Prostate-specific Antigen Velocity Research Articles

Prostate Specific Antigen Dynamics and Features in Prostate Cancer

Abstract Despite the common use of the prostate-specific antigen (PSA) serum level as a tumour marker in diagnosis of prostate cancer, it seems that the PSA doubling time (PSADT) and PSA velocity (PSAV) could be more useful indicators of tumour behaviour and prognosis for patients. The aim of the study was to evaluate the value of PSAV and PSADT in the diagnosis of prostate cancer and their relationship with prostate cancer histopathological characteristics. Eighty-six patients undergoing radical prostatectomy were enrolled in the study. Based on the PSA measurements the PSA dynamic values were calculated: PSADT and PSAV. In addition, clinical and histo-pathological characteristics, including disease stage and prognostic groups were evaluated. The obtained results showed that the first PSA value was 4.29 ng/ml (1.28–13.56), the second PSA value was 7.76 ng/ml (7.60–47.60), and the third PSA value was 9.67 ng/ml (2.56–98.50). The median PSADT was 51.01 months (7.80–311.81) and the median PSAV was 2.66 ng/ml/per year (0.22–4.66). In addition, significant correlations between PSAV and pre- and post-operative Gleason score, and prognostic groups were observed. Significant correlation between PSADT and pre- and pos-toperative Gleason score and prognostic risk groups was demonstrated. This study demonstrated that PSAV and PSADT were significantly correlated with postoperative Gleason score and prognostic risk groups, demonstrating its role in the diagnosis of prostate cancer progression.

The Prostate Saturation Point after Testosterone Replacement Therapy in Testosterone Deficiency Patient

Background: The effect of testosterone on the prostate gland is an unresolved question. The prostate saturation model is a recent hypothesis explaining that the stimulation of prostate tissue by testosterone is limited to a certain level of testosterone due to the limited number of androgen receptors. However, data from the Thai patients related to this issue are still lacking and need to be explored. Objective: To investigate prostate changes after testosterone replacement therapy (TRT). Materials and Methods: A retrospective study including testosterone-deficient patients who had TRT between 2011 and 2017 at Ramathibodi Hospital was conducted. The change in prostate-specific antigen (PSA) levels before and after TRT, or after a 1-year observation, was measured and analyzed as the primary objective. As a secondary objective, the authors measured and evaluated normal PSA velocity (PSAV) in the patients after TRT. Results: One hundred eleven testosterone deficient patients were included for analysis. The mean age was 62 years old. The baseline testosterone level and PSA level at the beginning were 247 ng/dL and 1.16 ng/mL, respectively. After undergoing TRT for one year, the results showed that the testosterone and the PSA levels were 307 ng/dL and 1.46 ng/mL, respectively. In addition, the subgroup analysis illustrated that patients who had low baseline testosterone levels such as 247 ng/dL or less, had significant increase of PSA level after treatment. However, when the baseline testosterone level was more than 247 ng/dL, the PSA levels were steady after treatment. For the secondary-objective results, the PSAV of the testosterone deficiency patients after TRT was 0.3 ng/mL/year. Conclusion: The evidence clearly indicates that TRT significantly increased the serum testosterone level. However, it had a limited effect on PSA change. The present study results supported the hypothesis of the prostate saturation model. The authors believe that a testosterone level of 247 ng/dL can saturate all androgen receptors in the prostate gland and no longer increase prostate stimulation. Keywords: Prostate-specific antigen; Prostate cancer; Testosterone replacement Therapy; Prostate saturation

PD17-06 PSA VELOCITY PREDICTS CLINICAL PROGRESSION IN AFRICAN AMERICAN AND NON-HISPANIC WHITE PATIENTS WITH LOW RISK PROSTATE CANCER UNDERGOING ACTIVE SURVEILLANCE

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance I (PD17)1 Sep 2021PD17-06 PSA VELOCITY PREDICTS CLINICAL PROGRESSION IN AFRICAN AMERICAN AND NON-HISPANIC WHITE PATIENTS WITH LOW RISK PROSTATE CANCER UNDERGOING ACTIVE SURVEILLANCE Juan Javier-DesLoges, Tyler Nelson, Rishi Deka, Patrick Courtney, Vinit Nalawade, Loren Mell, James Murphy, J. Kellogg Parsons, and Brent Rose Juan Javier-DesLogesJuan Javier-DesLoges More articles by this author , Tyler NelsonTyler Nelson More articles by this author , Rishi DekaRishi Deka More articles by this author , Patrick CourtneyPatrick Courtney More articles by this author , Vinit NalawadeVinit Nalawade More articles by this author , Loren MellLoren Mell More articles by this author , James MurphyJames Murphy More articles by this author , J. Kellogg ParsonsJ. Kellogg Parsons More articles by this author , and Brent RoseBrent Rose More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001999.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. METHODS: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. RESULTS: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p<0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). CONCLUSIONS: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols. Source of Funding: Department of Defense, grant number W81XWH-17-PCRP-PRA (RD and BSR) © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e286-e287 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan Javier-DesLoges More articles by this author Tyler Nelson More articles by this author Rishi Deka More articles by this author Patrick Courtney More articles by this author Vinit Nalawade More articles by this author Loren Mell More articles by this author James Murphy More articles by this author J. Kellogg Parsons More articles by this author Brent Rose More articles by this author Expand All Advertisement Loading ...

