Higher PSA Research Articles

Salvage low dose rate brachytherapy for prostate cancer recurrence following definitive external beam radiation therapy

PurposeWe sought to describe the safety and efficacy of salvage low dose rate (LDR) brachytherapy for local prostate cancer recurrence following definitive RT. Materials and methodsWe included patients from two prospectively maintained institutional databases who underwent salvage LDR brachytherapy for biopsy confirmed intra-prostatic recurrence following primary RT. All patients were without evidence of metastatic disease. Freedom from biochemical failure (FFbF), prostate cancer specific survival (PCaSS), and overall survival (OS) were determined using the Kaplan–Meier estimates. Cox proportional hazard models were used to identify factors predictive of FFbF. Toxicity was graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results108 patients were included. Median follow-up was 6.3 years. The 5- and 10-year actuarial survival outcomes were as follows: FFbF, 63.1% and 52.0%; PCaSS, 90.5% and 77.8%; OS, 80.9% and 56.7%. On multivariate modeling, increasing grade group (HR 1.41, 95% CI 1.02–1.95, p = 0.036) and initial PSA at diagnosis (HR 1.02, 95% CI 1.004–1.05, p = 0.022) were associated with worse FFbF. Grade 3 toxicity occurred in 16.7% of patients; including genitourinary events in 15.7% and gastrointestinal events in 2.8% of patients. IPSS scores increased following implant, peaking at 2 months (median IPSS 20, p = 0.002) and thereafter remaining elevated throughout follow-up. ConclusionsSalvage LDR brachytherapy is safe and efficacious, with acceptable grade 3+ toxicity and good biochemical control on long-term follow-up. Patients with higher grade group and higher PSA at initial diagnosis may be at increased risk for biochemical failure.

Prostat Spesifik Antijenin Akut Üriner Retansiyon Sonrası Üretral Kateter Yerleştirilen ve Benign Prostat Hiperplazisi Olan Hastalarda Prostat Adenokarsinomu Saptamadaki Rolü

Objective : Acute urinary retension (AUR) is one of the most important complications in benign prostate hyperplasia (BPH) patients and its treatment is generally urethral catheterization in acute period. There are studies showing that AUR and urethral catheter placement may cause an increase in serum PSA levels. Our objective in this study was to investigate the relation between increased PSA levels and prostate cancer (PCa) incidence in the patient group after AUR and urethral catheter placement. Materials and Methods : 77 patients who had an indwelling urethral catheter due to AUR, performed prostate biopsy due to high PSA levels and then surgical treatment for clinic BPH were retrospectively examined. Age, prostate volumes, pre-biopsy total serum PSA and PSA densities were noted. Total serum PSA rates, PSA densities and prostate volumes were compared for the groups that PCa was detected (n=6) and not detected (n=71) according to biopsy or surgical specimen results. Results : Mean age of the patients was 65.2±3.9 years. Mean prostate volume was measured as 64.1±12.8 g, mean serum total PSA level as 9.2±4.2 ng/mL and mean serum PSA density as 0.15±0.08 mg/mL/g. In PSA groups with a serum total PSA level of ≤4.0, 4-10, 10-20 and >20, PCa prevalence rates were detected 0%, 4.3%, 13.4% and 20%, respectively. Total PSA levels and PSA densities were found statistically higher in PCa detected group. Conclusion : PCa incidence is low in patients who were placed urethral catheter after AUR. For these patients prostate biopsy should be performed only in chosen cases.

Correlation between peripheral blood neutrophil-lymphocyte ratio and CD34 expression in prostate cancer

BackgroundsThe association of neutrophil-lymphocyte ratio (NLR) and CD34 expression level with PSA level, Gleason score, and clinical stage was investigated in patients with prostate cancer. The correlation between NLR and CD34 expression was also investigated to provide evidence supporting the use of NLR for predicting the prognosis of prostate cancer patients.MethodsClinical data of 75 patients diagnosed with prostate cancer by prostate aspiration biopsy were retrospectively analyzed. The correlation between NLR, CD34 expression, and clinicopathological characteristics was analyzed using the χ2 test and one-way analysis of variance. The correlation between NLR and CD34 was determined using the Pearson coefficient. Disease free survival was estimated by Kaplan-Meier analysis.ResultsBoth NLR and CD34 expression were significantly positively correlated with PSA, Gleason score, and clinical stage (P < 0.05 both). Patients in the NLRHigh/CD34High group were characterized by high PSA level and Gleason score and late clinical stage. NLR was positively correlated with CD34 expression (r = 0.529, P < 0.001).ConclusionsPretreatment NLR was a valuable marker of prognosis in prostate cancer. NLR is positively correlated with CD34 expression.

