Risk Prostate Cancer Patients Research Articles

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

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

Benefit and harm of lymphadenectomy in intermediate risk prostate cancer: comparison of five nomograms

BackgroundPelvic lymph node dissection (PLND) is recommended method for detecting prostate cancer (PCa) nodal metastases although associated with serious complications. In this study, we aimed to assess benefit/harm of routine PLND in intermediate risk PCa patients and to compare diagnostic yield of five different nomograms in predicting lymph node invasion (LNI).MethodsRetrospective analysis of consecutive PCa patients with intermediate risk of biochemical recurrence who underwent open radical prostatectomy (RP) with bilateral PLND between January 2017 and December 2019 at our institution. Partin, 2012-Briganti, 2018-Briganti, Cagiannos and Memorial Sloan Kettering Cancer Center (MSKCC) values were calculated. To compare accuracy, sensitivity, specificity, and area under receiver-operating curve (AUC) were calculated and then optimal cutoff values were estimated, analyses repeated and compared. To assess benefit and harm of PLND, relative risk (RR) and number need to treat (NNT) with LNI and complications set as outcome were calculated.ResultsTotal 309 subjects. Average age 62.2 years, average PSA 7.2 ng/mL; 18 (5.8%) had LNI; 88 (28.5%) suffered Clavien-Dindo grade 3–5 complication. AUC for predicting LNI: 0.729 for 2012-Briganti, 0.660 for MSKCC, 0.521 for 2018-Briganti, 0.486 for Cagiannos, and 0.424 for Partin. None of pairwise AUC comparisons based on default and newly established cutoff values were statistically significant. Lowest NNT was for Partin and Cagiannos with default cutoff (≥ 5%). Risks of serious complications between higher/lower than cutoff values were non-significant across nomograms.Conclusions2012-Briganti nomogram outperforms, although not significantly, MSKCC, 2018-Briganti, Cagiannos, and Partin nomograms in classifying LNI in intermediate risk PCa patients. Routine PLND in these patients should be avoided, due to high rate and severity of complications.

P087 - Acute toxicity results from a multicenter randomized phase 3 trial comparing external beam radiotherapy alone with external beam radiotherapy combined with brachytherapy in intermediate/high risk prostate cancer patients

P087 - Acute toxicity results from a multicenter randomized phase 3 trial comparing external beam radiotherapy alone with external beam radiotherapy combined with brachytherapy in intermediate/high risk prostate cancer patients

The prevalence and clinical significance of HER2 expression in prostate adenocarcinoma

AimsAbnormalities in HER2 are well-established oncogenic drivers and are approved therapeutic targets in various malignancies. Prior studies evaluating HER2 expression in prostate cancer (PCa) have yielded variable results. Most of these studies used immunohistochemistry scoring systems based on breast cancer data. The goal of this study was to determine the prevalence and clinical significance of HER2 expression using a scoring system that better reflects the HER2 staining pattern observed in PCa. MethodsWe randomly selected similar numbers of localized low risk (AJCC stage I), locally advanced (AJCC stages II & III), and metastatic (AJCC stage IV) PCa patients treated at the DC VA Medical Center between 2000 and 2022. Among them, we included patients who had sufficient PCa tissue samples and clinical information required for this analysis. Two experienced pathologists independently scored HER2 expression (Ventana Pathway anti-HER2) according to a modified gastric cancer HER2 scoring system. ResultsOut of the 231 patients included, 85 % self-identified as Black. 58.9 % of patients expressed HER2 (1+: 35.5 %; 2+: 18.2 %; 3+: 5.2 %). Validity of the results was confirmed using the HercepTest antibody. Higher HER2 expression was associated with a higher Gleason Score/Grade Group and advanced disease. ConclusionsOur findings support the adverse prognostic impact on HER2 in PCa. We propose the use of a modified scoring system to evaluate HER2 expression in PCa. The observed high prevalence of HER2 expression supports the consideration of novel HER2-targeted therapies addressing even low levels of HER2 expression in future PCa trials.

