Self-reported Black race predicts significant prostate cancer independent of clinical setting and clinical and socioeconomic risk factors

Introduction and Objective

Studies have linked Black race to prostate cancer (CaP) risk but most fail to account for established risk factors such as 5-ARI use, prostate volume, socioeconomic status, and hospital setting. We assess whether Black race remains associated with CaP and Gleason ≥3?+?4 CaP, after adjusting for clinical setting and socioeconomic and clinical factors at prostate biopsy, with a focus on men aged 40-54 years, who may be excluded from current screening guidelines.

Getting back to equal: The influence of insurance status on racial disparities in the treatment of African American men with high-risk prostate cancer

ObjectivesTreating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP.Materials and methodsThe Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level >20 ng/ml or Gleason score 8–10 or stage>cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy.ResultsCompared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] = 0.60; 95% CI: 0.56–0.64; P<0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P_interaction = 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P<0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P<0.001) among insured men.ConclusionsAA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers.     

Low risk prostate cancer in men ≥ 70 years old: To treat or not to treat

ObjectivesProstate cancer (CaP) in the aging male will become an increasingly important and controversial health care issue. We evaluated the outcomes between a variety of treatments for low-risk CaP in patients 70 years of age and older.Methods and materialsA total of 3,650 men diagnosed with CaP between 1989 and 2009 were identified in the Center for Prostate Disease Research database to be 70 years of age or older at time of diagnosis. Of these patients, 770 men met the D'Amico criteria ^[13] for low-risk disease and were treated with radical prostatectomy, external beam radiation therapy, or watchful waiting. Cox proportional hazard models were used to compare clinicopathologic features across treatment groups. Kaplan-Meier analysis was used to compare biochemical recurrence-free, progression-free, and overall survival.ResultsOf the 770 patient cohort, 194 (25%) chose radical prostatectomy, 252 (33%) chose external beam radiation therapy, and 324 (42%) were initially managed by watchful waiting with 110 (34%) of this subset ultimately undergoing secondary treatment. The median follow-up was 6.4 years. There were no significant differences in distributions of race/ethnicity, number of medical comorbidities, or clinical stage across the treatment groups. Patients managed on watchful waiting without secondary treatment had the poorest overall survival on Kaplan-Meier analysis (P = 0.0001). Additionally, multivariate analysis confirmed this result for watchful waiting without secondary treatment as being a statistically significant predictor of overall mortality (HR 1.938, P = 0.0084).     

Statin use and risk of prostate cancer biochemical recurrence after radical prostatectomy

BackgroundMultiple studies have investigated the role of statins in prostate cancer (CaP), the leading cause of cancer related death in men. Retrospective cohort studies investigating the correlation between statin use and biochemical recurrence free (BCRF) survival in men with CaP have been inconclusive.ObjectivesIn the largest reported surgical cohort to date, we investigated the effect of statin therapy on BCRF and overall survival in patients with CaP who have undergone radical prostatectomy (RP).Patients and methodsWe performed a retrospective analysis of men (n = 3,088) participating in the NCI funded Specialized Program of Research Excellence (SPORE) in CaP at Northwestern University (NM) in Chicago, Illinois. Patients were treated with RP between 2002 and 2015. Patients in the statin users group received treatment within 2 years prior to or subsequent to RP. Wilcoxon rank-sum and Fisher's exact tests were used to compare age, race, Gleason score, clinical staging, and pathological stage between statin users and nonstatin users.ResultsThe analysis identified 1,222 statin users and 1,865 nonusers (mean age 71 years, 92% Caucasian). After a median follow-up time of 49.0 months, the 5-year BCRF survival rate was 93.3% (95% confidence interval [CI]: 91.9–94.8%) among statin users and 88.6% (95% CI: 87.1%–90%) among nonusers (log-rank P< 0.001). After 10 years, the progression-free survival (PFS) was 91.7% (95% CI: 90.1%–93.3%) among statin users and 86.5% (95% CI: 84.4%–88.2%) among nonusers (log-rank P< 0.001).ConclusionsExtended follow-up data in this large surgical cohort show statin use improves BCRF but not overall survival in RP patients.     