V14-11 MRI/US FUSION GUIDED PROSTATE BIOPSY USING A TRANSPERINEAL APPROACH: STEP-BY-STEP INSTRUCTIVE VIDEO ABSTRACT

You have accessJournal of UrologyProstate Oncology II & Testis Oncology & Misc. Oncology (V14)1 Sep 2021V14-11 MRI/US FUSION GUIDED PROSTATE BIOPSY USING A TRANSPERINEAL APPROACH: STEP-BY-STEP INSTRUCTIVE VIDEO ABSTRACT Eusebio Luna, Alberto Lopez-Prieto, Gloria Egui-Benatuil, Edward Gheiler, Ariel Kaufman, Dailianys Barrios, Farshad Shafizadeh, Michael Zachareas, and Fernando Bianco Eusebio LunaEusebio Luna More articles by this author , Alberto Lopez-PrietoAlberto Lopez-Prieto More articles by this author , Gloria Egui-BenatuilGloria Egui-Benatuil More articles by this author , Edward GheilerEdward Gheiler More articles by this author , Ariel KaufmanAriel Kaufman More articles by this author , Dailianys BarriosDailianys Barrios More articles by this author , Farshad ShafizadehFarshad Shafizadeh More articles by this author , Michael ZachareasMichael Zachareas More articles by this author , and Fernando BiancoFernando Bianco More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002111.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Multiparametric MRI has become an essential tool and is currently recommended by the AUA for the workup of men with suspected prostate cancer, the most common solid malignancy in the US.1-2 Office-based transrectal ultrasound prostate biopsies (TRUS) are still the standard in sampling the prostate.3 Notwithstanding its practicality, the transrectal approach harbors imprecision and a worse adverse events profile than a Transperienal approach.4 The perineum has been segregated to the operating room. However, we questioned this paradigm and develop a method to safely sample the prostate transperineally under local anesthesia in the office setting.5 Encouraging results led us to start an open-ended prospective registry NCT02381990 (clinicaltrials.gov), devised to evaluate outcomes of men treated with MRI/US- guided fusion in the office setting.6 Herein, we present a video-case showing a step-by-step execution of this technique. METHODS: This video shows a step-by-step transperineal MRI/US fusion guided prostate biopsy on a 75-year-old male with a PSA of 7.9 ng/ml and a PSA velocity > 1ng/ml/yr. He has no family history of prostate cancer and his digital rectal examination (DRE) was negative. An MRI was ordered and revealed several PI-RADS 3 regions of interest (ROI). The DICOM processing and incorporation into the fusion device was outsourced. On the procedure day, the fusion device was connected to the ultrasound and stepper with a grid. The biopsy was conducted as shown following the MRI plan. RESULTS: The procedure was performed successfully in 19 minutes. The patient reported a maximum pain of 3/10 and was discharged 20 minutes after its conclusion. He did not experience any adverse events. The biopsy was positive in one of the ROI. It was a Gleason 3+3 (GG1) prostate cancer in 50% of the core. Between 2014 and June 2020, we conducted 1,782 MRI/US Transperineal Biopsies under local anesthesia in the office setting at three different centers, a 91% (1,622) of these were MRI/US Fusion. Overall median biopsies time was 21 minutes (IQR 16,24). We abandoned transrectal biopsies in 2017. CONCLUSIONS: The purpose of this video is to show the tremendous benefits of such a feasible and convenient procedure. MRI/US fusion guided Prostate Biopsy using a Transperineal approach in an office-setting is reliable and reproducible. It deals with the “Harm” described by the US Task Force associated with prostate cancer screening, by thorough sampling in an office setting, providing accurate and precise information about the location of tumors to target, and opening a door for MRI/US-guided therapies in the office setting. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1168-e1169 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Eusebio Luna More articles by this author Alberto Lopez-Prieto More articles by this author Gloria Egui-Benatuil More articles by this author Edward Gheiler More articles by this author Ariel Kaufman More articles by this author Dailianys Barrios More articles by this author Farshad Shafizadeh More articles by this author Michael Zachareas More articles by this author Fernando Bianco More articles by this author Expand All Advertisement Loading ...

MP46-08 A MULTI-INSTITUTIONAL STUDY OF MRI/ULTRASOUND FUSION IMAGING AND BIOPSY IN COMBINATION WITH NANOPARTICLE DIRECTED FOCAL THERAPY FOR ABLATION OF PROSTATE TISSUE

