The excess burden of side-effects from treatment in men allocated to screening for prostate cancer. The Göteborg randomised population-based prostate cancer screening trial
Introduction
Large-scaled randomised trials have reported about the effectiveness of prostate cancer screening in terms of decreased disease-specific mortality. The first report from the European Randomised Study of Screening for Prostate Cancer (ERSPC) in Europe showed a 20% reduction in prostate cancer mortality after a median follow-up of 9 years.1 The smaller prostate, lung, colorectal and ovary (PLCO) trial in the United States that included many previously screened men could not corroborate this finding.2 With longer follow-up (median 14 years) in the Göteborg randomised population-based prostate cancer screening trial, we recently reported that prostate cancer mortality was reduced almost by half.3
Although PSA screening seems to prevent prostate cancer deaths it is still questioned whether this outweighs the large risk for over-diagnosis and subsequent over-treatment. In the ERSPC study, the number needed to treat (NNT) to save one prostate cancer death was estimated to 48.1 In the Göteborg screening trial, we now estimate NNT to 12. This number, though considerably lower, still implies a significant risk for over-diagnosis. In prostate cancer screening, most cancers are detected at early stages and even if many of these cancers are subjected to active monitoring there is a lack of reliable prognostic factors resulting in a considerable risk of over-treatment of indolent cancers. A high frequency of over-treatment could be accepted if the treatment is associated with few side-effects, as for example in cervical cancer. In Sweden, radical prostatectomy is the most common treatment option for localised disease.4 The most bothersome permanent side-effects after prostatectomy are urinary incontinence and erectile dysfunction.5 In reviews, the incidence of post prostatectomy potency rates has varied between 11% and 87%6, 7 and post prostatectomy incontinence between 0.3% and 87%.6, 8
In order to get a balanced picture of screening for prostate cancer, there is an urgent need to quantify the potentially negative side-effects following treatment in screening trials. The Göteborg randomised population-based prostate cancer screening trial is a prospective, randomised trial evaluating the effects of biennial PSA-based screening.
The present study aims at investigating the side-effects of the most common therapy for early stage prostate cancer – radical prostatectomy – and to compare the outcome between the screening and control arm. As the study is truly population-based with up-front randomization, it should be possible to calculate reliable estimates on how much more surgically induced morbidity screening will cause on a population level if a screening program is to be introduced.
Section snippets
Materials and methods
The Göteborg randomised population-based prostate cancer screening trial was established in 1995. The study design has been described in detail previously.3 The study protocol of the Göteborg trial was approved by the Ethical Review Committee at Göteborg University in 1994. The present study is based on men detected within this screening trial. The frequencies of side-effects in a subset of these men are extrapolated to the total number of men treated within the trial. Fig. 1a depicts the study
Statistics
Descriptive statistics was calculated by conventional methods and tables created using SPSS® 17.0 statistical software. Analyses were made according to intention to screen and compared screened men with controls (i.e. standard clinical care). Missing answers were reported but excluded from analyses. Data were extrapolated from our results (patients operated upon from 2001 to 2008) to the full screening setting with 14 years of follow-up. Extrapolated numbers of pre-operatively partially or fully
Results
With 14 years of PSA-screening in the Göteborg randomised population-based prostate cancer screening trial 1849 men were detected with prostate cancer (1138 screened, 711 controls, excluding 7 cancers detected at autopsy in the control group). Overall, 1047 received treatment with curative intent (radical prostatectomy, radiation therapy and cryosurgery), out of which 829/1047 (79.2%) were radical prostatectomies. The different types of treatments are presented in Table 1. Of these, 414 men were
Comment
The men included in the present study represent a truly population-based sample of men aged 50–64 years (at randomization), randomised between a PSA-based, biennial screening program and common clinical practice (including PSA-testing when needed) in Sweden. The present report focus on self-reported side-effects of the most commonly used curative therapy for men with localised prostate cancer – radical prostatectomy – and a comparison between men randomised to screening and the control group.
Conclusions
In conclusion, pre-operative erectile dysfunction is common in men with prostate cancer subjected to radical prostatectomy even if diagnosed by screening. The vast majority of men suffer from erectile dysfunction post prostatectomy. Even with advances in surgical technique and despite the best efforts of experienced surgeons, side-effects are sometimes inevitable.
The present study provides one of the first reports of how an organised, population-based prostate cancer screening program will
Role of funding sources
None of the funding sources have had access to the data or been involved in the data collection, data management or writing of this paper.
Conflict of interest statement
None declared.
Acknowledgements
We sincerely thank Helén Ahlgren and Maria Nyberg for providing assistance in data management of the study. The study was supported by grants from the Swedish Cancer Society (Grant No. 3792-B96-01XAB). The study has also been supported by grants from Wallac Oy, Turku, Finland, Schering Plough, Sweden and Abbott Pharmaceuticals, Sweden. Support for this work was further provided by grants from Gunvor and Ivan Svensson’s foundation, Af Jochnick’s foundation and Percy Falk’s foundation.
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