Higher PSA Research Articles

The role of spatial transcriptomic profiling to determine androgen receptor signaling and immune infiltration in prostate cancer

272 Background: Prostate cancer (PCa) in the transition zone (TZ) accounts for approximately 30% of disease and tends to present with higher PSAs with a lower risk of seminal vesicle invasion, extra-capsular extension, and risk of biochemical recurrence compared with peripheral zone (PZ) tumors. The underlying biological mechanism for these differences is poorly understood. Here, we performed spatial transcriptomic profiling to elucidate the molecular differences between TZ and PZ PCa. Methods: We identified three patients who underwent radical prostatectomy for PCa (one each with PZ only, TZ only, and both PZ and TZ tumors) and used the NanoString’s Digital Spatial Profiling (DSP) platform to quantify whole transcriptomic gene expression data (17,128 genes) in multiple regions of interest (ROI) per patient (42 cancer and 8 normal samples). Four morphology markers to facilitate ROI selection in both cancer and normal areas (SYTO13 for nucleus, PanCK for epithelium, SMA for stroma and CD45 for immune cells) were selected. Raw counts for 17,128 genes were imported to R v.4.1.0 for downstream data analyses. Counts were Q3 normalized and scaled (Z-score) to enable plotting of all genes on the same axes. Differential gene expression analysis using a linear model fit by empirical Bayes moderation, gene set enrichment analysis (GSEA) by cancer hallmarks, XCell gene sets for pathway enrichment and immune cell deconvolution using CIBERSORT was performed. Results: There were grade group (GG) 4 (n=10) and 5 (n=10) tumors in PZ and GG 3 (n=10), 4 (n=11) and 5 (n=1) cancers in TZ regions. We observed distinct gene expression profiles between PZ (n = 20) and TZ (n=22) tumors. Interestingly, androgen receptor (AR) signaling was significantly higher in TZ PCa ROIs compared to PZ ROIs in both GSEA (false discovery rate < 5%) and the androgen subcomponent of the genomic prostate score (p<0.001), regardless of grade, epithelial, stromal or immune component of the region. To standardize the comparison, CIBERSORT’s absolute immune signature scores were only computed for GG4 tumors and found to be significantly higher in PZ GG4 tumors compared to TZ GG4 tumors. Notably, CD4+ memory T cells were significantly higher in PZ GG4 regions compared to TZ GG4 tumor regions (p<0.05). Conclusions: Here, we demonstrate distinct gene expression profiles of PZ and TZ PCa. Specifically, we observed higher AR signaling in TZ cancers and higher levels of immune infiltration on PZ cancers. This is in concordance with prior knowledge that TZ tumors may be associated with higher serum PSA and PZ tumors may be associated with inflammation. Further studies are needed to discern the biological and clinical significance of the different molecular features of PZ and TZ PCa.

Prevalence and natural history of non-metastatic castrate resistant prostate cancer: A population-based analysis.

65 Background: The natural history of non-metastatic castrate resistant prostate cancer (nmCRPC) prior to the introduction of novel anti-androgen agents in a real-world setting is largely unknown. Methods: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada. Patients with a diagnosis of prostate cancer, castrate level of testosterone ( < 1.7nmol/L) and a PSA > 2.0nmol/L with a subsequent rise > 25% from the nadir, and without diagnostic or treatment codes for metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and death are presented as medians with interquartile range (IQR). Predictors of time from nmCRPC to prostate cancer death were compared using univariable and multivariable Fine and Gray subdistributional hazard models to account for the competing risk of non-prostate cancer death. Results: From January 2007 until March 2018, we identified 2045 patients with nmCRPC. Median age was 79 years (IQR: 72-84). A total of 984 patients (48.1%) received upfront hormonal therapy while 584 (25.8%) received initial radiotherapy (RT) and 478 (23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years (IQR: 3-10). PSA at the time of meeting nmCRPC criteria was a median of 3.0 ng/L. Patients were followed for a median 31.1 months (IQR: 19.8-47.9). The overall annual prevalence of nmCRPC ranged from 1,519-1,913 patients, representing 7-12% of men with prostate cancer prescribed androgen deprivation therapy each year. Crude median time from nmCRPC to all-cause death was 37.6 months (IQR: 22.1-55.4). Median time from nmCRPC to metastasis and metastasis to all-cause death was 20.0 and 8.3 months, respectively. On regression analysis, older age, ADT use with primary treatment, higher PSA at the time of meeting nmCRPC criteria, and grade group predicted time from nmCRPC to prostate cancer death. Conclusions: This is the largest analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and advancements in systemic therapy for patients with nmCRPC impact prevalence estimates and disease trajectory over time.

Disparities in prostate cancer: An ethnicity comparative focus among Hispanic Americans versus non-Hispanic whites.

