Percentage Of Positive Biopsies Research Articles

Microboost dose escalation for localized prostate cancer within a statewide radiation oncology quality consortium.

298 Background: The phase III FLAME trial demonstrated that in localized prostate cancer, an external beam radiotherapy (EBRT) simultaneous integrated microboost to an MRI-defined dominant intraprostatic lesion improves biochemical control without affecting toxicity and quality of life. Given the complexity required to deliver high microboost doses, we hypothesized that practice patterns are variable in clinical practice. We aimed to characterize microboost utilization and evaluate dosimetric parameters within the statewide Michigan Radiation Oncology Quality Consortium (MROQC). Methods: Men with intermediate or high-risk prostate adenocarcinoma treated with curative intent radiotherapy for intact disease were included. Data was prospectively collected, including T/N-category, Gleason score, prostate-specific antigen, and percent positive biopsy cores. Full DICOM files were available for dosimetric data. Multivariable analyses (MVA) were used to evaluate associations between receipt of microboost, known prognostic factors, and fiducial marker and rectal spacer placement (advanced image guided radiation therapy (IGRT)). Results: From 10/26/20 to 06/26/23, 741 patients across 26 centers were enrolled, 71% (n=528) with intermediate-risk and 29% (n=213) with high-risk disease. Androgen deprivation therapy was planned in 61%. EBRT + whole-gland brachytherapy boost was utilized in 29% (n=217/741) of patients. Of those treated with EBRT (71%, n=524/741), 10% received a microboost (n = 53/524). Brachytherapy boost and microboost were used in 9 and 7 centers, respectively. Most patients received either conventional fractionation or moderate hypofractionation- 11% and 66% in EBRT without microboost and 21% and 60% with microboost, respectively. Microboost treatment was associated with use of a planning MRI (91% vs. 62%, p <0.0001) as well as fiducial marker and rectal spacer placement (76% vs. 45%, p <0.0001). Median prostate planning target volume (PTV) was smaller in microboost patients (127 cc vs. 91 cc, p = 0.002); median boost volume was 21 cc. Median boost dose (D0.1cc) was 117% (IQR 115% – 119%) of the PTV prescription. Microboost patients had significantly higher mean bladder D1cc[%] (105.7% vs. 103.4%, p = 0.002) and numerically lower rectal D1cc[%] (90.7% vs. 94.1%, p = 0.065). On MVA, receipt of microboost was significantly associated with grade group 4 or 5 disease, planning MRI use, and fiducial and rectal spacer use. Conclusions: Within a large, diverse prospective cohort of men with prostate cancer treated in both academic and community settings, a microboost was utilized in 10% of EBRT cases. Microboost use was associated with higher grade group, MRI planning, and advanced IGRT. EBRT microboost is an emerging dose escalation strategy and further studies confirming safety and improved clinically meaningful outcomes may increase uptake in routine practice.

Assessment of the Iraqi Breast Cancer Early Detection and Downstaging Program: Mammography Cancer Detection Rate

Background: In Iraq, early detection and downstaging of breast cancer programs were launched to control breast cancer (BC) in 2000. In the program model, mammography is conducted for normal and symptomatic women. The aim of this study is to assess the program’s model effectiveness in terms of mammography cancer detection rates and other screening determinates in the Iraqi Early Detection Program. Method: This is a retrospective study based on data attained from the Breast Disease Treatment Centre (BDTC) in Sulaimani, Iraq. From September 2016 to August 2021, 35,045 women visited the centre for BC screening and diagnosis of breast disorders. In BDTC, 16,186 mammograms and 1,289 biopsies were conducted, and 404 women were diagnosed with BC. This study measured the percentage of women who visited BDTC for screening, the women’s ages at diagnosis, the cancer detection rate (BC per 1,000 women visiting), mammography detection rate (BC per 1,000 mammograms) and the percentage of positive core biopsies. Results: The cancer detection rate (CDR) in 1,000 women was 11.53, the overall mammography detection rate was 24.96, and the highest rate was observed in 2018 (42.2). The overall percentage of positive core biopsies was 31.34%. The highest percentage biopsy rate was in 2017 (43.84%). From 2016 to 2021, the percentage of visits for screening increased gradually, rising from 9.5% to 28.6%. Conclusion: The early detection program in Iraq is considered to be effective in terms of high mammography cancer detection rates and the percentage of positive biopsy. Compared to the previous data, more women participated in the program for screening than for diagnosis.

Machine Learning and Explainable Artificial Intelligence to Predict Occult Pelvic Nodal Metastases in Prostate Cancer.