Ten-Year Outcomes of Hypofractionated (45 Gy in 9 Fractions) Intensity Modulated Radiotherapy for Localized Prostate Cancer.

We reported 10-year outcomes of localized prostate cancers treated with hypofractionated intensity-modulated radiotherapy of 45 Gy in 9 consecutive fractions. From October 2011 to April 2017, thirty patients with localized prostate cancer were enrolled in this prospective trial. The median age of the patients was 72.5 years. According to NCCN recurrence risk criteria, eight patients were at low-risk group, 17 at intermediate risk group, 5 at high-risk group. All patients were treated with hypofractionated intensity-modulated radiotherapy (IMRT) of 45 Gy in 9 consecutive fractions to their prostate with or without seminal vesicles. Before radiotherapy, three gold fiducials were implanted into the prostate. In order to reduce the rectal high dose irradiation volume, an inflated rectal balloon was placed in the rectum at simulation and every treatment and patients were treated with comfortable full bladder. Static Intensity-modulated radiotherapy (SIMRT) was applied in 1 patient, Volumetric Modulated Arc Therapy (VMAT) in 27 patients, and tomotherapy in 2 patients. Image guided radiotherapy (IGRT) with gold fiducial registration was adopted. Twenty-six patients also received androgen deprivation therapy (ADT). The median time of ADT was 6 months. Progression⁃free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier analysis. All grade ≥1 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 5.0 (CTCAE 5.0) and Radiation Therapy Oncology Group (RTOG) late morbidity criteria, and GU and GI toxicities were cumulatively calculated. After a median follow-up of 102 months (65∼131 months), the 10-year OS was 90.0% (95% confidence interval, 83.3%-96.7%), and the 10-year PFS was 86.5% (95% confidence interval, 79.1%-93.9%). According to CTCAE 5.0, grade 1 acute gastrointestinal (GI) toxicity developed in 12 patients, grade 2 in 2 patients, grade 3 in 2 patients, and grade 1 acute genitourinary (GU) toxicity developed in 12 patients, grade 2 in 2 patients, and no grade 3 or higher toxicity occurred. According to RTOG late morbidity criteria, late (≥3 months after radiotherapy) grade 1 GI toxicity developed in 4 patients (13.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%), and late grade 1 GU toxicity occurred in 1 patient (3.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%). No grade 4 or higher GI and GU toxicities developed. Only one grade 3 GI and one grade 2 GU toxicities were observed for the maximum toxicity at the last follow-up. The potency was not evaluated. The 10-year oncologic outcomes of this shortened hypofractionated IMRT regimen for mainly low/intermediate risk prostate cancer patients is favorable with acceptable acute and late toxicities.

High monoamine oxidase a expression predicts poor prognosis for prostate cancer patients

BackgroundMonoamine oxidase A (MAOA) is a mitochondrial enzyme that is involved in prostate tumorigenesis and cancer metastasis. The predictive power of the preoperative clinical and pathological indicators for prostate cancer(PC) remains to be improved. To enrich evidence regarding the value of MAOA as a prognostic biomarker in clinical practice, this study explored the significance of MAOA expression as a prognostic marker for patients with PC after radical prostatectomy-pelvic lymph node dissection (RP-PLND).MethodsMAOA expression was analyzed in 50 benign prostate tissues and 115 low-intermediate risk and 163 high-risk PC tissues using tissue immunohistochemistry (IHC). Propensity score matching, survival analysis and COX regression analysis were conducted to investigate the correlation between high MAOA expression and progression free survival (PFS) in PC patients.ResultsMAOA expression was increased in PC patients, especially in those with high risk PC and pathological lymph node (pLN) metastasis. High MAOA expression was significantly associated with PSA recurrence for both low-intermediate risk PC patients (log-rank test: P = 0.02) and high risk PC patients (log-rank test: P = 0.03). Cox regression analysis revealed that high MAOA expression was an adverse prognostic factor for both low-intermediate risk PC patients (hazard ratio [HR] 2.74, 95% confidence interval [CI] 1.26–5.92; P = 0.011) and high risk PC patients (HR 1.73, 95% CI 1.11–2.71; P = 0.016). High MAOA expression was also significantly associated with PSA recurrence in high risk PC patients developed into castration-resistant prostate cancer (CRPC) and were receiving abiraterone therapy (log-rank: P = 0.01).ConclusionsMAOA expression correlates with the malignant progression of PC. High MAOA expression may be a poor prognostic marker for patients with PC after RP-PLND. More careful follow up or potential of adjuvant hormonal therapy may be addressed for patients with high MAOA expression.

