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Abstract: The management of low risk prostate cancer, defined as Gleason’s sum ≤6, PSA <10 ng/ml, and clinical stage T1c to T2a, remains controversial. There is substantiating evidence to suggest that a subset of early stage, low risk cancers can cause significant patient morbidity and death in the long term. Studies have shown that the natural history of untreated prostate cancer is to progress, particularly after 15 years of followup. The majority of men seeking definitive surgical treatment in contemporary series fall within 55 to 65 years of age and are expected to enjoy an overall life expectancy ranging from about 15 to 30 years, placing these men at long-term risk for disease progression and prostate cancer-specific death if managed expectantly. During the past 2 decades, refinements in surgical technique and in the delivery of external beam radiation have resulted in excellent long-term cancer control and favorable quality of life outcomes following treatment. Active surveillance with selective delayed intervention assumes that an individual’s cancer will not progress outside the window of curability during the surveillance period, that markers for disease progression are reliable, and that patients are compliant. Until we understand better the long-term natural history of untreated prostate cancer, have more reliable and accurate markers to detect disease progression with certainty, and can risk stratify more precisely the subgroup of men with low risk cancers who will eventually succumb to their disease, early definitive therapy seems prudent. [Copyright &y& Elsevier]

• The natural history of MIBC treated without curative intent is not well known. • Most patients (88%) were not treated due to low performance status. • 2-year cancer specific and overall survivals were 18% and 12%, respectively. • During follow-up 65% of patients suffered from recurrent hematuria. • About 59% of patients required catheter insertion and 37% had a nephrostomy tube. Muscle-invasive bladder cancer is an aggressive disease. Yet, many patients, especially those with advanced age and multiple comorbidities, do not receive treatment with curative intent. We evaluated the disease course and health care burden of these patients. Bi-center, retrospective analysis of patients diagnosed with muscle-invasive bladder cancer who did not undergo curative-intent treatment (radical cystectomy or trimodal therapy) between 2016 and 2021. Patient characteristics and treatment burden were described. Metastasis-free, cancer-specific, and overall survivals were evaluated using the Kaplan-Meier method. Sixty-six patients with a median age of 86 (IQR 78,90) were evaluated. The median follow-up for survivors was 29 months (IQR 9, 44). All patients were diagnosed with muscle-invasive bladder cancer, and 32 (48%) presented with clinical T3 and T4 disease. The median age adjusted Charlson comorbidity index at diagnosis was 7 (IQR 6,8). Treatment with curative intent was not provided due to comorbidities and low-performance status in 58 patients (88%) and patient refusal in 8 (12%). Two-year estimated metastasis-free survival, cancer-specific survival, and overall survival were 11%, 18%, and 12%, respectively. During follow-up, 7 patients (10%) were treated with chemotherapy, 4 (6%) received immunotherapy, 21 (32%) radiation, and 17 (26%) had emergent operations due to hematuria. Twenty-four patients (37%) required nephrostomy tubes, and 39 (59%) required an indwelling urinary catheter for various periods. Forty-three patients (65%) suffered from recurrent hematuria episodes. Overall, median emergency room visits were 4 (IQR 2, 6), and median hospital admission was 16 days (IQR 9, 29). Untreated muscle-invasive bladder cancer is associated with a limited lifespan and a high disease burden for the patient and health system. These data should be taken into consideration and portrayed to the patient when curative intent treatment is chosen to be avoided. [ABSTRACT FROM AUTHOR]