Pathologic upgrading in favorable intermediate risk active surveillance patients: Clinical heterogeneity and implications for active surveillance decision

IntroductionCurrent guidelines support active surveillance (AS) for select patients with favorable intermediate risk (FIR) prostate cancer (CaP). A significant proportion of FIR CaP patients undergoing surgical treatment are found to have evidence of adverse pathology. Our objective was to determine the incidence and predictors of pathologic upgrading in FIR AS patients undergoing radical prostatectomy.Materials and methodsThe Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting (WW) database was used to identify men younger than 80 years with National Comprehensive Cancer Network FIR CaP initially opting for AS and/or WW between 2010 and 2015 and subsequently underwent radical prostatectomy at least one year following diagnosis. Patients were assigned into one of three subgroups based on their intermediate risk factor: Gleason Score 7(3 + 4) (Group 1), prostate specific antigen level of 10-20 ng/ml (Group 2), and cT2b-c (Group 3). Pathologic upgrading was present in Group 1 if pathologic GS was 7 (4 + 3) or worse. For patients in Groups 2 and 3, upgrading occurred if pathologic GS was 7 (3 + 4) or worse. Oncologic and sociodemographic predictors of pathologic upgrading were evaluated univariable and multivariable logistic regression analysis.Results18,760 patients were identified. Pathologic upgrading occurred in 138 (13.3%), 59 (25.0%), and 8,011 (45.8%) patients in groups 1, 2, and 3 respectively. Pathologic downgrading occurred in 226 (21.7%) patients in group 1. Significant predictors of pathologic upgrading on multivariable analysis included older age at diagnosis: 70 to 79 vs. 40 to 49 years (Groups 1 and 3, P < 0.05), a more recent diagnosis: 2014 to2015 vs. 2010-2011 (Groups 2 and 3, P < 0.005), higher volume disease: 37.5% to 49.9% vs. 0% to 12.4% (Groups 2 and 3, P < 0.005), and clinically palpable disease (Groups 1 and 2, P < 0.05). Additional risk factors for upgrading included uninsured or Medicaid status, diagnosis in a Western region (Group 2), African American ethnicity and higher socioeconomic status (Group 3)ConclusionsFIR CaP is a clinically heterogeneous risk group with incidence of pathologic upgrading ranging from 13.3% in those with GS 7 (3 + 4) to 45.8% in those with cT2b-c disease. Risk of pathologic upgrading in FIR CaP patients initially managed with AS and/or WW is significantly associated with multiple patient-level oncologic and sociodemographic variables.     

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men

PurposeTo explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment—postsurgery (CAPRA-S) features following prostatectomy (RP).MethodsThe overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores.ResultsWith a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08–3.72; P = 0.029).ConclusionsAA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment.     

Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions

ObjectivesWe sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Materials and MethodsMulticenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.ResultsMen with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 μm²/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml², P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92–0.97), lower ADC value (OR: 0.99, 95% CI: 0.99–1.00), and Prostate-specific antigen density >0.15 ng/ml² (OR: 3.51, 95% CI 1.61–7.68) were independently associated with significant CaP.ConclusionHigher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.     

Radical prostatectomy for patients with high-risk,very-high risk,or radiographic suspicion for metastatic prostate cancer: Perioperative and early oncologic results from the MUSIC statewide collaborative

ObjectiveHigh-risk (HR) prostate cancer (CaP) patients are at greatest risk for occult metastases and disease progression. Radical prostatectomy (RP) provides benefit, but remains of unknown oncologic value compared with other options. We investigated outcomes of RP for HR, very-high-risk (VHR), or metastatic CaP.MethodsIncluded are 1,635 patients undergoing RP between January 2012 and December 2018 (prior to widespread availability of CaP-specific PET imaging). VHR CaP was defined as having ≥2HR features, >4cores of biopsy Gleason ≥4+4, or primary Gleason pattern 5. Metastatic CaP was defined by radiographic evidence of N1 and/or M1 CaP and grouped as cN1M_any and cN0M1. Pre-treatment, perioperative, and early oncologic data were compared. Patient/tumor characteristics were compared according to risk groups using Chi-squared and Wilcoxon rank-sum tests. Kaplan-Meier analysis of cancer progression and multivariable analyses were performed.ResultsLength of stay >2days and readmission following RP was 10.8% and 5.5% for patients with HR or higher CaP. Median time to progression was 3.9 months (IQR:1.6–13.9), and 2-year progression-free probability was 67% for HR, 53% for VHR, 51% for cN1M_any, and 58% for cN0M1. In multivariable analysis, VHR (hazard ratio:1.70; P < 0.0001) and cN1M_any (1.96, P < 0.0001) were highly significant predictors of progression, while cN0M1 was not (P = 0.54), compared with non-metastatic HR CaP. Limitations include selection biases and imprecision of imaging methodologies.ConclusionsMost patients with HR or higher CaP remain progression-free 2 years after RP, with acceptable perioperative outcomes. Progression-free survival was similar in cN1 and VHR patients, better with non-metastatic HR CaP, and between these for cN0M1 patients indicating the imprecise clinical staging occurring with conventional imaging modalities alone.     