Ten-year outcomes of hypofractionated (45 Gy in 9 fractions) intensity-modulated radiotherapy for localized prostate cancer.

e17100 Background: We reported 10-year outcomes of localized prostate cancers treated with hypofractionated intensity-modulated radiotherapy of 45 Gy in 9 consecutive fractions. Methods: From October 2011 to April 2017, thirty patients with localized prostate cancer were enrolled in this prospective trial. The median age of the patients was 72.5 years. According to NCCN recurrence risk criteria, eight patients were at low risk group, 17 at intermediate risk group, 5 at high risk group. All patients were treated with hypofractionated intensity-modulated radiotherapy (IMRT) of 45 Gy in 9 consecutive fractions to their prostate with or without seminal vesicles. Before radiotherapy, three gold fiducials were implanted into the prostate. In order to reduce the rectal high dose irradiation volume , an inflated rectal balloon was placed in the rectum at simulation and every treatment and patients were treated with comfortable full bladder. Static Intensity-modulated radiotherapy (SIMRT) was applied in 1 patient, Volumetric Modulated Arc Therapy (VMAT) in 27 patients, and tomotherapy in 2 patients. Image guided radiotherapy (IGRT) with gold fiducial registration was adopted. Twenty-six patients also received androgen deprivation therapy (ADT). The median time of ADT was 6 months. Progression⁃free survival(PFS) and overall survival(OS) were analyzed using Kaplan-Meier analysis. All grade ≥1 genitourinary (GU) and gastrointestinal (GI) toxicities were recorded using Common Terminology Criteria for Adverse Event version 5.0 (CTCAE 5.0) and Radiation Therapy Oncology Group (RTOG) late morbidity criteria , and GU and GI toxicities were cumulatively calculated. Results: After a median follow-up of 102 months (65~131 months), the 10-year OS was 90.0%(95% confidence interval, 83.3%-96.7%), and the 10-year PFS was 86.5% (95% confidence interval, 79.1%-93.9%). According to CTCAE 5.0, grade 1 acute gastrointestinal (GI) toxicity developed in 12 patients, grade 2 in 2 patients, grade 3 in 2 patients, and grade 1 acute genitourinary (GU) toxicity developed in 12 patients, grade 2 in 2 patients, and no grade 3 or higher toxicity occurred. According to RTOG late morbidity criteria, late (≥3 months after radiotherapy) grade 1 GI toxicity developed in 4 patients (13.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%), and late grade 1 GU toxicity occurred in 1 patient (3.3%), grade 2 in 1 (3.3%), grade 3 in 1 (3.3%). No grade 4 or higher GI and GU toxicities developed. Only one grade 3 GI and one grade 2 GU toxicities were observed for the maximum toxicity at the last follow-up. The potency was not evaluated. Conclusions: The 10-year oncologic outcomes of this shortened hypofractionated IMRT regimen for mainly low/intermediate risk prostate cancer patients is favorable with acceptable acute and late toxicities.

Immune-Activated B Cells Are Dominant in Prostate Cancer.