• Tumor density is calculated by dividing the tumor and prostate volumes. • Median peripheral zone tumor density was 0.01. • Peripheral tumor density was associated with clinically significant prostate cancer. • The peripheral tumor density threshold was defined as 0.006. • Sensitivity, specificity, PPV, and NPV were 0.9, 0.51, 0.57, and 0.88, respectively. Multiparametric magnetic resonance imaging (mpMRI) is central to diagnosing prostate cancer; however, not all imaged lesions represent clinically significant tumors. We aimed to evaluate the association between the relative tumor volume on mpMRI and clinically significant prostate cancer on biopsy. We retrospectively reviewed the medical records of 340 patients who underwent combined transperineal targeted and systematic prostate biopsies between 2017 and 2021. Tumor volume was estimated based on the mpMRI diameter of suspected lesions. Relative tumor volume (tumor density) was calculated by dividing the tumor and prostate volumes. The study outcome was clinically significant cancer on biopsy. Logistic regression analyses were used to evaluate the association between tumor density and the outcome. The cutoff for tumor density was determined with ROC curves. Median estimated prostate and peripheral zone tumor volumes were 55cm3 and 0.61cm3, respectively. Median PSA density was 0.13 and peripheral zone tumor density was 0.01. Overall, 231 patients (68%) had any cancer and 130 (38%) had clinically significant cancer. On multivariable logistic regression age, PSA, previous biopsy, maximal PI-RADS score, prostate volume, and peripheral zone tumor density were significant predictors of outcome. Using a threshold of 0.006, the sensitivity, specificity, positive and negative predictive values of peripheral zone tumor density were 0.9, 0.51, 0.57, and 0.88, respectively. Peripheral zone tumor density is associated with clinically significant prostate cancer in patients with PI-RADS 4 and 5 mpMRI lesions. Future studies are required to validate our findings and evaluate the role of tumor density in avoiding unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Introduction: Concurrent systematic biopsies during image-guided targeted biopsies of the prostate were found to improve the detection rate of clinically significant prostate cancer (CSPC). However, these biopsies do not routinely include anterior or apical sampling. We aimed to evaluate the significance of anterior and apical samplings during combined biopsies.Methods: After obtaining institutional review board approval we identified 303 consecutive patients who underwent transperineal combined biopsies of the prostate between 2017-2020. Systematic biopsies were obtained from the peripheral zone, anterior zone, and apex. Study outcomes included CSPC and any cancer on anterior or apical biopsies. Logistic regression analyses were used to evaluate the association between pre-biopsy characteristics and study outcomes.Results: Median prostatic-specific-antigen value was 6.8 ng/dL. Most patients had stage T1c disease (77%). Overall, combined biopsies detected CSPC in 87 patients (29%). Any cancer and CSPC in the anterior zone were found in 54 (18%) and 19 (6%) patients, respectively. Any cancer and CSPC in the apex were found in 54 (18%) and 16 (5%) patients, respectively. Anterior/apical samplings upgraded the pathological result in 19 patients (6%). Logistic regression analyses demonstrated that PI-RADS 5 lesions predicted the presence of CSPC in both the anterior zone (OR = 8, 95%CI = 3-22, P <0.001) and apex (OR = 4, 95%CI = 1-10, P = 0.01).Conclusions: Avoiding anterior and apical samplings during prostate biopsy does not result in substantial under-diagnosis of significant cancer. However, these areas are easily accessible using the transperineal approach and should be sampled in selected patients, particularly those with PI-RADS 5 lesions. [ABSTRACT FROM AUTHOR]

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

Introduction: Data on the accuracy of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with intermediate/high-risk prostate cancer are being accumulated. Its role in assessing the extent of local disease has not been fully elaborated.Aim: To determine the performance characteristics of 68Ga-PSMA PET/CT in identifying local disease extension in patients with intermediate/high risk prostate cancer.Methods: 68Ga-PSMA PET/CT studies of 61 consecutive patients with intermediate/high-risk prostate cancer who underwent radical prostatectomy were reviewed by nuclear medicine specialists. Tumor location, extraprostatic extension (EPE), seminal vesicle invasion (SVI), and lymph nodes involvement (LNI) were compared to pathological findings. The incremental value of 68Ga-PSMA PET/CT to established nomograms was determined.Results: Two patients without pathologic uptake of 68Ga-PSMA were excluded. Seventeen patients were diagnosed with EPE (29%), 12(20%) had SVI and 3(5%) LNI. The concordance between tumor location and 68Ga-PSMA PET/CT findings was 48%, and EPE was not indicated by PET in any of the patients. The sensitivity, specificity, positive, and negative predictive value for SVI were 58%, 96%, 78%, 90%, respectively (area under the receiver operating characteristic curve = 0.77) and for LNI 67%, 98%, 67%, 98%, respectively (area under the receiver operating characteristic curve = 0.82). Incorporating imaging findings into the MSKCC-SVI nomogram enhanced the diagnostic accuracy from 0.84 to 0.95 (Integrated Discrimination Increment 0.24, P = 0.004).Conclusion: In patients with intermediate/high-risk prostate cancer, 68Ga-PSMA PET/CT provides information regarding intraprostatic tumor location, SVI and LNI but has no role in assessment for EPE. This information might be useful for pretreatment counseling, decision-making and possibly preoperative planning. [ABSTRACT FROM AUTHOR]

