TY - JOUR
T1 - Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)
AU - Josefsson, Andreas
AU - Jellvert, Åsa
AU - Holmberg, Erik
AU - Brasso, Klaus
AU - Meidahl Petersen, Peter
AU - Aaltomaa, Sirpa
AU - Luukkaa, Marjaana
AU - Verhagen, Paul
AU - de Wit, Ronald
AU - Ahlgren, Göran
AU - Andrén, Ove
AU - Castellanos, Enrique
AU - Seke, Mihalj
AU - Widmark, Anders
AU - Damber, Jan-Erik
AU - SPCG14-investigators
PY - 2023/4
Y1 - 2023/4
N2 - BACKGROUND: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).MATERIALS AND METHODS: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.RESULTS: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.CONCLUSION: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
AB - BACKGROUND: Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).MATERIALS AND METHODS: Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8-10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.RESULTS: Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0-5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50-0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49-0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.CONCLUSION: Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.
KW - Androgen Antagonists/therapeutic use
KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects
KW - Chronic Disease
KW - Disease-Free Survival
KW - Docetaxel
KW - Hormones/therapeutic use
KW - Humans
KW - Male
KW - Neoplasm Recurrence, Local/pathology
KW - Prostate-Specific Antigen
KW - Prostatic Neoplasms/pathology
KW - Treatment Outcome
KW - psa relapse
KW - randomized clinical trial
KW - bicalutamide
KW - docetaxel
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85153790361&partnerID=8YFLogxK
U2 - 10.1080/0284186X.2023.2199940
DO - 10.1080/0284186X.2023.2199940
M3 - Journal article
C2 - 37073813
VL - 62
SP - 372
EP - 380
JO - Acta Oncologica
JF - Acta Oncologica
SN - 0284-186X
IS - 4
ER -