due to accrual limitation. Subgroup analyses suggest potential benefit for patients with Gleason grade ≤7 and stage ≥ pT3b (ClinicalTrials.gov number NCT00132301). Patient summary: In this randomized trial, we tested whether addition of chemotherapy to surgery for high-risk prostate cancer decreased the risk of prostate-specific antigen rise after surgery. We found no benefit from docetaxel given after radical prostatectomy, although some subgroups of patients may benefit.
AB - Background: The Veterans Affairs Cooperative Studies Program study #553 was designed to evaluate the efficacy of adjuvant chemotherapy added to the standard of care (SOC) for patients who are at high risk for relapse after prostatectomy. Objective: To test whether addition of chemotherapy to surgery for high-risk prostate cancer improves progression-free survival (PFS). Design, setting, and participants: Eligible patients after prostatectomy were randomized to the SOC group with observation or to the chemotherapy group with docetaxel and prednisone administered every 3 wk for six cycles. Randomization was stratified for prostate-specific antigen, Gleason, tumor stage, and surgical margin status. Outcome measurements and statistical analysis: The primary endpoint was PFS. Secondary endpoints included overall, prostate cancer–specific, and metastasis-free survival, and time to androgen deprivation therapy. Results and limitations: A total of 298 of the planned 636 patients were randomized. The median follow-up was 59.1 mo (0.2–103.7 mo). For the primary endpoint, the two groups did not statistically differ in PFS (median 55.5 mo in the chemotherapy group and 42.2 mo in the SOC group; test adjusted for site via gamma frailty p = 0.21; adjusted hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.58–1.11; p = 0.18). Prespecified subgroup analyses showed benefit in PFS for patients with tumor stage ≥T3b (HR 0.54, 95% CI 0.32–0.92; p = 0.022) and patients with Gleason score ≤7 (HR 0.65, 95% CI 0.43–0.99; p = 0.046). Secondary endpoint analyses are hampered by low event rates. The most common adverse events (≥grade 3 related or possibly related to chemotherapy) included neutropenia (43%), hyperglycemia (20%), and fatigue (5%), with febrile neutropenia in 2%. Conclusions: Adjuvant chemotherapy in high-risk prostate cancer using docetaxel and prednisone did not lead to statistically significant improvement in PFS for the intention-to-treat population as a whole. The analysis was challenged by lower power due to accrual limitation. Subgroup analyses suggest potential benefit for patients with Gleason grade ≤7 and stage ≥ pT3b (ClinicalTrials.gov number NCT00132301). Patient summary: In this randomized trial, we tested whether addition of chemotherapy to surgery for high-risk prostate cancer decreased the risk of prostate-specific antigen rise after surgery. We found no benefit from docetaxel given after radical prostatectomy, although some subgroups of patients may benefit.
KW - Adjuvant
KW - Chemotherapy
KW - Clinical trial
KW - Prostate cancer
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UR - http://www.scopus.com/inward/citedby.url?scp=85077710246&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2019.12.020
DO - 10.1016/j.eururo.2019.12.020
M3 - Article
C2 - 31924316
AN - SCOPUS:85077710246
SN - 0302-2838
VL - 77
SP - 563
EP - 572
JO - European Urology
JF - European Urology
IS - 5
ER -