The clinical status and working capacity in patients included in the All-Russian Psoriatic Arthritis Registry

Objective: to study the clinical characteristics of PsA and working capacity in patients included in the All-Russian PsA Registry.Patients and methods. The investigation enrolled 614 patients aged 19–84 years with psoriasis from 39 subjects the Russian Federation, who were followed up in the All-Russian PsA Registry. On the basis of the assessment of demographic data, the spectrum of comorbidities, the degree of activity of the underlying disease according to Disease Activity Index for PsA (DAPSA) and Disease Activity in 28 joints (DAS28), clinical, functional, and social indicators were analyzed in the patients. The investigators studied information on the patients employment, working capacity, and disability, by assessing the group of the latter. The health status and the presence and severity of functional impairment in the patients were analyzed using the Health Assessment Questionnaire (HAQ), while their working efficiency was estimated according to the Workers Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP questionnaire), by calculating the following parameters: absenteeism, presenteeism, an overall decrease in labor productivity, and impairment in daily functional activity.Results and discussion. The analysis of the All-Russian PsA Registry showed that most of them were of working age (30 to 59 years); 48.4% had concomitant diseases. Data on DAPSA changes were obtained in 349 patients, who were recorded to have mainly moderate (34.7%) or high (42.7%) disease activity, multiple dactylitides and enthesitides, and limited joint function. The registry reflects information on the social status of 521 patients: employed (61.2%) and unemployed (22.1%) persons, pensioners (15.2%), and students (1.5%). More than one third (37.1%) of patients with PsA had disability, mainly of Group III. The changes in the HAQ disability index were assessed in 326 patients; mild, moderate, and severe functional impairments were observed in 36, 26.4, and 3.7%, respectively. Absenteeism was detected in less than one third of patients with PsA, presenteeism was found in about half; there was an overall decrease in labor productivity in more than 60% and daily activity impairment in 68.8%. Statistically significant direct moderate correlations were established between the indicators of PsA activity (DAPSA and DAS28) and the level of productivity impairment in the patients; this was mostly related to an overall decline in labor productivity and to a decrease in daily activity.Conclusion. The data obtained from real clinical practice suggest that half of the PsA patients had high disease activity and a third had severe functional impairment, which led to a lower quality of life and to disability. The overall decrease in labor productivity and daily activity, which was detected in more than half of the patients, was associated with high PsA activity. The follow-up in the All-Russian PsA Registry, regular anti-inflammatory therapy with disease-modifying antirheumatic drugs and biological agents can improve the clinical and functional status and, consequently, working capacity in patients with PsA.

Abstract 3513: Genome-wide scan for novel prostate cancer susceptibility loci with clinical consequence utilizing increased genetic drift of the Finnish population

Abstract Background: Prostate cancer (PC) is the second most common cancer in men worldwide with a rising prevalence. However, only limited number of clinically actionable variants are known. The objective of this study is to identify novel PC susceptibility loci with potential clinical relevance utilizing the increased genetic drift and reduced selective pressure of the recently bottlenecked powerful resource of the Finnish population. Methods: We meta-analysed &amp;gt;185.000 germline single nucleotide polymorphisms (SNPs) in 2738 PC cases and 2401 controls of Finnish origin in the Collaborative Oncological Gene-Environment Study (COGS) using Illumina iSelect custom SNP genotyping platform. Results: Altogether 160 variants remain significant on GWAS level (p&amp;lt;5 × 10−8) in 18 different gene regions. Out of the 160 identified PC susceptibility hits 78 (49%) are novel variants not reported earlier in association with PC. PC associated signals are in close proximity to one another forming genetic hot-spots on chromosomes 8, 7, 11, 17 and 19. The strength of association varies for 101 PC risk variants (OR 1.24-1.86) and 59 protective SNPs (OR 0.59-0.80). The strongest risk gene is CASC8 (OR=1.86; p=1.214 × 10−11). The most significant signals were found at the 8p21.2 chromosomal region (p&amp;lt;7.6 × 10−16). Functional annotation identified a missense coding SNP at KLK3 gene to be a candidate causal variant. We showed evidence for association both with early-onset PC (OR 1.73; P=0.02), high serum PSA level at diagnosis (OR 1.36; P=0.024) and with aggressive PC (Gleason score ≥8; OR 1.44; P=0.02) at 17q21. Conclusion: The results facilitate risk stratification for screening, clinical studies, treatment choices and functional research of PC Citation Format: Csilla Sipeky, Teuvo L. Tammela, Anssi Auvinen, Johanna Schleutker. Genome-wide scan for novel prostate cancer susceptibility loci with clinical consequence utilizing increased genetic drift of the Finnish population [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3513.

The effect of delaying transperineal fusion biopsy of the prostate for patients with suspicious MRI findings—Implications for the COVID-19 era

ObjectiveImage guided biopsies are an integral part of prostate cancer evaluation. The effect of delaying biopsies of suspicious prostate mpMRI lesions is uncertain and clinically relevant during the COVID-19 crisis.We evaluated the association between biopsy delay time and pathologic findings on subsequent prostate biopsy. Materials and methodsAfter obtaining IRB approval we reviewed the medical records of 214 patients who underwent image-guided transperineal fusion biopsy of the prostate biopsy between 2017 and 2019.Study outcomes included clinically significant (ISUP grade group ≥2) and any prostate cancer on biopsy. Logistic regression was used to evaluate the association between biopsy delay time and outcomes while adjusting for known predictors of cancer on biopsy. ResultsThe study cohort included 195 men with a median age of 68. Median delay between mpMRI and biopsy was 5 months, and 90% of patients had a ≤8 months delay. A significant association was found between PI-RADS 5 lesions and no previous biopsies and shorter delay time.Delay time was not associated with clinically significant or any cancer on biopsy. A higher risk of significant cancer was associated with older age (P = 0.008), higher PSA (0.003), smaller prostate volume (<0.001), no previous biopsy (0.012) and PI-RADS 5 lesions (0.015). ConclusionsOur findings suggest that under current practice, where men with PI-RADS 5 lesions and no previous biopsies undergo earlier evaluation, a delay of up to 8 months between imaging and biopsy does not affect biopsy findings.In the current COVID-19 crisis, selectively delaying image-guided prostate biopsies is unlikely to result in a higher rate of significant cancer.

