Prostate-specific Antigen Velocity Research Articles

Towards improved diagnosis: radiomics and quantitative biomarkers in 18F-PSMA-1007 and 18F-fluorocholine PET/CT for prostate cancer recurrence.

This study compared the radiomic features and quantitative biomarkers of 18F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUVmean, PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUVmax value was significantly higher for 18F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUVmean, TL-PSMA/FCH, and PSMA/FCH-TV as per table 2 between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUVmean/SUVmax and PSA level was moderate, both for 18F-PSMA (r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH (r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18F-PSMA (r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH (r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUVmax values for both radiotracers compared with those who did not, the difference was statistically significant only for 18F-PSMA (P < 0.05). Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

Hybrid Machine Learning Algorithms to Evaluate Prostate Cancer

The adequacy and efficacy of simple and hybrid machine learning and Computational Intelligence algorithms were evaluated for the classification of potential prostate cancer patients in two distinct categories, the high- and the low-risk group for PCa. The evaluation is based on randomly generated surrogate data for the biomarker PSA, considering that reported epidemiological data indicated that PSA values follow a lognormal distribution. In addition, four more biomarkers were considered, namely, PSAD (PSA density), PSAV (PSA velocity), PSA ratio, and Digital Rectal Exam evaluation (DRE), as well as patient age. Seven simple classification algorithms, namely, Decision Trees, Random Forests, Support Vector Machines, K-Nearest Neighbors, Logistic Regression, Naïve Bayes, and Artificial Neural Networks, were evaluated in terms of classification accuracy. In addition, three hybrid algorithms were developed and introduced in the present work, where Genetic Algorithms were utilized as a metaheuristic searching technique in order to optimize the training set, in terms of minimizing its size, to give optimal classification accuracy for the simple algorithms including K-Nearest Neighbors, a K-means clustering algorithm, and a genetic clustering algorithm. Results indicated that prostate cancer cases can be classified with high accuracy, even by the use of small training sets, with sizes that could be even smaller than 30% of the dataset. Numerous computer experiments indicated that the proposed training set minimization does not cause overfitting of the hybrid algorithms. Finally, an easy-to-use Graphical User Interface (GUI) was implemented, incorporating all the evaluated algorithms and the decision-making procedure.

Comment on: "Initial Postoperative Prostate Specific Antigen and PSA Velocity Are Important Indicators of Underlying Malignancy After Simple Prostatectomy" by Livingston et al.

N/A.

Machine-learning Algorithm-based Risk Prediction and Screening-detected Prostate Cancer in A Benign Prostate Hyperplasia Cohort.

Prostate cancer (PCa) is lethal. Our aim in this retrospective cohort study was to use machine learning-based methodology to predict PCa risk in patients with benign prostate hyperplasia (BPH), identify potential risk factors, and optimize predictive performance. The dataset was extracted from a clinical information database of patients at a single institute from January 2000 to December 2020. Patients newly diagnosed with BPH and prescribed alpha blockers/5-alpha-reductase inhibitors were enrolled. Patients were excluded if they had a previous diagnosis of any cancer or were diagnosed with PCa within 1 month of enrolment. The study endpoint was PCa diagnosis. The study utilized the extreme gradient boosting (XGB), support vector machine (SVM) and K-nearest neighbors (KNN) machine-learning algorithms for analysis. The dataset used in this study included 5,122 medical records of patients with and without PCa, with 19 patient characteristics. The SVM and XGB models performed better than the KNN model in terms of accuracy and area under curve. Local interpretable model-agnostic explanation and Shapley additive explanations analysis showed that body mass index (BMI) and late prostate-specific antigen (PSA) were important features for the SVM model, while PSA velocity, late PSA, and BMI were important features for the XGB model. Use of 5-alpha-reductase inhibitor was associated with a higher incidence of PCa, with similar survival outcomes compared to non-users. Machine learning can enhance personalized PCa risk assessments for patients with BPH but more research is necessary to refine these models and address data biases. Clinicians should use them as supplementary tools alongside traditional screening methods.

Whole-body tumour burden on [18F]DCFPyL PET/CT in biochemical recurrence of prostate cancer: association with tumour biology and PSA kinetics.

