Age-Adjusted PSA Levels in Prostate Cancer Prediction: Updated Results of the Tyrol Prostate Cancer Early Detection Program

Abstract

ObjectiveTo reduce the number of unnecessary biopsies in patients with benign prostatic disease, however, without missing significant PCa the present study re-evaluates the age-dependent PSA cut-offs in the Tyrol Prostate Cancer (PCa) early detection program.Patients and MethodsThe study population included 2225 patients who underwent prostate biopsy due to elevated PSA levels at our department. We divided our patient collective into four age groups: ≤49 years (n = 178), 50-59 years (n = 597), 60-69 years (n = 962) and ≥70 years (n = 488). We simulated different scenarios for PSA cut-off values between 1.25 and 6 ng/mL and fPSA% between 15 and 21% for all four age groups and calculated sensitivity, specificity, confidence intervals and predictive values.ResultsPCa was detected in 1218 men (54.7%). We found that in combination with free PSA ≤21% the following PSA cut-offs had the best cancer specificity: 1.75 ng/ml for men ≤49 years and 50-59 years, 2.25 ng/ml for men aged 60-69 years and 3.25 ng/ml for men ≥70 years. Using these adjusted PSA cut-off values all significant tumors are recognized in all age groups, yet the number of biopsies is reduced. Overall, one biopsy is avoided in 13 to 14 men (number needed to screen = 13.3, reduction of biopsies = 7.5%) when decision regarding biopsy is done according to the “new” cut-off values instead of the “old” ones. For the different age groups the number needed to screen to avoid one biopsy varied between 9.2 (≤49 years) and 17.4 (50-59 years).ConclusionWith “new”, fine-tuned PSA cut-offs we detect all relevant PCa with a significant reduction of biopsies compared to the “old” cut-off values. Optimization of age-specific PSA cut-offs is one step towards a smarter strategy in the Tyrol PCa Early Detection Program.

Pattern of age-adjusted serum prostate specific antigen reference intervals among men in Benin City, Nigeria

“…This trend was also replicated in other Nigerian studies (Amadi and Odum, 2018;Al-Abdin andAl-Beeshi, 2018). However, the mean PSA values obtained in this study were about two to two and half times higher than values reported by some researchers in the western world (Luboldt et al, 2007;Heidegger et al, 2015) . Nonetheless, this was lower than other studies from Nigeria (Al-Abdin andAl-Beeshi, 2018) probably due the different population sizes, the types of the cohort, inter-assay variabity, inconsistent calculation of age specific reference ranges and verification bias (Luboldt et al, 2007).…”

“…It is believed that using these threshold values which are lower and higher than 0-4ng/ml in the younger age and older age group respectively, localised prostatic cancers would be detected early leading to appropriate interventions, reduced morbidity and mortality and a reduction in unnecessary biopsies in patients with benign prostatic hyperplasia without missing the presence of prostatic carcinoma (Heidegger et al, 2015). It has been suggested that using the ageadjusted serum PSA ranges, sensitivity and specificity for prostatic cancer detection is enhanced in the younger male and older male respectively (Luboldt et al, 2007).…”

“…For these reasons, the age -adjusted PSA reference range values were developed by reducing this threshold well below the time honoured value of 4ng/ml for the younger male and raising it in the older male. This allowed for early detection of prostatic cancer, reduction in tumour stage at diagnosis, morbidity and mortality and reduction in the number of unnecessary biopsies in patients with benign prostatic hyperplasia (BPH) without signs and symptoms of prostatic cancer (Luboldt et al, 2007;Heidegger et al, 2015).…”

PSA screening—a matter of debate?

“…In line with the ERSPC data, survival analyses revealed a significant reduction in PCa mortality with a risk ratio of 0.70 (95% CI: 0.57-0.87) for Tyrol compared with the mortality rate in the period from 1989 to 1993 in Austria [11,12]. However, a significant problem of the Tyrol study was that more than 50% of diagnosed cancers were low risk, opening the discussion of overdiagnosis and overtreatment [13]. Thus, we recently evaluated the age-dependent PSA cut-offs used since 1995 in our early detection program in order to reduce the number of unnecessary biopsies in patients with benign disease, but without missing PCa, in particular without missing significant PCa [13].…”

“…However, a significant problem of the Tyrol study was that more than 50% of diagnosed cancers were low risk, opening the discussion of overdiagnosis and overtreatment [13]. Thus, we recently evaluated the age-dependent PSA cut-offs used since 1995 in our early detection program in order to reduce the number of unnecessary biopsies in patients with benign disease, but without missing PCa, in particular without missing significant PCa [13]. With "new," fine-tuned PSA cut-offs, we detect all relevant PCa with a significant reduction of biopsies compared with the "old" cut-off values, which is one step toward a smarter strategy in the Tyrol PCa Early Detection Program.…”