Salvage I-125 brachytherapy for locally-recurrent prostate cancer after radiotherapy.

Retrospective, single-institution analysis of clinical outcomes and treatment-related toxicity in patients treated with salvage I-125 low-dose rate (LDR) brachytherapy (BT) for locally-recurrent prostate cancer after radiotherapy. Between 2008 and 2018, 30 patients with biopsy-confirmed prostate cancer recurrence underwent salvage treatment with I-125 LDR-BT. Of these 30 patients, 14 were previously treated with primary external beam radiotherapy (EBRT; median dose, 73 Gy) and 16 with primary I-125 LDR-BT (145 Gy and 160 Gy in 14 and 2 cases, respectively). At seed implantation, the mean age was 75.8 years, with a median Gleason score of 7 and pre-salvage PSA of <10 ng/mL. Six patients received androgen deprivation therapy for six months after relapse diagnosis. The prescribed salvage I-125 BT dose to the gland was 120-130 Gy, with dose restrictions of Dmax <135% (urethra) and <100% (rectum). Toxicity was evaluated according to the CTCAE scale (v4.0). At a median follow-up of 45 months, the biochemical recurrence-free survival rates at 1, 3 and 5 years were 86.7%, 56.7% and 53.3%, respectively. Overall survival at 5 years was 87%. On the multivariate analysis, two variables were significant predictors of recurrence: PSA at relapse and nadir PSA post-salvage. Grade 3 genitourinary toxicity was observed in 5 patients (radiation-induced cystitis in 3 cases and urethral stenosis in 2) and G3 gastrointestinal toxicity in 3 patients (rectal bleeding). Salvage therapy with I-125 brachytherapy is a safe and effective treatment option for locally-recurrent prostate cancer in previously-irradiated patients. High pre-salvage PSA and post-salvage nadir PSA values were significantly associated with a worse disease control after salvage I-125 LDR-BT. In well-selected patients, I-125 LDR-BT is comparable to other salvage therapies in terms of disease control and toxicity. However, more research is needed to determine the optimal management of locally-recurrent prostate cancer.

The value of a first MRI and targeted biopsies after several years of active surveillance for low-risk prostate cancer – results from the SAMS trial

ObjectiveTo assess the value of a first MRI examination and image-fusion-guided biopsies in men with low-risk prostate cancer who have been on active surveillance (AS) for several years with no signs of progression.Patients and MethodsAll 45 participants from two centers who had not previously had an MRI were included. They had been on AS for T1c Gleason score 6 prostate cancer for 2.6 to 6.7 years and had 2 to 5 sets of systematic biopsies with a total of 1640 cores. All underwent a bi-parametric MRI, PI-RADS ≥ 3 lesions were targeted with image-fusion-guided biopsies. Primary outcome measure: detection of Gleason score ≥7 cancer.ResultsTwenty-five of the 45 men (56%) had a total of 30 suspicious MRI lesions. The lesion with the highest score was a PI-RADS 3 in 18, a PI-RADS 4 in 5 and PI-RADS 5 in 3 men. Targeted biopsies from the 30 lesions detected Gleason score 7 cancer in 6 men. Of these six cancers, four were located in the apical and one in the anterior/apical part of the prostate. A Gleason score 7 cancer was detected in 3 of 5 men with PSA density >0.15 ng/ml/cm3.ConclusionsEven after several years of AS with stable PSA values and many sets of systematic biopsies, a first MRI and targeted biopsies lead to the detection of Gleason score 7 (ISUP 2 and ISUP 3) cancer in a significant proportion of men, particularly among those with a high PSA density.

The significance of a high preoperative PSA level for the detection of incidental prostate cancer in LUTS patients with large prostates.

To evaluate the diagnostic value of a high preoperative PSA level for the detection of incidental prostate cancer (iPCa) in LUTS patients with very large prostates (> 100cc). We conducted a retrospective analysis of 1125 men treated for LUTS with holmium laser enucleation of the prostate (HoLEP). Patients were stratified according to a preoperative PSA level higher (high PSA; n = 365) or lower than 10ng/ml (low PSA; n = 760). Preoperative and histopathological parameters were compared between both cohorts. Logistic regression models were used to identify independent predictors of iPCa. Demographic parameters were similar between both cohorts. The median PSA levels were 14.2ng/ml (11.5-19.9) and 4ng/ml (2.4-6.0). The prostate volume was significantly higher in the high PSA group (105cc vs. 75cc; p < 0.001). Correspondingly, the PSA density was significantly increased in the high PSA cohort compared to the low PSA cohort (0.14 vs. 0.05; p < 0.001). The overall detection rate of iPCa showed no difference between groups (9.5% vs. 9.9%). More preoperative prostate biopsies were performed in the high PSA group compared to the low PSA group (46.8% vs. 17.6%; p < 0.001). However, the rate of false negative results was comparable between groups (12.7% vs. 11.1%; p = 0.726). In logistic regression models all PSA-related parameters failed to predict iPCa. PSA-guided approaches to predict iPCa in LUTS patients with very large prostates are not accurate. This finding is useful in clinical practice for counselling our patients and to prevent unwarranted diagnostic procedures.

