Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case–Control Study

Abstract

Background A disadvantage of prostate-specific antigen (PSA) for the early detection of prostate cancer (PCa) is that many men must be screened, biopsied, and diagnosed to prevent one death. Objective To increase the specificity of screening for lethal PCa at an early stage. Design, setting, and participants We conducted a case–control study nested within a population-based cohort. PSA and three additional kallikreins were measured in cryopreserved blood from a population-based cohort in Västerbotten, Sweden. Of 40 379 men providing blood at ages 40, 50, and 60 yr from 1986 to 2009, 12 561 men were followed for >15 yr. From this cohort, the Swedish Cancer Registry identified 1423 incident PCa cases, 235 with distant metastasis. Outcome measurements and statistical analysis Risk of distant metastasis for different PSA levels and a prespecified statistical model based on the four kallikrein markers. Results and limitations Most metastatic cases occurred in men with PSA in the top quartile at age 50 yr (69%) or 60 yr (74%), whereas 20-yr risk of metastasis for men with PSA below median was low (≤0.6%). Among men with PSA >2 ng/ml, a prespecified model based on four kallikrein markers significantly enhanced the prediction of metastasis compared with PSA alone. About half of all men with PSA >2 ng/ml were defined as low risk by this model and had a ≤1% 15-yr risk of metastasis. Conclusions Screening at ages 50–60 yr should focus on men with PSA in the top quartile. A marker panel can aid biopsy decision making. Patient summary For men in their fifties, screening should focus on those in the top 10% of PSA scores because close to half of subsequent cases of distant metastasis are found in this group. Testing of four kallikrein markers in men with an elevated PSA could aid biopsy decision making.

Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal Prostate Cancer

“…[7][8][9][10][11][12][13][14][15][16] Because prostate carcinogenesis likely initiates in men during their fourth and fifth decade, the baseline PSA level at a younger age may be more accurate in predicting the presence of aggressive PCa, because it will be less confounded by benign prostate hyperplasia typical in older men. 17 Autopsy studies show that approximately 22% of white men harbor PCa by age 60 years.…”

Differences in cancer characteristics of Chinese patients with prostate cancer who present with different symptoms

“…Currently, some newly proposed strategies, such as determination of the baseline PSA level earlier in life 27,28 and the use of newer diagnostic tools, 29,30 might help to reduce unnecessary prostatic biopsies and overdiagnosis of low-risk prostate cancer. Nonetheless, since most of these studies were conducted in Caucasian-based populations, further studies in Asian populations are necessary to verify their suitability in our region.…”

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective

“…In another recent study, 4K score was as accurate and specific in predicting PCa and GS ≥7 PCa as PHI [37]. Implementation of 4K test was recently proposed in men >50 years of age in top 10-25% of PSA values to detect metastatic disease as well as to provide biopsy decision support in uncertain cases with elevated PSA [38]. Although 4K score test is yet to be approved by FDA, it is already offered as a Laboratory Developed Test by CLIA-Certified and CAP-Accredited laboratories.…”