B cells are multifaceted immune cells responding robustly during immune surveillance against tumor antigens by presentation to T cells and switched immunoglobulin production. However, B cells are unstudied in prostate cancer (PCa). We used flow cytometry to analyze B-cell subpopulations in peripheral blood and lymph nodes from intermediate-high risk PCa patients. B-cell subpopulations were related to clinicopathological factors. B-cell-receptor single-cell sequencing and VDJ analysis identified clonal B-cell expansion in blood and lymph nodes. Pathological staging was pT2 in 16%, pT3a in 48%, and pT3b in 36%. Lymph node metastases occurred in 5/25 patients (20%). Compared to healthy donors, the peripheral blood CD19+ B-cell compartment was significantly decreased in PCa patients and dominated by naïve B cells. The nodal B-cell compartment had significantly increased fractions of CD19+ B cells and switched memory B cells. Plasmablasts were observed in tumor-draining sentinel lymph nodes (SNs). VDJ analysis revealed clonal expansion in lymph nodes. Thus, activated B cells are increased in SNs from PCa patients. The increased fraction of switched memory cells and plasmablasts together with the presence of clonally expanded B cells indicate tumor-specific T-cell-dependent responses from B cells, supporting an important role for B cells in the protection against tumors.

Association between multiple sclerosis and prostate cancer risk: A systematic review and meta‑analysis.

Prostate cancer (PCa) risk in patients with multiple sclerosis (MS) remains to be elucidated. The present study conducted a meta-analysis to assess the relationship between MS and PCa. PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to identify studies on the PCa risk in patients with MS up to September 2022. A random effects meta-analyses model was performed to estimate the relative risk (RR) and the 95% confidence intervals (CI). All eight studies involving 210,943 patients with MS were identified and included in the meta-analysis. The present study revealed that there was no significant association between MS and the risk of PCa (RR=0.78, 95% CI: 0.56-1.08, P<0.0001). Subgroup analyses verified this conclusion when stratified by regions. However, after adjusting for potential confounders, the findings suggested conflicting results. The current evidence shows that compared with the population control, patients with MS have no relationship with PCa risk and further large samples and long-term trials are needed to verify these results.

Gene Expression Markers of Prognostic Importance for Prostate Cancer Risk in Patients with Benign Prostate Hyperplasia.

Comparative analyses utilizing publicly available big data have the potential to generate novel hypotheses and knowledge. However, this approach is underutilized in the realm of cancer research, particularly for prostate cancer. While the general progression of prostate cancer is now well understood, how individual cell types transition from healthy, to pre-cancerous, to cancerous cell types, remains to be further elucidated. To address this, we re-analyzed two publicly available single-cell RNA-seq datasets of prostate cancer and benign prostate hyperplasia cell types. The differential expression analysis of 15,505 epithelial cell profiles across 18,638 genes revealed 791 genes that were up regulated in prostate cancer epithelial cells. Here we report six markers that show significant upregulation in prostate cancer cells relative to BPH epithelial cells: HPN (5.62X), RAC3 (3.51X), CD24 (2.18X), HOXC6 (1.77X), AGR2 (1.71X), and IGFBP2 (1.28X). In particular, the significant differential expression of AGR2 further supports its clinical relevance in supplementing prostate-specific antigen screening for detecting prostate cancer. These findings have the potential to further advance our knowledge of genes governing the development of cancer in prostate epithelial cells. Clinical Relevance- Our results establish the importance of 6 prostate cancer markers (HPN, RAC3, CD24, HOXC6, AGR2, and IGFBP3) in distinguishing between prostate cancer epithelial cells and benign prostate hyperplasia epithelial cells.

Feasibility of aspirin and/or vitamin D3 for men with prostate cancer on active surveillance with Prolaris® testing.

ObjectivesTo test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing.Patients and MethodsNewly‐diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi‐centre randomised, double‐blind, placebo‐controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12‐month disease re‐assessment (imaging/biochemical/histological), and 12‐month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging‐Reporting and Data System (PI‐RADS) 4/5 lesion(s) on multi‐parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length.ResultsOf 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve‐month disease progression rate was 43.3%. Assessable 12‐month treatment adherence in non‐progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug‐attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms.ConclusionRecruitment of AS PCa patients into a multi‐centre multi‐arm placebo‐controlled RCT of minimally‐toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome‐associated biomarkers.

