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This study assesses the impact of percutaneous nephrostomy (PCN) presence on standard intended neoadjuvant chemotherapy (NAC) quality, its related complications and outcome after radical cystectomy. We found that PCN-patients received less adequate NAC protocols, suffered from more infections and hospitalizations during the NAC period, with no difference in the postoperative outcomes after cystectomy. This finding may potentially lead to consideration of NAC avoidance and upfront cystectomy in PCN-patients. Introduction: Symptomatic hydronephrosis associated with muscle invasive bladder cancer (MIBC) necessitates percutaneous nephrostomy (PCN) insertion before neoadjuvant chemotherapy (NAC). This study assesses the impact of PCN presence on standard intended NAC quality, its related complications and outcome after radical cystectomy (RC). Materials and Methods: The study comprises a retrospective, multicenter cohort of 193 consecutive RCs performed between 2016 and 2019. Eighty (42%) of these patients received NAC and were divided in 2 comparison groups by presence (n = 26; 33%) or absence (n = 54; 67%) of PCN. Endpoints included completion of adequate NAC treatment (cisplatin-based chemotherapy for at least 4 courses), complications during NAC, post-RC complications and hospital stay. Results: Overall, patients with PCN (45/193; 23%) featured a higher referral rate to NAC (58% vs. 36%, P = .01), worse glomerular filtration rates (P < .001) and more adverse events (P = .04), in comparison to non-PCN patients. In the NAC cohort, PCN patients had less adequate treatment rates (54% vs. 85%, P = .005), and more infections (35% vs, 7%; P = .008) and hospitalizations (58% vs. 13%; P < .001) during chemotherapy. Post-RC outcome was similar for both comparison groups. PCN was an independent risk factor for inadequate NAC (OR = 3.9, P = .04), and infections (OR = 11.3, P = .01) and hospitalizations (OR = 7.5, P = .004) during NAC. Conclusions: PCN in MIBC patients is a significant risk factor for inadequate NAC and adverse events during treatment. This finding may quire the rationale of NAC, potentially leading to consideration of NAC avoidance and upfront RC in PCN patients. Further survival studies with long follow-up are needed for elucidating this issue. [ABSTRACT FROM AUTHOR]

To investigate the association between modified frailty index (mFI) scores and radical cystectomy outcomes. We conducted a multicenter retrospective analysis of 292 patients who underwent radical cystectomy between 2015 and 2019. The patients were stratified according to mFI scores (mFI 0–1 vs. mFI ≥2). Baseline characteristics were compared between groups. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS), and the secondary endpoint was the 30-day postoperative complication rate. One group included 164 patients with mFI 0–1 and the other included 128 patients with mFI ≥2. The cohort's median age was 69 years, and median follow-up for survivors was 33 months. Thirty-day major postoperative complication rate was 19%. Ninety patients (31%) died during the study period, 70 of them (24%) from bladder cancer. Older age, male sex, lower kidney function, and diversion to an ileal conduit were significantly more common in the mFI ≥2 group. The postoperative complication rates were comparable between groups, but the CSS and OS were significantly lower in the frailer group (p = 0.007 and p = 0.03, respectively). An mFI score ≥ 2 emerged as an independent risk factor for cancer-specific death (hazard ratio [HR] = 1.7, p = 0.03) and overall-mortality (HR = 1.8, p = 0.008). High mFI scores are associated with shorter CSS and OS after radical cystectomy. Healthcare providers should be encouraged to calculate frailty preoperatively for judicious patient selection in light of the predicted outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Context: The clinical significance of positive surgical margins (PSMs) in radical prostatectomy (RP) specimens and the management of affected patients remain unclear. Objective: To address pitfalls in the pathologic interpretation of margin status; provide an update on the incidence, predictors, and long-term oncologic implications of PSMs in the era of robot-assisted laparoscopic RP (RALRP); and suggest a practical evidence-based approach to patient management. Evidence acquisition: A systematic review of the literature was performed in April 2013 using Medline/PubMed, Web of Science, and Scopus databases and the Cochrane Database of Systematic Reviews. Studies focusing on PSMs in RP pertinent to the objectives of this review were included. Particular attention was paid to publications within the last 5 yr and those concerning RALRP. Evidence synthesis: A total of 74 publications were retrieved. Standardized measures to overcome variability in the pathologic interpretation of surgical margins have recently been established by the International Society of Urological Pathology. The average rate of PSMs in contemporary RALRP series is 15% (range: 6.5–32%), which is higher in men with a more advanced pathologic stage and equivalent to the rate reported in prior open and laparoscopic prostatectomy series. The likelihood of PSMs is strongly influenced by the surgeon's experience irrespective of the surgical approach. Technical modifications using the robotic platform and the role of frozen-section analysis to reduce the margin positivity rate continue to evolve. Positive margins are associated with a twofold increased hazard of biochemical relapse, but their association with more robust clinical end points is controversial. Level 1 evidence suggests that adjuvant radiation therapy (RT) may favorably affect prostate-specific antigen recurrence rates, but whether the therapy also affects systemic progression, prostate cancer–specific mortality, and overall survival remains debatable. Conclusions: Although positive margins in prostate cancer are considered an adverse oncologic outcome, their long-term impact on survival is highly variable and largely influenced by other risk modifiers. Adjuvant RT appears to be effective, but further study is required to determine whether early salvage RT is an equivalent alternative. [Copyright &y& Elsevier]