Objectives: High-grade nonmuscle-invasive urothelial tumors of the bladder that fail intravesical Bacillus Calmette-Guérin (BCG) immunotherapy are at the highest risk of progression. Initial evidence links heat shock protein expression levels and outcome of bladder cancer after BCG treatment. We aimed to determine the association between HSP60, 70, and 90 expression levels and long-term outcomes of T1 high-grade (T1HG) urothelial bladder tumors treated with BCG immunotherapy.Materials and Methods: Data of 54 consecutive patients with primary T1HG bladder tumors who underwent transurethral resection between 2002 and 2008 and received at least an induction course of BCG were reviewed. Immunohistochemical staining for heat shock protein (HSP)60, 70, and 90 were performed on resected specimens. Study outcomes included disease recurrence and progression. The association between HSP expression levels and outcomes were evaluated with univariable and multivariable Cox proportional hazards models.Results: During a median follow-up of 9.6 years, 25 patients had a disease recurrence and 14 patients a disease progression. Estimated 5-year recurrence and progression-free survival were 59% and 81%, respectively. On multivariable analyses, HSP60 staining >65% was associated with a higher risk for progression (hazard ratio [HR] = 3.96, 95% confidence interval [CI] 1.35-11.58, P = 0.012), and HSP70 staining >5% was associated with a decreased risk for progression (HR = 0.33, 95% CI 0.11-0.98, P = 0.045), and recurrence (HR = 0.29, 95% CI 0.13-0.65, P = 0.003). HSP90 expression was not associated with disease recurrence or progression. Five patients had both a HSP60 staining >65% and a HSP70 staining ≤5% all of whom recurred at a median time of 6 months (interquartile range 3, 16) and 80% of whom progressed at a median time of 26 months (interquartile range 5, 60).Conclusions: HSP60 and 70 cellular expression levels are associated with long-term outcome following BCG treatment of T1HG urothelial bladder tumors. These findings, if further validated, may be used to better stratify the risk of disease recurrence and progression in this group of patients. [ABSTRACT FROM AUTHOR]

Purpose: The optimal form of urinary diversion following radical cystectomy remains controversial. We sought to compare the long-term health-related quality-of-life outcomes between patients with orthotopic neobladder and ileal conduit diversion (ICD).Patients and Methods: We enrolled 95 patients following radical cystectomy and ICD (n = 49) or orthotopic neobladder reconstruction (ONR) (n = 46), with a minimum interval of 1 year from surgery. All patients completed the Bladder Cancer Index questionnaire, assessing their urinary, bowel, and sexual function, and bother scores.Results: Patients treated with ONR were generally younger and healthier compared with those who underwent ICD (P<0.01). Sex, marital status, disease status at the time of enrollment, and mean duration elapsing from surgery to interview were similar between the subgroups. Better functional scores in favor of ICD were recorded in the urinary domain (P<0.01), whereas the corresponding bother scores were roughly identical in both groups. Conversely, although higher functional scores were recorded in the sexual domain of patients with ONR (P<0.01), the corresponding bother scores in this group were lower compared with their counterparts with ICD (53.2 vs. 65.3; P<0.05). As patients grew older they were more likely to report on better urinary function and worse sexual function, but were less likely to be bothered by the decline in sexual function.Conclusions: Our study suggests that the bother resulting from urinary incontinence and the risk of sexual dysfunction be highlighted to those electing for neobladder reconstruction, whereas patients preferring conduit diversion should be reassured that their expected quality of life is not compromised. [ABSTRACT FROM AUTHOR]

