Predicting Positive Repeat Prostate Biopsy Outcomes: Comparison of Machine Learning Approaches to Identify Key Parameters and Optimal Algorithms.

A Novel Nomogram to Predict the Probability of Prostate Cancer on Repeat Biopsy

PREDICTORS OF SUBSEQUENT PROSTATE CANCER IN MEN WITH A PROSTATE SPECIFIC ANTIGEN OF 2.6 TO 4.0 NG/ML AND AN INITIALLY NEGATIVE BIOPSY

IntroductionExtended transrectal ultrasound-guided prostate biopsy is a state-of-the-art tool for prostate cancer detection. Nevertheless, approximately 1/3 of cancers are missed when using this method and repeat biopsy sessions are often required. The aim of this study was to investigate how sampling density (a compound variable reflecting the number of biopsy cores and prostate volume) impacts on detection rate in multiple repeat TRUS-biopsies.Material and methodsA total of 1007 consecutive patients undergoing their 1st, 2nd, 3rd and any further repeat prostate biopsies were included. The relationship between sampling density and other clinical variables (age, prostate-specific antigen level, free/total PSA ratio, digital rectal examination, number of previous biopsies) and cancer detection rate were assessed by interaction analysis.ResultsThere were 562 primary re-biopsies, 267 second re-biopsies and 178 third and further re-biopsies included in the study. Detection rate was 25.4%, 25.8% and 25.3%, respectively. Interaction of sampling density with age was demonstrated in patients undergoing their first repeat biopsy (but not further re-biopsies). No interaction was observed with other variables investigated.ConclusionsA more extensive prostate sampling leads to a higher cancer detection rate on repeat prostate biopsies, as shown previously. However, this effect seems to be particularly pronounced in men younger than 65 years undergoing their first repeat prostate biopsy.

171 Background: Prostate-specific antigen (tPSA) based screening reduces mortality. But recent recommendations do not endorse PSA-screening due to possible over-diagnosis and over-treatment and the resulting harm afflicted to patients. Screening studies showed the maximum benefit in young men age 65 or younger. tPSA and percent free PSA (%fPSA) lack specificity in the diagnosis of PCa. [-2]proPSA and the "prostate health index" (phi) improve this diagnostic specifity in a non-age adjusted population. Markers to diagnose clinicaly relevant cancers in young men are needed. Methods: The clinical performance of [-2]proPSA and phi were evaluated in a multicenter study. A total of 1,362 patients (769 age 65 or younger) scheduled for initial or repeated prostate biopsy (668 with, 694 without PCa, each 10 or more core biopsies) were recruited in four different sites based on PSA level 1.6 to 8.0 ng/mL WHO-calibrated (2-10 ng/mL classically calibrated). Serum samples taken prior to digital rectal examination (DRE) were measured for the concentration of tPSA, fPSA and [-2]proPSA with Beckman Coulter immunoassays on Access 2 or DxI800 instruments. Phi was calculated as: [-2]proPSA/fPSA x √tPSA. Results: In univariate analysis [-2]proPSA/fPSA (%[-2]proPSA) and phi were the best predictors of PCa detection in patients at initial biopsy (AUC: 0,72 and 0,73) and repeated biopsy (AUC: 0,74 and 0,74). Analysis of the data for men age 65 and younger (n=593) showed that %[-2]proPSA and phi significantly improved PCa dectection (AUC: 0,72 and 0,73) as compared with tPSA (AUC: 0,53) or %fPSA (AUC: 0,62). In the detection of significant PCa (based on PRIAS criteria) %[-2]proPSA and phi demonstrated the best performance in the whole cohort and in young men (65 and younger) years as well (AUC 0,68 and 0,73). Conclusions: This multicenter study showed that [-2]proPSA and phi have a superior clinical performance in detecting PCa in the PSA range of 2 to 10 ng/mL compared to tPSA and %fPSA at initial and repeat biopsies. This superiority is maintained for the detection of PCa in young men (age 65 or younger).

PD46-11 LOW DOSE SPINAL SADDLE BLOCK ANESTHESIA IS ASSOCIATED WITH INCREASED PATIENT TOLERANCE OF AND WILLINGNESS TO HAVE A REPEAT PROSTATE BIOPSY.