Determination of risk of occult pelvic lymph node involvement (LNI) in patients with cN0 prostate cancer is critical for determination of optimal treatment options. Though several nomograms exist, machine learning (ML) approaches might enable physicians to better assess individual risk by incorporating multiple clinical risk factors. Herein, we developed a ML model to predict occult LNI, and explained its composition using an explainable artificial intelligence (XAI) framework. Patients with cN0 prostate adenocarcinoma diagnosed from 2018-2020 were identified in the National Cancer Database. The query was limited to patients with known clinical staging and biopsy results who did not receive neoadjuvant therapy prior to pelvic nodal examination. Occult LNI was defined as pN1 disease based on surgical evaluation, with a minimum of 10 nodes examined. Five ML models were trained to predict LNI. Variables incorporated into the model were age, core biopsy results, Gleason scores, preoperative prostate specific antigen (PSA), and clinical T-stage. Model performance, measured using area under the receiver operator characteristic curve (AUC) on a holdout testing dataset, was compared to multivariable logistic regression. The best-performing model was explained using SHapley Additive exPlanation (SHAP) values. To permit more clinically-meaningful statistical interpretation, using a novel approach SHAP values were converted into odds ratios (OR), confidence intervals (CI), and p-values. A total of 23,131 patients met inclusion criteria; 2,676 (11.6%) had occult LNI. The Extreme Gradient Boosting model outperformed all other models with an AUC of 0.82 (95% CI: 0.78-0.86) compared to 0.80 (95% CI: 0.76-0.84) for logistic regression. Increasing PSA (OR: 1.031; p<0.001), number of positive biopsy cores (OR: 1.055; p<0.001), and percent positive biopsy cores (OR: 1.01; p<0.001) were all associated with increased risk of LNI. Based on observation of SHAP dependence plots, risk of LNI plateaued at PSA>20 ng/dL and >11 positive cores, while no plateau was observed for percent positive biopsy cores. Relative to T1c disease, patients with T3b were at highest risk of LNI (OR: 1.461; p = 0.003). Gleason score of 9 was associated with significant risk of LNI (Ref: Gleason 6; OR: 1.891; p<0.001). This was primarily driven by the primary Gleason score; primary Gleason 5 disease was associated with significant risk of LNI (Ref: Gleason 3; OR: 1.915; p<0.001) while a secondary Gleason score of 5 was the only grade with significant increased risk of LNI (Ref: Gleason 3; OR: 1.185; p = 0.004). Age and number of cores examined were not significant predictors of LNI. Our ML achieved improved performance relative to logistic regression at predicting occult LNI. XAI provided insight into the inner-working of the ML model. ML can be used to identify patients at risk for occult LNI and therefore inform clinical decision-making.

The prognosis of patients with prostate cancer receiving permanent seed implantation stratified by prostate volume: Should we be reluctant to treat with brachytherapy because of a very small prostate (

PurposeWe evaluated the treatment outcomes of different prostate volumes (PVs), <15 cc, 15–20 cc, and > 20 cc, in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). Methods and MaterialsOf the 6721 patients in J-POPS from 2005 to 2011, 6652 were included in the analysis population. We categorized the patients into the following three PV groups: <15 cc, 15–20 cc, and > 20 cc. We evaluated the effect of PV on biochemical freedom from failure (bFFF), prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM) using the Phoenix definition and Cox proportional hazard models. ResultsThe median follow-up period was 60.0 months. Patients in each PV group was 491 (7.4%), 1118 (16.8%), and 5043 (75.8%), respectively. No difference was observed in bFFF (94.7%, 96.2%, and 95.7%, p = 0.407), PCSM (99.8%, 99.7%, and 99.8%, p = 0.682), and ACM (98.2%, 96.7%, and 97.2%, p = 0.119) at 5 years for each PV group. In univariate and multivariate analyses, PV was not associated with bFFF, PCSM, ACM, or grade 2 toxicity. The percentage of positive biopsies was the single most significant predictor for all treatment outcomes. ConclusionsOur results obtained by analyzing a very large Japanese prospective database showed no difference in treatment outcomes according to PV (<15 cc, 15–20 cc, and ˃20 cc). Our study confirmed that PI in small prostates (even < 15 cc) remains an effective treatment option.