The objective was to assess the association between molecular imaging (mi) variables on [18F]DCFPyL-PET/CT with clinical and disease characteristics and prostate specific antigen (PSA) related variables in patients with biochemical recurrence of prostate cancer (BRPC). We analysed patients with BRPC after radical treatment. We obtained clinical and PSA variables: International Society of Urology Pathology (ISUP) grade group, European Association of Urology (EAU) risk classification, PSA (PSA≤1ng/ml, 1<PSA≤2, PSA>2), PSA doubling time (PSAdt) and PSA velocity (PSAvel). All PET/CT scans were reviewed with the assistance of automated Prostate Molecular Imaging Standardized Evaluation (aPROMISE) software and lesions' segmentation in positive scans was performed using this platform. Standardized uptake value (SUV) derived variables; tumour burden variables [whole-body tumour volume (wbTV), whole-body tumour lesion activity (wbTLA) and whole-body mi PSMA (wbPSMA)] and miTNM staging were obtained. Cut-off of PSA and kinetics able to predict PET/CT results were obtained. Associations between disease and mi variables were analysed using ANOVA, Kruskal-Wallis and Spearman's correlation tests. Multivariate analysis was also performed. Two hundred and seventy-five patients were studied. [18F]DCFPyL-PET/CT were positive in 165/275 patients. In multivariate analysis, moment of biochemical recurrence, ISUP group, PSA level and PSAvel showed significant association with the detection rate. miTNM showed significant association with PSA level (p<0.001) and kinetics (p<0.001), being higher in patients with metastatic disease. Both PSA and PSAvel showed moderate correlation with wbTV, wbTLA and wbPSMA (p<0.001). A weak correlation with SUVs was found. Mean wbTV, wbTLA and wbPSMA values were significantly higher in PSA > 2ng/ml, PSAdt ≤ 6 months and PSAvel ≥ 0.2ng/ml/month groups. Also, wbTV (p=0.039) and wbPSMA (p=0.020) were significantly higher in patients with ISUP grade group 5. PSA and PSAvel cut-offs (1.15 ng/ml and 0.065 ng/ml/month) were significantly associated with a positive PET/CT. Higher PSA values, unfavourable PSA kinetics and ISUP grade group 5 were robust predictive variables of larger tumour burden variables on [18F]DCFPyL PET/CT assessed by aPROMISE platform.

EAU Biochemical Recurrence Risk Classification and PSA Kinetics Have No Value for Patient Selection in PSMA-Radioguided Surgery (PSMA-RGS) for Oligorecurrent Prostate Cancer.

To assess the influence of biochemical recurrence (BCR) risk groups and PSA kinetics on the outcomes of radioguided surgery against prostate-specific membrane antigen (PSMA-RGS). Currently, neither BCR risk group nor PSA doubling time (PSA-DT), or PSA velocity (PSA-V) are actively assigned or relevant for counseling prior to PSMA-RGS. We retrospectively analyzed PSMA-RGS cases for oligorecurrent prostate cancer between 2014 and 2023. BCR risk groups, PSA-DT, and PSA-V were analyzed as predictors for complete biochemical response (cBR, PSA < 0.2 ng/mL), BCR-free, and therapy-free survival (BCRFS, TFS). Of 374 included patients, only 21/374 (6%) and 201/374 (54%) were classified as low- and high-risk BCR (no group assignment possible in 152/374, 41%). A total of 13/21 (62%) patients with low- and 120/201 (60%) with high-risk BCR achieved cBR (p = 1.0). BCR classification was no predictor for BCRFS (HR:1.61, CI: 0.70-3.71, p = 0.3) or subsequent TFS (HR:1.07, CI: 0.46-2.47, p = 0.9). A total of 47/76 (62%) patients with PSA-DT ≤ 6 mo and 50/84 (60%) with PSA-DT > 6 mo achieved cBR (p = 0.4). PSA-DT was not associated with cBR (OR: 0.99, CI: 0.95-1.03, p = 0.5), BCRFS (HR: 1.00, CI: 0.97-1.03, p = 0.9), or TFS (HR: 1.02, CI: 0.99-1.04, p = 0.2). Consistent negative findings were recorded for PSA-V. The BCR risk groups and PSA kinetics do not predict the oncological success of PSMA-RGS performed at low absolute PSA values. Indolent low-risk BCR is rarely treated by PSMA-RGS.

Immunohistochemistry-Based Biomarkers and Impact on Outcomes Following Salvage Radiotherapy for Prostate Cancer.