RE: THE EFFECT OF DIGITAL RECTAL EXAMINATION, FLEXIBLE CYSTOSCOPY AND PROSTATIC BIOPSY ON FREE AND TOTAL PROSTATE SPECIFIC ANTIGEN, AND THE FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO IN CLINICAL PRACTICE

The purpose of the study was to assess the predictive value for prostate cancer of MRI using morphologic (T2-weighted imaging [T2WI]) and functional (MR spectroscopy [MRS], diffusion-weighted imaging [DWI], and dynamic contrast-enhanced [DCE] MRI) sequences and the free-to-total prostate-specific antigen (PSA) ratio, alone and combined. This retrospective study included 70 patients (PSA level, > 4 ng/mL; free-to-total PSA ratio, < 20%) who underwent endorectal 1.5-T MRI before biopsy. We graded the likelihood of cancer on a 5-point scale. Imaging data were compared with histologic results on biopsy or prostatectomy. Accuracies were estimated from the area under receiver operating characteristic using the hemiprostate as the unit of analysis. A p value less than 0.05 denoted statistical significance. The model combining all variables was more accurate than each variable alone (95.2% vs 73.5% for T2WI, 76.0% for MRS, 81.8% for DWI, 75.6% for DCE-MRI, and 78.8% for free-to-total PSA ratio). The complete model had accuracy similar to that of combining two imaging variables with free-to-total PSA ratio, especially free-to-total PSA ratio, T2WI, and DWI (94.0%); and free-to-total PSA ratio, DWI, and MRS (93.8%); with negative predictive values of 91.0% and 89.5%, respectively. The best models combining two imaging variables (MRS and DWI, 85.8%; T2WI and DWI, 84.8%) had accuracy that was similar to that of the combination of all imaging variables (87.3%) and higher than that of the best individual imaging variable (DWI, 81.8%), but lower than that of the complete model. The combination of at least one functional technique with free-to-total PSA ratio is more accurate than combining only imaging variables in cancer detection. The use of more than two imaging variables does not increase the detection rate. Functional MRI has the potential to help avoid a large number of negative biopsies.

Clinical evaluation of free PSA/total PSA (prostate-specific antigen) ratio in the diagnosis of prostate cancer.

RE: THE FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO IMPROVES THE SPECIFICITY OF PROSTATE SPECIFIC ANTIGEN IN SCREENING FOR PROSTATE CANCER IN THE GENERAL POPULATION

PurposeThis study was designed to identify a useful clinical parameter or model for prostate biopsy in surgery-indicated benign prostate hyperplasia (BPH) patients with elevated PSA levels and negative multiparametric prostate magnetic resonance imaging (MRI) results.Patients and methodsWe retrospectively analyzed clinical and pathological data from patients who were diagnosed with BPH and admitted to the inpatient department for surgery between January 2010 and September 2020. Clinical data, including age, prostate specific antigen (PSA) level, F/T PSA ratio, prostate volume, and PSA density (PSAD), were used for comprehensive analysis. Univariate and multivariate logistic regression analyses were performed to develop a predictive model. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were performed to assess the diagnostic value of the predictive model, PSA concentration, F/T PSA ratio and PSAD.ResultsA total of 318 patients were included in the study, 8.2% (26/318) of whom were histologically diagnosed with prostate cancer (PCa). Univariate and multivariate logistic regression analyses revealed that PSAD was the only independent predictor of PCa biopsy. ROC curve analysis of PCa detection revealed a larger area under the curve (AUC) for the predictive model (AUC 0.855) and for PSAD (AUC 0.848) than for PSA (AUC 0.722) or the F/T PSA ratio (AUC 0.635). DCA demonstrated that the optimal strategy would be to restrict biopsies to men with a PSAD of 0.30 ng/ml/cm3.ConclusionsOur study suggested that for BPH patients with surgical indications who present with PSA abnormalities and negative imaging findings, the use of a new PSAD threshold of 0.30 ng/ml/cm3 could facilitate convenient and sound biopsy decisions. This approach could reduce the complications and length of hospital stay associated with biopsies and reduce hospital costs.

