During a ten year period, men with localized prostate cancer were enrolled at centers in Sweden, Finland and Iceland and randomized to radical prostatectomy or to no initial treatment (watchful waiting) to investigate what is the best strategy for curative treatment.
The full name of the study is "Radical prostatectomy versus watchful waiting in early prostate cancer: Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4)"
During the late 1980s – when PSA screening for prostate cancer became increasingly wide-spread – radical prostatectomy was introduced as a curative treatment for early stage prostate cancer. However, the benefit of this treatment had never been documented in any finished or ongoing clinical trial. To fill this gap, Hans-Olov Adami and Jan-Erik Johansson initiated the SPCG-4 trial in 1988/1989. During the following ten year period altogether 695 men with localized prostate cancer were enrolled at centers in Sweden, Finland and Iceland and randomized to radical prostatectomy or to no initial treatment (watchful waiting). According to the protocol, the first analysis was published in 2002 and it has been followed by subsequent follow-ups every three years. During this period, a complex pattern of result has unfolded, documenting a clear and substantial reduction in prostate cancer mortality of at least 40% and a continuing decline in the number of men needed to treat in order to avert one prostate cancer death. There is also increasingly convincing evidence that the benefit of surgical treatment is larger among younger than among older men and also among patients considered to have intermediate – rather than low or high – risk prostate cancer. Although the need for palliative treatment was only half as common following radical prostatectomy, a substantial proportion of men managed by watchful waiting never needed any palliation during extended follow-up. The study has also been a useful source of information for studies on quality of life, health economics and development of prediction models. Follow-up – which is so far complete – will likely continue until the majority of men have died from prostate cancer or other causes. Still today, SPCG-4 is the only trial that provides randomized evidence of the benefit of radical prostatectomy, notably among men with clinically significant disease who comprise almost 90% of those included in the trial. A more recent US-based study of similar size enrolled about 90% men with PSA detected tumors and so far no overall survival benefit has been documented.
When we finalized the most recent publication in 2018, we also decided to amend the future publication schedule. Hence, the next and final analysis will take place in the fall of 2023 when all record linkages have been finalized. By that time, virtually 100% of all participants will be deceased. Our ambition is also to broadly characterize not only mortality outcomes but also other treatments and hospitalizations, drug prescriptions and any relevant information that can be retrieved in register data and will help to further characterize the life course between the two randomized groups. After that, no further follow-up is planned.
Principal Investigator: Anna Bill-Axelson, Uppsala University
Project leader at MEB: Hans-Olov Adami
Other participants: Ove Andrén, Swen-Olof Andersson, Hans Garmo, Lars Holmberg, Timmo Taari.
Main financing: National Cancer Institute, National Institutes of Health, USA, Swedish Cancer Society, Sweden.
A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer.
Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Häggman M, et al
N. Engl. J. Med. 2002 Sep;347(11):781-9
Quality of life after radical prostatectomy or watchful waiting.
Steineck G, Helgesen F, Adolfsson J, Dickman PW, Johansson JE, Norlén BJ, et al
N. Engl. J. Med. 2002 Sep;347(11):790-6
[Radical prostatectomy reduces the risk of death in prostatic cancer. The effect on total mortality can not be established yet as shown in a randomized controlled trial].
Bill-Axelson A, Holmberg L, Johansson JE, Norlén BJ
Lakartidningen 2003 May;100(19):1714-6
Radical prostatectomy versus watchful waiting in early prostate cancer.
Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, et al
N. Engl. J. Med. 2005 May;352(19):1977-84
Prognostic markers under watchful waiting and radical prostatectomy.
Holmberg L, Bill-Axelson A, Garmo H, Palmgren J, Norlén BJ, Adami HO, et al
Hematol. Oncol. Clin. North Am. 2006 Aug;20(4):845-55
Prostate-specific antigen levels as a predictor of lethal prostate cancer.