23 Background: Prostate cancer (PCa) is a clinically heterogeneous disease and the incidence and mortality risk varies widely among racial/ethnic groups. Among Hispanic American (HA) men, PCa accounts for nearly one-quarter of the total cancer burden; in addition, advanced stage and mortality rates are significantly higher in HA compared to Non-Hispanic White (NHW) men. Despite a decade of declining overall incidence rates, incidence rates of advanced PCa appear to be increasing over time among HA men, a similar pattern seen among Non-Hispanic Blacks (NHB). Methods: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA at diagnosis between 2010 and 2016. HAs were divided into four major subgroups: Mexican/Chicano, Puerto Ricans, Cubans, and Central/South Americans. NHB, Asian, and other racial groups were excluded. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Univariable and multivariable logistic regression models were used to evaluate the association of HA ethnic subgroups with metastatic presentation and primary treatment. Results: A total of 428,829 patients were included with 5,625 (1.3%) being HA. Mexican comprised 51.2% of HAs and presented with higher PSA and Gleason score at diagnosis and more advanced cT, N1 and M1 stage when compared to NHW men and other HA subgroups (all, p < 0.001) (Table). After adjusting for age, PSA, year of diagnosis, cT, N, insurance, income, education, and performance score, Mexican had 1.32 (95%CI: 1.07-1.63, p = 0.01) higher odds of initial metastatic presentation and 0.68 (95%CI: 0.55-0.85, p < 0.001) lower odds of receiving treatment compared to NHW men while no statistically significant difference was seen for the other HA subgroups. Conclusions: Even after accounting for socioeconomic disparities, Mexican men present with a more aggressive disease when compared to NHW and other HA subgroups. Our results warrant further investigations into potential biological factors affecting HA PCa as well as identifications of potential barriers to treatment for vulnerable populations.[Table: see text]

Timing of Ga68-PSMA PETCT and patterns of recurrence after prostate radiotherapy: Implications for potential salvage

PurposeTo study patterns of recurrence in Ga68-PSMA PETCT at rising serum PSA after radical radiotherapy for non-metastatic prostate cancer. MethodsAmong patients with non-metastatic prostate cancer treated with radical external beam radiotherapy and androgen deprivation therapy, those who underwent Ga68-PSMA PETCT for rising PSA during follow up were analysed. Patterns of recurrence in Ga68-PSMA PETCT were studied. Extra-prostatic recurrences ≤5 were considered oligometastases. Local and oligometastatic recurrences were deemed suitable for focal salvage therapy. Probabilities of identifying recurrent lesion and potentially salvageable recurrences in Ga68-PSMA PETCT in relation to PSA were calculated. ResultsTotal 114 patients were included (69% high-risk). Radiotherapy was hypofractionated in 57% (moderate 40%, extreme 17%), with median prostate EQD2 78.5 Gy. Median time from radiotherapy to Ga68-PSMA PETCT was 4.3 years (IQR 2.4–6.4), with median PSA 4.7 ng/mL (IQR 2.6–10.7) at scan. Uptake suggesting recurrence was observed in 91.2% patients, with positivity of 75%, 87%, 89%, and 100% at PSA thresholds ≤2, ≤5, ≤10, and >10 ng/mL respectively. Probability of detecting recurrence in Ga68-PSMA PETCT increased with higher PSA at scan (AUC = 0.82). Uptake was local in 20 (17.5%), oligometastatic in 39 (34.2%), and polymetastatic in 45 (39.5%) patients. Recurrence was potentially salvageable in 59/104 (56.7%) patients, being 67% at PSA ≤2 ng/mL but only 38% at PSA >10 ng/mL. Probability of recurrence being potentially salvageable declined with increasing PSA at scan (AUC = 0.68). ConclusionEarly Ga68-PSMA PETCT for rising PSA after definitive prostate radiotherapy detected majority of recurrent lesions and identified oligorecurrences amenable to focal salvage therapy.

The CAPRA-S Score and Immune Dysfunction as a Guide to Outcome in Men Treated with Prostatectomy Radical as Mono-Therapy for Prostate Cancer.

Incorporate the immune function as determined by the absolute lymphocyte count (ALC) into the CAPRA-S risk stratification score to determine if predictive values could be improved. The clinical pathological findings in the surgical specimen and total PSA were used to define the three CAPRA-S risk groups. One month after surgery and at each follow up total PSA and the ALC were determined, until biochemical failure (BF) or the end of the study period. A cut off value of <1,000 lymphocytes/mm3 was used to define lymphocytopenia (LCP). Each CAPRA-S group was sub-divided based on the presence or absence of LCP. Kaplan-Meier biochemical failure free survival (BFFS) curves and restricted mean biochemical failure free survival times were calculated for each group. 404 patients participated of whom 103 (25.5%) underwent BF. 270 men were CAPRA-S low risk (LR), 89 intermediate risk (IR) and 45 high risk (HR), of whom LCP was found in 22 (8%) of low risk, 24 (27%) of intermediate risk and 17 (38%) of high risk men. LCP was significantly associated with a higher PSA, higher Gleason and CAPRA-S scores and BF. HRs were 1.76 for IR, 2.49 for HR and 1.29 for LCP. Five-year BFFS for men without LCP, LR 93.5%, IR 61% and HR 36%, for those with LCP, LR 55%, IR 25% and HR 6%. All patients with LCP and IR or HR scores relapsed within 6 years. 10 year BFFS for men without LCP were 71% LR, 43% IR and 23% HR, LR with LCP 16%. Men with BF had increasing LCP approximately 18 months before BF. The incorporation of the ALC taken one month after surgery with the CAPRA-S improves risk stratification; decreases in the ALC suggest that BF is occuring. These results need to be confirmed with larger studies.