Abstract A066: Performance of the prostate health index (PHI) assay in black men

Abstract Introduction: The low specificity of PSA in prostate cancer (PCa) screening has caused excessive biopsies and PCa over-detection. PHI is more specific for clinically significant (cs) PCa (i.e. Gleason &amp;gt;6 PCa) and includes serum PSA, [-2]proPSA, and free PSA in its formula. Validation studies in diverse populations have suggested that PHI should be used as a reflex test and the optimal cutoffs for PHI vary across ethnic groups, but have not been determined in Black men. We sought to 1) assess the distributions of PHI and PSA in healthy controls and men with high-grade PCa and 2) assess the accuracy of PHI vs. PSA for detection of csPCa in Black men with elevated PSA. Methods: The present study population consists of two biopsy-naïve cohorts. The first cohort serves as healthy controls and includes Black men with PHI and PSA drawn at community screening events through the social networks of eight lay Black male Citizen Scientists. The second PHI Biopsy Study cohort consists of Black men referred with elevated PSA and/or abnormal digital rectal exam (DRE) who had PHI drawn immediately before prostate biopsy. We excluded men with prior biopsies or known PCa. Distributions of PHI and PSA were compared across controls and men with negative biopsies, Gleason 6 PCa and csPCa. Among men with biopsy, we compared the area under the receiver operating characteristics curves (AUC) for PSA and PHI for detecting csPCa and assessed specificity at selected sensitivities as a proxy of avoided biopsies. We descriptively assessed theoretically avoided biopsies and missed csPCa at previously established PHI cut points [27.0, 28.6, 29.9, and 35.0]. Results: For the first objective, 139 men (42.5%) were included as controls from the Citizens Scientist Study and 188 (57.5%) were from the PHI Biopsy Study cohort, out of which 82 (43.6%) had a negative biopsy for PCa, 40 (21.1%) had low-grade PCa, and 66 (35.1%) had a Gleason &amp;gt;6 PCa. Compared to the healthy control group, the PHI Biopsy Study cohort was older (median age 61 vs. 55 years), with higher PSA levels (7.1ng/mL vs. 0.9ng/mL) and PHI scores (61.1 vs. 20.1), and more commonly had a family history of PCa (19.4% vs. 5.0%) and benign prostatic hyperplasia diagnosis (21.3% vs. 2.2%) (all p&amp;lt;0.001). Relative to PSA, PHI has a higher degree of overlap in the distribution between controls and csPCas (p &amp;lt;0.05), suggesting PHI would not perform well as a primary screening test in Blacks. In men with PSA between 4-10, PHI outperformed PSA in the detection of HGPCa with an AUC of 0.70 (95% CI: 0.59-0.81) compared to 0.57 (95% CI: 0.46-0.69). As a reflex test in men with PSA of 4-10ng/mL and normal DRE, a PHI cutoff of 35.0 would spare 20 (27.8%) low-risk men a biopsy while missing 2 (7.4%) csPCas. Conclusion: PHI should not be used for primary screening but has higher accuracy and specificity than PSA in Black men with PSA levels of 4-10ng/mL as a reflex test. At a cutoff of 35.0, 28% of low-risk men avoid biopsy while missing 7% of csPCas. Citation Format: Samuel Carbunaru, Oluwarotimi Nettey, Edward M Schaeffer, Peter H Gann, Michael Abern, Courtney M.P Hollowell, Karriem Watson, Tiffany McDowell, Rick A Kittles, Adam B Murphy. Performance of the prostate health index (PHI) assay in black men [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A066.

Abstract D124: Racial differences in adverse pathology among men with prostate cancer at time of radical prostatectomy