The characteristics of bladder cancer after radiotherapy for prostate cancer

ObjectivesProstate radiotherapy (RT) has been associated with an increased risk of bladder cancer (CaB). However it is unknown how prior RT affects the stage, grade, and histology of secondary CaB. While irradiated patients have adverse surgical outcomes, how RT affects survival is also unknown. We sought to determine how RT for prostate cancer (CaP) affects the characteristics and outcomes of secondary CaB.Materials and methodsA retrospective review of 275,200 cases of clinically localized CaP submitted to the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2007 was performed. CaP treatment was stratified by radical prostatectomy (RP) alone, RT, or RP + RT. Diagnosis of CaB at least 1 year after CaP, and CaB death were the primary outcomes. The stage, grade, and histology of CaB of patients exposed to RT or RP were compared. A competing risks multivariable survival analysis was performed to determine the effect of RT on CaB-specific mortality.ResultsCaP patients treated with any RT were 1.70 times as likely to develop CaB (95% CI 1.57–1.86, P < 0.001) compared with RP alone. CaB in men who had RT were more likely non-urothelial (6.4% vs. 3.8%, P = 0.004), trigonal (6.9% vs. 5.4%, P = 0.012), and carcinoma in-situ (CIS) (9.2% vs. 7.0%, P < 0.001) compared with RP. RT increased CaB-specific mortality (HR = 1.30, P = 0.02), which remained significant when adjusted for CaB features (HR = 1.28, P = 0.05).ConclusionsPatients with localized CaP treated with RT have a higher risk of CaB. CaB after RT is more likely to be located at the trigone and contain CIS. Patients with CaB after RT have decreased cancer-specific survival compared with those undergoing RP alone.     

Serum levels of chromogranin A are not predictive of high-grade,poorly differentiated prostate cancer: Results from an Italian biopsy cohort

ObjectivesTo explore the association of chromogranin A (CgA) levels and the risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate biopsy.Materials and methodsBetween 2006 and 2012, we prospectively enrolled 1,018 men with no history of CaP undergoing prostate biopsy. The risk of detecting poorly differentiated CaP as a function of CgA concentration was evaluated using crude and adjusted logistic regressions. Further analyses were performed to determine whether CgA was a significant predictor of high-grade CaP in men with low PSA (<10 ng/ml).ResultsWe found a significantly higher level of CgA in men with poorly differentiated CaP. CgA was however co-linear with age, and serum CgA levels were not significantly associated with the overall risk of CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99–1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99–1.01; P = 0.66) and multivariate analysis (P = 0.85).ConclusionsIn our cohort of patients, the serum level of CgA is not a significant predictor of poorly differentiated CaP on initial prostate biopsy, even in men with low PSA levels (<10 ng/ml). According to our experience, CgA should not be considered a reliable marker to predict poorly differentiate cancer in the setting of initial prostate biopsy.     