The Relationship between the SUVmax Value Obtained in Ga-68 PSMA PET/CT and Lactate Dehydrogenase and Alkaline Phosphatase in Prostate Cancer

Objectives: ALP and LDH are serum markers of prognostic importance in prostate cancer patients. PET/CT imaging with Ga-68 PSMA has played an important role in prostate cancer imaging in recent years. Our aim in this study was to evaluate the relationship and prognostic significance between SUVmax values obtained with Ga-68 PSMA PET/CT and LDH and ALP levels in prostate cancer patients. Methods: We retrospectively evaluated 61 prostate cancer patients who had Ga-68 PSMA PET/CT imaging and who did not have a prostatectomy between 2019 and 2020. PSA, ALP and LDH levels were measured in all patients before or after imaging within a maximum of 28 days. Results: The median age of the patients included in this study was 73 (range: 57–89) and all 61 patients were prostatic adenocarcinoma. 50 (82%) of the patients had distant metastasis in Ga-68 PSMA PET/CT. There was a significant positive correlation between serum LDH and PSA levels. There was a positive correlation between serum ALP and PSA levels. A negative correlation was found between ALP levels and prostate SUVmax. Conclusions: While negative correlation was found between SUVmax and ALP levels, no correlation was found between LDH levels and SUVmax. High ALP levels were found to be related to metastasis rates and severity and high serum PSA levels.

The Effectiveness of Prostate Imaging and Reporting and Data System Version 2 in the Diagnosis of Prostate Cancer with Screening Parameters Correlation.

Prostate cancer is the most commonly diagnosed cancer and the second most common reason for cancer-related mortality in men. The purpose of cancer screening is to detect the disease at an early stage to help effective treatment. This study aimed to investigate the effectiveness of MRI and PI-RADS in the diagnosis of prostate cancer and examine the relation between screening parameters with prostate cancer. The PACS system was analyzed and MRI images between September 2016 and April 2018 were listed. The state of patients regarding having pathology results were obtained. PSA values were listed. The prostate volume and the prostate density was calculated. PI-RADS assessment was used for each prostate lesion. Data of 138 patients were included in the study. The mean age was 63±8.9. The mean prostate gland volume was 63.8±39.3ml, the mean PSA value was 12.51±25.22 and the mean PSA density was calculated as 0.319±0.945. A statistically significant difference was found between age and prostate volume and cancer. The age of the cancer cases was higher than those who did not have cancer (p<0.05). A negative correlation was found between prostate volume and cancer status. The prostate volume of non-cancer cases was higher compared to cancer cases (p=0.0001). 55 patients had no malignancy. It was observed that 56.4% of cancer patients had significant cancer. The frequency of using PI-RADS scores was 4% for P1, 36% for P2, 14% for P3, 28% for P4, and 18% for P5. Clinically significant cancer was present in 57.9% of patients with PI-RADS score4 and 69.6% of patients with PI-RADS score5. It was found that diagnostic values were significantly high for prostate cancer screening in patients with PI-RADS scores4 and 5 (Sensitivity 76.4%, Specificity 73.5%, Negative predictive value 82.4%, Positive predictive value 65.6%). PI-RADS and MRI can be useful for the diagnosis of the clinically significant prostate cancer in patients at risk for prostate cancer. It is a non-invasive, repeatable method for prostate cancer screening and diagnosis. In prostate screening PSA reliability may be questioned. Additional methods are needed for the diagnosis. For this reason MRI and PI-RADSv2 is an effective predictor of prostate cancer in patients with high PSA levels.

To Evaluate the Corelation between Age and Gleason Score in Patients with Prostate Cancer- A Tertiary Care Hospital Based Study

Objective: The aim of this study is to evaluate the corelation between age and Gleason score in patients with prostate cancer. Materials and Methods: From January 2009 to December 2021, 268 Asian Pakistani men who underwent prostate biopsy and were diagnosed with Prostate Adenocarcinoma have been included in this study, The age of patients ranged from 40 years to 94 years. The indications for biopsy were suspicious digital rectal examination and abnormally high PSA. The procedure was performed either transurethrally, transperineally or transrectally, Results: A total of 268 patients were diagnosed with Prostate Adenocarcinoma, the age range was from 40 to 94 years. The median age was found as 68 years with an interquartile range of 15 years. The median Gleason score was found as 8 with an interquartile range of 7 scores. A negative weak corelation was found between the age of the patients at the time of diagnosis and the Gleason score (r= -0.013, p=0.832). Conclusion: Though there are many studies that support the existence of corelation between increasing age and Gleason Score, our study, like a couple of others, showed no association between the two and a weak positive corelation. Our conclusion of the study is that while studying the relationship between the two, other variables like PSA, DRE findings and TNM classification of the tumor are also important. Hence, more work needs to be done in this regard.