Fall K, Garmo H, Andrén O, Bill-Axelson A, Adolfsson J, Adami HO, et al
J. Natl. Cancer Inst. 2007 Apr;99(7):526-32
Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial.
Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, et al
J. Natl. Cancer Inst. 2008 Aug;100(16):1144-54
Experiences of randomization: interviews with patients and clinicians in the SPCG-IV trial.
Bill-Axelson A, Christensson A, Carlsson M, Norlén BJ, Holmberg L
Scand. J. Urol. Nephrol. 2008 ;42(4):358-63
Time, symptom burden, androgen deprivation, and self-assessed quality of life after radical prostatectomy or watchful waiting: the Randomized Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) clinical trial.
Johansson E, Bill-Axelson A, Holmberg L, Onelöv E, Johansson JE, Steineck G, et al
Eur. Urol. 2009 Feb;55(2):422-30
Development of a new method for monitoring prostate-specific antigen changes in men with localised prostate cancer: a comparison of observational cohorts.
Tilling K, Garmo H, Metcalfe C, Holmberg L, Hamdy FC, Neal DE, et al
Eur. Urol. 2010 Mar;57(3):446-52
Inguinal hernia after radical prostatectomy for prostate cancer: results from a randomized setting and a nonrandomized setting.
Stranne J, Johansson E, Nilsson A, Bill-Axelson A, Carlsson S, Holmberg L, et al
Eur. Urol. 2010 Nov;58(5):719-26
Radical prostatectomy versus watchful waiting in early prostate cancer.
Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, et al
N. Engl. J. Med. 2011 May;364(18):1708-17
Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial.
Johansson E, Steineck G, Holmberg L, Johansson JE, Nyberg T, Ruutu M, et al
Lancet Oncol. 2011 Sep;12(9):891-9
Managing localized prostate cancer by radical prostatectomy or watchful waiting: Cost analysis of a randomized trial (SPCG-4).
Andersson SO, Andrén O, Lyth J, Stark JR, Henriksson M, Adami HO, et al
Scand. J. Urol. Nephrol. 2011 Apr;45(3):177-83
Individualized estimation of the benefit of radical prostatectomy from the Scandinavian Prostate Cancer Group randomized trial.
Vickers A, Bennette C, Steineck G, Adami HO, Johansson JE, Bill-Axelson A, et al
Eur. Urol. 2012 Aug;62(2):204-9
Results from the Scandinavian Prostate Cancer Group Trial Number 4: a randomized controlled trial of radical prostatectomy versus watchful waiting.
Holmberg L, Bill-Axelson A, Steineck G, Garmo H, Palmgren J, Johansson E, et al
J. Natl. Cancer Inst. Monographs 2012 Dec;2012(45):230-3
A decision support model for cost-effectiveness of radical prostatectomy in localized prostate cancer.
Lyth J, Andersson SO, Andrén O, Johansson JE, Carlsson P, Shahsavar N
Scand. J. Urol. Nephrol. 2012 Feb;46(1):19-25
Long-term distress after radical prostatectomy versus watchful waiting in prostate cancer: a longitudinal study from the Scandinavian Prostate Cancer Group-4 randomized clinical trial.
Bill-Axelson A, Garmo H, Holmberg L, Johansson JE, Adami HO, Steineck G, et al
Eur. Urol. 2013 Dec;64(6):920-8
Radical prostatectomy or watchful waiting in early prostate cancer.
Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, et al
N. Engl. J. Med. 2014 Mar;370(10):932-42
Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up.
Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, et al
N. Engl. J. Med. 2018 12;379(24):2319-2329
Time without PSA recurrence after radical prostatectomy as a predictor of future biochemical recurrence, metastatic disease and prostate cancer death: a prospective Scandinavian cohort study.
Ahlberg MS, Garmo H, Adami HO, Andrén O, Johansson JE, Steineck G, Holmberg L, Bill-Axelson A
BMJ Open 2022 Dec;12(12):e057242