Marital status independently predicts testis cancer survival—an analysis of the SEER database

ObjectivesPrevious reports have shown that married men with malignancies have improved 10-year survival over unmarried men. We sought to investigate the effect of marital status on 10-year survival in a U.S. population-based cohort of men with testis cancer.Materials and methodsWe examined 30,789 cases of testis cancer reported to the Surveillance, Epidemiology, and End Results (SEER 17) database between 1973 and 2005. All staging were converted to the 1997 AJCC TNM system. Patients less than 18 years of age at time of diagnosis were excluded. A subgroup analysis of patients with stages I or II non-seminomatous germ cell tumors (NSGCT) was performed. Univariate analysis using t-tests and χ² tests compared characteristics of patients separated by marital status. Multivariate analysis was performed using a Cox proportional hazard model to generate Kaplan-Meier survival curves, with all-cause and cancer-specific mortality as the primary endpoints.Results20,245 cases met the inclusion criteria. Married men were more likely to be older (38.9 vs. 31.4 years), Caucasian (94.4% vs. 92.1%), stage I (73.1% vs. 61.4%), and have seminoma as the tumor histology (57.3% vs. 43.4%). On multivariate analysis, married status (HR 0.58, P < 0.001) and Caucasian race (HR 0.66, P < 0.001) independently predicted improved overall survival, while increased age (HR 1.05, P < 0.001), increased stage (HR 1.53–6.59, P < 0.001), and lymphoid (HR 4.05, P < 0.001), or NSGCT (HR 1.89, P < 0.001) histology independently predicted death. Similarly, on multivariate analysis, married status (HR 0.60, P < 0.001) and Caucasian race (HR 0.57, P < 0.001) independently predicted improved testis cancer-specific survival, while increased age (HR 1.03, P < 0.001), increased stage (HR 2.51–15.67, P < 0.001), and NSGCT (HR 2.54, P < 0.001) histology independently predicted testis cancer-specific death. A subgroup analysis of men with stages I or II NSGCT revealed similar predictors of all-cause survival as the overall cohort, with retroperitoneal lymph node dissection (RPLND) as an additional independent predictor of overall survival (HR 0.59, P = 0.001), despite equal rates of the treatment between married and unmarried men (44.8% vs. 43.4%, P = 0.33).ConclusionsMarital status is an independent predictor of improved overall and cancer-specific survival in men with testis cancer. In men with stages I or II NSGCT, RPLND is an additional predictor of improved overall survival. Marital status does not appear to influence whether men undergo RPLND.     

Pathologic nodal downstaging in men with clinically involved lymph nodes undergoing radical prostatectomy: Implications for definitive locoregional therapy

A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.     

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy,with vs. without hormonal therapy

IntroductionCombined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT).MethodsPatients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time.ResultsOf 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores.ConclusionCombined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.     

Decisional regret after robotic-assisted laparoscopic prostatectomy is higher in African American men

ObjectivesLongitudinal studies report racial disparities in prostate cancer (PCa) including greater incidence, more aggressive tumor biology, and increased cancer-specific mortality in African American (AA) men. Regret concerning primary treatment selection is underevaluated in patients with PCa. We investigated the relationships between clinicopathologic variables across racial and socioeconomic lines following robotic-assisted laparoscopic prostatectomy.Materials and methodsWe assessed treatment decisional regret using a validated questionnaire in a total of 484 white and 72 AA patients with PCa who were followed up for a median of 16.6 months post–robotic-assisted laparoscopic prostatectomy. Socioeconomic status (SES) information was aggregated from 2010 US census zip code data. Perioperative clinicopathologic characteristics and functional outcomes were compared between groups. Univariate and multivariate regression analyses were used to evaluate the influence of race, aggregate SES, and other clinical and demographic characteristics on decisional regret.ResultsThe majority (87.7%) of the population was not regretful of their decision to undergo treatment. However, a greater proportion of AA vs. white patients were regretful (20.6% vs. 11.2%, respectively; P = 0.03). AA and white men were similar on all functional, clinical, and pathologic features with the exception of younger age among AA men (56 vs. 60 y, respectively; P<0.001). Although there were significant differences in SES by race (P<0.001), regret did not differ by SES (β =?1.53; P = 0.15). Race, postoperative sexual dysfunction, pad usage, and length of hospital stay, however, were significantly associated with decisional regret.ConclusionsAA men were more regretful than white men, after adjusting for clinicopathologic characteristics and postoperative functional outcomes.     