Abstract: Context: This review focuses on positive surgical margins (PSM) in radical prostatectomy (RP). Objective: To address the etiology, incidence, and oncologic impact of PSM and discuss technical points to help surgeons minimize their positive margin rate. An evidence-based approach to assist clinicians in counseling patients with a PSM is provided. Evidence acquisition: A literature search in English was performed using the National Library of Medicine database and the following key words: prostate cancer, surgical margins, and radical prostatectomy. Seven hundred sixty-eight references were scrutinized, and 73 were selected for rigorous review based on their pertinence, study size, and overall contribution to the field. Evidence synthesis: In contemporary series, PSM are reported in 11–38% of patients undergoing RP. Although variability exists in the pathologic interpretation of surgical margins, PSM are associated with an increased hazard of biochemical recurrence (BCR) and local disease recurrence as well as the need for secondary cancer treatment. A posterolateral PSM appears to confer the greatest risk of recurrence, whereas the prognostic significance of positive apical margins remains controversial. The role of preoperative imaging and intraoperative frozen section analysis are being investigated to reduce margin positivity rates. Level-1 evidence indicates that adjuvant radiotherapy (RT) in men with PSM reduces BCR rates and clinical progression and possibly improves overall survival (OS). Conclusions: PSM in RP specimens are uniformly considered an adverse outcome. Regardless of approach (open or laparoscopic), attention to surgical detail is essential to minimize rates. For patients with a PSM destined to experience a cancer recurrence, RT is the only established treatment with curative potential. A randomized trial in patients with PSM comparing immediate postoperative RT to salvage RT is critically needed before definitive recommendations can be made. [Copyright &y& Elsevier]

Objectives: For prostate cancer screening, the role of prostate-specific antigen (PSA) velocity (PSAV) in conjunction with total PSA is controversial. We evaluated the relationship of PSAV to histologic findings on biopsy and assessed whether PSAV provides independent predictive information. Methods: From a community-based cohort of 25,276 men screened from 1991 to 2001, 1851 underwent a first biopsy for an elevated PSA and nonsuspicious digital rectal examination with a PSAV available from the year before biopsy. We analyzed the association between PSAV and biopsy histology. Results: The histologic findings on biopsy were cancer in 468 (25%), prostatic inflammation in 135 (7%), and benign prostate tissue in 1248 (68%). The cancer detection rate was associated with PSAV and, depending on PSAV, ranged from 13% to 36% (P <0.001). Among men with a PSAV less than 0.5 ng/mL per year, the cancer rate ranged from 27% to 36%, at a PSAV of 0.5 to 3.0 ng/mL per year was 24% to 28%, and at a PSAV greater than 3.0 ng/mL per year was 13% to 18%. On multivariable analysis adjusting for age and PSA, PSAV was independently associated with risk of cancer on biopsy (P <0.0005). The rate of prostatic inflammation was directly associated with PSAV (PSAV of 3.0 ng/mL per year or less: 5% to 9%; PSAV greater than 3.0 ng/mL per year: 11% to 13%, P = 0.01). Conclusions: In screened men with an elevated PSA undergoing biopsy, PSAV provides independent predictive information for estimating prostate cancer risk. Modest increases in PSA are associated with an increased risk of cancer, whereas more dramatic PSA rises are associated with a diminishing risk of cancer and higher rate of inflammation. [Copyright &y& Elsevier]

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]

Objectives: To examine whether radical prostatectomy (RP) conducted before 4 or 6 weeks after prostate biopsy is associated with surgical difficulty or efficacy. Many urologists recommend an interval of at least 4 to 6 weeks between prostate biopsy and RP. Methods: Using our surgical database, we identified 2996 men undergoing open RP and compared the outcomes after surgery stratified by the interval from biopsy, analyzed as a dichotomous variable with cutpoints of either 4 or 6 weeks. The estimated blood loss and operating room time were considered surrogates for surgical difficulty, and surgical margin status and postoperative urinary and erectile function surrogates for surgical efficacy. We used regression models to assess whether the time to RP affected these surgical outcomes after controlling for the surgeon, surgeon experience, and various clinical and pathologic disease features. Results: The interval between biopsy and RP was 4 weeks or less for 168 men (6%) and 6 weeks or less for 416 men (14%). Using an interval of 4 weeks or less or 6 weeks or less, multivariate mixed effects regression analyses did not show a significant association between early surgery and operating room time, estimated blood loss, surgical margin status, urinary continence, or erectile function (all P ≥0.18). Our results were sufficiently precise to exclude an important effect of early surgery. Conclusions: The results of our study have shown that performing radical prostatectomy shortly after prostate biopsy, within 4 to 6 weeks, does not adversely influence surgical difficulty or efficacy. [Copyright &y& Elsevier]