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-08 A MULTI-INSTITUTIONAL STUDY OF MRI/ULTRASOUND FUSION IMAGING AND BIOPSY IN COMBINATION WITH NANOPARTICLE DIRECTED FOCAL THERAPY FOR ABLATION OF PROSTATE TISSUE Arvin George, Steven Canfield, Joshua Jue, Sara Lewis, Matthew Davenport, Varaha Tammisetti, Mahir Maruf, Leonardo Borregalaes, Jon Schwartz, Naomi Halas, and Ardeshir Rastinehad Arvin GeorgeArvin George More articles by this author , Steven CanfieldSteven Canfield More articles by this author , Joshua JueJoshua Jue More articles by this author , Sara LewisSara Lewis More articles by this author , Matthew DavenportMatthew Davenport More articles by this author , Varaha TammisettiVaraha Tammisetti More articles by this author , Mahir MarufMahir Maruf More articles by this author , Leonardo BorregalaesLeonardo Borregalaes More articles by this author , Jon SchwartzJon Schwartz More articles by this author , Naomi HalasNaomi Halas More articles by this author , and Ardeshir RastinehadArdeshir Rastinehad More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Focal therapy is currently being evaluated as an alternative to whole gland therapy in men with low to intermediate risk prostate cancer. There are several different modalities that are utilized to focally treat prostate tissue/tumors, however most modalities have some degree of non-target ablation. We report the final results of the first in human, nanoparticle directed focal ablation of prostate tissue using MRI/Ultrasound fusion guidance. METHODS: This is an open-label, multi-center study of men with low to intermediate risk localized prostate cancer treated with a single-dose of AuroLase therapy and the focal excitation of neoplastic prostate tissue via nanoparticle directed excitation. Up to two focal areas of prostate cancer confirmed by MRI/Ultrasound guided biopsy with no disease appreciated outside of the region of each lesion were included. Efficacy of focal prostate tissue ablation was assessed by MRI/Ultrasound guided biopsy and serum PSA at 3 and 12 months. RESULTS: 45 men were enrolled in the study. 44 men completed infusion and ablation, with a total of 45 lesions included in the study. The mean PSA at baseline was 9.6, which decreased to 3.6 at 3 months and 4.9 at 12 months, p<0.01. 33 lesions (73.3%) were negative and 12 lesions (26.7%) were positive on 3 month and 12 month postablation biopsy, p=0.54. 1 patient underwent salvage cryotherapy at 12 months. Serum PSA, PSA velocity, change in PSA, and proportional change in PSA at baseline, 3 months, and 12 months were not significant predictors of lesion biopsy result. CONCLUSIONS: Ultra-focal ablation of neoplastic prostate tissue via nanoparticle directed excitation results in a 73.3% lesion ablation success rate confirmed by an end of study MRI/Ultrasound fusion guided biopsy of the treated lesion and standard template. Source of Funding: Sponsored by Nanospectra Biosciences, Inc. and Philips Healthcare © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e816-e816 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Arvin George More articles by this author Steven Canfield More articles by this author Joshua Jue More articles by this author Sara Lewis More articles by this author Matthew Davenport More articles by this author Varaha Tammisetti More articles by this author Mahir Maruf More articles by this author Leonardo Borregalaes More articles by this author Jon Schwartz More articles by this author Naomi Halas More articles by this author Ardeshir Rastinehad More articles by this author Expand All Advertisement Loading ...

LBA02-07 PROSPECTIVE STUDY OF 68 GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING

You have accessJournal of UrologyLate-breaking Abstract II - Malignant1 Sep 2021LBA02-07 PROSPECTIVE STUDY OF 68GA-RM2 PET/MRI IN PATIENTS WITH BIOCHEMICALLY RECURRENT PROSTATE CANCER AND NEGATIVE CONVENTIONAL IMAGING Lucia Baratto, Hong Song, Heying Duan, Farshad Moradi, Guido Davidzon, and Andrei Iagaru Lucia BarattoLucia Baratto More articles by this author , Hong SongHong Song More articles by this author , Heying DuanHeying Duan More articles by this author , Farshad MoradiFarshad Moradi More articles by this author , Guido DavidzonGuido Davidzon More articles by this author , and Andrei IagaruAndrei Iagaru More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002149.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 68Ga-RM2 is a synthetic bombesin receptor antagonist targeting gastrin-releasing peptide receptors (GRPr) that are overexpressed in several human tumors, including prostate cancer (PC). Men with biochemical recurrence (BCR) and negative CT/MRI and bone scintigraphy were evaluated for the presence of prostate cancer. METHODS: We enrolled 127 men with BCR PC, 45-83-year-old (mean±SD: 68.3±6.9). Imaging started at 40-89 minutes (mean±SD: 51.0±8.9) after injection of 113.8-152.6 MBq (mean±SD: 140.5±6.4) of 68Ga-RM2 using a time-of-flight (TOF)-enabled simultaneous positron emission tomography (PET) / magnetic resonance imaging (MRI) scanner. RESULTS: All patients had rising PSA and negative conventional imaging prior to enrollment. 68Ga-RM2 PET identified recurrent PC in 85 of the 127 participants. Positivity rate of 68Ga-RM2 PET was: 37.9% for PSA <0.5 ng/dl (n=29), 61.1% for PSA 0.5 – 1.0 ng/dl (n=18), 64.7% for PSA 1.0 – 2.0 ng/dl (n=17), 82.6% for PSA 2.0 – 5.0 ng/dl (n=23) and 87.5% for PSA >5.0 ng/dl (n=40). PSA velocity values were 1.9±2.7 ng/ml/year (range: 0-9.1) in patients with negative PET scans and 5.8±9 ng/ml/year (range: 0.2-45.4) in patients with positive PET scans (P: 0.01). CONCLUSIONS: 68Ga-RM2 PET identifies GRPr expression in BCR PC lesions despite negative conventional imaging, indicating it is a promising PET radiopharmaceutical in this clinical scenario. 68Ga-RM2 may identify higher risk patients given the highly statistically significant difference PSA velocity values between patients with negative and positive scans and may be a complementary radiopharmaceutical to the PSMA-targeting tracers to ultimately allow for personalized medicine. Source of Funding: DoD © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1178-e1178 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lucia Baratto More articles by this author Hong Song More articles by this author Heying Duan More articles by this author Farshad Moradi More articles by this author Guido Davidzon More articles by this author Andrei Iagaru More articles by this author Expand All Advertisement Loading ...