Abstract Objective: For black men, the concern that they are at greater risk of worse oncologic outcomes for prostate cancer compared to white counterparts may drive the greater push to surgery although reasons are likely multifactorial. While adverse pathology is associated with worse survival, data surrounding race-based differences in rates of adverse pathology is limited. We aim to examine the association between race and adverse pathology on surgical pathology among black and white men with prostate cancer. Methods: Using our institutional prospective oncologic database, we identified 3,826 patients diagnosed with prostate cancer since 1990 and underwent primary RP. Adverse pathology was defined as GS&amp;gt;=4+3 or pT3/4 or pN1 on surgical pathology. Race was dichotomized as black or non-Hispanic white. Multivariable logistic regression modeling was utilized to examine the association between race and AP after adjusting for age, year of diagnosis, and clinical risk by UCSF-CAPRA category (low 0-2, intermediate 3-5, or high 6-10). PIRADS and GPS scores were not included in the regression models due to the limited sample size. There was no significant effect of interaction between race and CAPRA, therefore no interaction term was included in the regression analysis. Results: Of 3826 patients included, 3682 (96%) were white and 144 (4%) were black. At diagnosis, mean age was 60.4 years (SD 7.1), median PSA density was 0.19 (IQR 0.13-0.20), and most were intermediate- (44%) or high-risk (15%) by CAPRA. Mean GPS scores was 26.85 (SD 12). The majority of those who underwent prostate MRI had PIRADS 4-5 lesions (89% vs 7% PIRADS 3, 4% PIRADS 1-2). Most had a systematic ultrasound-guided prostate biopsy alone (98%, 1% TRUS targeted alone, 1% MRI-TRUS fusion biopsy). Compared to white counterparts, black men were younger (53% &amp;lt;60 years vs 43%, p=0.02) with higher PSA density (PSAD 0.25 vs PSAD 0.19, p&amp;lt;0.01), and a larger proportion was high-risk by CAPRA (24% vs 15%, p=0.03) at diagnosis. PI-RADS at diagnosis, Genomic Prostate Score at diagnosis, and rate of targeted biopsy at did not differ significantly by race. Post-RP, pathologic Gleason grade, T-stage, and positive surgical margins rates were similar between races (p&amp;gt;0.05 for all). Nodal disease was more common in black men compared to white counterparts (8% vs 5%, p&amp;lt;0.01) On multivariate analysis, black race was not associated with higher risk of AP (OR 1.04, 95% CI 0.67-1.61, p=0.86) after adjusting for age, clinical CAPRA score, and year of diagnosis. Conclusions: Black race was not associated with increased risk of AP at RP compared to white counterparts after adjusting for clinical factors. While race-based differences in oncologic outcomes exist, this study supports the growing body of research challenging the prior attribution of these differences solely on biology. Further investigation into how multiple factors such as biology/genetics, quality of care, social environment, and health-related behaviors may interact to contribute to these observations is warranted. Citation Format: Sikai Song, Janet Cowan, Shoujun Zhao, Matthew R Cooperberg, Peter R Carroll, Samuel L Washington. Racial differences in adverse pathology among men with prostate cancer at time of radical prostatectomy [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D124.

Superscan: Superiority of xSPECT/CT over OSEM SPECT/CT in bone scans of prostate cancer patients.

Prostate cancer is one of the most common cancers affecting men. Bone scan is part of the staging modality commonly used to evaluate bone metastasis. A bone scan with diffused increased skeletal tracer uptake relative to soft tissue, combined with faint renal activity is known as a superscan. However, a primary concern are false negatives associated with bone scans, where diffuse metastasis is indistinguishable on superscans. In this study, we performed xSPECT/CT Bone and standard OSEM SPECT/CT reconstruction algorithm in ten prostate cancer patients with high PSA levels, where they initially seem relatively unremarkable on planar images. All patients with extensive bone metastases showed either relatively unremarkable scans or did not demonstrate the true extent of metastatic burden as seen on planar images. Uptake was further confirmed by the correlative diffuse bone lesions on CT images. Our reports also indicated that xSPECT/CT reconstructed images were far superior in delineating focal areas of osteoblastic bone metastasis, when compared with whole body planar images or SPECT/CT images. The extent of metastatic evidence is delineated with excellent clarification by xSPECT/CT images. We propose that whole body xSPECT/CT image reconstruction, or at least SPECT/CT, should be performed in patients with high PSA levels, along with planar imaging, to improve diagnostic accuracy of bone scans in prostate cancer staging.

Accuracy of 68Ga-PSMA-11 for pelvic nodal metastasis detection prior to radical prostatectomy and pelvic lymph node dissection: A multicenter prospective phase III imaging study.

5502 Background: To determine the accuracy of 68Ga-PSMA-11 PET for the detection of pelvic nodal metastases (N1) compared to histopathology at time of radical prostatectomy (RP). Methods: This is a prospective multicenter single-arm open-label phase 3 imaging trial. Patients with intermediate to high risk prostate cancer (PCa) considered for RP with lymph node dissection (PLND) were enrolled at the University of California, Los Angeles (UCLA) and at the San Francisco (UCSF) (NCT03368547, NCT02611882, NCT02919111), and underwent one 68Ga-PSMA-11 PET. The primary endpoint was the sensitivity (Se) and specificity (Sp) of 68Ga-PSMA-11 PET for the N1 detection compared to PLND histopathology (reference-standard) on a per patient basis using nodal region-based correlation. Each scan was read by three blinded independent central readers (BICR). Consensus was based on majority rule. Results: From December 2015 to August 2019, 633 patients underwent one 68Ga-PSMA-11 PET for primary staging, and 277/633 (44%) subsequently underwent RP and PLND. The median initial PSA was 11.1 [0.04-147]. 75/277 patients (27%) had N1 disease per histopathology. Using a regional based analysis, Se, Sp, positive predictive value (PPV) and negative predictive value (NPV) for N1 detection was 0.40 [0.34, 0.46], 0.95 [0.92, 0.97], 0.75 [0.70, 0.80], 0.81 [0.76, 0.85], respectively. Se was higher for patients with higher PSA: 0.29 [0.24, 0.35] for PSA &lt; 11 ng/ml versus 0.48 [0.42, 0.54] for PSA &gt; 11. Se was higher when the nodes were larger: 0.30 [0.25, 0.36] for nodes &lt; 10 mm versus 0.68 [0.63, 0.74] for nodes &gt; 10. The average node size in true positive patients was 10 mm versus 4 mm in false negative patients. Conclusions: In intermediate to high risk PCa patients who underwent RP and PLND, 68Ga-PSMA-11 PET detected pelvic nodal metastases with a sensitivity of 0.40 and a specificity of 0.95. Higher PSAs and larger node size correlated with increased sensitivity. Clinical trial information: NCT03368547, NCT02611882, NCT02919111 .