Determination of critical cut-off values of PCA3 index in patients with prostate gland pathology

Introduction. Prostate cancer antigen-3 (PCA3) is a genetic biomarker, which got widespread and demonstrated high diagnostic potential. This gene expresses only in prostate gland tissue, furthermore, malignant prostate neoplastic transformation leads to 70 – 100 time overexpression of it. Polyadenylated matrix RNA (mRNA) is a functional product of this gene, which do not translating into protein. Gene contains of four introns and three exon. Product of PCA’s gene detecting in post massage urine using polymerase chain reaction (PCR) in combination with reverse transcription. It could use as prognostic biomarker in patients with first negative biopsy or before it performing. Moreover, index of PCA3 can be useful in detecting tumor aggressiveness and decisions about further treatment options. Taking into account these facts, patients with high initial PSA level can avoid unnecessary biopsies. Objective: to determine critical cut-off value of PCA3 index as prognostic biomarker of PCa development. Materials and methods. Research based on routine and special test’s data of 243 men in Institute of Urology, National Academy of Medical Sciences of Ukraine in period of 2015–2020 year. RNA extraction from postmassage urine samples performed using RNeasy (Qiagen) kit. Statistical analysis performed using SPSS Statistics 19.0 (IBM SPSS Statistics 19.0) та SAS 12.0 (IBM Statistical Analysis System 12.0). Critical cut-off values determined using three methods: calculating of average value and (Xave) and standard deviation (SD) of it, Heiner index, and Youden’s index. Evaluation of optimality of determined critical cut-off values performed by comparative analysis using index of positive prognosis (IPP), index of negative prognosis (INP), diagnostic accuracy of method (DAM), Sp and Se for each of used methods. Results and discussion. First method demonstrated than 97,5 % of all results, which means absent of disease, was below critical cut-off values, due to statistical deviations and accurate demonstrate than in case of asymmetry or multimodal distribution this method was unsatisfied. Wherein IPP was 95 %, INP – 72 %, DAM – 78 %, Sp – 97,5 % and Se – 52 %. Calculation of PCA3 index area under ROC-curve was 0,810 (0,771–0,849). Using Heiner’s method critical cut-off value of PCA3 index was 14,0 с. u., where in IPP was 75 %, INP – 82 %, DAM – 78 %, Sp – 78 % and Se – 78 %. Critical cut-off values of PCA3 index 33,4 c. u. which calculated by Youden’s index demonstrated IPP – 98 %, INP – 73 %, DAM – 80 %, Sp – 99 % and Se – 57 %. Conclusions. The most optimal critical cut-off value for PCA3 index was determined using Youden’s index and was 33,4 c. u. Keywords: prostate cancer, PCA , prostate cancer antigen-3, PCA3, prostate cancer antigen-3 index, PCA3 index, critical cut-off values of PCA3 index.

Prevalence and Determinants of Psychiatric Morbidities in Nigerian Men with LUTS Due to Prostatic Diseases

Aims: This study aimed at determining the prevalence and significant factors associated with psychiatric morbidity in men with LUTS secondary to prostatic diseases in a tertiary health centre in a developing country.&#x0D; Study design: This is a prospective, cross-sectional study.&#x0D; Place and duration: The urology unit of Ekiti State University Teaching Hospital, Ado-Ekiti. Ekiti State, Nigeria. The study period was from 1stJanuary2018 to 31stDecember2019.&#x0D; Methodology: Hospital Anxiety and Depression Scale (HADS) was used to assess for psychiatric morbidity among 224 patients with LUTS. While, International prostate symptom score (IPSS) was used to assess the severity of LUTS. The data was analysed using SPSS version 20.&#x0D; Results: The prevalence of depression and anxiety were 17% and 9.8% respectively. The mean IPSS and PSA scores of the respondents were 19.95±8.06 and 31.48±37.03 respectively. The only factors found to be significantly associated with depression were use of alcohol by the respondents (T-test = .058, P = .01, CI = -2.885 ˗˗ -0.391) and high scores on IPSS (T-test = .765, P value = .003, CI = 1.436 ˗˗ 6.995). While the factors found to be associated with anxiety disorders were alcohol use by the respondents (T-test =2.661, P = .033, CI = -2.519 ˗˗ -0.103) and high PSA scores (T-test =9.473, P value = .036, CI = -28.942 ˗˗ -1.068).&#x0D; Conclusion: This study shows that there is a high rate of psychiatric morbidity among patients with LUTS. Main factors associated with these morbidities were alcohol use, severity of the LUTS and high PSA scores. Assessment of psychiatric morbidity in patients with LUTS using simple psychological instruments will help in early detection and prompt treatment of psychological morbidities.

Prognostic impact of dose reduction in androgen receptor pathway inhibitors for castration-resistant prostate cancer.

BackgroundAndrogen receptor pathway inhibitors (ARPIs) such as abiraterone and enzalutamide have been shown to prolong survival in patients with advanced prostate cancer. However, there is limited evidence on the anticancer effect of a reduced dose of ARPIs. This study compared the prognosis in patients with chemotherapy-naïve castration-resistant prostate cancer (CRPC) between ARPI treatment with standard dose and treatment with reduced dose.MethodsJapanese patients who were treated with ARPI as first-line treatment for CRPC between 2014 and 2018 were included. The associations between dose reduction and clinicopathological factors, progression-free survival, and overall survival were investigated.ResultsOf the 162 patients included, 33 (20.4%) patients had their dose reduced during ARPI treatment. In the multivariate analysis, higher PSA, abiraterone treatment, and dose reduction were significant prognostic factors for progression-free survival (PFS); however, dose reduction was not associated with overall survival. In the enzalutamide-treated group, the median PFS was 12.1 months (95% CI, 8.5–21.4 months) in the standard-dose group and 7.2 months (95% CI, 5.0–11.5 months) in the reduced-dose group (P = 0.038).ConclusionThis study suggests inferior oncological outcome when treated with reduced-dose ARPI for CRPC. Full-dose administration of ARPI for CRPC may be appropriate if feasible.