Value of Serial PSA Measurements for Prostate Cancer Prediction on Screening Using a Maximum Likelihood Estimation − Prostate Specific Antigen (MLE-PSA) Model

PSA measurements are used to assess the risk for prostate cancer. PSA range and PSA kinetics such as PSA velocity have been correlated with in creased cancer detection and assist the clinician in deciding when prostate biopsy should be performed. Our aim is to evaluate the use of a novel, maxi mum likelihood estimation - prostate specific antigen (MLE-PSA) model for predicting the probability of prostate cancer using serial PSA measurements combined with PSA velocity in order to assess whether this reduces the need for prostate biopsy. A total of 1976 Caucasian patients were included. All these patients had at least 6 PSA serial measurements; all underwent trans-rectal biopsy with minimum 12 cores within the past 10 years. A multivariate logistic re gression model was developed using maximum likelihood estimation (MLE) based on the following parameters (age, at least 6 PSA serial measurements, baseline median natural logarithm of the PSA (ln(PSA)) and PSA velocity (ln(PSAV)), baseline process capability standard deviation of ln(PSA) and ln(PSAV), significant special causes of variation in ln(PSA) and ln(PSAV) detected using control chart logic, and the volatility of the ln(PSAV). We then compared prostate cancer probability using MLE-PSA to the results of prostate needle biopsy. The MLE-PSA model with a 50% cut-off probability has a sensitivity of 87%, specificity of 85%, positive predictive value (PPV) of 89%, and negative predictive value (NPV) of 82%. By contrast, a single PSA value with a 4ng/ml threshold has a sensitivity of 59%, specificity of 33%, PPV of 56%, and NPV of 36% using the same population of patients used to generate the MLE-PSA model. Based on serial PSA measurements, the use of the MLE-PSA model significantly (p-value &lt; 0.0001) improves prostate cancer detection and reduces the need for prostate biopsy.

Natural history of an immediately detectable PSA following radical prostatectomy in a contemporary cohort.

A detectable prostate-specific antigen (PSA) following radical prostatectomy (RP) is an unfavorable prognostic factor. However, not all men with a detectable PSA experience recurrence. We describe the natural history and outcomes in men with a detectable PSA following RP in a contemporary cohort. A retrospective analysis of men who underwent RP for non-metastatic prostate cancer at the University of California, San Francisco from 2000 to 2020 was performed. A detectable PSA was defined as PSA ≥ 0.03 ng/ml within 6 months of RP. Cox regression models tested the effect of detectable PSA on the development of metastasis, prostate cancer-specific mortality, and overall survival. We identified 2941 men who had RP with 408 (13.9%) with a detectable PSA within the first 6 months. The median follow-up was 4.42 years (interquartile range [IQR], 2.58-8.00). In total, 296 (72.5%) men with a detectable PSA had salvage treatment at a median of 6 months (IQR, 4-11). One hundred sixteen of these men had PSA failure after salvage treatment at a median of 2.0 years (IQR, 0.7-3.8). On multivariable Cox regression, the risk of development of metastasis (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.09; p = .01), prostate cancer-specific mortality (HR, 1.13; 95% CI, 1.05-1.21; p = .0005), and overall mortality (HR, 1.07; 95% CI, 1.03-1.12; p = .002) was associated with PSA velocity after salvage treatment in men with a detectable PSA. Men with a detectable PSA after RP may have excellent long-term outcomes. PSA velocity after salvage treatment may be an important predictor for the development of metastasis, prostate cancer-specific mortality, and overall mortality.

A bicentric retrospective analysis of clinical utility of 18F-fluciclovine PET in biochemically recurrent prostate cancer following primary radiation therapy: is it helpful in patients with a PSA rise less than the Phoenix criteria?

18F-Fluciclovine PET imaging has been increasingly used in the restaging of prostate cancer patients with biochemical recurrence (BCR); however, its clinical utility in patients with low prostate-specific antigen (PSA) levels following primary radiation therapy has not been well-studied. This study aims to determine the detection rate and diagnostic accuracy of 18F-fluciclovine PET and the patterns of prostate cancer recurrence in patients with rising PSA after initial radiation therapy, particularly in patients with PSA levels below the accepted Phoenix definition of BCR (PSA nadir +2ng/mL). This retrospective study included patients from two tertiary institutions who underwent 18F-fluciclovine PET scans for elevated PSA level following initial external beam radiation therapy, brachytherapy, and/or proton therapy. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed to determine the diagnostic accuracy of 18F-fluciclovine PET and associations of PSA kinetic parameters with 18F-fluciclovine PET outcome. One hundred patients were included in this study. The overall detection rate on a patient-level was 79% (79/100). 18F-Fluciclovine PET was positive in 62% (23/37) of cases with PSA below the Phoenix criteria. The positive predictive value of 18F-fluciclovine PET was 89% (95% CI: 80-94%). In patients with PSA below the Phoenix criteria, the PSA velocity had the highest predictive value of 18F-fluciclovine PET outcome. PSA doubling time (PSADT) and PSA velocity were associated with the presence of extra-pelvic metastatic disease. 18F-Fluciclovine PET can identify recurrent disease at low PSA level and PSA rise below accepted Phoenix criteria in patients with suspected BCR after primary radiation therapy, particularly in patients with low PSADT or high PSA velocity. In patients with low PSADT or high PSA velocity, there is an increased probability of extra-pelvic metastases. Therefore, these patients are more likely to benefit from PET/CT or PET/MRI than pelvic MRI alone.

Role of PSA Kinetics in Hormone-refractory Prostate Cancer.