MP77-08 PROSTATE CANCER PRESENTATION IN A COMMUNITY SETTING A DECADE SINCE THE USPSTF GRADE D RECOMMENDATION

You have accessJournal of UrologyCME1 Apr 2023MP77-08 PROSTATE CANCER PRESENTATION IN A COMMUNITY SETTING A DECADE SINCE THE USPSTF GRADE D RECOMMENDATION Franklin Gaylis, Edward Cohen, Paul Dato, Rose Prime, Julie Cramer, Katayune Golshan, Sonia Romo, Sepi Mahooti, Michael Leapman, Robert Topp, and William Catalona Franklin GaylisFranklin Gaylis More articles by this author , Edward CohenEdward Cohen More articles by this author , Paul DatoPaul Dato More articles by this author , Rose PrimeRose Prime More articles by this author , Julie CramerJulie Cramer More articles by this author , Katayune GolshanKatayune Golshan More articles by this author , Sonia RomoSonia Romo More articles by this author , Sepi MahootiSepi Mahooti More articles by this author , Michael LeapmanMichael Leapman More articles by this author , Robert ToppRobert Topp More articles by this author , and William CatalonaWilliam Catalona More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The United States Preventative Services Task Force (USPSTF) issued a grade “D” recommendation against PSA-based prostate cancer (PCa) screening in 2012. We present an analysis of a prospectively collected data repository including PCa tumor burden, Gleason score group, PSA and prostate biopsy positivity rates in a community setting a decade since the Task Force recommendation METHODS: We identified 7,914 patients undergoing prostate biopsy between April 2011 and December 2021 from the Genesis Healthcare Partner’s (large urology group practice) electronic medical record (EMR). For 2011, we annualized the number of biopsies performed based on an imputed estimate from April through December of 2011. We compiled the number of prostate biopsies and proportions of biopsies demonstrating cancer, Gleason score (6, 7, 8-10), and the maximum positive biopsy core percentage involvement with cancer. Statistical analysis included Chi Square and a one-way ANOVA. RESULTS: The annual biopsy rate was significantly higher in 2011 (997 cases [748 actual cases plus 249 estimated cases] than for all other years. Chi Square analysis indicated a significant consistent increase (p<0.001) in the percentage of positive biopsies between 2011 (44.25%) and 2021 (65.91%). The proportion of low grade disease significantly decreased (p<0.001) between 2011 and 2021 from 49.12% to 33.33%, while the proportion high grade disease significantly increased (p<0.001) from 16.47% to 27.59%. The proportion of intermediate grade disease significantly increased (p<0.001) from 34.41% in 2011 to 39.08% in 2021. The mean maximum positive biopsy core percentage was lower in 2011 (48.00+.33%) versus 2021 (55.00+.29%) (p<0.001). A non-parametric independent samples Kruskal-Wallis test with Bonferroni post hoc comparisons indicated that the median PSA levels were similar during 2011-2012 (6.7 – 6.9 ng/ml) and were significantly lower (p<.05) than the median PSA values measured during 2020-2021 (8.5 – 9 ng/ml). Study limitations include uncertainty about the extent of adoption of USPSTF guidelines in the practices, possible inaccurate attribution of causality (versus imaging and biomarker effects). Its strengths include prospective acquisition of granular data and findings that align with studies showing increases in metastatic disease and PCa-specific mortality during this interval. CONCLUSIONS: We identified a temporal association between the USPSTF 2012 recommendation against screening and increasing volume and proportion of high-grade prostate cancer. This trend was not reversed following the 2018 ‘Grade C’ revision to the USPSTF guideline. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1104 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Franklin Gaylis More articles by this author Edward Cohen More articles by this author Paul Dato More articles by this author Rose Prime More articles by this author Julie Cramer More articles by this author Katayune Golshan More articles by this author Sonia Romo More articles by this author Sepi Mahooti More articles by this author Michael Leapman More articles by this author Robert Topp More articles by this author William Catalona More articles by this author Expand All Advertisement PDF downloadLoading ...

Biochemical outcomes and toxicities in young men with prostate cancer after permanent iodine-125 seed implantation: Prospective cohort study in 6662 patients

PURPOSEWe evaluated the effect of age, <60 and ≥60 years, on biochemical outcomes and toxicities in patients with prostate cancer who underwent permanent seed implantation (PI) ± external beam radiation therapy ± hormone therapy in a national Japanese prospective cohort study (J-POPS). METHODS AND MATERIALSThe safety and efficacy analyses included 6721 and 6662 patients, respectively. We categorized patients into two age groups: <60 (n = 716) and ≥60 (n = 6,005) years. We used propensity score matching (PSM) to estimate the marginal effect of age on biochemical freedom from failure (bFFF) using a Phoenix definition and Cox proportional hazard models. RESULTSThe median followup period was 60.0 months. Without PSM, men <60 years demonstrated similar 5-year bFFF (96.3%) compared with men ≥60 years (95.6%; p = 0.576); percent positive biopsies, biologically effective dose, Gleason score, risk classification, and supplemental external beam radiation therapy (p <0.001, <0.001, <0.001, 0.008, and <0.001) were significantly associated with bFFF while age was not (p = 0.576). With PSM, bFFF was not significantly different between age groups (p = 0.664); however, men <60 years showed a significantly lower incidence of declining erectile function, grade ≥2 all urinary toxicities, urinary frequency/urgency, and rectal bleeding (p <0.001, 0.024, 0.031, and 0.010) than men ≥60 years. CONCLUSIONSAfter PI, men <60 years achieved a comparable 5-year biochemical control rate and showed a lower incidence of several toxicities compared to men ≥60 years. This suggests that PI should be an excellent treatment option for men <60 years with prostate cancer.

Utility of Novel Mapping Biopsy for Improvement of Extramammary Paget Disease Outcomes: A Case Series