To determine whether the free/total prostate-specific antigen (PSA) ratio can discriminate between patients with prostate cancer or benign prostatic hyperplasia (BPH). A prospective study was conducted using free and total PSA assays in patients who underwent transrectal-ultrasound guided biopsies indicated by a total serum PSA level of > 4 ng/mL and/or a positive digital rectal examination. Sixty-nine men (median age 68 years, range 57-86) who presented to our out-patient department with symptoms of prostatism were included in the study. Blood samples were drawn from all patients before biopsy. Histopathological examination detected prostate cancer in 17 of 69 (25%) patients and 13 of these 17 patients had a free/total PSA ratio of < 0.15; only 12 of 52 (23%) patients with BPH had a ratio of < 0.15. Receiver operating characteristic analysis indicated a threshold free/total PSA ratio of < or = 0.15 was the optimum discriminatory level. In the whole study group, this threshold had sensitivity, specificity, positive- and negative-predictive values of 76%, 77%, 52% and 91%, respectively. There were 40 patients with serum PSA levels of 4-10 ng/mL and 17.5% (7/40) of these were diagnosed with cancer. Using a free/total PSA ratio of 0.15 would have failed to diagnose two patients of seven with prostate cancer but 30 patients would have avoided a biopsy. In this subgroup, the threshold ratio of 0.15 had sensitivity, specificity, positive- and negative-predictive values of 71%, 85%, 50% and 93%, respectively. The rates for a PSA density (PSAD) at a threshold of > or = 0.15 were 71%, 76%, 38%, 93%, respectively. These results indicate that using the free/total PSA ratio gives a significant improvement over PSAD and total PSA values alone in the diagnosis of prostate cancer: its use may also enhance the diagnostic accuracy in patients with intermediate PSA levels.

Several methods for the identification of patients with prostate carcinoma have been proposed to enhance the clinical usefulness of prostate specific antigen (PSA). However, it remains unclear which method is superior in practical use. The authors attempted prospectively to identify the most powerful method with which to detect prostate carcinoma, especially among patients with intermediate PSA levels. Between October 1997 and August 1999, systematic sextant biopsies were performed on 281 patients, including 147 with PSA levels between 4.1 ng/mL and 10.0 ng/mL. The clinical values of PSA, the free PSA to total PSA ratio (free/total PSA ratio), alpha-1-antichymotrypsin-PSA complex (PSA-ACT), the calculated derivatives, PSA density (PSAD), and PSA density of the transition zone (PSATZD) for the detection of prostate carcinoma were compared by using receiver operating characteristic (ROC) curves and logistic regression analyses. According to ROC curve analysis, PSATZD had the greatest area under the curve in the overall patient population and in patients with intermediate PSA levels. In patients with intermediate PSA levels, at the sensitivity of 90%, PSATZD would have prevented unnecessary biopsies in 68 of 117 patients who were without prostate carcinoma, whereas PSA, free/total PSA ratio, and PSA-ACT would have prevented unnecessary biopsies in 25, 28, and 25 patients, respectively. Stepwise logistic regression analysis showed that PSATZD and findings on digital rectal examination were significant independent predictors. PSATZD had the most useful validity in the differentiation between prostate carcinoma and benign prostatic enlargement in the overall patient population and in patients with intermediate PSA levels.

Prostate specific antigen (PSA), used for the early diagnosis of prostate cancer (PCa), is one of the best tumour markers known so far. However, in situations when PSA is between 2-10 ng/mL, which is named as grey zone, PSA falls short of distinguishing benign prostate diseases from PCa. On the other hand, it was demonstrated in many previous studies that microRNA (miRNA) could be a marker for cancer. Therefore, in this study, it was aimed to enhance the diagnostic power of PSA, especially with grey zone patients, by the use of miRNA. Ninety-four patients included in the study were divided into three groups as "control group" (n=44, PSA=2-10 ng/mL and benign), "PCa 1 group" (n=37, PSA=2-10 ng/mL), and "PCa 2 group" (n=13, PSA >10 ng/mL), according to their pathological results and PSA levels. Free PSA (fPSA) and total PSA (T-PSA) levels were measured with chemiluminometric sandwich immunoassay method. Expressions of miRNAs were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) method. The most appropriate specificity, sensitivity and prediction values were found by drawing the receiver operating characteristic (ROC) curves of total PSA, free/total PSA (f/T PSA) ratio, and miRNAs, and the diagnostic powers were compared with each other. Diagnostic powers of the f/T PSA ratio and miRNA were compared in PCa 1 and the control groups to determine the marker with higher area under the curve (AUC). It was shown that the diagnostic power of the combination of miR-16-5p and f/T PSA was higher than that obtained when they were used separately. As a result, while making the the discrimination between benign and malignant prostate in patients with grey zone, it was determined that the combination of miR-16-5p and f/T PSA was more valuable than T-PSA or f/T PSA alone. It was thought that diagnostic role of miRNAs in the early diagnosis of the different stages of PCa needed to be examined in further studies with larger groups.

Prebiopsy multiparametric MRI and PI-RADS version 2.0 for differentiating histologically benign prostate disease from prostate cancer in biopsies: A retrospective single-center comparison

Multimodal urinary biomarker panel achieves superior prostate cancer detection accuracy and reduces unnecessary biopsies.