To demonstrate the predictive effect of PSA derivatives and time markers that is prostate-specific antigen (PSA) doubling time (PSADT) and PSA velocity (PSAV) on survival in men with hormone-refractory prostate cancer (HRPCa). Descriptive, analytical study. Department of Urology, Erciyes University, Faculty of Medicine, Kayseri, Turkey, between 2012 and 2020. One hundred patients, who were treated with prostate cancer, were subjected. The PSA values were noted, nadir PSA values were detected, times to nadir PSA, HRPCa, and follow-up times were recorded. PSADT and PSAV were calculated. The relationships between the groups were analyzed. Kaplan-Meier curves were used to estimate overall survival between the groups. The patients were grouped according to the mean PSADT, median PSAV, median nadir PSA, and mean time to HRPCA. The survival of those with high PSADT, low PSAV and low nadir PSA were found to be significantly longer (p=0.006, p<0.001, p<0.001). High PSAV was also associated with significantly increased PSA, nadir PSA and death (p<0.001, p=0.47, and p<0.001, p=0.52, respectively). The survival of those with a longer time to HPRCa was found to be significantly longer (p<0.001). There was no statistically significant difference in terms of survival between patients who received chemotherapy after HRPCa and those who did not (p=0.477). PSAV (p=0.007 HR: 1.004 95% CI: 1.001 - 1.007), bone metastasis at diagnosis (p=0.001 HR: 0.357 95% CI: 0.197 - 0.645) and time to HRPCa development (p=0.001 HR: 0.936 95% CI: 0.900 - 0.974) were significantly effective to the survival. Conclusion:PSADT, PSAV, and nadir PSA serve as independent prognostic markers for survival in patients with HRPCa. These three PSA derived calculation products, with the help of other parameters, could work as prognostic factors, and help clinicians predict survival in men with HRPCa. Key Words: PSA kinetics, Hormone-refractory prostate cancer, Survival, Prognostic factors.

A phase II randomized controlled trial of exercise on biochemical progression in men with prostate cancer on active surveillance.

5080 Background: Men with prostate cancer (PCa) undergoing active surveillance (AS) are at increased risks of cardiovascular death and disease progression. Any intervention that can address these issues during AS would be highly beneficial. Clinical and preclinical studies have demonstrated the benefits of exercise to improve cardiovascular health in cancer patients and suggested the potential role of exercise in suppressing PCa progression in men with PCa undergoing AS. Therefore, the purpose of this study was to investigate the effects of exercise on cardiorespiratory fitness and biochemical progress of PCa in men with PCa on AS. Methods: The Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial was a single-centre, two-armed, randomized controlled trial in Edmonton, Canada. 52 men with localized PCa who were undergoing AS were randomized to high-intensity interval training (HIIT; n = 26) or usual care (UC; n = 26). The HIIT group performed thrice-weekly, supervised, aerobic HIIT on a treadmill at 85-95% of peak cardiorespiratory fitness (VO2peak) for 12 weeks. The primary outcome was VO2peak, and the secondary and exploratory outcomes included biochemical progression of PCa (prostate-specific antigen [PSA]), PSA kinetics, and growth of prostate cancer cell line LNCaP. Results: 46/52 participants (88%) completed the postintervention VO2peak assessment and adherence to HIIT was 96%. Compared to UC, HIIT significantly improved VO2peak (adjusted between-group mean difference, 1.6 ml·kg-1·min-1; 95% confidence interval [CI], 0.3 to 2.9; p= 0.014). HIIT also significantly reduced PSA level (adjusted between-group mean difference, -1.1 ug/L; 95% CI, -2.1 to 0.0; p= 0.043) and PSA velocity ( p= 0.040), and suppressed LNCaP cell growth ( p =0.024). No significant differences were found in PSA doubling time ( p= 0.10) and testosterone ( p= 0.24). Conclusions: The ERASE Trial is the first randomized controlled trial to demonstrate the impact of HIIT exercise for improving physical fitness and inhibiting biochemical progression of PCa in men with localized PCa on AS. Our findings suggest that supervised aerobic HIIT may be a promising intervention in this clinical setting. Larger-scale randomized controlled trials are warranted to determine if improvements in physical fitness and PCa-related markers translate into improved long-term clinical outcomes in these men such as disease progression, receipt of radical treatments, posttreatment complications, and survival. Clinical trial information: NCT03203460.

Potential Value of PSA Velocity in Prostate Cancer Patients Undergoing Active Surveillance

In the continuing search for ways to identify progression of prostate cancer in patients who are managed by active surveillance, researchers used the

Association of Prostate-Specific Antigen Velocity With Clinical Progression Among African American and Non-Hispanic White Men Treated for Low-Risk Prostate Cancer With Active Surveillance