Patterns of Failure in Men With Radiorecurrent Prostate Cancer: A Post-Hoc Analysis of Two Prospective Ga-68-PSMA PET/CT Imaging Trials

<h3>Purpose/Objective(s)</h3> The advent of novel nuclear medicine imaging modalities, such as prostate specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), has significantly impacted the ability to localize disease in patients with biochemically recurrent prostate cancer (PCa). However, the topography of recurrence in men with radiorecurrent disease remains poorly understood. <h3>Materials/Methods</h3> This was a <b>post-hoc</b> analysis of men from two prospective studies of PSMA PET/CT for radiorecurrent prostate cancer, previously treated with definitive radiotherapy (RT), who had detailed clinicopathologic and treatment characteristics available and at least one PSMA PET/CT finding. Patterns of failure were defined as local-only (intraprostatic or seminal vesicle), nodal (regional lymph node with or without local failure), and distant (with or without local or nodal failures). Univariable multinomial logistic regression (UVA) was performed to evaluate predictors of nodal or distant recurrence vs. local only, and subsequent multivariable analyses (MVAs) were conducted including only variables with <i>P</i> < 0.1 on UVA. Variables evaluated included years since radiation, post-radiation nadir PSA, PSA at time of PSMA, initial disease features (cT stage, iPSA, Gleason grade group), and treatment variables (type of radiation, use of ADT, use of whole pelvis radiotherapy). <h3>Results</h3> There were 118 patients included in this study. Of these 118 patients, 17 (14%) were initially diagnosed with low-risk, 61 (52%) with intermediate-risk, and 40 (34%) with high-risk PCa. Median time since RT was 4.4 years (interquartile range [IQR], 2.5-7.4 years), and median PSA at time of PSMA was 4.9 ng/mL (IQR, 2.7-9.6). Local only failures were seen in 47 patients (40%), regional failures (without distant failures) in 23 patients (19%), and distant failures in 48 patients (41%). On UVA, higher iPSA and higher PSA at time of PSMA were associated with regional recurrence, while shorter interval from RT, higher Gleason grade, higher initial PSA, and higher PSA at time of PSMA were associated with distant disease. On MVA, only PSA at time of PSMA remained significant for distant recurrence (<i>P</i> = 0.003) and trended toward significance for regional recurrence (<i>P</i> = 0.07). <h3>Conclusion</h3> Nearly 40% of patients with radiorecurrent prostate cancer have local-only recurrences on PSMA imaging, while another 40% have distant disease. PSA at the time of PSMA imaging is a significant predictor of distant recurrence. Prospective studies evaluating salvage treatment approaches that integrate PSMA imaging data are warranted, and imaging at a lower PSA threshold should be considered.

A phase 2 randomized clinical trial of abiraterone plus ADT, apalutamide, or abiraterone and apalutamide in patients with advanced prostate cancer with non-castrate testosterone levels (LACOG 0415)

BackgroundAndrogen deprivation therapy (ADT) combined with apalutamide, abiraterone acetate plus prednisone, enzalutamide, or docetaxel are the standard treatments for advanced castration-sensitive prostate cancer (CSPC). We investigated ADT-free alternatives for advanced CSPC. Patients and methodsLACOG 0415 is a phase 2, open-label, non-comparative, randomized trial. Patients with advanced CSPC were randomized (1:1:1) to receive goserelin plus abiraterone acetate and prednisone (ADT plus AAP arm), apalutamide (APA arm), or apalutamide plus abiraterone acetate and prednisone (APA plus AAP arm). The primary endpoint was the proportion of patients with PSA of ≤0.2 ng/mL at week 25 in the modified intention-to-treat population. Safety analyses were performed in all patients with at least one dose of the study drug. ResultsOf 128 randomized patients, 120 patients were evaluable for PSA response at week 25; 17.2% had a high-risk biochemical recurrence, 8.6% had locally advanced disease, and 74.2% had distant metastases. At week 25, PSA of ≤0.2 ng/mL was observed in 75.6% (95%CI 59.7%–87.6%), 60.0% (95%CI 43.3%–75.1%), and 79.5% (95%CI 63.5%–90.7%) of patients in ADT plus AAP, APA, and APA plus AAP arms, respectively. PSA decline of ≥80% was observed in 100%, 90.0%, and 97.4%, respectively. Grade 3–4 AEs were observed in 31.0%, 21.4% and 36.4%, respectively. Testosterone levels increased significantly in the APA arm and decreased significantly in ADT plus AAP and APA plus AAP arms. ConclusionsADT-free alternatives provide a high PSA response in advanced CSPC, although the APA arm did not reach the expected rate of PSA of ≤0.2 ng/mL at week 25. These results warrant further investigation of ADT-free treatments as alternatives in advanced CSPC. Source study registrationClinicalTrials.govNCT02867020.

Factors Associated with Discontinuation of Active Surveillance among Men with Low-Risk Prostate Cancer: A Population-Based Study.

