Definition of Outcome-Based Prostate-Specific Antigen (PSA) Thresholds for Advanced Prostate Cancer Risk Prediction

We defined prostate-specific antigen (PSA) thresholds from a well calibrated risk prediction model for identifying and excluding advanced prostate cancer (PCa). We retrieved 902 biopsied patients with a pre-biopsy PSA determination (Roche assay). A logistic regression model predictive for PCa including the main effects [i.e., PSA, age, histological evidence of glandular inflammation (GI)] was built after testing the accuracy by calibration plots and Hosmer-Lemeshow test for goodness of fit. PSA thresholds were derived by assuming a diagnostic sensitivity of 95% (rule-out) and 80% (rule-in) for overall and advanced/poorly differentiated PCa. In patients without GI, serum PSA concentrations ≤ 4.1 (<65 years old) and ≤3.7 μg/L (≥65 years old) excluded an advanced PCa (defined as Gleason score ≥ 7 at biopsy), with a negative predictive value of 95.1% [95% confidence interval (CI): 83.0–98.7] and 88.8% (CI: 80.2–93.9), respectively, while PSA > 5.7 (<65) and >6.1 μg/L (≥65) should address biopsy referral. In presence of GI, PSA did not provide a valid estimate for risk of advanced cancer because of its higher variability and the low pre-test probability of PCa. The proposed PSA thresholds may support biopsy decision except for patients with asymptomatic prostatitis who cannot be pre-biopsy identified.

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Between-Method Differences in Prostate-Specific Antigen Assays Affect Prostate Cancer Risk Prediction by Nomograms

Clinical Chemistry ◽

10.1373/clinchem.2010.151472 ◽

2011 ◽

Vol 57 (7) ◽

pp. 995-1004 ◽

Cited By ~ 24

Author(s):

Carsten Stephan ◽

Kerstin Siemßen ◽

Henning Cammann ◽

Frank Friedersdorff ◽

Serdar Deger ◽

...

Keyword(s):

Prostate Cancer ◽

Prostate Specific Antigen ◽

Risk Prediction ◽

Specific Antigen ◽

Prostate Cancer Risk ◽

Roc Curves ◽

Median Percentage ◽

Free Psa ◽

Different Types ◽

Total Psa

BACKGROUND To date, no published nomogram for prostate cancer (PCa) risk prediction has considered the between-method differences associated with estimating concentrations of prostate-specific antigen (PSA). METHODS Total PSA (tPSA) and free PSA were measured in 780 biopsy-referred men with 5 different assays. These data, together with other clinical parameters, were applied to 5 published nomograms that are used for PCa detection. Discrimination and calibration criteria were used to characterize the accuracy of the nomogram models under these conditions. RESULTS PCa was found in 455 men (58.3%), and 325 men had no evidence of malignancy. Median tPSA concentrations ranged from 5.5 μg/L to 7.04 μg/L, whereas the median percentage of free PSA ranged from 10.6% to 16.4%. Both the calibration and discrimination of the nomograms varied significantly across different types of PSA assays. Median PCa probabilities, which indicate PCa risk, ranged from 0.59 to 0.76 when different PSA assays were used within the same nomogram. On the other hand, various nomograms produced different PCa probabilities when the same PSA assay was used. Although the ROC curves had comparable areas under the ROC curve, considerable differences were observed among the 5 assays when the sensitivities and specificities at various PCa probability cutoffs were analyzed. CONCLUSIONS The accuracy of the PCa probabilities predicted according to different nomograms is limited by the lack of agreement between the different PSA assays. This difference between methods may lead to unacceptable variation in PCa risk prediction. A more cautious application of nomograms is recommended.

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Prostate Cancer

10.1093/oso/9780190676827.003.0020 ◽

2018 ◽

Author(s):

Kathryn M. Wilson ◽

Lorelei Mucci

Keyword(s):

Prostate Cancer ◽

Risk Factors ◽

Family History ◽

Prostate Specific Antigen ◽

Advanced Prostate Cancer ◽

Advanced Disease ◽

African Ancestry ◽

Specific Antigen ◽

Dietary Factors ◽

Increased Risk

Prostate cancer is among the most commonly diagnosed cancers among men, ranking second in cancer globally and first in Western countries. There are marked variations in incidence globally, and its incidence must be interpreted in the context of diagnostic intensity and screening. The uptake of prostate-specific antigen screening since the 1990s has led to dramatic increases in incidence in many countries, resulting in an increased proportion of indolent cancers that would never have come to light clinically in the absence of screening. Risk factors differ when studying prostate cancer overall versus advanced disease. Older age, African ancestry, and family history are established risk factors for prostate cancer. Obesity and smoking are not associated with risk overall, but are associated with increased risk of advanced prostate cancer. Several additional lifestyle factors, medications, and dietary factors are now emerging as risk factors for advanced disease.

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