Salvage radiation therapy (SRT) is a mainstay of treatment for prostate cancer patients who experience biochemical relapse following radical prostatectomy. We sought to characterize the prognostic impact of previously identified deleterious molecular phenotypes-loss of PTEN, ERG expression, and p53 mutation- upon survival in patients undergoing SRT. We analyzed an institutional database of 320 patients treated with SRT for whom prostatectomy tissue was available; tissue microarrays (TMAs) were constructed and used for genetically validated immunohistochemistry assays for PTEN, ERG, and p53. Chi-squared and Mann-Whitney's tests were used to assess association between molecular expression and clinical risk factors for adverse survival. Uni- and multivariate Cox-proportional hazards models were constructed to determine effects on biochemical (bRFS) and metastasis-free survival (MFS), calculated from end of SRT to event. Loss of PTEN (n = 123, 50%) and ERG expression (n = 118, 39.1%) were common, while p53 overexpression (signifying TP53 missense mutation) was less common (n = 21, 6.6%). On univariate Cox regression, loss of PTEN portended worse bRFS [HR 1.86; 95% CI 1.36-2.57] and MFS [HR 1.89; 1.21-2.94], with homogeneous loss associated with particularly worse MFS [HR 2.47; 1.54-3.95]. Similarly, p53 overexpression predicted worse bRFS [HR 1.95; 1.14-3.32] and MFS [HR 2.79; 1.50-5.19]. ERG expression was associated with only worse MFS [HR 1.6; 1.03-2.48]. On multivariate analysis adjusting for known prognostic features (grade, nodal involvement, pathologic stage, androgen deprivation therapy (ADT), and PSA velocity), homogeneous PTEN loss remained predictive of adverse bRFS [HR 1.73; 1.06-2.82] and MFS [HR 2.35; 1.04-5.34]. PTEN loss identified by immunohistochemistry is an independent adverse prognostic factor for both biochemical and metastasis-free survival in prostate cancer patients treated with SRT. Although clinically validated RNA expression assays also exist which are prognostic for outcomes following SRT, stromal contamination in bulk RNA could mask "loss" signals specific to tumor cells, such as PTEN. Further work is necessary to determine the optimal approach to treating patients with poor molecular prognostic features in a salvage setting.

An MRI assessment of prostate cancer local recurrence using the PI-RR system: diagnostic accuracy, inter-observer reliability among readers with variable experience, and correlation with PSA values.

The Prostate Imaging for Recurrence Reporting (PI-RR) system has been recently proposed to promote standardisation in the MR assessment of prostate cancer (PCa) local recurrence after radical prostatectomy (RP) and radiation therapy (RT). This study aims to evaluate PI-RR's diagnostic accuracy, assess the inter-observer reliability among readers with variable experience, and correlate imaging results with anatomopathological and laboratory parameters. Patients who underwent a pelvic MRI for suspicion of PCa local recurrence after RP or RT were retrospectively enrolled (October 2017-February 2020). PI-RR scores were independently assessed for each patient by five readers with variable experience in prostate MRI (two senior and three junior radiologists). Biochemical data and histopathological features were collected. The reference standard was determined through biochemical, imaging, or histopathological follow-up data. Reader's diagnostic performance was assessed using contingency tables. Cohen's kappa coefficient (κ) and intraclass correlation coefficient (ICC) were calculated to measure inter-observer reliability. The final cohort included 120 patients (median age, 72years [IQR, 62-82]). Recurrence was confirmed in 106 (88.3%) patients. Considering a PI-RR score ≥ 3 as positive for recurrence, minimum and maximum diagnostic values among the readers were as follows: sensitivity 79-86%; specificity 64-86%; positive predictive value 95-98%; negative predictive value 33-46%; accuracy 79-87%. Regardless of reader's level of experience, the inter-observer reliability resulted good or excellent (κ ranges across all readers: 0.52-0.77), and ICC was 0.8. Prostate-specific antigen (PSA) velocity, baseline-PSA, and trigger-PSA resulted predictive of local recurrence at imaging. The PI-RR system is an effective tool for MRI evaluation of PCa local recurrence and facilitates uniformity among radiologists. This study confirmed the PI-RR system's good diagnostic accuracy for the MRI evaluation of PCa local recurrences. It showed high reproducibility among readers with variable experience levels, validating it as a promising standardisation tool for assessing patients with biochemical recurrence. • In this retrospective study, the PI-RR system revealed promising diagnostic performances among five readers with different experience (sensitivity 79-86%; specificity 64-86%; accuracy 79-87%). • The inter-observer reliability among the five readers resulted good or excellent (κ ranges: 0.52-0.77) with an intraclass correlation coefficient of 0.8. • The PI-RR assessment score may facilitate standardisation and generalizability in the evaluation of prostate cancer local recurrence among radiologists.