The association of prostate-specific antigen velocity (PSAV) with clinical progression in patients with localized prostate cancer managed with active surveillance remains unclear and, to our knowledge, has not been studied in African American patients. To test the hypothesis that PSAV is associated with clinical progression in patients with low-risk prostate cancer treated with active surveillance and to identify differences between African American and non-Hispanic White patients. This was a retrospective population-based cohort study using patient records from the Veterans Heath Administration Informatics and Computing Infrastructure on 5296 patients with a diagnosis of localized prostate cancer from January 1, 2001, to December 31, 2015, who were managed with active surveillance. Follow-up extended through March 31, 2020. Low-risk prostate cancer was defined as International Society of Urologic Pathology grade group (GG) 1 clinical tumor stage 2A or lower, PSA level of 10 ng/dL or lower, active surveillance, and no definitive treatment within the first year after diagnosis with at least 1 additional staging biopsy after diagnostic biopsy. Prostate-specific antigen testing. The primary outcome was GG progression detected after repeated biopsy or prostatectomy, defined as GG2 or higher or GG3 or higher. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards regression models were used to test associations between PSAV and outcomes. The final cohort (n = 5296) included 3919 non-Hispanic White men (74.0%; mean [SD] age, 65.7 [5.8] years) and 1377 African American men (26.0%; mean [SD] age, 62.8 [6.6] years). Compared with African American patients, non-Hispanic White patients were older (mean [SD] age, 65.7 [5.8] years vs 62.8 [6.6] years; P < .001), presented with higher cT stage (stage T2, 608 [15.5%] vs 111 [8.1%]; P < .001), had a higher Charlson Comorbidity Index score (1 and ≥2, 912 [23.3%] vs 273 [19.8%]; P = .002), had higher median income ($60 000 to ≥$100 000, 1223 [31.2%] vs 282 [20.5%]; P < .001), and had a higher median level of education (20% to ≥30% with college degree, 1192 [30.4%] vs 333 [24.2%]; P < .001). Progression to GG2 or higher occurred in 2062 patients (38.9%), with a cumulative incidence of 43.2%, and progression to GG3 or higher occurred in 728 patients (13.7%). Fifty-four patients (1.0%) developed metastases. On multivariable analysis, PSAV was significantly associated with progression to GG2 (hazard ratio, 1.32 [95% CI, 1.26-1.39]), GG3 (hazard ratio, 1.51 [95% CI, 1.41-1.62]), and metastases (hazard ratio, 1.38 [95% CI, 1.10-1.74]). Optimal PSAV thresholds that were associated with progression were significantly lower for African American patients (0.44 ng/mL/y) compared with non-Hispanic White patients (1.18 ng/mL/y). This study suggests that PSAV is significantly associated with grade progression among patients with low-risk prostate cancer managed with active surveillance, but at lower values for African American patients compared with non-Hispanic White patients. These data suggest that serial PSA measures may potentially substitute for multiple prostate biopsies and that African American patients may merit increased frequency of PSA testing.

Parameters predicting [18F]PSMA-1007 scan positivity and type and number of detected lesions in patients with biochemical recurrence of prostate cancer

BackgroundDetection of the site of recurrence using PSMA-PET/CT is important to guide treatment in patients with biochemical recurrence of prostate cancer (PCa). The aim of this study was to evaluate the positivity rate of [18F]PSMA-1007-PET/CT in patients with biochemically recurrent PCa and identify parameters that predict scan positivity as well as the type and number of detected lesions. This monocentric retrospective study included 137 PCa patients with biochemical recurrence who underwent one or more [18F]PSMA-1007-PET/CT scans between August 2018 and June 2019. PET-positive malignant lesions were classified as local recurrence, lymph node (LN), bone or soft tissue lesions. The association between biochemical/paraclinical parameters, as PSA value, PSA doubling time, PSA velocity, Gleason score (GS) and androgen deprivation therapy (ADT), and scan positivity as well as type and number of detected lesions was evaluated using logistic regression analysis (binary outcomes) and Poisson models (count-type outcomes).ResultsWe included 175 [18F]PSMA-1007-PET/CT scans after radical prostatectomy (78%), external beam radiation therapy (8.8%), ADT (7.3%), brachytherapy (5.1%) and high intensity focused ultrasound (0.7%) as primary treatment (median PSA value 1.6 ng/ml). Positivity rate was 80%. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence of bone and soft tissue lesions and number of bone, LN and soft tissue lesions, both in uni- and/or multivariable analysis. Multivariable analysis also showed prior ADT as predictor of bone and soft tissue lesions, GS as predictor of the number of bone lesions and ongoing ADT as predictor of the number of LN lesions.Conclusion[18F]PSMA-1007-PET/CT showed a high positivity rate in patients with biochemically recurrent PCa. PSA value and PSA velocity were significant predictors of scan positivity as well as of the presence and number of bone and soft tissue lesions and the number of LN lesions. Our findings can guide clinicians in optimal patient selection for [18F]PSMA-1007-PET/CT and support further research leading to the development of a prediction nomogram.

Application of metastatic biopsy based on "When, Who, Why, Where, How (4W1H)" principle in diagnosis and treatment of metastatic castration-resistance prostate cancer.

BackgroundTo determine the feasibility of secondary biopsy of metastatic castration-resistance prostate cancer based on the “4W1H—When, Who, Why, Where, How” principle and analyze the factors that affect tumor detection. Its application will further direct the patients for individualized precision therapy.MethodsA total of 55 patients were collected for secondary biopsy (27 prostate biopsies and 55 metastases biopsies). The parameters of biopsy location, computed tomography attenuation coefficient, lesion size, core number, laboratory tests, and the use of bone protection were evaluated. Histopathological data and the pathogenesis and etiology classification were used to guide precision treatment.ResultsFifteen/27 patients had a positive prostate biopsy, and 47/55 had positive metastasis biopsy. Bone metastasis biopsy was positive in 21/29 of cases. Also, parenchymal organs and lymph node biopsies were positive. In the prostate rebiopsy, significant differences were observed between total prostate volume (P=0.028), prostate-specific antigen (PSA) density (P=0.047), PSA velocity (P=0.036), and positive biopsy results. In the bone metastasis biopsy, we divided the patients into biopsy-positive and -negative groups. The computed tomography attenuation coefficient, PSA, alkaline phosphatase, and hemoglobin were related to tumor positive detection. However, the lesion size, core number, bone-sparing agents and previous treatments did not affect tumor detection.ConclusionsIn metastatic castration-resistant prostate cancer (mCRPC) patients, the “4W1H” principle was applied in the second biopsy. The biopsy site, image, and laboratory variables affected the positive of tumor tissue. Further pathological analysis of tumor tissue is essential to guide the precision medicine of mCRPC etiological classification.

PSA velocity to predict clinical progression in African American and non-Hispanic White patients with low-risk prostate cancer undergoing active surveillance.

