EAU 2017: An evaluation of a selective prostate cancer screening program using family history as a supplementary screening tool to PSA: Results from the ProtecT trial

London, England (UroToday.com) The ProtecT trial, a large randomized trial published here in the UK, is a large prospective trial assessing “active monitoring”, surgery and radiation therapy in men aged 50-69 for prostate cancer between 1999 and 2009. Results were published Sept 2016. As part of the recruitment for the study, over 82,000 British men were screened for prostate cancer with PSA’s.

Due to this rich dataset, the authors of this study wished to assess if selective screening based on family history could either supplement or replace generalized PSA screening guidelines. Specifically, for this study, after PSA testing, men with a PSA ≥ 3ng/ml were referred for a transrectal ultrasound-guided systematic biopsy. Prior to PSA testing, baseline data on any history of cancer amongst first degree relatives was obtained – which was available for 80,240 men. The detection rate, risk ratio (RR), positive predictive value (PPV) and specificity of PSA testing in men with and without a family history of prostate cancer were calculated.

A total of 4319 men (5.9%) had a positive first degree family history, of which 571 (13.2%) had a PSA ≥ 3ng/ml. 234 tumors were identified in this cohort of 4319 men, corresponding to a detection rate of 5.4%, a specificity of 91.8% and a PPV of 41%. Of the 69,234 men without a family history, 7,275 men (10.5%) were screen positive which led to a prostate biopsy detection rate of 3.7%, specificity 92.9% and PPV 35%.

A subset analysis of A total of 1230 cases (62%) and 1528 controls (38%) completed the extended family history questionnaire. A total of 224 cases (18.2%) reported a family history (all degree) of prostate cancer, compared with 146 (9.5%) controls (OR, 2.11, 95% CI 1.67 – 2.64). One hundred and seventy cases (13.8%) reported a first degree (father or brother), compared with 102 (6.7%) controls (OR 2.24, 95% CI 1.73 – 2.90). Of the 170 cases with an effect first degree relative, 80 (6.5%) had an affected father with prostate cancer (OR 1.65,95% CI 1.17 – 2.31) and 90 (7.3%) reported an affected brother (OR, 3.01, 95% CI 2.05 – 4.23). Men with a positive family history had an increased risk of PrCA (RR 1.47; 95%CI 1.28 – 1.68) with the greatest risk due to affected relatives in men below 60 years (RR 1.65; 95%CI 1.33 – 2.05) and men with an affected brother (RR 2.49; 95%CI 1.41 – 2.02). A positive family history led to a higher risk of developing more aggressive cancer (Gleason score ≥ 8: RR 2.19; 95%CI 1.34 – 3.57).

This selective screening program would therefore have missed 91.6% of PSA detectable cancers. As such, the authors, correctly so, do not support selective screening based on family history alone. However, in men less than 60 years of age with family history, it should be noted that they have a higher risk of developing cancer, and in particular high-risk prostate cancer.

Dr. Johnson did mention that they have SNP data for patients in their matched control analysis. Further results to follow.

Of note, the authors start by saying that “Prostate specific antigen (PSA) population-based screening is not recommended as too many men would be harmed from over-diagnosis and over-treatment.” However, that is a controversial statement, with which most urologists and urologic oncologists would disagree. While overtreatment is a concern, PSA screening guidelines vary from country to country, and based on the organization. At this time, most international urologic guidelines still recommend PSA screening. The men between age 50-60 are often already captured with the screening guidelines in place.

Presented by: T. Johnston

Co-authors: Lamb A., Vowler S., Xiong T., Moore A., Holding P., Herbert P., Davis M., Lane A., Donovan J., Hamdy F., Neal D.

Written by: Thenappan Chandrasekar , Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 -March 24-28, 2017- London, England
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