ABSTRACT Introduction Extramammary Paget's Disease (EMPD) is a rare neoplasm typically found in the genital and perianal region. It typically presents as a pruritic, painful rash and is often mistaken for a fungal infection before biopsy is taken. Staging and biopsy technique have not yet been standardized given the cancer's rarity, leading to a recurrence rate ranging from 21-61% recurrence upon literature review. Objective To analyze outcomes of EMPD patients receiving mapping biopsy prior to tumor excision Methods Retrospective chart review was conducted of 19 EMPD patients treated with biopsy and/or surgery by co-author at our institution from 2013 to 2021. We extracted patient demographic data, length of follow-up time, percent positive biopsy sites, margin status, recurrence status, and other pertinent disease characteristics. Results Within our 19 total patients, median age at diagnosis was 72 with a range between 62 and 88. The majority of patients had a prior history of cancer (13/19), with the most common type being skin cancer (12) followed by prostate cancer (4). No patients were diagnosed with secondary malignancy during mandatory EMPD workup of cystoscopy and colonoscopy before WLE. The majority of patients had not been treated for EMPD prior to presenting to Moffitt (16/19). Of the 16 patients receiving novel mapping biopsy, 8/16 had at least one positive core biopsy site, with a mean of 7% positivity of the total core sites (4/60). Mapping biopsy positive sites helped shape perimeters for wide local excision (WLE) of tumor for patients opting for surgical treatment. Margins of WLE were positive for 11/17 patients. Calculating the length of follow-up time after WLE revealed a median of 6 months, with a range from 0 to 74 months and a mean of 14. No patients received postoperative radiation. One patient did receive topical 5-FU, but use was discontinued after several days due to irritation. Only 1 episode of recurrence was reported during this period of follow-up. Conclusions Our novel mapping biopsy technique is an effective way to delineate surgical margins before WLE. Margin positivity is not an accurate indicator of the likelihood of recurrence for EMPD patients, as only 1/17 saw recurrence post-WLE despite 11/17 with positive margins. Disclosure No

Nomogram Predicting Adverse Pathology Outcome on Radical Prostatectomy in Low-Risk Prostate Cancer Men

ObjectiveTo develop and validate a prediction model to predict the risk of adverse pathology outcome on final pathology in low-risk prostate cancer (PCa) men. Materials and MethodsThis study was a monocentric retrospective analysis of 426 men who underwent radical prostatectomy (RP) for low-risk PCa. The validation cohort included 103 men from another hospital. Adverse pathology outcome was defined either by upgrading on RP Gleason Score (GS) (from GS 3+3 to GS ≥ 3+4 with Gleason pattern 4 ≥ 10%) or a non-organ confined disease (pathologic stage ≥ pT3a). Multivariable logistic regression analysis was performed to build nomogram for predicting adverse pathology outcome. Nomogram validation was performed by calculating the area under receiver operating characteristic curves (AUC) and comparing nomogram-predicted probabilities with actual rates of adverse pathology outcome in the external cohort. The Kaplan-Meier method was used to estimate and compare the biochemical recurrence-free survival rates between the two groups. ResultsOf 426 men in the development cohort, 45.7% showed adverse pathology outcome on RP. Age, body mass index, prostate specific antigen density, history of prior negative biopsy, magnetic resonance imaging prostate imaging reporting and data system score 4-5 and percentage of positive biopsies were significant predictors in multivariate analysis. A nomogram was constructed with an area under curve of 87%. There was agreement between predicted and actual rates of adverse pathology outcome in the validation cohort. The 5-year biochemical recurrence-free survival rates in patients with and without adverse pathology outcome was 70% and 98%, respectively. ConclusionThis novel nomogram would help identify low-risk PCa men at risk of adverse pathology outcome and can be relevant for treatment decision-making.

The risk of death from prostate cancer in men with Gleason score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.

We evaluated whether intermediate-risk factors, in addition to age, were associated with risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer. We conducted a prospective cohort study of 1,920 men with Gleason 3+4 adenocarcinoma of the prostate who received brachytherapy (BT) or BT and a median of 4 months of androgen deprivation therapy (ADT). Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether percentage of positive biopsies (PPB), cT2b-T2c stage, prostate-specific antigen (PSA) of 10.1-20.0 ng/ml, and age >70 years (median) were associated with risk of PCSM after adjustment for comorbidity. After median follow-up of 7.8 years, 284 men (14.8%) had died (31 from prostate cancer). For BT alone, increasing PPB, PSA of 10.1-20.0 vs. 4.0-10.0 ng/mL, and age >70 vs. ≤70 were significantly associated with increased risk of PCSM (adjusted hazard ratio 1.015, 95% confidence interval 1.000-1.031, P = 0.048; 5.55, 2.01-15.29, P<0.001; and 3.66, 1.16-11.56, P = 0.03, respectively). The respective results for BT and ADT were 1.009, 0.987-1.031, P = 0.44; 4.17, 1.29-13.50, P = 0.02; and 3.74, 0.87-16.05, P = 0.08. Among men with Gleason score 3+4 prostate cancer treated with BT, the risk of PCSM was elevated in those with PSA of 10.1-20.0 ng/mL and possibly age >70 years, despite the addition of ADT. Should these findings be validated in future studies, then advanced imaging and targeted biopsy of suspicious areas should be investigated in an effort to personalize treatment and minimize the risk of PCSM in these men.