A prospective phase I trial of dendritic cell-based cryoimmunotherapy in metastatic castration-resistant prostate cancer.

3029 Background: Dendritic cell (DC)-based cryoimmunotherapy (CryoIT) was used to treat metastatic castration-resistant prostate cancer in a Phase I clinical trial. Primary objective was safety of treatment. Secondarily, clinical, radiological and immunological treatment responses were investigated. Methods: In 18 patients cryoablation by a freeze-thaw process under general anesthesia was performed, followed by intratumoral autologous immature DC injection. In the last 9 patients checkpoint inhibition of either CTLA-4 or PD-1 was added. Subjects had minimum 46 weeks follow-up. Adverse events (AEs) and blood analyses were registered at all visits. Disease progression was determined by three imaging modalities according to (i)RECISTv1.1 and progression-free survival (PFS) by Kaplan-Meier method. Circulating tumor cells (CTC/7.5 mL, CellSearch) and ultradeep T-cell receptor (TCR) b-chain sequences (TCRSafe) were enumerated. Patients were separated by CTC into none (n=10), 1-4 (n=4) and ≥ 5 (n=4). Health related quality of life (HRQoL) measured by EORTC-QLQ C30 questionnaire were answered at inclusion, and 10, 22 and 46 weeks post CryoIT. Scores were calculated according to the EORTC manual. Results: Subjects progressing within 22 weeks had higher PSA (p=0.03). AE profile of the total cohort (n=18) was comparable with interim reports (n=13); of 20 possible DC-related AEs one was severe (urinary retention) and 19 mild-to-moderate, and spread independent of treatment regime. Maximum tolerated dose of DC was not reached. By 46 weeks, imaging showed 6 patients partial response or stable disease. Median PFS was 150 days in total cohort. Pretreatment CTC counts ≥5 indicated higher progression rates and recurring CTC. Ultradeep TCR-sequencing showed more prevalent and higher expressed (&gt;5-fold) new TCR clonotypes at 2-6 weeks in men without progression. Participants reported high and stable HRQoL scores throughout the study. However, presence of CTC was associated with worse HRQoL scores at week 10 (p=0.031) and 22 (p=0.005). Conclusions: DC treatment seems safe and well tolerated, also combined with checkpoint inhibitors. Effect is indicated in subjects with moderate pre-treatment PSA levels. Immune responses are suggested by higher number of novel TCR clonotypes in men with non-progressive disease. Clinical trial information: NCT02423928 .

Clinical, genetic, and pathologic determinants of prostate cancer brain metastasis.

5536 Background: Prostate cancer (PCa) brain metastasis (BM) is a rare event occurring in 0.16-0.63% of PCa patients. Current clinical data on this phenomenon is limited to small retrospective cohorts and our understanding of it is incomplete. We sought to identify clinical and molecular predictors of PCa BM in a large retrospective cohort treated at our institution. Methods: Men diagnosed with Pca from 1995-2017 with ≥6 months of follow-up were included. Data was collected on clinical and tumor characteristics at diagnosis, PCa treatment, brain and bone metastasis, and tumor genetic profile based on Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) analysis. Results were examined using Kyoto Encyclopedia of Genes and Genome (KEGG) pathway. Genes altered in ≥5% of patients were included. Time to brain metastasis (TTBM) and overall survival (OS) were analyzed with univariable (UVA) Fine-Gray competing risks regression and Cox proportional hazards. TTBM and OS were landmarked at 6 months after PCa diagnosis. False discovery rate (FDR) adjustment accounted for multiple comparisons. Results: 27,887 men met inclusion criteria; 74 developed BM. Clinical variables associated with increased hazard of TTBM in UVA were high-clinical and pathologic-* (p&lt;.001) T stage, node-positive disease* (p&lt;.001), primary* and total* Gleason (p&lt;.001), receipt of abiraterone* (HR 52.51 (95% CI 7.1-389.8), p&lt;.001), and receipt of leuprolide* (HR 3.0 (95% CI 1.7-5.4), p&lt;.001). Tumor alterations associated with BM include mutations in BRCA2 (HR 2.94 (95% CI 1.1-8.0), p=.04), MYC (HR 3.41 (95% CI 1.2-9.5), p=.02), PTEN (HR 2.90 (95% CI 1.2-6.9), p=.02), RB1 (HR 3.09 (95% CI 1.2-8.0), p=.02), and pathways involving homologous recombination (HR 2.70 (95% CI 1.1-6.4), p=.02), Fanconi anemia* (HR 4.22 (95% CI 1.8-10.0), p&lt;.001), Ras signaling* (HR 4.6 (95% CI 1.5-13.9), p=.006), mTOR signaling (HR 2.88 (95% CI 1.1-7.9), p=.04), VEGF signaling* (HR 3.60 (95% CI 1.5-8.8), p=.005), and GnRH signaling* genes (HR 3.93 (95% CI 1.6-9.6), p0.003). Variables associated with increased hazard of BM after FDR adjustment are denoted with an asterisk. Variables associated with reduced OS after FDR adjustment were neuroendocrine or blastoma histology, node-positive disease, high-T stage, high initial PSA, receipt of leuprolide, and alterations in AR, TP53, and CDK12 genes. Conclusions: PCa BM is significantly associated with high-stage and grade disease, receipt of androgen deprivation agents such as abiraterone and leuprolide, and alterations in the Fanconi anemia, Ras, VEGF, and GnRH pathways.