The purpose of this study was to describe the uptake, discontinuation and variation of active surveillance (AS) by provider and patient level characteristics. This observational, population-based study used linked administrative databases and pathology reports to identify all men diagnosed with Gleason score ≤6 prostate cancer (PC) between January 1, 2008 and December 31, 2014 in Ontario, Canada. The Cochran-Armitage test was used for AS trend over time. Treatment-free survival was estimated using cumulative incidence function. Factors associated with discontinuation of AS were evaluated using Cox proportional hazard models. Active surveillance was the initial management strategy for 8,541 cases (51%). Use of AS significantly increased from 38% in 2008 to 69% in 2014 (p=0.001). Men on AS were significantly older (64 years, SD 8.0) than those on initial treatment (62 years, SD 7.7; p=0.001). After a median followup of 48 months, 4,337 (51%) patients had discontinued AS. Treatment-free survival for AS patients at 1, 3, and 5 years were 85%, 58% and 52%, respectively. Median time to definitive treatment after initial AS was 16 months (IQR 11-25 months). Factors associated with AS discontinuation were younger age at diagnosis, year of diagnosis, higher comorbidities, treatment at academic center, treatment by physician and institution in the highest volume tertile, and adverse cancer-specific characteristics (higher prostate specific antigen [PSA], higher number of positive cores and higher percentage of core involvement at diagnosis). Although the uptake of AS significantly increased over time, there has been a relatively high rate of discontinuation over 5 years. Factors associated with transition to definitive treatment were younger age, care provided by higher volume physicians and institutions, higher PSA and greater PC volume at diagnosis. These results may help guide policy making, developing quality indicators, and developing targeted continued education for physician and patients embarking on AS to establish realistic expectations.

MP46-18 PATIENTS REPORT SATISFACTION/REGRET FOLLOWING FOCAL THERAPY FOR LOCALIZED PROSTATE CANCER: A PROSPECTIVE MULTICENTER EVALUATION

You have accessJournal of UrologyProstate Cancer: Localized: Ablative Therapy (MP46)1 Sep 2021MP46-18 PATIENTS REPORT SATISFACTION/REGRET FOLLOWING FOCAL THERAPY FOR LOCALIZED PROSTATE CANCER: A PROSPECTIVE MULTICENTER EVALUATION Alireza Ghoreifi, Masatomo Kaneko, Samuel Peretsman, Atsuko Iwata, Aliasger Shakir, Dordaneh Sugano, Jie Cai, Giovanni Cacciamani, Daniel Park, Osamu Ukimura, Duke Bahn, Inderbir Gill, and Andre Luis Abreu Alireza GhoreifiAlireza Ghoreifi More articles by this author , Masatomo KanekoMasatomo Kaneko More articles by this author , Samuel PeretsmanSamuel Peretsman More articles by this author , Atsuko IwataAtsuko Iwata More articles by this author , Aliasger ShakirAliasger Shakir More articles by this author , Dordaneh SuganoDordaneh Sugano More articles by this author , Jie CaiJie Cai More articles by this author , Giovanni CacciamaniGiovanni Cacciamani More articles by this author , Daniel ParkDaniel Park More articles by this author , Osamu UkimuraOsamu Ukimura More articles by this author , Duke BahnDuke Bahn More articles by this author , Inderbir GillInderbir Gill More articles by this author , and Andre Luis AbreuAndre Luis Abreu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002067.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The objective is to evaluate the treatment decision satisfaction and regret among patients who underwent Focal Therapy (FT) for localized prostate cancer (PCa) with high-intensity focused ultrasound (HIFU) or cryoablation (CRYO). METHODS: We identified consecutive patients who underwent hemi-gland HIFU or CRYO FT as primary treatment for localized PCa at three US institutions (IRB# HS-17-00749). A survey with validated questionnaires was mailed between February and December of 2020, including: 5-question Decision Regret Scale (DRS); International Prostate Symptom Score (IPSS); and International Index of Erectile Function (IIEF-5). Potency was defined as IIEF-5 ≥ 18. The regret score was calculated based on the 5 items of DRS (Figure). Agreement with each item is measured on a 5-point scale and the final score is converted to a 0-100 scale. Regret was defined as DRS ≥ 26. Multivariable logistic regression models were applied to assess baseline and post-FT predictors for treatment decision regret. Statistically significant if p<0.05. RESULTS: Out of 236 patients, 143 (61%) responded the survey (71/116 HIFU and 72/120 CRYO). Baseline characteristics were similar between responders and no-responders. For the responders, the median (IQR) follow-up was 43 (26-68) months. The treatment decision regret rate was 19.6%, being CRYO 23.6% vs. HIFU 15.5% (OR 1.7, p=0.22). The Figure shows the details of patients’ responses to each DRS question. Higher PSA at nadir (OR 1.48, 95%CI 1.1-2, p=0.009) post FT, presence of PCa on the follow-up biopsy (OR 3.98, 95%CI 1.5-10.6, p=0.006), higher IPSS after FT (OR 1.18, 95%CI 1.01-1.04, p=0.03), and de-novo impotence (OR 6.67, 95%CI 1.57-27, p=0.03) were independent predictors of treatment decision regret. CONCLUSIONS: Focal therapy for localized PCa is well-accepted by the patients. Higher PSA at nadir, presence of cancer on the follow-up biopsy, higher post-operative IPSS, and de-novo impotence are independent predictors of treatment decision regret. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e820-e821 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Masatomo Kaneko More articles by this author Samuel Peretsman More articles by this author Atsuko Iwata More articles by this author Aliasger Shakir More articles by this author Dordaneh Sugano More articles by this author Jie Cai More articles by this author Giovanni Cacciamani More articles by this author Daniel Park More articles by this author Osamu Ukimura More articles by this author Duke Bahn More articles by this author Inderbir Gill More articles by this author Andre Luis Abreu More articles by this author Expand All Advertisement Loading ...