Initial Postoperative Prostate Specific Antigen and Prostate Specific Antigen Velocity Are Important Indicators of Underlying Malignancy After Simple Prostatectomy.

Background: There is a paucity of guidelines for prostate-specific antigen (PSA) monitoring after simple prostatectomy (SP) despite these patients remaining at risk for prostate cancer (PCa). Our objective was to determine if PSA kinetics can be a potential indicator of PCa after SP. Methods: A retrospective review was performed of all simple prostatectomies at our institution from 2014 to 2022. All patients who met criteria were included in the study. Relevant clinical variables were collected preoperatively, including PSA value, prostate size, and voiding symptoms. Surgical and urinary function outcomes were analyzed. Results: A total of 92 patients were divided into two groups based on malignancy status. Sixty-eight patients did not have PCa, while 24 patients had known PCa before surgery (14) or were diagnosed as having incidental PCa from the pathological specimen (10). Patients with benign prostates had an initial postoperative PSA value of 0.76 ng/mL compared with 1.68 ng/mL for those with cancer (p < 0.01). PSA velocity for the first 24 months after surgery was 0.042 ± 1.61 ng/(mL·year) for the benign cohort compared with 1.29 ± 1.02 ng/(mL·year) for the malignant cohort (p = 0.01). Voiding improvements were noted by objective (postvoid residual and flow rate) and subjective (American Urological Association symptom score and quality of life score) measures in both groups. Conclusions: PSA interpretation and monitoring after SP have not been well established. Our study indicates that initial postoperative PSA value and PSA velocity are important indicators of underlying malignancy in patients after SP. Further efforts are needed to establish threshold values and formal guidelines.

Correlation between metformin intake and prostate cancer

Background: The relationship between metformin intake and prostate cancer incidence remains unclear. Therefore, we examined the correlation between prostate cancer and metformin use.Methods: The subjects were diabetes patients aged ≥50 years who had been diagnosed with prostate cancer and had undergone surgery at Seoul St. Mary's Hospital. Groups taking metformin (MET(+) group) and not taking metformin (MET(–) group) were divided and compared.Results: The mean preoperative prostate-specific antigen (PSA) levels in the MET(–) and MET(+) groups were 10.7±11.9 and 8.0±5.6 ng/mL, respectively, with no statistically significant difference between the two groups (P=0.387). The average prostate volume of the MET(–) group was 82.4±98.0 mL, and the average prostate volume of the MET(+) group was 55.4±20.1 mL, but there was no statistically significant difference between the two groups (P=0.226). The mean PSA velocity also did not show a significant difference between the two groups (0.025±0.102 ng/mL vs. 0.005±0.012 ng/mL, P=0.221).Conclusions: We did not identify a significant positive correlation between metformin and prostate cancer. However, preoperational PSA and PSA velocity tended to be lower in the MET(+) group. A sophisticated prospective study with a large sample size should be planned.

Diagnostic Accuracy of Urinary PCA3 for Prostate Cancer in Thai Patients With PSA Levels of 3 to 10 ng/ml Undergoing an Initial Prostate Biopsy