SP7.1.14 Our experience of the first 100 cases of prostate biopsy using the Transperineal PrecisionPoint Access system at a hospital in the North West of England

Abstract Aims The diagnosis of prostate cancer has evolved over the past 2 decades with rapid changes occurring in the last 5 years. Traditionally transrectal prostate biopsies were the standard. However due to the risk of sepsis and sub optimal diagnostic accuracy, this method has been superseded by biopsies of the prostate now being performed via the transperineal (TP) route more frequently. Our hospital was the first in our region to use the PrecisionPoint Transperineal Access system to perform TP biopsy under local anaesthetic, and here we present our experience of the first 100 cases. Aims of this study included determining cancer detection rate and MRI correlation, as well as looking at rates of complications post procedure. Method This was a retrospective study with 100 patients in our cohort. We assessed MRI and histology correlation and post procedure complication rates. Results Histology in 72% of patients was positive for prostate cancer. Correlation between MRI findings and histology were noted to be high. As Likert score decreased, so did percentage of positive biopsies. Rates of significant complications were low, with no hospital admissions required following the procedure. Conclusion Our study demonstrates TP biopsy using the PrecisionPoint transperineal access system is a safe and effective method of detecting prostate cancer, which is well tolerated by patients.

Risk of adverse pathological features for intermediate risk prostate cancer: Clinical implications for definitive radiation therapy.

Intermediate risk prostate cancer represents a largely heterogeneous group with diverse disease extent. We sought to establish rates of adverse pathological features important for radiation planning by analyzing surgical specimens from men with intermediate risk prostate cancer who underwent immediate radical prostatectomy, and to define clinical pathologic features that may predict adverse outcomes. A total of 1552 men diagnosed with intermediate risk prostate cancer who underwent immediate radical prostatectomy between 1/1/2005 and 12/31/2015 were reviewed. Inclusion criteria included available preoperative PSA level, pathology reports of transrectal ultrasound-guided prostate biopsy, and radical prostatectomy. Incidences of various pathological adverse features were evaluated. Patient characteristics and clinical disease features were analyzed for their predictive values. Fifty percent of men with high risk features (defined as PSA >10 but <20 or biopsy primary Gleason pattern of 4) had pathological upstage to T3 or higher disease. The incidence of upgrade to Gleason score of 8 or higher and the incidence of lymph node positive disease was low. Biopsy primary Gleason pattern of 4, and PSA greater than 10 but less than 20, affected adverse pathology in addition to age and percent positive biopsy cores. Older age and increased percentage of positive cores were significant risk factors of adverse pathology. Our findings underscore the importance of comprehensive staging beyond PSA level, prostate biopsy, and CT/bone scan for men with intermediate risk prostate cancer proceeding with radiation in the era of highly conformal treatment.

Association of Age With Risk of Adverse Pathological Findings in Men Undergoing Delayed Radical Prostatectomy Following Active Surveillance

ObjectivesTo determine if older men with Gleason grade group (GG) 1 prostate cancer have a higher risk of having adverse pathology at radical prostatectomy after initially being managed with active surveillance (AS). MethodsA total of 365 patients with GG1 prostate cancer initially managed with AS followed by delayed radical prostatectomy were identified. The primary outcome was adverse pathology after delayed radical prostatectomy in the men that were <65 years vs. men ≥65 years at the initiation of AS. Adverse pathology was defined as GG ≥3 or pT3 or pN1. Multivariable Cox proportional hazards regression models were used to calculate risk of adverse pathological findings at radical prostatectomy by age group. ResultsAt diagnosis, there were no significant differences in median prostate specific antigen density, percent positive biopsy cores, multiparametric magnetic resonance imaging (mpMRI) results or composite genomic classifier scores (derived from three commercially available genomic tests) between the two age groups. Men ≥65 years had more adverse pathology at radical prostatectomy (59.2% vs. 44.1%, P <0.01) and lower rates of biopsy upgrade-free survival and adverse pathology-free survival (log-rank P <0.01). On multivariable analysis age ≥65 years (Hazard Ratio (HR) 2.21, 95% Confidence Interval (CI) 1.57, 3.12) was associated with adverse pathology at radical prostatectomy. In separate multivariable analyses done for each age group, mpMRI (HR 3.33, 95% CI 1.01, 10.95) was predictor of adverse pathology in the group ≥65 years. ConclusionOlder patients might require closer monitoring on AS and additional testing such as mpMRI might improve their risk stratification.

A prospective validation of the genomic classifier to define high-metastasis risk in a subset of African American men with early localized prostate cancer: VanDAAM study.