PD03-02 RACIAL DISPARITIES IN PROSTATE CANCER TREATMENT IN A MULTI-INSTITUTIONAL REGIONAL COLLABORATIVE

You have accessJournal of UrologyHealth Services Research: Practice Patterns, Quality of Life and Shared Decision Making I (PD03)1 Sep 2021PD03-02 RACIAL DISPARITIES IN PROSTATE CANCER TREATMENT IN A MULTI-INSTITUTIONAL REGIONAL COLLABORATIVE Adrien Bernstein, Ruchika Talwar, Elizabeth Handorf, Kaynaat Syed, John Danella, Serge Ginzburg, Laurence Belkoff, Adam Reese, Jeffery Tomaszewski, Eric Singer, Edouard Trabulsi, Bruce Jacobs, Jay Raman, Alex Kutikov, Thomas Guzzo, Robert Uzzo, Marc Smaldone, and Andres Correa Adrien BernsteinAdrien Bernstein More articles by this author , Ruchika TalwarRuchika Talwar More articles by this author , Elizabeth HandorfElizabeth Handorf More articles by this author , Kaynaat SyedKaynaat Syed More articles by this author , John DanellaJohn Danella More articles by this author , Serge GinzburgSerge Ginzburg More articles by this author , Laurence BelkoffLaurence Belkoff More articles by this author , Adam ReeseAdam Reese More articles by this author , Jeffery TomaszewskiJeffery Tomaszewski More articles by this author , Eric SingerEric Singer More articles by this author , Edouard TrabulsiEdouard Trabulsi More articles by this author , Bruce JacobsBruce Jacobs More articles by this author , Jay RamanJay Raman More articles by this author , Alex KutikovAlex Kutikov More articles by this author , Thomas GuzzoThomas Guzzo More articles by this author , Robert UzzoRobert Uzzo More articles by this author , Marc SmaldoneMarc Smaldone More articles by this author , and Andres CorreaAndres Correa More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001967.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Minority communities disproportionately shouldered poor COVID-19 outcomes, however the impact of the pandemic on prostate cancer (PCa) surgery is unknown. To that end, we sought to determine the racial impact on PCa care during the first wave of the pandemic. METHODS: Using a multi-institutional collaborative we evaluated practice patterns for Black and White patients with untreated non-metastatic PCa during the initial COVID-19 lockdown (March-May 2020) compared to prior (March-May 2019). Patient and practice characteristics were compared by race using Fisher’s exact and Pearson’s chi-square to compare categorical variables and Wilcoxon rank sum to evaluate continuous covariates. We determined the covariate-adjusted impact of year and race on surgery, using logistic regression models with a race*year interaction term. RESULTS: Among the 647 men with non-metastatic PCa, 269 received care during the pandemic and 378 prior. Surgery was significantly less likely in Black men (1.3% v 25.9%; p<0.001), despite similar COVID-19 risk factors, biopsy Gleason grade group, and comparable surgery rates prior (17.7% vs. 19.1%; p=0.75). Black men had higher PSA (8.8 vs. 7.2 p=0.04) and were younger (38.2% vs. 24.4% <60 yr; p=0.09). Regression results demonstrated an 94% reduced odds of surgery (OR=0.06, 95% CI 0.007-0.43; p=0.006) for Black patients, with no change for White patients (OR=1.41, 95% CI 0.89-2.21; p=0.142), after adjusting for covariates. Changes in surgical volume varied by site (33% increase to complete shutdown), with sites that experienced the largest reduction in cancer surgery, caring for a greater proportion of Black patients (figure). CONCLUSIONS: In a large multi-institutional regional collaborative, odds of prostatectomy declined only among Black patients during the initial wave of the COVID-19 pandemic. While localized prostate cancer does not require immediate treatment, this study illuminates systemic inequities within healthcare. Public health efforts are needed to fully recognize the unintended consequence of diversion of cancer resources to the pandemic in order to develop balanced mitigation strategies as viral rates continue to fluctuate. Source of Funding: PURC is funded by the Health Care Improvement Foundation through practice participation © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e43-e43 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adrien Bernstein More articles by this author Ruchika Talwar More articles by this author Elizabeth Handorf More articles by this author Kaynaat Syed More articles by this author John Danella More articles by this author Serge Ginzburg More articles by this author Laurence Belkoff More articles by this author Adam Reese More articles by this author Jeffery Tomaszewski More articles by this author Eric Singer More articles by this author Edouard Trabulsi More articles by this author Bruce Jacobs More articles by this author Jay Raman More articles by this author Alex Kutikov More articles by this author Thomas Guzzo More articles by this author Robert Uzzo More articles by this author Marc Smaldone More articles by this author Andres Correa More articles by this author Expand All Advertisement Loading ...