Purpose: To examine the diagnostic accuracy of the urinary prostate cancer gene 3 score for prostate cancer in Thai patients with prostate-specific antigen levels of 3 to 10 ng/ml undergoing an initial prostate biopsy. Materials and methods: In this prospective, single-center study, urine samples were collected after prostate massage. Urinary prostate cancer gene 3 mRNA levels were measured by real-time quantitative polymerase chain reaction. Data, including age, biopsy results, preoperative prostate-specific antigen levels, prostate-specific antigen density, prostate-specific antigen velocity, prostate volume, and prostate imaging findings, were collected between June 1, 2020, and May 15, 2021. Results: The median prostate-specific antigen level of the 70 included patients was 6.31 ng/ml. Sixteen patients had positive biopsy results (22.9%). The prostate cancer gene 3 score (695.09 vs 268.79, P &lt; .01), prostate-specific antigen density (0.19 vs 0.13, P &lt; .01), and prostate-specific antigen velocity (2.68 vs 0.44, P &lt; .01) significantly differed between the positive and negative biopsy groups. The predictive power of the prostate cancer gene 3 score was evaluated using receiver operating characteristic curves. At a prostate cancer gene 3 score threshold of 366.02, the sensitivity and specificity were 78.57% and 79.25%, respectively. Meanwhile, the areas under the curve of the prostate cancer gene 3 score, prostate-specific antigen velocity, and prostate-specific antigen density were better than that of prostate-specific antigen for predicting a positive biopsy. Conclusion: Our study confirmed the diagnostic accuracy of prostate cancer gene 3 for predicting a positive biopsy in Thai men with prostate-specific antigen levels of 3 to 10 ng/mL. Combining the prostate cancer gene 3 score and prostate-specific antigen derivatives might be helpful for identifying patients who can avoid unnecessary biopsies and subsequent complications.

Head-to-Head Comparison of [18F]F-choline and Imaging of Prostate-Specific Membrane Antigen, Using [18F]DCFPyL PET/CT, in Patients with Biochemical Recurrence of Prostate Cancer.

To analyse diagnostic and therapeutic impact of molecular imaging TNM (miTNM) stage obtained with [18F]DCFPyL versus [18F]F-choline in head-to-head comparison in biochemical recurrence (BCR) of prostate cancer (PCa). Patients with BCR of PCa after radical treatment with previous [18F]F-choline-PET/CT (negative or oligometastatic disease) were recruited to [18F]DCFPyL-PET/CT. Patients were classified according to: grade group, European Association of Urology classification, PSA, PSA doubling time (PSAdt) and PSA velocity (PSAvel). The overall detection rate (DR) and miTNM stage according to PROMISE criteria were assessed for both radiotracers and also correlated (Kappa). The influence of PSA and kinetics on both PET/CT (DR and miTNM) and predictive value of unfavourable kinetics on miTNM were determined. Cut-off PSA, PSAdt and PSAvel values able to predict PET/CT results were determined. Change in miTNM and treatment derived from [18F]DCFPyL information compared with [18F]F-choline were also evaluated. We studied 138 patients. [18F]DCFPyL showed a higher DR than [18F]F-choline (64.5% versus 33.3%) with a fair agreement. [18F]DCFPyL and [18F]F-choline detected T in 33.3% versus 19.6%, N in 27.5% versus 13.8%, and M in 30.4% versus 8.7%. Both tracers' DR showed significant associations with PSA and PSAvel. Significant association was only found between miTNM and PSA on [18F]F-choline-PET/CT (p = 0.033). For [18F]F-choline and [18F]DCFPyL-PET/CT, a PSAdt cut-off of 4.09 and 5.59 months, respectively, were able to predict M stage. [18F]DCFPyL changed therapeutic management in 40/138 patients. [18F]DCFPyL provides a higher DR and superior miTNM staging than [18F]F-choline in restaging BCR, especially with high PSA and unfavourable PSA kinetics, showing a fair agreement to [18F]F-choline.

Upgrading on Per Protocol versus For Cause surveillance prostate biopsies: An opportunity to decreasing the burden of active surveillance.

Most prostate cancer (PC) active surveillance (AS) protocols recommend "Per Protocol" surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for "For Cause" surveillance biopsy (FCSBx) versus PPSBx. We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Surveillance prostate biopsies obtained 1 year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed FCSBx if any of these criteria were met: PSA velocity > 0.75 ng/mL/year; rise in PSA > 3 ng from baseline; surveillance magnetic resonance imaging (MRI) (sMRI) with a PIRADS ≥ 4; change in DRE. Biopsies were classified PPSBx if none of these criteria were met. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. The secondary objective was to assess for the association of reassuring (PIRADS ≤ 3) confirmatory or surveillance MRI findings and upgrading for patients undergoing PPSBx. Proportions were compared with the chi-squared test. We identified 1773 men with GG1 PC in MUSIC who underwent a surveillance biopsy. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared with those meeting criteria for PPSBx (26% and 4.9%, respectively, p < 0.001 and p < 0.001). Men with a reassuring confirmatory or surveillance MRI undergoing PPSBx had less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively) disease compared with men without an MRI (31% and 7.4%, respectively). Patients undergoing PPSBx had significantly less upgrading compared with men undergoing FCSBx. Confirmatory and surveillance MRI seem to be valuable tools to stratify the intensity of surveillance biopsies for men on AS. These data may help inform the development of a risk-stratified, data driven AS protocol.