HIFU as salvage first-line treatment for palpable, TRUS-evidenced, biopsy-proven locally recurrent prostate cancer after radical prostatectomy: a pilot study

ObjectiveTo test high-intensity focused ultrasound (HIFU) as salvage first-line treatment for palpable, TRUS-evidenced, biopsy-proven locally recurrent prostate cancer (CaP) after radical prostatectomy (RP).Materials and methodsNineteen patients with palpable, TRUS-evidenced, biopsy-proven local recurrence of CaP after RP, unwilling to undergo salvage radiotherapy (SRT), underwent HIFU as a single-session procedure. Pre-, intra-, and postoperative data including early and late complications, and oncologic outcomes (PSA nadir, biochemical recurrence (BCR)-free survival, and need of secondary adjuvant treatment) were prospectively evaluated. Success was defined as PSA nadir ≤0.1 ng/ml obtained within 3 months from HIFU. In case of PSA nadir >0.1 ng/ml or PSA increase ≥1 ng/ml above the PSA nadir, a biopsy of the treated lesion was performed, and if negative, maximum androgen blockade (MAB) was adopted. In case of positive biopsy, RT was performed. Failure was defined as use of secondary adjuvant treatment (MAB or RT).ResultsMedian follow-up was 48 months. All cases were performed as overnight procedure. No case of urethrorectal fistula or anastomotic stricture was observed. Two cases of acute urinary retention were resolved with prolonged urethral catheterization. Four cases of stress urinary incontinence were observed; 2 (mild incontinence) were resolved after pelvic floor exercises within 6 months, while 2 cases of severe incontinence required surgical minimally invasive treatment;17/19 patients (89,5%) were classified as success. Two patients failed to show a PSA nadir <0.1 ng/ml. During follow-up, 8/17 patients (47%) were classified as failure, with consequent total rate of failures 10/19 (52.6%). A statistically significant difference was observed in pre-HIFU median PSA (2 vs. 5.45 ng/ml, respectively, P = 0.013) and Gleason score of the RP specimen (P = 0.01) between the success and failure group.ConclusionsSalvage first-line HIFU for palpable, TRUS-evidenced, biopsy-proven local recurrence of CaP is a feasible, minimally invasive day-case procedure, with an acceptable morbidity profile. It seems to have a good cancer control in the short- and mid-term. Patients with lower pre-HIFU PSA level and favorable pathologic Gleason score presented better oncologic outcomes. A prospective randomized trial with an adequate recruitment and follow-up is necessary to confirm our preliminary oncologic results.     

Prostatic-specific antigen density behavior according to multiparametric magnetic resonance imaging result

ObjectiveTo analyze prostatic-specific antigen density (PSAD) according to the Prostate Imaging Reporting and Data System (PIRADSv.2) score, in order to determine how it should be used.MethodsThis correlative series considered 952 men with prostatic-specific antigen >3 ng/ml and/or abnormal digital rectal examination who were subjected to prostatic biopsy (PB) between 2016 and 2017. Of these men, 768 had no previous 5-α-reductase inhibitor use or history of prostate cancer (CaP) and had previously undergone 3-T multiparametric magnetic resonance imaging (mpMRI). In this sample, 549 men were biopsy-naïve and 219 had at least 1 previous negative PB. A 12-core transrectal ultrasound-guided PB was performed in all participants, as well as at least 2-core targeted biopsies of every detected lesion with a PIRADSv.2 score ≥3. Significant CaP (sCaP) was defined as an International Society of Uropathologist grade >1 or tumor length >4 mm.ResultsThe overall CaP detection was 41.7%, with sCaP detected in 37.4%. sCaP was detected in 4.3% of PIRADSv.2 <3, 21.5% of PIRADSv.2 =3, 56.6% of PIRADSv.2 =4, and 78.5% of PIRADSv.2 =5, (P < 0.001). Insignificant CaP detection ranged from 6.5% to 1.5% respectively (P = 0.099). PSAD was an independent predictor of sCaP (odds ratios 1.971, 95% confidence interval [1.633, 2.378], P <0.001) and mpMRI (OR 3.179, 95%CI [2.593, 4.950], P < 0.001). Age (P = 0.013), family history of CaP (P = 0.021), and the type of PB (initial vs. repeated, P < 0.001) were also independent predictors of sCaP. PSAD was determined by PIRADSv.2 (P = 0.013) and the presence of sCaP (P < 0.001). PSAD increased with PIRADSv.2 score, even in men with CaP (P < 0.001) and slightly in men without CaP (P = 0.019). The area under the curve for mpMRI increased from 0.830 to 0.869 when PSAD was associated, (P < 0.001). The area under the curve of PSAD decreased from 0.727 in men with a PIRADSv.2 score <3 to 0.706 in those with a score of 5.ConclusionsThe efficacy of PSAD to detect sCaP decreases with PIRADSv.2. Predictors other than mpMRI and PSAD exist. Considering these conditions, independent predictors should be integrated in a nomogram and risk-calculator to personalize PB recommendation.     