68 Ga-PSMA PET/CT for preoperative lymph nosde staging of high-risk prostate cancer.

38 Background: The present study evaluates the potential role of 68Ga-PSMA PET/CT to detect pelvic lymph node metastases in newly diagnosed, treatment-naïve high risk prostate cancer (PCa) patients prior to radical prostatectomy and extended pelvic lymphadenectomy. Methods: A total of 165 men with newly diagnosed high risk PCa (ISUP grade 4/5, PSA &gt; 20 ng/ml or ≥cT3a) were included in this retrospective analysis. All men had undergone a transperineal MR fusion biopsy and all men underwent RPE with epLND. Patients with neoadjuvant ADT, TRUS guided biopsies, previous radiation or surgeries in the small pelvis were excluded. Imaging findings and pathohistological findings were correlated and sensitivity, specificity, positive and negative predictive values were calculated. The correlation of clinical and biopsy characteristics with PSMA PET/CT. Results: The median PSA was 24.5 (6.7-185) ng/ml, the median number of dissected lymph nodes was 21-5 (14-45). A total of 68/165 (41,2%) patients had lymph node metastases (LNM) of which 43 (63.2%) were positive on PSMA-PET/CT whereas 25 (36.8%) LNM were negative on PSMA PET/CT. 97/165 (58.8%) pts had pN0 disease of whom 93 (95.9%) and 3 (4.1%) demonstrated negative and positive PSMA PE/CT findings, resp. n = 47 had positive PSMA PET/CT and 40 (85.1%) demonstrated LNM, 7 (14.9%) had pN0 disease. N = 118 had negative PSMA PET/CT of which 93 (78.8%) and 25 (21.2%) were true and false negative, resp. Sensitivity was 63.2%, specificity was 97.0%, and positive and negative predictive values were 93.5% and 78,8%, respectively. 3564 lymph nodes were resected, 149 (4.2%) had LNM. 88/149 (59.1%) were detected on PSMA PET/CT and 61 (40.9%) were undetected. On a per lymph node base, sensitivity and specificity were 40.4% and 94.5%, resp; positive and negative predictive values were 59.1% and 97.3%. Conclusions: PSMA-PET/CT has a high reliability to identify patients with high risk PCA and LNM. If a positive lesion is detected, epLND is mandatory due to high frequency of undetected small LNM. PSMA-PET/CT, is superior to standard imaging and it might replace CT/MRI of the small pelvis.

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy.

PurposeLong-term data regarding the disease control outcomes of proton beam therapy (PBT) for patients with favorable risk intact prostate cancer (PC) are limited. Herein, we report our institution's long-term disease control outcomes in PC patients with clinically localized disease who received PBT as primary treatment.MethodsOne hundred sixty-six favorable risk PC patients who received definitive PBT to the prostate gland at our institution from 2010 to 2012 were retrospectively assessed. The outcomes studied were biochemical failure-free survival (BFFS), biochemical failure, local failure, regional failure, distant failure, PC-specific survival, and overall survival. Patterns of failure were also analyzed. Multivariate Cox proportional hazards modeling was used to estimate independent predictors of BFFS.ResultsThe median length of follow-up was 8.3 years (range, 1.2–10.5 years). The majority of patients had low-risk disease (58%, n = 96), with a median age of 64 years at the onset of treatment. Of 166 treated men, 13 (7.8%), 8 (4.8%), 2 (1.2%) patient(s) experienced biochemical failure, local failure, regional failure, respectively. Regional failure was seen in an obturator lymph node in 1 patient and the external iliac lymph nodes in the other. None of the patients experienced distant failure. There were 5 (3.0%) deaths, none of which were due to PC. The 5- and 8-year BFFS rate were 97% and 92%, respectively. None of the clinical disease characteristics or treatment-related factors assessed were associated with BFFS on multivariate Cox proportional hazards modeling (all P > .05).ConclusionDisease control rates reported in our assessment of PBT were similar to those reported in previous clinically localized intact PC analyses, which used intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, or radical prostatectomy as definitive therapy. In addition, BFFS rates were similar, if not improved, to previous PBT studies.

SC101 - The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: a single institutional analysis

SC101 - The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: a single institutional analysis

In1-Ghrelin Splicing Variant as a Key Element in the Pathophysiological Association Between Obesity and Prostate Cancer.