A big data-based prediction model for prostate cancer incidence in Japanese men

To define a normal range for PSA values (ng/mL) by age and create a prediction model for prostate cancer incidence. We conducted a retrospective analysis using 263,073 observations of PSA values in Japanese men aged 18–98 years (2007–2017), including healthy men and those diagnosed with prostate cancer. Percentiles for 262,639 PSA observations in healthy men aged 18–70 years were calculated and plotted to elucidate the normal fluctuation range for PSA values by age. Univariable and multivariable logistic regression analyses were performed to develop a predictive model for prostate cancer incidence. PSA levels and PSA velocity increased with age in healthy men. However, there was no difference in PSA velocity with age in men diagnosed with prostate cancer. Logistic regression analysis showed an increased risk of prostate cancer for PSA slopes ranging from 0.5 to 3.5 ng/mL/year. This study provides age-specific normal fluctuation ranges for PSA levels in men aged 18–75 years and presents a novel and personalized prediction model for prostate cancer incidence. We found that PSA slope values of > 3.5 ng/mL/year may indicate a rapid increase in PSA levels caused by pathological condition such as inflammation but are unlikely to indicate cancer risk.

MP38-07 UPGRADING ON PER PROTOCOL VS FOR CAUSE SURVEILLANCE PROSTATE BIOPSIES: AN OPPORTUNITY TO DECREASING THE BURDEN OF ACTIVE SURVEILLANCE

You have accessJournal of UrologyCME1 Apr 2023MP38-07 UPGRADING ON PER PROTOCOL VS FOR CAUSE SURVEILLANCE PROSTATE BIOPSIES: AN OPPORTUNITY TO DECREASING THE BURDEN OF ACTIVE SURVEILLANCE Michael Wang, Andrew Lange, David Perlman, Ji Qi, Arvin George, Stephanie Ferrante, Alice Semerjian, Richard Sarle, Michael Cher, Kevin Ginsburg, and For the Michigan Urological Surgery Improvement Collaborative Michael WangMichael Wang More articles by this author , Andrew LangeAndrew Lange More articles by this author , David PerlmanDavid Perlman More articles by this author , Ji QiJi Qi More articles by this author , Arvin GeorgeArvin George More articles by this author , Stephanie FerranteStephanie Ferrante More articles by this author , Alice SemerjianAlice Semerjian More articles by this author , Richard SarleRichard Sarle More articles by this author , Michael CherMichael Cher More articles by this author , Kevin GinsburgKevin Ginsburg More articles by this author , and For the Michigan Urological Surgery Improvement Collaborative More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003276.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Most prostate cancer (PC) active surveillance (AS) protocols recommend “per protocol” surveillance biopsy (PPSBx) every 1-3 years, even if clinical and imaging parameters remained stable. Herein, we compared the incidence of upgrading on biopsies that met criteria for “for cause” surveillance biopsy (FCSBx) vs PPSBx. METHODS: We retrospectively reviewed men with GG1 PC on AS in the Michigan Urological Surgical Improvement Collaborative (MUSIC) registry. Prostate biopsies obtained one year after diagnosis were classified as either PPSBx or FCSBx. Biopsies were retrospectively deemed as FCSBx if any of these criteria were met: PSA velocity >0.75ng/ mL/year; rise in PSA >3ng from baseline; surveillance MRI (sMRI) with a PIRADS ≥4; change in DRE. Biopsies were classified as PPSBx if none of these criteria were met. MRI obtained within 1 year of diagnosis was considered a confirmatory MRI (cMRI), not sMRI. The primary outcome was upgrading to ≥GG2 or ≥GG3 on surveillance biopsy. Secondary objective was to assess for the association of cMRI and sMRI with biopsy upgrading in men undergoing PPSBx. Proportions were compared with the chi-squared test. RESULTS: We identified 1,773 men diagnosed with GG1 PC in MUSIC from 2016 to 2020 that underwent a surveillance biopsy, of which 41% and 59% met criteria for FCSBx and PPSBx, respectively. Men meeting criteria for FCSBx had more upgrading to ≥GG2 (45%) and ≥GG3 (12%) compared to those meeting criteria for PPSBx (26% and 4.9%, respectively, p<0.001 and p<0.001). Men who had PIRADS 1-3 on cMRI or sMRI undergoing PPSBx had even less upgrading to ≥GG2 (17% and 17%, respectively) and ≥GG3 (2.9% and 1.8%, respectively). In the unique scenario in which men had both a cMRI and sMRI with PIRADS 1-3 (n=28), only 14% were upgraded to ≥GG2 and no patients were upgraded to ≥GG3 (Figure 1). CONCLUSIONS: Patients undergoing PPSBx had significantly less upgrading compared to those undergoing FCSBx. Due to the low upgrading seen with PPSBx in men with stable clinical parameters, especially men with non-concerning cMRI or sMRIs, patients and their urologists may omit a PPSBx after a detailed shared decision making process. Source of Funding: funding from Blue Cross Blue Shield of Michigan © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e526 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Wang More articles by this author Andrew Lange More articles by this author David Perlman More articles by this author Ji Qi More articles by this author Arvin George More articles by this author Stephanie Ferrante More articles by this author Alice Semerjian More articles by this author Richard Sarle More articles by this author Michael Cher More articles by this author Kevin Ginsburg More articles by this author For the Michigan Urological Surgery Improvement Collaborative More articles by this author Expand All Advertisement PDF downloadLoading ...