Clinical analysis of the extracellular vesicle-fingerprint score blood test to refine the prediction of clinically significant prostate cancer and avoid prostate biopsy.

5530 Background: The accuracy of the extracellular vesicle-fingerprint score (EV-FPS) test to predict clinically significant prostate cancer (PCa; Gleason grade (GG) ≥ 3) from indolent disease (GG ≤ 2) and avoid unnecessary prostate biopsies was determined at the point of prostate biopsy decision. Methods: Clinical data, health information, and blood samples were collected from a prospective validation cohort of 415 men, without prior PCa diagnosis, referred to urology clinics for prostate biopsy or transurethral prostate surgery (June 2014-Dec 2016). The patient’s EV-FPS risk score was calculated by combining machine learning model-analyzed microflow cytometry data from EV biomarkers with logistic regression-analyzed patient-centric clinical features. The plasma-derived EV biomarkers were prostate-specific membrane antigen, polysialic acid and ghrelin-growth hormone receptor. The patient clinical features were; age, ethnicity, PCa family history, PSA levels, abnormal digital rectal examination (DRE) and prior negative prostate biopsy. Together, the biomarkers and clinical features provided specificity for clinically significant PCa. Results: The EV-FPS test identified clinically significant PCa patients with high accuracy (0.81 area under curve) at 95% sensitivity and 97% negative predictive value. Using a 7.85% probability cut-off after test validation; 95% of the patients with GG ≥ 3 would have been found before biopsy, 35% biopsies would have been avoided and diagnosis of GG ≥ 3 PCa would have been missed in only 5% of the cohort. Conclusions: This minimally invasive EV-FPS test accurately predicted clinically significant PCa in men with high EV-FPS risk scores, high PSA level and/or abnormal DRE. Therefore, men with low EV-FPS risk scores could potentially avoid unnecessary prostate biopsies. Clinical care cut-offs to calculate the number of biopsies that could have been avoided, and the percentage of GG ≥ 1 to GG ≥ 3 PCa that could have had a delayed diagnosis. [Table: see text]

CARD: Overall survival (OS) analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel versus abiraterone or enzalutamide.

5569 Background: The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing ≤ 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel (25 mg/m2 IV Q3W + daily prednisone + prophylactic G-CSF) vs. abiraterone (1000 mg PO + daily prednisone) or enzalutamide (160 mg PO). OS was calculated from date of diagnosis of metastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis, low hemoglobin, high baseline neutrophil to lymphocyte ratio, and high PSA values at baseline were associated with worse OS. In presence of these factors, the OS benefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), whatever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691 . [Table: see text]

The role of programmed death-ligand 1 and non-epithelial circulating tumor cells in locally advanced prostate cancer.

e17557 Background: Circulating tumor cells (CTCs) is considered as an effective prognostic biomarker in malignancies. It is recently recognized that detections of programmed death-ligand 1 (PD-L1) and mesenchymal markers in CTCs may improve the predictive value. Therefore, we aimed to determine the cut-off values of these CTCs biomarkers in prostate cancer (PCa), assess the rates of PD-L1 positive and non-epithelial (NE) subgroup in CTCs among patients with high-risk (HRPC) and locally advanced PCa (LAPC) before surgery, and evaluate the clinical values of these markers. Methods: Four PCa cell lines selected from Cancer Cell Line Encyclopedia were applied in spiking experiments to establish the cut-offs of PD-L1 positive and NE CTCs. 182 HRPC and 89 LAPC patients were enrolled from June 2016 to December 2018. All patients underwent radical prostatectomy after blood sample collection. CTCs enumeration and biomarkers identification were conducted by Canpatrol CTC enrichment system and the RNA in situ hybridization technique. Lastly, using the cut-offs,we evaluated the association between CTCs markers and other variables in terms of clinical data, disease outcome, tumor tissues immunochemistry (IHC) staining, and the response of immunotherapy. Results: The cut-offs were determined as the lowest rates of NE and PD-L1+ CTCs among the cell lines, 45% and 25%, respectively. In HRPC patients, a higher PSA level and more advanced T stage were observed in the NE CTCs positive group (≥45%), compared with the negative group ( P= 0.041 and P= 0.004). Multivariate analysis showed that the NE CTCs rate, instead of total CTCs number, was an independent risk predictor for progression-free survival (PFS) (HR = 3.85, P= 0.013). In LAPC patients, the PD-L1+ CTCs positive group (≥25%) presented a higher PSA level and higher percentage of lymph node metastasis than negative group ( P= 0.027 and P= 0.028). The median PFSs between the two groups were 16.6 mouths vs. 21.8 mouths, respectively. (HR = 2.87, P= 0.002 ). No significant correlation was found between PD-L1 expression in CTCs and in tumor tissue IHC staining. However, we observed a significant correlation between PD-L1+ CTCs rate and ERG or PTEN expression in tissues ( P= 0.010 and P= 0.009). In addition, patients in PD-L1+ CTCs positive group presented a better PSA response to Durvalumab treatment than those in negative group. Conclusions: PD-L1+ and NE CTCs were an effective prognosis predictors for HRPC and LAPC patients with radical prostatectomy. LAPC patients with PD-L1+ CTCs might benefit from adjuvant immunotherapy