Recent studies emphasize the importance of considering the metabolic status to develop personalized medicine approaches. This is especially relevant in prostate cancer (PCa), wherein the diagnostic capability of prostate-specific antigen (PSA) dramatically drops when considering patients with PSA levels ranging from 3 to 10 ng/mL, the so-called grey zone. Hence, additional noninvasive diagnostic and/or prognostic PCa biomarkers are urgently needed, especially in the metabolic-status context. To assess the potential relation of urine In1-ghrelin (a ghrelin-splicing variant) levels with metabolic-related/pathological conditions (eg, obesity, diabetes, body mass index, insulin and glucose levels) and to define its potential clinical value in PCa (diagnostic/prognostic capacity) and relationship with PCa risk in patients with PSA in the grey zone. Urine In1-ghrelin levels were measured by radioimmunoassay in a clinically, metabolically, pathologically well-characterized cohort of patients without (n = 397) and with (n = 213) PCa with PSA in the grey zone. Key obesity-related factors associated with PCa risk (BMI, diabetes, glucose and insulin levels) were strongly correlated to In1-ghrelin levels. Importantly, In1-ghrelin levels were higher in PCa patients compared to control patients with suspect of PCa but negative biopsy). Moreover, high In1-ghrelin levels were associated with increased PCa risk and linked to PCa aggressiveness (eg, tumor stage, lymphovascular invasion). In1-ghrelin levels added significant diagnostic value to a clinical model consisting of age, suspicious digital rectal exam, previous biopsy, and PSA levels. Furthermore, a multivariate model consisting of clinical and metabolic variables, including In1-ghrelin levels, showed high specificity and sensitivity to diagnose PCa (area under the receiver operating characteristic curve = 0.740). Urine In1-ghrelin levels are associated with obesity-related factors and PCa risk and aggressiveness and could represent a novel and valuable noninvasive PCa biomarker, as well as a potential link in the pathophysiological relationship between obesity and PCa.

The use of 29 MHz transrectal micro-ultrasound to stratify the prostate cancer risk in patients with PI-RADS III lesions at multiparametric MRI: A single institutional analysis

IntroductionMagnetic Resonance Imaging (MRI) has emerged as the most accurate diagnostic tool, showing a high sensitivity in the diagnosis of clinically significant prostate cancer (csCaP). However only a minority of patients with a PI-RADS 3 lesion at multiparametric magnetic resonance imaging (MRI) are diagnosed with csCaP. The aim of the current study was to assess whether high resolution micro-ultrasound (microUS) could help in sub-stratifying the risk of csCaP in this specific population. Material and methodsWe retrospectively analyzed the records of 111 consecutive patients scheduled for a prostate biopsy with at least 1 PI-RADS 3 lesions at MRI. We excluded patients with a PIRADS >3 lesion, even if they had a coexisting PIRADS 3 lesions. MicroUS was performed in all patients before prostate biopsy by an operator blind to MRI results. The Prostate Risk Identification using MicroUS (PRI-MUS) protocol was used to assess the risk of CaP and csCaP. All patients received both targeted and systematic biopsies. The primary endpoint was to determine the diagnostic accuracy of microUS in detection of csCaP in patients with a PI-RADS 3 lesion at MRI. Specifically, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of microUS were determined. Multivariable logistic regression models (MLRMs) were fitted to identify predictors of CaP. The diagnostic accuracy was reported as area under the receiver operator characteristic (ROC) curve. ResultsOverall, 43 patients (38.7%) harboured CaP and 22 (20%) csCaP. MicroUS showed a high sensitivity and negative predictive value (100%), while its specificity and positive predictive value were 33.7% and 27.2%, respectively. Among patients without lesions at microUS, 25 (83.3%) did not harbour CaP, while 5 (16.7%) patients were diagnosed with a Gleason score 6 CaP, with no patients harbouring csCaP. Using microUS, the csCaP detection would have remained 100%, while reducing the detection of insignificant CaP of a 23.8% extent (n = 5). In MLRMs, lesion identified at microUS and continuously-coded PSAd were independent predictors of CaP. The accuracy of a model including PRI-MUS score, digital rectal examination (DRE), PSA density, age and family history was 0.744 (95% CI: 0.645 – 0.843). ConclusionIn our single-institutional retrospective study, microUS was potentially capable to stratify the presence of CaP in patients with an equivocal MRI. Further prospective studies on larger populations are needed to validate our results.