196 Background: The utility of prostate-specific antigen velocity (PSAV) to predict clinical progression in patients with localized prostate cancer (PC) on active surveillance remains unclear, and in African American (AA) patients on active surveillance remains undefined. Methods: We performed a cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure (VINCI). We identified 5296 patients diagnosed with localized prostate cancer (PC) from 2001 to 2015 managed with active surveillance. Follow-up extended through March 31, 2020. We defined low-risk PC as ISUP grade group 1 (GG1) clinical tumor stage ≤ 2A, and PSA level ≤ 10 ng/dl; and active surveillance as no definitive treatment within the first year after diagnosis with at least one additional staging biopsy after diagnostic biopsy. The primary outcome was grade progression on repeat biopsy/prostatectomy defined as GG2 or GG3. The secondary outcome was incident metastases. Cumulative incidence functions and multivariable Cox proportional hazards models were used to test associations between PSAV and outcomes. Results: The final cohort included 3919 Non-Hispanic White patients (NHW) (74%) and 1377 AA (26%) patients. GG2 progression on repeat biopsy occurred in 2062 (38.9%) patients, with a cumulative incidence (CI) of 43.2 % and GG3 progression occurred in 728 (13.7%) patients, with a CI of 18% at seven years. Fifty-four (0.8%) patients developed metastases, with a CI of 1.4% at ten years. In unadjusted analyses, compared to NHW patients, AA patients were significantly more likely to progress to GG2 (52.8% vs 39.8%, p&lt;0.001), and GG3 (22.2% vs 16.8%, p=0.01). On MV analysis, PSAV was a significant predictor of GG2 (HR 1.32 [1.26-1.39]), GG3 (1.5 [1.40-1.62]), and metastases (1.38 [1.10-1.74]). A significant interaction term between race and PSAV indicated the need for different PSAV thresholds for AA and NHW men. Based on maximally selected rank statistics, optimal thresholds for separating outcomes were different in AA vs NHW men. (0.44 vs. 1.18). Conclusions: In this analysis of PSAV in low-risk prostate cancer patients on AS—to our knowledge, the largest to date for AA patients—we observed that PSAV is a robust predictor of upgrading on restaging biopsy as well as metastasis. Compared to NHW patients, AA patients were more likely to progress at lower values of PSAV and therefore merit close follow-up on active surveillance protocols.

A phase I, dose-expansion cohort study on the safety of a cannabidiol for biochemical recurrence in prostate cancer patients.

TPS263 Background: Cannabinoids, widely used in pain control, as an appetite stimulant, and anti-emetic in cancer patients, may play role as an anti-carcinogenic agent. A preclinical study demonstrated that cannabinoid receptors (CB1 and CB2) were highly expressed in human androgen-responsive prostate cancer (PCa) cells (LNCaP) as compared to normal prostate epithelial cells (PrEC). When these two cell lines were treated with a potent cannabinoid receptor agonist, PCa cells showed a decrease in prostate-specific antigen (PSA) protein expression and increased apoptosis in a dose and time-dependent manner with no effect seen in PrEC cells. An FDA-approved cannabidiol (CBD) agent, is derived from Cannabis sativa L. plants. Extracts from these plants are processed to yield pure CBD and contain less than 0.5% THC. We will expand these preclinical studies with a phase I trial. Methods: This trial is an open-label, single-center, phase I dose escalation study followed by dose expansion to evaluate acute toxicity, long-term safety and tolerability, and preliminary antitumor activity of cannabidiols in patients with biochemically recurrent (BCR) PC after primary definitive local therapy and prostate-specific antigen doubling time ≤ 12 months. The dose escalation will be determined by a Bayesian Optimal Interval design and the target dose-limiting toxicity rate is set at 30%. An additional 6-9 patients will be enrolled as an expansion cohort once the maximum tolerated dose is determined. Patients will be treated for a total 90 days with a 10 day taper. The primary objective is to evaluate the acute toxicity and long-term safety and tolerability of cannabidiols in patients with BCR. The secondary objective includes measuring changes in serial PSA levels, PSA velocity, and testosterone levels and to assess health-related quality of life (EORTC QLQ-C30 and QLQ-PR 25) from baseline throughout the treatment period. CB receptor 1 and 2 expression levels by immunohistochemistry staining will be evaluated from archival prostatectomy specimens if available as an exploratory objective. This trial opened on 7.28.2020 and has started enrollment. Clinical trial information: NCT04428203.

Predictive factors of tumor sink effect: Insights from 177Lu-Prostate-specific membrane antigen therapy.