5005 Background: Risk stratification of prostate cancer (PC) using routine clinical variables remains suboptimal as they do not account for underlying tumor biology. The genomic classifier provides information on underlying biology and independently predicts an individual patient’s risk of metastasis. Although the performance of the genomic classifier has been tested across different cohorts primarily comprised of White men, its validation as an optimal genomic risk classifier for African American men (AAM) is thus far lacking in a prospective trial. We report the initial results on the prospective validation of the genomic classifier in a matched cohort of AAM and non-AAM (NAAM). Methods: This was a multisite, prospective validation trial of the genomic classifier i.e. Decipher score in AAM. Participants were recruited on a 1:1 enrollment ratio of AAM to NAAM diagnosed with low-intermediate risk PC. Patient on active surveillance were ineligible. NAAM were matched to AAM on PSA, age, biopsy Gleason score, clinical stage, and percent positive biopsy cores. Diagnostic biopsy specimens were processed at a CLIA certified laboratory and Decipher score was assessed using whole transcriptome profiling platform. Total target accrual was 250 men treated for low-intermediate PC over three years. Statistical analyses include categorical comparison of race dependent risk group migration between NCCN risk group and genomic classifier. Relative risk of metastasis was estimated using negative binomial model. Results: Final analytical cohort included 207 evaluable cases (AAM = 102 and NAAM = 107) with comprehensive genomic information. Risk of metastasis was determined based on pretreatment biopsy Decipher score, and patients were classified as low, favorable-, and unfavorable intermediate risk. Despite achieving a robustly matched clinical cohort, we observed significant genomic heterogeneity between AAM and NAAM across NCCN risk groups. In a comparative analysis, 49% of low-favorable intermediate risk AAM harbored high genomic risk tumors as compared to only 10% NAAM, p = 0.02. Similarly, using the modified clinico-genomic risk classifier (cGC), comprised of both Decipher score and clinical variables, AAM experienced an extreme deviation of risk status (difference [δ] between cGC and NCCN ≥ 2) as compared to NAAM (26.8% vs 8.1%, p = 0.03). In a binomial model, low-favorable NCCN risk AAM were 3.9 times more likely to be reclassified as high genomic risk for distant metastasis compared to NAAM (RR = 3.99, 95% CI, 1.15 – 13.86, p = 0.02). Conclusions: Clinical NCCN risk classification is an inadequate surrogate of tumor biology and offers suboptimal risk stratification for AAM with PC. Integration of patient specific genomic classifier into standard of care will improve accuracy in disease risk classification and treatment recommendations for AAM. Clinical trial information: NCT02723734.

Analyzing the learning curves of a novice and an experienced urologist for transrectal magnetic resonance imaging-ultrasound fusion prostate biopsy.

BackgroundThe aim of the current study was to evaluate and compare the learning curves of transrectal magnetic resonance imaging-ultrasound fusion biopsy for two urologists with different backgrounds (Operator 1: experienced, self-trained and Operator 2: novice, trained by a mentor/MRI reading courses).MethodsA cohort of 400 patients who underwent fusion prostate biopsy in our department was analyzed. The learning curves were assessed in terms of overall and clinically significant prostate cancer (PCa) detection rates, percentage of positive biopsy cores/targeted and the percentage of PCa tissue on positive targeted cores.ResultsIncreasing trends were observed for both urologists in terms of all biopsy outcomes during the study time. For the novice urologist, a significant increase was observed for overall PCa detection rate, but not for clinically significant disease (25.44%, P=0.04/15%, P=0.145). Operator 1 showed an increasing diagnosis yield of clinically significant disease up to 104 cases. Similar cancer detection rates were observed when comparing the first and last biopsies performed by both operators. Multivariate analysis adjusted for age, PSA, prostate volume, lesion diameter and PIRADS score showed an increase of PCa detection with 51% for every 52 biopsies performed (P=0.022).ConclusionsWhen starting with magnetic resonance imaging-ultrasound fusion prostate biopsy, mentoring and prostate magnetic resonance imaging reading training allow a novice urologist to demonstrate a good initial PCa detection rate. After about 52 cases, he reached a stable PCa and clinically significant PCa detection rate, that was similar to that of an experienced urologist.

Impact of percent positive biopsy cores on cancer-specific mortality for patients with high-risk prostate cancer

A high percent positive biopsy cores (PBC), typically dichotomized at ≥50% is prognostic of worse cancer-specific outcomes for patients with low- and intermediate-risk prostate cancer (CaP). The clinical significance of ≥50% PBC for patients with high-risk disease is poorly understood. We examined the association between ≥50% PBC, compared to <50% PBC, and prostate cancer-specific mortality (PCSM) for patients with high-risk disease. We identified 7,569 men from the Surveillance, Epidemiology, and End Results program who were diagnosed with high-risk CaP (Gleason score of 8-10, prostate-specific antigen >20 ng/mL, or cT3-T4 stage) in 2010-2011 and had 6 to 24 cores sampled at biopsy. Multivariable Fine and Gray competing risks regression was utilized to examine the association between ≥50% PBC and PCSM. Median follow-up was 3.8 years. 56.2% of patients (4,253) had ≥50% PBC. On competing risks regression, ≥50% PBC was associated with a significantly higher risk of PCSM compared to <50% PBC (adjusted hazard ratio [AHR] 2.00, 95% confidence interval [CI] 1.48-2.70, P < 0.001). On subgroup analyses, ≥50% PBC was associated with a significantly higher risk of PCSM only for cT1-T2 disease (AHR 2.23, 95% CI 1.62-3.07) but not cT3-T4 disease (AHR 0.83, 95% CI 0.39-1.76), with a significant interaction (Pinteraction = 0.016). No significant interactions by Gleason score, prostate-specific antigen level, use of definitive therapy, or number of biopsy cores sampled were observed. In this large cohort of patients with high-risk CaP, ≥50% PBC was independently associated with an approximately 2-fold increased risk of PCSM for patients with cT1-T2, but not cT3-T4, tumors. Percent PBC, which is a widely available clinical value, should be routinely used to risk stratify men with high-risk disease and identify patients whom may benefit from treatment intensification.

Perineural invasion by prostate adenocarcinoma in needle biopsies predicts bone metastasis: Ten year data from the TROG 03.04 RADAR Trial.

