Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)

Andreas Josefsson; Åsa Jellvert; the SPCG14-investigators; Erik Holmberg; Klaus Brasso; Peter Meidahl Petersen; Sirpa Aaltomaa; Marjaana Luukkaa; Paul Verhagen; Ronald de Wit; Göran Ahlgren; Ove Andrén; Enrique Castellanos; Mihalj Seke; Anders Widmark; Jan Erik Damber

doi:10.1080/0284186X.2023.2199940

Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)

Andreas Josefsson
, Åsa Jellvert
, the SPCG14-investigators
, Erik Holmberg
, Klaus Brasso
, Peter Meidahl Petersen
, Sirpa Aaltomaa
, Marjaana Luukkaa
, Paul Verhagen
, Ronald de Wit
, Göran Ahlgren
, Ove Andrén
, Enrique Castellanos
, Mihalj Seke
, Anders Widmark
, Jan Erik Damber^*

^*Corresponding author for this work

The Sahlgrenska Academy at the University of Gothenburg
Umeå University
NU Hospital Group
Sahlgrenska University Hospital
Regional Cancer Centre West (Sweden)
Rigshospitalet
Kuopio University Hospital
Turku University Hospital
Skåne University Hospital
Örebro University
Karolinska University Hospital
Centrallasarettet

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

48 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	372-380
Number of pages	9
Journal	Acta Oncologica
Volume	62
Issue number	4
DOIs	https://doi.org/10.1080/0284186X.2023.2199940
Publication status	Published - 19 Apr 2023

Bibliographical note

Funding Information:
The authors acknowledge financial support from the Swedish Prostate Cancer Federation, the County Council for West Sweden (ALFGBG-428341 and ALFGBG-724321), the Knut and Alice Wallenberg Foundation, and the SPCG foundation. The trial was also supported by an unconditional research grant from Sanofi Aventis. Knut och Alice Wallenbergs Stiftelse. The authors gratefully acknowledge all patients and the trial personnel at each clinical trial unit. Additionally, we thank Birgitta Olsson and Agnetha Sundberg for administrative assistance with the database, and we thank Sandra Grandell for administrative support. We also thank the Trial Safety Committee: Erik Holmberg (statistician), Prof Ola Bratt (consultant urologist), and Prof Sten Nilsson (a consultant oncologist). We also thank Esa Kähkönen for their contributions to the study.Special thanks to all the study nurses at the sites for all their work in this trial.

Publisher Copyright:
© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

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Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)Final published version, 1.88 MBLicence: CC BY

Cite this

Josefsson, A., Jellvert, Å., the SPCG14-investigators, Holmberg, E., Brasso, K., Meidahl Petersen, P., Aaltomaa, S., Luukkaa, M., Verhagen, P., de Wit, R., Ahlgren, G., Andrén, O., Castellanos, E., Seke, M., Widmark, A., & Damber, J. E. (2023). Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14). Acta Oncologica, 62(4), 372-380. https://doi.org/10.1080/0284186X.2023.2199940

@article{da31752f705c4d89949a774f4e7e80d3,

title = "Effect of docetaxel added to bicalutamide in Hormone-Na{\"i}ve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)",

abstract = "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-na{\"i}ve, 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.",

author = "Andreas Josefsson and {\AA}sa Jellvert and \{the SPCG14-investigators\} and Erik Holmberg and Klaus Brasso and \{Meidahl Petersen\}, Peter and Sirpa Aaltomaa and Marjaana Luukkaa and Paul Verhagen and \{de Wit\}, Ronald and G{\"o}ran Ahlgren and Ove Andr{\'e}n and Enrique Castellanos and Mihalj Seke and Anders Widmark and Damber, \{Jan Erik\}",

note = "Funding Information: The authors acknowledge financial support from the Swedish Prostate Cancer Federation, the County Council for West Sweden (ALFGBG-428341 and ALFGBG-724321), the Knut and Alice Wallenberg Foundation, and the SPCG foundation. The trial was also supported by an unconditional research grant from Sanofi Aventis. Knut och Alice Wallenbergs Stiftelse. The authors gratefully acknowledge all patients and the trial personnel at each clinical trial unit. Additionally, we thank Birgitta Olsson and Agnetha Sundberg for administrative assistance with the database, and we thank Sandra Grandell for administrative support. We also thank the Trial Safety Committee: Erik Holmberg (statistician), Prof Ola Bratt (consultant urologist), and Prof Sten Nilsson (a consultant oncologist). We also thank Esa K{\"a}hk{\"o}nen for their contributions to the study.Special thanks to all the study nurses at the sites for all their work in this trial. Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Informa UK Limited, trading as Taylor \& Francis Group.",

year = "2023",

month = apr,

day = "19",

doi = "10.1080/0284186X.2023.2199940",

language = "English",

volume = "62",

pages = "372--380",

journal = "Acta Oncologica",

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Josefsson, A, Jellvert, Å, the SPCG14-investigators, Holmberg, E, Brasso, K, Meidahl Petersen, P, Aaltomaa, S, Luukkaa, M, Verhagen, P , de Wit, R, Ahlgren, G, Andrén, O, Castellanos, E, Seke, M, Widmark, A & Damber, JE 2023, 'Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)', Acta Oncologica, vol. 62, no. 4, pp. 372-380. https://doi.org/10.1080/0284186X.2023.2199940

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 - the SPCG14-investigators

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

N1 - Funding Information: The authors acknowledge financial support from the Swedish Prostate Cancer Federation, the County Council for West Sweden (ALFGBG-428341 and ALFGBG-724321), the Knut and Alice Wallenberg Foundation, and the SPCG foundation. The trial was also supported by an unconditional research grant from Sanofi Aventis. Knut och Alice Wallenbergs Stiftelse. The authors gratefully acknowledge all patients and the trial personnel at each clinical trial unit. Additionally, we thank Birgitta Olsson and Agnetha Sundberg for administrative assistance with the database, and we thank Sandra Grandell for administrative support. We also thank the Trial Safety Committee: Erik Holmberg (statistician), Prof Ola Bratt (consultant urologist), and Prof Sten Nilsson (a consultant oncologist). We also thank Esa Kähkönen for their contributions to the study.Special thanks to all the study nurses at the sites for all their work in this trial. Publisher Copyright: © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

PY - 2023/4/19

Y1 - 2023/4/19

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.

UR - https://www.scopus.com/pages/publications/85153790361

U2 - 10.1080/0284186X.2023.2199940

DO - 10.1080/0284186X.2023.2199940

M3 - Article

C2 - 37073813

AN - SCOPUS:85153790361

SN - 0284-186X

VL - 62

SP - 372

EP - 380

JO - Acta Oncologica

JF - Acta Oncologica

IS - 4

ER -

Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)

Abstract

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