PSMA-11 PET/CT for Detection of Recurrent Prostate Cancer in Patients With Negative Choline PET/CT.

Prostate adenocarcinoma (CaP) is the leading cancer in men. After curative treatment, from 27% to 53% of patients will experience biochemical recurrence (BR). With the development of focal therapies, precise early identification of recurrence's sites is of utmost importance in order to deliver individualized treatment on positive lesions. The aim of this study was to assess the detection rate (DR) of 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) in selected patients with prostate cancer BR and recent negative 18F-choline PET/CT. We performed a retrospective analysis including all patients with CaP referred for BR with a negative 18F-choline PET/CT, and who underwent 68Ga-PSMA-11 PET/CT between October, 2018 and December, 2019. The overall DR of 68Ga-PSMA-11 PET/CT was calculated, and described according to BR characteristics especially PSA levels and velocity. Patients were followed up for at least 1 year. Patient management following 68Ga-PSMA-11 PET/CT and PSA levels evolution after treatment were also recorded. One hundred fifty-nine patients comprising 164 examinations were analyzed. The overall DR of 68Ga-PSMA-11 PET/CT for BR was 65.9% (95CI, 58.6-73.1). The DR was 52.5% (95CI, 39.9-65.0), 70.6% (95CI, 55.3-85.9), 70.4% (95CI, 53.1-87.6), and 78.6% (95CI, 66.2-91.0) for PSA levels between 0.2 and 0.49 ng/mL, 0.5 to 0.99 ng/mL, 1 to 1.99 ng/mL and PSA ≥ 2 ng/mL, respectively. The DR was 70.7% (95CI, 59.0-82.4) with a PSA doubling time (PSA-DT) ≤6 months and 65.2% (95CI, 55.5-74.9) with a PSA-DT >6 months. Around 3/4 of patients (75.9%) with a positive 68Ga-PSMA-11 PET/CT initiated treatment, including surgery (2.4%), stereotactic radiotherapy ± androgen deprivation therapy (ADT) (22%) or external conformational radiotherapy ± ADT (46.3%). Patient management changed in 43 cases (39.8%). Our study confirmed the ability of 68Ga-PSMA-11 PET/CT to detect occult biochemical recurrence, even in a selected population of CaP patients with negative 18F-choline PET/CT, even at low PSA levels.

Outcomes and prognostic predictors of Lu-177 PSMA radioligand therapy in metastatic castration-resistant prostate cancer (Asian Population Study).