Perineural invasion (PNI) by prostatic adenocarcinoma is debated as a prognostic parameter. This study investigates the prognostic predictive value of PNI in a series of patients with locally advanced prostate cancer treated with radiotherapy and androgen deprivation using 10years outcome data from the TROG 03.04 RADAR trial. Diagnostic prostate biopsies from 976 patients were reviewed and the presence of PNI noted. Patients were followed for 10years according to the trial protocol or until death. The primary endpoint for the study was time to bone metastasis. Secondary endpoints included time to soft tissue metastasis, transition to castration resistance, prostate cancer-specific mortality and all-cause mortality. PNI was detected in 449 cases (46%), with 234 cases (24%) having PNI in more than one core. The presence of PNI was significantly associated with higher ISUP grade, clinical T staging category, National Comprehensive Cancer Network risk group, and percent positive biopsy cores. The cumulative probability of bone metastases according to PNI status was significant over the 10years follow-up interval of the study (log-rank test P<0.0001). PNI was associated with all endpoints on univariable analysis. After adjusting for baseline clinicopathological and treatment factors, bone metastasis was the only endpoint in which PNI retained its prognostic significance (hazard ratio 1.42, 95% confidence interval 1.05-1.92, P=0.021). The association between PNI and the development of bone metastases supports the inclusion of this parameter as a component of the routine histology report. Further this association suggests that evaluation of PNI may assist in selecting those patients who should be monitored more closely during follow-up.

The risk of death from prostate cancer in men with Gleason Score 3+4 prostate cancer treated using brachytherapy with or without a short course of androgen deprivation therapy.

330 Background: We evaluated whether the intermediate-risk factors of percentage of positive biopsies (PPB), clinical tumor category, and prostate-specific antigen (PSA) level, in addition to age, were associated with the risk of prostate cancer-specific mortality (PCSM) among men with Gleason 3+4 prostate cancer treated with brachytherapy (BT) alone or BT and a short course of androgen deprivation therapy (ADT). Methods: We conducted a prospective cohort study of 1920 consecutively treated men with Gleason 3+4 adenocarcinoma of the prostate who received BT or BT and a median of 4 months of ADT between 10/14/1997 and 5/28/2013. Separate multivariable Fine and Gray competing risks regression models among men treated with BT or BT and ADT were used to assess whether PPB, cT2b-T2c, and PSA of 10.1-20.0 ng/ml, in addition to age greater than the median of 70 years, were associated with the risk of PCSM after adjustment for comorbidity. Results: After a median follow-up of 7.8 years (interquartile range 5.2-10.4 years), 284 men (14.8%) had died, including 31 (10.9% of deaths) from PC of which 18 (58.1%) and 13 (41.9%) occurred in men treated with BT or BT and ADT, respectively. For men treated with BT alone, increasing PPB, PSA of 10.1-20.0 vs 4.0-10.0 ng/mL, and age &gt;70 vs ≤70 years were significantly associated with an increased risk of PCSM (adjusted hazard ratio [AHR] 1.015 95% confidence interval [CI] 1.000-1.031, P=0.048; AHR 5.55, 95% CI 2.01-15.29, P&lt;0.001; and AHR 3.66, 95% CI 1.16-11.56, P=0.03, respectively). The respective results for men treated with BT and ADT were AHR 1.009, 95% CI 0.987-1.031, P=0.44; AHR 4.17, 95% CI 1.29-13.50, P=0.02; and AHR 3.74, 95% CI 0.87-16.05, P=0.08. The clinical tumor category was not significantly associated with the risk of PCSM. Conclusions: Among men with biopsy Gleason score 3+4 PC, both age &gt;70 years and PSA of 10.1-20.0 ng/ml were significantly associated with an increased risk of PCSM following BT, and adding 4 months of ADT may not be sufficient to mitigate this risk. Advanced imaging and targeted biopsy of suspicious areas should be considered to personalize treatment in order to minimize the risk of PCSM in these men.

Advancing age and the risk of adverse pathology at radical prostatectomy in men with biopsy Gleason score 6 prostate cancer.

289 Background: We evaluated the impact of age &gt; 65 years versus younger on the odds of finding adverse pathologic features (pT3/T4 and/or R1 and/or Gleason score 8, 9, 10) at radical prostatectomy (RP) among men with biopsy Gleason score 6 prostate cancer (PC). Methods: The study cohort comprised 3191 men with biopsy Gleason score 6 PC treated with a RP between February 28, 1992 and February 15, 2016 at the Martini-Klinik Prostate Cancer Center. Multivariable logistic regression was used to evaluate the impact of age &gt; 65 years versus younger on the adjusted odds ratio (AOR) of finding adverse pathology at RP adjusting for pre-RP prostate specific antigen (PSA), clinical tumor category, year of diagnosis, percent positive biopsies (PPB), and PSA density (PSAd). Results: Men age &gt; 65 years as compared to younger had significantly lower median PPB (16.67% vs 20.0%; p = 0.01) and PSAd (0.13 ng/mL vs 0.15 ng/mL; p &lt; 0.0001). Yet, while both increasing PPB (AOR 1.018, 95% CI 1.013, 1.023; p- &lt; 0.0001) and PSAd (AOR 4.28, 95% CI 1.66, 11.01; p = 0.003) were significantly associated with an increased odds of finding adverse pathology at RP, men age &gt; 65 years versus younger had a higher odds of adverse pathology at RP (AOR 1.28, 95% CI 1.002, 1.62; p = 0.048). Conclusions: Despite a more favorable median PPB and PSAd, men with biopsy Gleason score 6 PC and who are age &gt; 65 years compared to younger men are at higher risk for having adverse pathology at RP and may benefit from a multiparametric MRI and targeted biopsy before proceeding with active surveillance. If higher grade/stage disease is discovered and treatment indicated then this information could guide both the use and duration of supplemental androgen deprivation therapy in men considering radiation therapy.