Factors associated with appropriate and low-value PSA testing

BackgroundProstate-specific antigen (PSA) testing for early detection of prostate cancer is low-value when it is not indicated by guidelines and the harms outweigh the benefits. In this retrospective cohort study, we identify provider and patient factors associated with PSA testing, particularly in situations where testing would be low-value. MethodsWe used electronic health record data from 2011 to 2018 representing 1,738,021 health system encounters in the United States. Using logistic generalized estimating equation models, we examined patient factors (age, comorbid illness, family history, race and prior PSA results), provider factors (gender, specialty, graduation year and medical school rank), and overall time trends associated with PSA testing in low-value and appropriate settings. ResultsComorbid illness (odds ratio (OR) 0.0 for 3+ conditions vs none) and no prior PSA testing (OR 0.2) were associated with a lower likelihood of PSA testing in low-value situations, while family history of prostate cancer (OR 1.6) and high prior PSA test results (OR 2.2 for PSA > 6 vs 0–1) were associated with a greater likelihood. Men aged 55–65 years were at greatest risk for PSA testing in low-value situations.The provider factor associated with PSA testing in low-value situations was specialty, with urologists being most likely (OR 2.3 versus advanced practice providers). Internal medicine physicians were more likely to perform PSA testing during low-value situations (OR 1.3 versus advanced practice providers) but much more likely to order a PSA test where appropriate (OR 2.2). All PSA testing decreased since 2011. ConclusionWe identified several patient and provider factors associated with PSA testing in low-value settings. Some aspects suggest attention to relevant factors for PSA testing in low-value settings (e.g. comorbid illness), while others may encourage PSA testing in low-value settings (e.g. family history). The greatest likelihood of PSA testing in low-value settings is among men within the age range most commonly recommended by guidelines.

MP56-16 A NEW SCORING SYSTEM USING PROSTATE IMAGING REPORTING AND DATA SYSTEM (PI-RADS) TO DETECT SIGNIFICANT CANCER FOR MAGNETIC RESONANCE IMAGING-TARGETED PROSTATE BIOPSY

INTRODUCTION AND OBJECTIVE: Prostate Imaging Reporting and Data system (PI-RADs) is associated with significant cancer (SC) detection. Although PI-RADs≥ 3 is considered to be positive, there are many reports suggesting the significant different of the detection rates of SC between PI-RADs 3 and 4-5. In using PIRADs for MRI-targeted prostate biopsy (TgB), what kind of men have SC have been not fully examined. In this study, we examined the detective ability between PI-RADs 3/4-5 and developed a new scoring system for prediction for SC detection of TgB using PI-RADs. METHODS: Between April 2013 and April 2019, 470 men with PSA <20 ng/mL received TgB. PI-RADs ver. 2 was used and considered as positive in ≥3. TgB was performed 4 cores for a lesion and TgB was performed for each lesions with multiple positive PI-RADs. SC in this study was defined as Gleason Score ≥ 3+4 or maximum cancer length ≥ 5 mm. We assessed the association between the detection of SC and PI-RADs using multivariable regression analyses. Clinical variables examined included age, PSA, DRE finding, prostate volume (PV), TgB location (TZ/PZ), and PI-RADS score (3/4-5). We developed a new scoring system with first 300 cases using estimated value of multivariable analysis; we validated it with the latter 170 cases. Predictive accuracy and performance characteristics were assessed using the area under the receiver operating characteristic curve (AUC), respectively. RESULTS: In first 300 cases, the median age and PSA were 69 years and 7.7 ng/mL, respectively. Location of TgB was TZ/PZ in 75/225 men. PI-RADs were 3/4/5 in 65/178/57 men. SC was detected in 160 (53 %) men of TgB. In multivariable analysis, PI-RADS 4-5 (odds ratio [OR] 5.9, p<.01), the positive DRE (OR 4.4, p<.01), lower PV (< 30 mL, OR 2.6, p<.01), higher PSA (> 8.0 ng/mL, OR 2.4, p<.01) and PZ (OR 1.9, p< .01) were significantly associated with positive TgB for SC. From the results of the analysis, we assigned 1 to 3 points to each variable and developed a scoring system predicting positive TgB for SC (total of 0-8 points, as shown in Table) and AUC for detecting SC was 0.813. In validated group (170 cases) for this new scoring system, AUC for detecting SC was 0.811. CONCLUSIONS: We developed a new scoring system using PI-RADs for detecting SC by TgB and verified its validity. PIRDAS3 might not predict SC.Source of Funding: none