Background The multiple pathways that are involved in neuroendocrine differentiation (NED) in prostate cancer (PCa) are poorly elucidated. Evidence suggests that several environmental triggers induce NED leading to the adaptation of PCa to its close environment to maintain cell proliferation. Nevertheless, there is conflicting evidence regarding the prognostic role of NED in PCa. Methods In this review, we aimed to summarize all available data about NED and to assess the prognostic role of NED in disease progression and therapy resistance, and its role in routine clinical practice. This review was based on articles found through a PubMed literature search between 1993 and 2013. The study outcome measure was the effect of NED on oncologic outcomes at each PCa stage. Results In total, 59 articles reporting on the effect of NED on oncologic outcomes have been selected. In clinical practice, immunostaining for NED markers could have interesting predictive value for assessing the oncologic outcomes in patients receiving androgen-deprivation therapy. Thus, patients with high NED burden may be candidates for more aggressive treatment strategies targeting NED pathways. Conversely, strong evidence is lacking concerning its potential independent prognostic value in hormone-naïve PCa. Conclusions Current published data are not sufficient to recommend the use of NE markers in routine practice, particularly at early PCa stage. [ABSTRACT FROM AUTHOR]

Objective To test the expandability of active surveillance (AS) to Gleason score 3+4 cancers by assessing the unfavorable disease risk in a large multi-institutional cohort. Materials and methods We performed a retrospective analysis including 2,323 patients with localized Gleason score 3+4 prostate cancer who underwent a radical prostatectomy between 2005 and 2013 from 6 academic centers. We analyzed the rates of biopsy downgrading/upgrading and advanced stage in the overall cohort by employing standardized AS criteria (using biopsy Gleason score 3+4). Results The final pathologic Gleason score was 3+3 = 6 in 8%, 3+4 = 7 in 67%, 4+3 = 7 in 20%, and 8 to 10 in 5% cases. The overall rate of unfavorable disease (upgrading or advanced stage or both) was 46%. In multivariable analysis, prostate-specific antigen (PSA) level>10 ng/ml, PSA density (PSAD) >0.15 ng/ml/g, clinical stage >T1, and>2 positive cores were predictors of unfavorable disease. According to the AS criteria used, the risk of unfavorable disease ranged from 30% to 42%. In patients without any risk factor (PSA level≤10 ng/ml, PSAD ≤0.15 ng/ml/g, T1c, and≤2 positive cores), the unfavorable disease rate was 19%. The main limitations of this study are the retrospective design and nonstandardization of pathologic assessment between centers. Conclusions Approximately half of patients with biopsy Gleason score 3+4 cancer have unfavorable disease at final pathology. Nevertheless, expanding AS eligibility to these patients may be acceptable provided adherence to strict selection criteria leading to a<20% risk of unfavorable disease. Future tools for selection such as magnetic resonance imaging, early rebiopsy, and serum markers may be especially beneficial in this group of patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Orthotopic neobladder urinary diversion is associated with a high rate of infectious complications, especially in the early postoperative period. The aim of the study was to assess the incidence, associated pathogens, and predictors of symptomatic urinary tract infection (UTI) in patients with an orthotopic neobladder. Methods and materials: The medical records of 79 patients treated with radical cystectomy and orthotopic neobladder urinary diversion at a tertiary medical center in 2004 to 2012 were reviewed for data pertaining to bacteriuria and symptomatic UTI after hospital discharge. Cumulative incidences of clinical events were assessed with the Kaplan-Meier method. Univariate and multivariate Cox regression models were used to identify clinical predictors of infection. Results: A total of 69 men and 10 women were included in the study cohort. The estimated cumulative rates of symptomatic UTI were 34% at 3 months, 40% at 6 months, and 43% at 12 months. New events of symptomatic UTI occurred in 36% of the patients during the first 3 postoperative months, but only in 10% at 3 to 6 months and 8% at 6 to 12 months. Common pathogens were Pseudomonas aeruginosa (24%) and Escherichia coli (24%); 78% of bacterial pathogens were susceptible to amikacin. On multivariate analysis, there was no effect of age, gender, intermittent catheterization, bowel segment used for reconstruction, or perioperative chemotherapy on rates of UTI. Conclusions: Symptomatic UTI is a common complication after neobladder reconstruction, usually occurring within the first 3 months of surgery. P. aeruginosa infection is common. Inpatient empirical treatment with amikacin is recommended in this setting. [Copyright &y& Elsevier]