Oncologic outcomes of organ-confined Gleason grade group 4-5 prostate cancer after radical prostatectomy

BackgroundOrgan-confined prostate cancer (CaP) at radical prostatectomy (RP) is associated with good long-term outcomes. However, information for aggressive Gleason organ-confined CaP is scant. To investigate the impact of Gleason grade group (GG) 4-5 on long-term oncologic outcomes after RP.MethodsWithin a high-volume center database we identified patients who harbored organ-confined CaP (pT2) at RP between 1992 and 2017. Only patients with negative surgical margins, without lymph node invasion and without neo- and/or adjuvant androgen deprivation therapy and/or adjuvant radiotherapy were included. Patients with GG1 were excluded. Kaplan-Meier analyses and Cox regression models tested the effect of GG4 and GG5 on biochemical recurrence-free (BFS), metastasis-free (MFS), overall survival (OS) and cancer-specific mortality (CSM) free survival.Results and limitationsOf 10,855 identified pT2 patients, 0.1% (n=81) and 0.1% (n=114) harbored GG4 and GG5, respectively. At 10-years after RP, BFS, MFS, OS and CSM-free rates were 80.3 vs. 68.6 vs. 55.4% (P<0.001), 96.7 vs. 89.9. vs. 83.4% (P<0.001), 93.2 vs. 78.3 vs. 72.6% (P<0.001) and 99.3 vs. 98.0 vs. 82.7% (P<0.001) for GG2 and GG3 vs. GG4 vs. GG5, respectively. In multivariable Cox regression models, GG5 represented an independent predictor for biochemical recurrence (Hazard ratio [HR] 3.00, P<0.001), metastasis (HR 5.01, P<0.001), death (HR 2.72, P<0.01) and cancer-specific death (HR 30.1, P<0.001). Conversely, GG4 represented an independent predictor for death (HR 2.10, P=0.04) and cancer-specific death (HR 6.09, P=0.01) but not for biochemical recurrence and metastasis.ConclusionGG4/5 in organ-confined CaP is rare. But its associated with worse oncologic outcomes after RP, namely biochemical recurrence, metastasis, death and cancer-specific death. Patients with organ-confined GG4/5 and negative margins should be closely followed and may be candidates for risk stratification by genomic markers.     

A replication study examining association of rs6983267, rs10090154, and rs1447295 common single nucleotide polymorphisms in 8q24 region with prostate cancer in Siberians

IntroductionMultiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer (CaP). However, the risk conferred in men living in Russia is unknown.Materials and methodsIn this work we studied the association of rs6983267, rs10090154, and rs1447295 single nucleotide polymorphisms (SNPs) with a risk of CaP development in men of Caucasoid descent living in the Siberian region of Russia. Three 8q24 SNPs were genotyped by real-time polymerase chain reaction in histologically confirmed CaP “cases” (n = 392) and clinically evaluated “controls” (n = 344). To evaluate the SNP effects on CaP susceptibility, odds ratio (OR) and confidence interval (CI) 95% were calculated. Allele and genotype frequencies in the groups were compared using logistic regression; differences were considered statistically significant if P<0.05.ResultsWe showed statistically significant association of the A allele of rs1447295 (OR [CI 95%] = 1.96 [1.37–2.81], P<0.0001) and the T allele of rs10090154 (OR [CI 95%] = 2.14 [1.41–3.26], P<0.0001) with CaP. The T-A rs10090154 to rs1447295 haplotype was also associated with CaP (OR [CI 95%] = 2.47 [1.59–3.85], P<0.0001). There was no significant association with the T allele of rs6983267: OR [CI 95%] = 0.9 [0.73–1.11], P> 0.05.ConclusionThus, our investigation confirms the role of chromosomal region 8q24 in the development of CaP in the Russian population.