Tumor sink effect (TSE) has been defined as; decreased uptake in healthy tissue with increased tumor sequestration of the radiopharmaceuticals. It enables us to give high tumoral radiation doses while resulting in lower absorbed radiation to critical organs. However, the factors which influence this effect are yet to be defined. In this study, we have investigated the predictive factors of the tumor sink effect in a group of patients who received 177Lu-Prostate-specific membrane antigen (PSMA) therapy due to progressive metastatic castration-resistant prostate cancer (mCRPC). We have retrospectively analyzed the pre-therapy 68Ga-PSMA positron-emission tomography (PET)-computed tomography (CT) and post-therapy planar whole-body scans of 65 patients who received at least two cycles of 7.4GBq of 177Lu-PSMA therapy. All patients with mCRPC were referred to our department after multiple treatment lines. Age, previous therapies, International Society of Urological Pathology (ISUP) score, and pre-therapy serum tumor marker levels were recorded. Post 177Lu-PSMA therapy images were analyzed for TSE. 68Ga-PSMA PET-CT images were used for the calculation of SUVmax in malignant and healthy tissues as well as metabolic tumor volume (MTV) and total lesion PSMA index (TLPI). Based on the post-therapy scans, TSE was seen in 17/65 (26.2%) patients. In univariate analysis, patients with TSE had higher pre-therapy PSA, PSA velocity, and ALP (p < 0.0001). In relation to PET parameters, patients with TSE had higher 68Ga-PSMA MTV, 68Ga-PSMA TLPI and lower pretherapy renal SUVmax (p < 0.0001)), pretherapy liver SUVmax (p:0.012), pretherapy parotid gland SUVmax (p:0.032), and pretherapy parotid gland SUVmean (p:0.038). In the multivariant analysis, 68Ga-PSMA TLPI, pre-therapy PSA, and PSA velocity were found to be statistically significant. When analyzed according to Youden index, pretherapy PSA level of 133ng/ml (sensitivity 0.765 and 0.875), PSA velocity of 246ng/ml/year (sensitivity 0.765 and 0.833), and 68Ga-PSMA TLPI of 2969g (sensitivity 0.765 and 0.875) was found to be the best cut-off points to predict TSE. The tumor sink effect was seen in 26.2% of patients. 68Ga- PSMA TLPI, pre-therapy PSA, and PSA velocity was found to be the predictors of TSE. Accurate prediction of TSE may lead to increased tumoral doses while sparing healthy organs. Clinical trials that consider this effect as a part of a dose algorithm may further increase therapeutic efficacy.

Performance of [68Ga]Ga-PSMA-11 PET/CT in patients with recurrent prostate cancer after prostatectomy\u2014a multi-centre evaluation of 2533 patients

PurposeTo evaluate the performance of [68Ga]Ga-PSMA-11 PET/CT in the diagnosis of recurrent prostate cancer (PC) after prostatectomy in a large multicentre cohort.MethodsThe centres, which contributed to this study, were the departments of nuclear medicine of Heidelberg (Germany), Technical University of Munich (Germany) and Albert Einstein Hospital of São Paulo (Brazil). A total of 2533 patients who were scanned with [68Ga]Ga-PSMA-11 PET/CT at 1 h p.i. due to recurrent PC after prostatectomy were included in this retrospective analysis. Exclusion criteria were as follows: patients with untreated primary tumour, previous chemotherapy or Xofigo®; those previously treated with exclusively external beam radiation therapy or HIFU; those referred for PSMA-therapy; and those treated with ADT (including first- and second-generation ADT) within the last 6 months. Potential influences of different factors such as PSA level, PSA doubling-time (PSADT), PSA velocity (PSAVel), Gleason Score (GSC, including the separate analysis of 7a and 7b), age and amount of injected tracer were evaluated in a multivariable analysis.ResultsThe rate of pathologic PET/CT-scans was 43% for PSA ≤ 0.2 ng/ml, 58% for PSA > 0.2 to ≤ 0.5, 72% for PSA > 0.5 to ≤ 1.0 and increased to a maximum of 93% for PSA > 10 ng/ml. A pathological PET/CT was significantly (p = 0.001) associated with PSA level and higher GSC. Amount of injected tracer, age, PSADT and PSAVel were not associated with a higher probability of a pathological scan.Conclusion[68Ga]Ga-PSMA-11 PET/CT at 1 h p.i. confirmed its high performance in the largest patient cohort yet analysed. Tumour detection showed a clear association with higher PSA and higher GSC. No association was found between a pathological [68Ga]Ga-PSMA-11 PET/CT and age, amount of injected tracer, PSADT or PSAVel.

Evaluation of heterogeneous factors of low-grade prostate cancer in patients before and after radical prostatectomy

Objective: to determine the degree of heterogeneity of prostate cancer Gleason 6 (3 + 3) by assessing: long-term oncological results, mismatch of pre- and postoperative degree of prostate cancer aggressiveness, preoperative clinical component.Materials and methods. 528 patients with clinically localized prostate cancer and Gleason»s preoperative score of 6 (3 + 3). All patients were divided into 3 groups: group 1 (n = 151) — Gleason 6, prostate specific antigen (PSA) density &lt;0.15ng/ml/cm3, ≤4 positive biopsy cores, &lt;50 % lesion of the biopsy cores, group 2 (n = 229) — Gleason 6, PSA &lt;10 ng/ml and group 3 (n = 148) — Gleason 6, PSA &gt;10 ng/ml.Results. Statistically significant differences between group 1 and group 2 were observed only when assessing PSA velocity (p &lt;0.017). The median time to the development of biochemical relapse (BCR) in the study population was 12 (3—77) months. BCR in group 1 was observed in 1.98 % of patients, in group 2 and 3 — 7.86 and 14.19 %, respectively. Statistically significant differences in the time of onset of BCR within 2 years after surgery were found between groups 1 and 2 (p = 0.002) and group 1 and 3 (p = 0.0001). An increase in the degree of malignancy after surgery in group 1 was determined only in 13 % of patients, in group 2 in 27 %, in group 3 in 43 % of patients. The contribution of a greater postoperative degree of malignancy of prostate cancer to the development of BCR in group 1 was 1.32 % (2 out of 3 patients). Thus, in group 1 in the case of true Gleason 6 (3 + 3), the probability of BCR was 0.66 %.Conclusion. PSA velocity before surgery showed a statistical difference between groups 1 and 2. Based on long-term oncological results after surgery, heterogeneous behavior of the tumor is observed among the study groups. Group 1 in comparison with group 2 and 3 showed the lowest frequency of increase in the Gleason score and the likelihood of developing BCR after surgery. These results may be useful in planning an individual patient treatment plan.