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Among the OPKO 4Kscore Test, PHI, and PCA3, the 4Kscore Test is the "most promising" States Dr. Per-Anders Abrahamsson

#AUA15 – European Association of Urology (EAU) Lecture: Early detection of prostate cancer: The European view – Session Highlights

UroToday.com
Published: 18 May 2015

NEW ORLEANS, LA USA (UroToday.com) – In today’s EAU lecture, Dr. Per-Anders Abrahamsson presented the European view on the early detection of prostate cancer. The goal in any screening program is to find cancer when it is localized, and when cure can be possible. In this group of patients, we must be able to differentiate those for whom cure is possible and necessary, and those for whom cure is possible and unnecessary. Historically, as identified by CAPSURE data, we have aggressively overtreated low-risk disease and undertreated high-risk disease, both in Europe and the United States.

Dr. Abrahamsson reviewed the landmark Swedish studies that showed a difference in OS of 5% at 10 years between RP and watchful waiting (WW) with a NNT of 20. Benefit was most pronounced in those men who received surgery under the age of 65 years. The 18-year update showed 29% CaP death in the WW arm vs 18% in the RP arm, 38% incidence of metastases in WW vs 26% in RP, and 67% incidence of ADT in WW arm vs 43% in RP.

The primary question that requires an answer is whether PSA screening decreases cancer-specific mortality. The PLCO attempted to answer this, but showed no difference between a contaminated usual care arm vs a screened arm. The ERSPC showed 21% reduction in death due to prostate cancer at 11 years in the screening group, but had a NNS of 1 055 and NNT of 37 in a “relaxed screening” paradigm. The Göteborg trial had more stringent screening of q2 years and had moderately improved NNS of 293 and NNT of 12. The conclusions that can be drawn are that at long-term follow up, the relative difference in CaP incidence is decreasing; the absolute difference in CaP mortality between the arms is still increasing; the relative difference in CaP mortality is stable; and NNS and NND are decreasing. We have still yet to find a balance between maximizing benefits of decreasing morbidity and CaP mortality while minimizing harms of over diagnosis and over treatment.

An ideal screening test primarily identifies potentially lethal cancer, can improve upon the performance of PSA, and can find cancers that need to be treated while eliminating needless biopsies. Past ways of improving PSA include use of PSA cutoffs, PSA density, and PSA velocity to risk stratify those who should undergo biopsy. Currently, we use nomograms, risk calculators, and new markers to target biologically significant cancers. Future direction includes individualized risk assessment, along with early baseline PSA at age 40-45, and genetic testing in those with family history.

Tests that have shown recent promise include the PHI, 4K score, and PCA3. All improve prediction of PC over PSA alone in multivariable models, and all have good AUC and can reduce unnecessary biopsies. Of these, the most promising is the 4K score, which is based on total PSA, free PSA, intact PSA, and HK2, and has an AUC of 0.80-0.85 for finding high-risk prostate cancer.

Obtaining a baseline PSA can also predict risk of harboring aggressive disease. In a study of 1 167 men who had PSA taken at age 60 and were followed to 85 years, only 43 patients developed metastases, and 35 died of disease. 90% of CaP deaths occurred in men with PSA > 2. Among men with a PSA of < 1, there was a 0.5% risk of metastases and 0.2% risk of cancer-related death (Vickers et al, BMJ 2011). These figures have led to re-screening guidelines, that men with a PSA < 1 at age 60 should not be screened. Those with PSA between 1-2 should have a discussion of re-screening, and those with a PSA > 2 should get re-screened. This data better refines our selection of men for AS, and pooled analysis of AS in low-risk CaP confirms that CSM is on the order of 0-1% in the intermediate term (Dall’Era et al, Eur Urol 2012). Obtaining a baseline PSA at age 45 is also predictive: those with PSA < 0.5 are at extremely low risk and should have their next PSA in 5 years. Those with PSA > 3 are at high risk and should have biopsy performed.

Dr. Abrahamsson then delivered his 5 golden rules for transforming PSA screening:

Get consent,
Don’t screen men who won’t benefit,
Don’t biopsy without compelling reason,
Don’t treat low-risk disease, and
Treat at high-volume centers.

He closed with the EAU position on early detection of prostate cancer screening: A baseline PSA at age 45 (or 40 if positive family history) has been suggested upon which a subsequent screening interval may be based. Furthermore, screening in men with a life expectancy greater than 10 years is recommended, independent of chronological age.

Presented by Per-Anders Abrahamsson, MD at the American Urological Association (AUA) Annual Meeting – May 15 – 19, 2015 – New Orleans, LA USA

Lund University, Lund, Sweden

Reported by Nikhil Waingankar, medical writer for UroToday.com

Per-Anders Abrahamsson, M.D., Ph.D.

Dr. Abrahamsson is an internationally respected leader in urology who currently serves as Secretary General of the European Association of Urology, the leading professional organization overseas. He is Chairman of the Department of Urology at Skåne University Hospital, Malmö, Lund University, in Sweden, and an Adjunct Professor in the Department of Urology, University of Rochester Medical Center, in New York. The author of numerous scientific publications, including book chapters and books, he serves on the editorial boards of several scientific journals. He has received a number of national and international awards and is the organizer of international conferences that bring physicians together from multiple disciplines.