Lutetium-177 (Lu-177) prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is a promising therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is limited data of its efficacy and safety in Asian population. We aim to explore the clinical outcomes of Lu-177 PSMA-RLT in this population. We evaluated 84 patients with progressive mCRPC receiving Lu-177 PSMA-RLT between 9 May 2018 and 21 February 2022. Lu-177-PSMA-I&T was administered at 6-8-week intervals. Primary end point was overall survival (OS), and secondary end points included prostate-specific antigen (PSA) progression-free survival (PFS), PSA response rate, clinical response, toxicity assessment, and prognostic indicators. The median OS and PSA PFS were 12.2 and 5.2 months, respectively. PSA decline of ≥50% was observed in 51.8% of patients. Patients achieving PSA response had longer median OS (15.0 vs. 9.5 months, p=.03) and PSA PFS (6.5 vs. 2.9 months, p<.001). Pain score improvement was seen in 19 out of 34 patients. A hematotoxicity of ≥grade 3 was observed in 13 out of 78 patients. Multivariable analyses showed that PSA velocity, alkaline phosphatase, hemoglobin (Hb), and the number of treatment cycles were independent prognostic indicators for OS. The retrospective design was the main limitation of the study. Our study demonstrated a similar safety and efficacy of Lu-177 PSMA-RLT in Asian mCRPC patients compared to the existing literature. A PSA decline ≥50% was associated with longer OS and PSA PFS. Several prognostic indicators for patient outcomes were also identified.

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology: A single centre retrospective study

ObjectiveTo review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. MethodsRetrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. ResultsThree percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4–5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). ConclusionIn this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

Prostate-specific antigen kinetics contributes to decision making for biopsy referral: the predictive implication for PSA retest in patients with elevated PSA levels.

It is common to repeat prostate-specific antigen (PSA) measurements for men with PSA elevation before prostate biopsy. In this scenario, they may have considerable psychological distress in fear of the presence of cancer until retests. We assessed possible clinical factors causing transient PSA rise and explored the parameters predictive of subsequent PSA change. As interfering conditions, the history of ejaculation, bicycling, and any types of infections were assessed using the questionnaire. The pattern of PSA change was compared in association with the various clinical factors. Predictive significance of PSA kinetics such as coefficient of variation (CV) and PSA velocity (PSAV) for PSA values at retest was evaluated. The rate of reversion to the normal range was 38.3% at retest. The rate of 12.8% of men showed a large increase by ≥20%, whereas 38.2% of men showed a large decline by ≥20% from the baseline. Men with younger age (≤60 years), small prostate (<20cc), and prior history of ejaculation or infections showed significantly larger PSA decrease than their counterparts. Those with large CV or PSAV before the baseline more frequently showed PSA decrease below the age-specific cutoff or decline by ≥10% from the baseline at retest. These parameters associated with PSA kinetics had independent predictive values for relevant PSA change at retest. Ejaculation and any types of infections should be avoided before PSA tests. Men with large PSA fluctuation before the baseline are likely to show a significant PSA decrease at retest. This predictive information may help both physicians to determine whether to proceed to an immediate biopsy and patients to reduce their psychological burden.

Factors impacting on sexual function among men on active surveillance for prostate cancer.

Active surveillance (AS) aims to reduce overtreatment and minimize the negative side effects of radical therapies (i.e., prostatectomy or radiotherapy) while preserving quality of life. However, a substantial proportion of men can experience a decline in sexual function during AS follow-up. The aim of this study was to identify predictors of declining sexual function among men on AS. Men enrolled from 2008 to 2018 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a prospective clinical registry-were studied. Sexual function outcomes were measured using expanded prostate cancer index composite (EPIC-26) at baseline and 12-months postdiagnosis. Multivariable regression models adjusted for baseline score and other sociodemographic and clinical factors were applied to identify predictors of sexual function score at 12-months. A total of 554 men were included. Variables that showed significant association with decline in sexual function score at 12-months were: having two or more biopsies after diagnosis (mean change score (MCS): -16.3, p < 0.001) compared with no biopsy, higher number of positive biopsy cores (MCS: -1.6, p = 0.004), being in older age category (above 70 vs. below 60: MCS: -16.7, p < 0.001; 65-70 vs. below 60: MCS: -9.7, p = 0.024), having had depression (MCS: -9.0, p = 0.020), and impaired physical function (MCS: -10.0, p = 0.031). Greater socioeconomic advantage (highest vs. lowest quintile: MCS: 15.7, p = 0.022) and year of diagnosis (MCS: 2.6 for every year, p < 0.001) were positively associated with 12-months sexual function score. Neither biopsy type, biopsy timing nor PSA velocity were associated with declines in sexual function. Our findings suggest that multiple factors affected sexual function during AS. Interventions towardreducing the number of biopsies through less invasive monitory approaches, screening for physical and mental well-being, and targeted emotional support and counseling services may be helpful for men on AS.