P1092 - Long-term overall survival of radical prostatectomy patients is often superior to the general population: A comparison using life-table data

Background To examine overall survival rates within a large cohort of German prostate cancer (PCa) patients and to compare these with life-expectancy (LE) predictions derived from German life tables. We hypothesized that the advantage of good general health in radical prostatectomy (RP) patients combined with favorable cancer outcomes might lead to even higher overall survival rates over 10 years compared to the LE of a general population. Methods A total of 6483 patients were treated with RP between 1992 and 2007 at the Martini-Klinik Prostate Cancer Center. Preoperative risk classification was performed according to D'Amico. Postoperative risk classification was performed according to the Cancer of the Prostate Risk Assessment score (CAPRA-S). A simulated cohort was created that resembled the exact age distribution of the RP population using Monte Carlo simulation which was based on data derived from official male German life tables (1992-2017). Markov chain was used to represent natural age progression of the simulated cohort. Kaplan-Meier plots were created to display the differences between 10-year observed overall survival (OS) and the simulated, predicted LE. Results For D'Amico low risk and intermediate risk, 10-year OS was 12.0% and 9.2% above predicted LE in the simulated cohort, respectively. For D'Amico high risk, OS was virtually the same as predicted LE (0.8% difference in favor of RP treated patients). For CAPRA-S low and intermediate risk, OS was 11.8% and 9.7% above predicted LE. For CAPRA-S high risk, OS was virtually the same as predicted LE (0.3% difference in favor of the simulated cohort). Conclusions Low- and intermediate risk PCa patients treated with RP can expect a very favorable overall survival, that even exceeds LE predictions. High risk patients' overall survival perfectly aligns with LE predictions.

The role of pre-biopsy mpMRI in lymph node staging for prostate cancer.

Prostate cancer (PCa) staging is an integral part in the management of prostate cancer. The gold standard for diagnosing lymph node invasion is a surgical lymphadenectomy, with no superior imaging modality available at the clinician's disposal. Our aim in this study is to identify if a pre-biopsy multiparametric MRI (mpMRI) can provide enough information about pelvic lymph nodes in intermediate and high risk PCa patients, and whether it can substitute further cross sectional imaging (CSI) modalities of the abdomen and pelvis in these risk categories. Patients with intermediate and high risk prostate cancer were collected between January 2015 and June 2019, while excluding patients who did not undergo a pre-biopsy mpMRI or a CSI. Date regarding biopsy result, PSA, MRI results, CSI imaging results were collected. Using Statistical Package for the Social Sciences (SPSS) version 24.0, statistical analysis was conducted using the Cohen's Kappa agreement for comparison of mpMRI with CSI. McNemar's test and receiver operator curve (ROC) curve were used for comparison of sensitivity of both tests when comparing to the gold standard of lymphadenectomy. A total of 143 patients fit the inclusion criteria. We further stratified our patients into according to PSA level and Gleason score. Overall, agreement between mpMRI and all CSI was 0.857. When stratifying patients based on Gleason score and PSA, the higher the grade or PSA, the higher agreement between mpMRI and CSI. The sensitivity of mpMRI (73.7%) is similar to CSI (68.4%). When comparing CSI sensitivity to that of mpMRI, no significant difference was present by utilizing the McNemar test and very similar receiver operating characteristic curve. A pre-biopsy mpMRI can potentially substitute further cross sectional imaging in our cohort of patients. However, larger prospective studies are needed to confirm our findings.

