By: Dan Sperling, MD
The Göteborg randomized screening trial is a longitudinal study comparing prostate cancer (PCa) screening by the PSA blood test vs. not screening at all. It is the Swedish arm of the world’s largest randomized PCa screening study, the European Randomized Study of Screening for Prostate Cancer (ERSPC), which was launched in the early 1990s starting with registries in seven countries. The Swedish arm began in late 1995, and has continued to accumulate data. When it began, 20,000 men ages 50-65 in the city of Göteborg were randomized to either a screening cohort (invited for PSA testing every two years) or a control cohort (not invited). Each cohort had roughly 10,000 participants. The broad purpose of the study was to evaluate whether PSA conferred a survival benefit when compared with no screening. When men in the screening group were found to have an elevated PSA, they were offered additional tests (e.g. digital rectal exam and biopsy). As data accumulated, it was also used to shed light on other questions such as a safe age to discontinue PSA screening. Even though such questions were outside the original purpose, the information was relevant.
Although the earliest results from the Göteborg study suggested that PSA screening significantly reduced the prostate death rate for the men who were screened, controversy over PSA testing and follow-up has continued. Problems that arise from screening include risks associated with invasive biopsies, overdetection of insignificant or very low risk cancer that may not require any treatment, underdetection of significant or aggressive disease leading to undertreatment, and treatment-related side effects that leave men incontinent and impotent—in many cases for years. In theory, PSA screening would be of benefit if it led to accurate early detection; in practice, PSA screening has saved thousands of lives at the high price of damaging quality of life for countless numbers.
As the Göteborg study developed, new detection methods were incorporated into the testing services offered those with elevated PSA. The use of multiparametric magnetic resonance imaging (mpMRI) was added in hopes of improving detection and helping avoid unnecessary biopsies. In a paper delivered at the 2015 European Association of Urology Congress (Madrid, Spain), evidence was presented that mpMRI successfully provided an accurate filter for identifying those needed a biopsy. The research was awarded the association’s First Prize for Best Abstract by a Resident.
The research involved 384 patients in the Göteborg screening cohort. From this group, 124 were asked to undergo a prostate MRI prior to biopsy. Those who were found to have suspicion for PCa on their MRI and/or a PSA > 3 ng/mL were referred for biopsy. According to the study abstract, 10-core systematic TRUS biopsy was performed blinded to MRI results, and 3 additional MRI-guided targeted needles were taken from men with suspicious MRI results. Comparisons were made among three screening strategies:
PSA > 3 plus systematic TRUS biopsy
PSA > 3 plus suspicious MRI plus MRI-guided targeted biopsy
PSA > 1.8 plus suspicious MRI plus MRI-guided targeted biopsy
The results showed that combining PSA and MRI, followed by MRI-targeted biopsy only in men with suspicious MRI resulted in 7.0% detection of PCa (as confirmed by biopsy) vs. 5.2% detection from PSA scores alone followed by standard random biopsy. The numbers also showed that more significant (potentially aggressive) cancers were detected with PSA + MRI combined compared with using PSA as a stand-alone test in screening.
The authors acknowledge that larger, randomized studies need to be done to validate their initial results, and in fact are planning to implement a large-scale trial. Still, the benefits of what mpMRI brings to PSA screening are obvious. For men with an elevated but still lower PSA score, undergoing mpMRI can determine if a biopsy is indicated. If so, the ability of mpMRI to localize the suspicious area means fewer biopsy needles. There is less likelihood of missing cancer, greater probability of accurately diagnosing aggression, and lower patient anxiety and stress over the biopsy procedure. It also reduces the risk of infection and other biopsy-related side effects.
Future considerations are ways to make mpMRI more economically feasible for wider availability. There are some who believe mpMRI has possibilities for screening, but at the present time it is too costly for widespread PCa screening.
Grenabo Bergdahl A, Homberg E, Moss S, Hugosson J. Incidence of prostate cancer after termination of screening in a population-based randomised screening trial. HYPERLINK “http://www.ncbi.nlm.nih.gov/pubmed/?term=grenabo+bergdahl” o “European urology.” Eur Urol. 2013 Nov;64(5):703-9. doi: 10.1016/j.eururo.2013.05.024. Epub 2013 May 17.
Grenabo Bergdahl A, Carlsson S, Damber J-E, Franlund M, Geterud K, Khatami A, Socratous A, Stranne J, Hellstrom M, Hugosson J. Role of magnetic resonance imaging in prostate cancer screening; results from a pilot study within the Gothenburg randomized screening trial. Presented at the 2015 European Urology Association Congress (Madrid, Spain, March 20-24)