MP67-18 CLINICAL CHARACTERISTICS OF PROSTATE CANCER PATIENTS IN WEST AND SOUTH AFRICA IN THE MEN OF AFRICAN DESCENT AND CARCINOMA OF THE PROSTATE (MADCAP) CONSORTIUM STUDY

MP67-18 CLINICAL CHARACTERISTICS OF PROSTATE CANCER PATIENTS IN WEST AND SOUTH AFRICA IN THE MEN OF AFRICAN DESCENT AND CARCINOMA OF THE PROSTATE (MADCAP) CONSORTIUM STUDY

MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) II (MP24)1 Sep 2021MP24-13 PERCENTAGE AND RATIONALE OF GUIDELINE-DISCORDANT ANDROGEN DEPRIVATION THERAPY IN PROSTATE CANCER PATIENTS Renée Hogenhout, Ivo de Vos, Sebastiaan Remmers, Martijn Busstra, Lionne Venderbos, Monique Roobol, and the ERSPC Rotterdam Study Group Renée HogenhoutRenée Hogenhout More articles by this author , Ivo de VosIvo de Vos More articles by this author , Sebastiaan RemmersSebastiaan Remmers More articles by this author , Martijn BusstraMartijn Busstra More articles by this author , Lionne VenderbosLionne Venderbos More articles by this author , Monique RoobolMonique Roobol More articles by this author , and the ERSPC Rotterdam Study Group More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002015.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recommendations on Androgen Deprivation Therapy (ADT) for prostate cancer (PCa) patients arise from a critical appraisal of scientific evidence which is a lot of work. Despite these efforts, the known side-effects of ADT and the lack of benefit in certain risk groups, guidelines may not always be adhered to. Here, we determined guideline adherence to ADT recommendations and analyzed the physicians’ motivation in case of disconcordance. METHODS: We included subjects from the Rotterdam section of the European Randomized Study of Screening for PCa who were diagnosed with PCa in all stages since the publication of the first EAU guidelines on PCa in 2001 up to and including 2019, and received any form of ADT within the first year after diagnosis. They were categorized into guideline-concordant or -discordant ADT according to the EAU guidelines recommendations within the study period. RESULTS: A total of 1037/3211 (32%) men diagnosed with PCa received ADT within the first year after diagnosis, of which 162/1037 (16%) men received guideline-discordant ADT. In 79% (823/1037) ADT was administered guideline-concordant and in 4% (45/1037) adherence was not assessable due to incomplete medical files. In seven patients (4%) who were unfit/unwilling for curative treatment, lower urinary tract symptoms (LUTS) contributed to the decision to prescribe ADT monotherapy. These cases were also considered as not assessable since LUTS is not clearly defined as “symptomatic” in the guideline. Most of the guideline discordance was noticed in patients receiving ADT monotherapy for intermediate- and high-risk PCa (73%). A common reason for discordant prescription of ADT as monotherapy in this group was suspicion of (lymph node) metastases due to high PSA level (28%). Other reasons were unwillingness (24%) and/or unfitness (51%) to undergo curative treatment without being symptomatic. Three patients (3%) were symptomatic but not unfit or unwilling for curative treatment. In 16% of the discordant cases, prescription of ADT monotherapy was not motivated. CONCLUSIONS: Guidelines and clinical practice do not necessarily correspond. Physicians did not adhere to EAU guidelines on ADT in a Dutch cohort in 16% of the cases. However, guideline-discordant prescription of ADT may not always indicate “inappropriate” treatment. Physicians are able to make a more nuanced clinical assessment taking into account comorbidities, patients’ wishes and social context. Although guidelines support clinical decision-making, better defined and more tailored guidelines are needed. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e416-e417 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Renée Hogenhout More articles by this author Ivo de Vos More articles by this author Sebastiaan Remmers More articles by this author Martijn Busstra More articles by this author Lionne Venderbos More articles by this author Monique Roobol More articles by this author the ERSPC Rotterdam Study Group More articles by this author Expand All Advertisement Loading ...

Validation of Cell-Free RNA and Circulating Tumor Cells for Molecular Marker Analysis in Metastatic Prostate Cancer.

Since tissue material is often lacking in metastatic prostate cancer (mPCa), there is increasing interest in using liquid biopsies for treatment decision and monitoring therapy responses. The purpose of this study was to validate the usefulness of circulating tumor cells (CTCs) and plasma-derived cell-free (cf) RNA as starting material for gene expression analysis through qPCR. CTCs were identified upon prostate-specific membrane antigen and/or cytokeratin positivity after enrichment with ScreenCell (Westford, Massachusetts, USA) filters or the microfluidic ParsortixTM (Guildford, Surrey, United Kingdom) system. Overall, 50% (28/56) of the patients had ≥5 CTCs/7.5 mL of blood. However, CTC count did not correlate with Gleason score, serum PSA, or gene expression. Notably, we observed high expression of CD45 in CTC samples after enrichment, which could be successfully eliminated through picking of single cells. Gene expression in picked CTCs was, however, rather low. In cfRNA from plasma, on the other hand, gene expression levels were higher compared to those found in CTCs. Moreover, we found that PSA was significantly increased in plasma-derived cfRNA of mPCa patients compared to healthy controls. High PSA expression was also associated with poor overall survival, indicating that using cfRNA from plasma could be used as a valuable tool for molecular expression analysis.

The Positive Correlations between the Expression of Histopathological Ubiquitin-Conjugating Enzyme 2O Staining and Prostate Cancer Advancement.

Background: The mTOR signaling pathway is inactivated by AMPK’s tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. Methods: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. Results: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox’s proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. Conclusion: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.