Evaluation of daily online contour adaptation by radiation therapists for prostate cancer treatment on an MRI-guided linear accelerator

Background and purposeMagnetic resonance (MR)-guided linear accelerator (MR-Linac) systems have changed radiotherapy workflows. The addition of daily online contour adaptation allows for higher precision treatment, but also increases the workload of those involved. We train radiation therapists (RTTs) to perform daily online contour adaptation for MR-Linac treatment of prostate cancer (PCa) patients. The purpose of this study was to evaluate these prostate contours by performing an interfraction and interobserver analysis. Materials and methodsClinical target volume (CTV) contours generated online by RTTs from 30 low-intermediate risk PCa patients, treated with 5x7.25 Gy, were used. Two physicians (Observers) judged the RTTs contours and performed adaptations when necessary. Interfraction relative volume differences between the first and the subsequent fractions were calculated for the RTTs, Observer 1, and Observer 2. Additionally, interobserver dice’s similarity coefficient (DSC) for fraction 2–5 was calculated with the RTTs- and physician-adapted contours. Clinical acceptability of the RTTs contours was judged by a third observer. ResultsMean (SD) online contour adaptation time was 12.6 (±3.8) minutes and overall median (interquartile range [IQR]) relative volume difference was 9.3% (4.4–13.0). Adaptations by the observers were mostly performed at the apex and base of the prostate. Median (IQR) interobserver DSC between RTTs and Observer 1, RTTs and Observer 2, and Observer 1 and 2 was 0.99 (0.98–1.00), 1.00 (0.98–1.00), and 1.00 (0.99–1.00), respectively. Contours were acceptable for clinical use in 113 (94.2%) fractions. Dose-volume histogram (DVH) analysis showed significant CTV underdosage for one of the seven identified outliers. ConclusionDaily online contour adaptation by RTTs is clinically feasible for MR-Linac treatment of PCa.

Impact of 68Ga-PSMA-11 PET/CT on Initial Staging of High-Risk Prostate Cancer Patients: Post-Hoc Analysis of a Prospective Single Center Experience

Conventional imaging for initial staging of prostate cancer (PCa) lacks sensitivity and underestimates disease burden. Prostate-specific membrane antigen PET/CT (PSMA PET) is an emerging imaging modality shown to have improved sensitivity over conventional imaging in the setting of biochemical recurrence. We sought to evaluate the impact of 68Ga-PSMA PET on initial staging of patients with high risk PCa, as well as clinicopathologic features that might predict for upstaging, by analyzing patients who prospectively underwent PSMA PET on a clinical trial. This was a post hoc analysis of 249 eligible patients with NCCN high/very high risk PCa who underwent a staging PSMA PET (12/2016 to 1/2020) on a prospective trial. Patients with known non-regional lymph node or distant metastasis on prior imaging, or initiation of androgen deprivation therapy more than 3 months before PSMA PET were excluded. Chi square analysis was used to evaluate the association of clinicopathologic features (Gleason grade group [GG], initial PSA [iPSA], T stage, percent positive cores [PPC]≥50%) with upstaging. Overall, 22.9% patients were upstaged by PSMA PET; 18.9% of patients with iN0 disease by CT or MRI were found to have N1 disease by PSMA PET, and 10.6% of patients who had M0 disease by CT or bone scan had M1 disease by PSMA PET. New M1a disease was found in 7.4% and M1b/M1c disease was found in 5.3% of patients. PSMA PET detected ECE, SVI or invasion of surrounding structures in 8.1% patients deemed T2 on prior MRI imaging. PPC≥50% was significantly associated with regional and any nodal upstage (23.9% vs. 12.1%, p = 0.0227 and 22.6% vs. 3.7%, p = 0.0261, respectively), and any upstage in general (29.3% vs. 14.6%, p = 0.0102). Patients with GG 5 or ≥50% PPC were more likely to have regional nodal upstage (23.4% vs. 6.3%, p = 0.0031) and any upstage in general (28.2% vs. 9.4%, p = 0.0024), while GG 5 together with ≥50% PPC was predictive of M stage upstage (23.3% vs. 4.7%, p = 0.0063). cT and iPSA were not associated with upstaging. PSMA PET/CT has a significant impact on initial staging of high risk PCa patients. This impact appears to be most marked in patients with GG 5 or PPC≥50%.