Таргетная биопсия простаты в диагностике рака предстательной железы: результаты проспективного группового исследования

Background. Detection of prostate cancer by various targeting methods of prostate biopsy is an important problem now. Aim. To improve the detection of prostate cancer (PCa), compare the methods of targeted biopsy – cognitive biopsy guided by MRI with biopsy guided by histos-canning, using a randomized biopsy of the prostate from twelve cores as a control method. Materials and methods. A total of 145 respondents who underwent a randomized biopsy of the prostate in combination with targeted techniques were divided into 3 samples in accordance with the methods of targeted biopsy. In the results, the detectability by targeted methods was compared with each other and with a randomized biopsy as a control method. The results were subjected to statistical processing in order to form the conclusions of the study. Results. The detection rate of prostate cancer in the cognitive biopsy group was 64.4%, in the histofusion group – 51.1%, in the cognitive biopsy with histofusion group – 69% (p&lt;0.05). The detection of PCa when comparing positive targeted biopsies did not differ statistically significantly between the methods (38 and 36%, p=0.05). The percentage of positive biopsies was higher with histofusion biopsy (34.2%) than with cognitive biopsy (29.7%), the incidence of clinically sig-nificant cancer was higher according to the results of targeted methods compared with randomized biopsy (73% vs 37.5%, p&lt;0.05). The highest complication rate with the combined use of the studied targeting techniques was 13.6%, while all complications belonged to the 1st category according to Clavien–Dindo. Conclusion. To optimize the diagnosis of prostate cancer, it is advisable to use a combination of targeted and “randomized” cores. The combination of the targeted methods studied has been shown to be effective and safe. Carrying out a histofusion biopsy using a unified technique allows obtaining information on the clinical and morphological characteristics of prostate adenocarcinoma, which in terms of prognostic value is practically not inferior to the data of a cognitive biopsy performed taking into account the results of MRI. The use of targeted prostate biopsy methods increases the detection of clinically significant prostate cancer without adversely affecting the safety of the procedure in conjunction with standard prostate biopsy.

Overexpression of certain transient receptor potential and Orai channels in prostate cancer is associated with decreased risk of systemic recurrence after radical prostatectomy.

Several studies had suggested the potential role of calcium signaling in prostate cancer (PCa) prognosis and agressiveness. We aimed to investigate selected proteins contributing to calcium (Ca2+ ) signaling, (Orai, stromal interaction molecule (STIM), and transient receptor potential (TRP) channels) and involved in cancer hallmarks, as independent predictors of systemic recurrence after radical prostatectomy (RP). A case-control study including 112 patients with clinically localized PCa treated by RP between 2002 and 2009 and with at least 6-years' follow-up. Patients were divided into two groups according to the absence or presence of systemic recurrence. Expression levels of 10 proteins involved in Ca2+ signaling (TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, STIM1, STIM2, Orai1, Orai2, and Orai3), were assessed by immunohistochemistry using tissue microarrays (TMAs) constructed from paraffin-embedded PCa specimens. The level of expression of the various transcripts in PCa was assessed using quantitative polymerase chain reaction (qPCR) analysis. RNA samples for qPCR were obtained from fresh frozen tissue samples of PCa after laser capture microdissection on RP specimens. Relative gene expression was analyzed using the method. Multivariate analysis showed that increased expression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 was significantly associated with a lower risk of systemic recurrence after RP, independently of the prostate-specific antigen (PSA) level, percentage of positive biopsies, and surgical margin (SM) status (P = .007, P = .01, P < .001, P = .0065, P = .007, and P = .01, respectively). For TRPC4, TRPV5, and TRPV6, this association was also independent of Gleason score and pT stage. Moreover, overexpression of TRPV6 and Orai2 was significantly associated with longer time to recurrence after RP (P = .048 and .023, respectively). Overexpression of TRPC4, TRPV5, TRPV6, and Orai2 transcripts was observed in group R- (3.71-, 5.7-, 1.14-, and 2.65-fold increase, respectively). This is the first study to suggest the independent prognostic value of certain proteins involved in Ca2+ influx in systemic recurrence after RP: overexpression of TRPC1, TRPC4, TRPV5, TRPV6, TRPM8, and Orai2 is associated with a lower risk of systemic recurrence. TRPC4, TRPV5, and TRPV6 appear to be particularly interesting, as they are independent of the five commonly used predictive factors, that is, PSA, percentage of positive biopsies, SM status, Gleason score, and pT stage.