Abstract: Objectives: To assess whether immunostaining for deleted-in-colon-cancer (DCC) protein, a previously established prognostic marker in colon and bladder cancer, may assist in resolving the uncommon differential diagnostic dilemma of distinguishing primary from secondary urothelial adenocarcinoma. Methods: The study group consisted of 12 patients with adenocarcinoma involving the bladder or ureter and previously resected colorectal carcinoma between 1988 and 2002. All patients were initially considered to have primary urothelial transitional cell carcinoma, and the management strategy was conducted accordingly. The clinical data were recorded from the charts, and immunohistochemical staining for DCC was performed on formalin-fixed paraffin-embedded tissues containing the primary colorectal cancer and ensuing urinary tract tumor. Staining was defined as positive when at least 25% of the tumor cells were immunoreactive for DCC. Results: Of the 12 patients, 10 presented with bladder and 2 with ureteral adenocarcinoma. All secondary tumors originated from a primary carcinoma invariably located along the left colon or rectum. The overall 5-year disease-specific survival rate from the time of colectomy was 31% at a median follow-up of 50 ± 8 months. Of the 12 patients, 5 (41%) had positive DCC immunoreactivity. In all cases, concordant expression of DCC was found in the primary colorectal cancer and the ensuing tumor in the urinary tract. The survival time from colectomy was significantly longer for the DCC-positive subgroup (median 59 months, 95% confidence interval 41 to 77) than in the DCC-negative subgroup (median 23 months, 95% confidence interval 13 to 37). Likewise, the time lag between colectomy and tumor recurrence in the urinary tract was significantly longer in the patients with DCC-positive tumors (median 35 months) than in those with DCC-negative tumors (median 10 months). Conclusions: DCC immunoreactivity was consistently observed in secondary bladder or ureteral adenocarcinoma when the primary colorectal lesion expresses DCC, and thus may serve to establish the origin of the tumor. Positive DCC protein expression in secondary urinary tract adenocarcinoma of colorectal origin may identify a subset of patients with a relatively favorable prognosis. Additional studies are required to confirm our results. [Copyright &y& Elsevier]

: ObjectivesTo review the experience with partial nephrectomy for the diagnosis and treatment of renal cortical tumors at the Memorial Sloan-Kettering Cancer Center with a particular focus on the histologic findings at the time of surgery.: MethodsThe results of 292 consecutive partial nephrectomies were reviewed. Demographic data, perioperative complications, and disease status were recorded. The specimens were reviewed for histologic subtyping in accordance with the Heidelberg classification for renal cortical tumors. The probabilities of recurrence and disease-specific death were assessed with the cumulative incidence estimate.: ResultsThe median follow-up was 25.3 months (range 1 to 155). A total of 246 patients (87%) were diagnosed with a renal cortical tumor, 1 patient (less than 1%) was diagnosed with another cancer, and 34 (12%) were diagnosed with benign lesions. The most frequent histologic finding among the renal cortical tumor subgroup was conventional clear cell carcinoma in 148 cases (51%), followed by papillary carcinoma in 54 (18%), oncocytoma in 32 (11%), and chromophobe carcinoma in 21 (7%). Bilateral disease and multifocality were most prevalent in the conventional and papillary subtypes, respectively. The 5-year probability of recurrence and disease-specific death was 12% and 8%, respectively, for the conventional clear cell type. No local or distant disease recurrence was observed in any other renal cortical tumor subtypes.: ConclusionsPartial nephrectomy should be considered a diagnostic and therapeutic surgical approach for renal cortical masses. Conventional clear cell carcinoma is the most frequent histologic subtype and is associated with a less favorable outcome compared with papillary carcinoma and chromophobe carcinoma. Radical nephrectomy for renal lesions that could be removed by partial nephrectomy will risk renal impairment in a substantial proportion of patients with benign disease. [Copyright &y& Elsevier]

Nephroureterectomy is considered the reference standard treatment for invasive transitional cell carcinoma of the ureter. When this malignancy occurs in a patient with renal fusion anomaly, separating the involved kidney from its conjoint mate becomes a challenging task for the surgeon. We report a unique case in which a patient with an L-shaped left-to-right crossed ectopic kidney was diagnosed with invasive ureteral transitional cell carcinoma. The preoperative assessment in these uncommon cases should include renal angiography or computed tomography angiography to provide key information about the renal vasculature, which is essential for planning the surgical dissection and line of separation between the kidneys. [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]

Objective: To evaluate whether meatal stenosis treated concomitantly with urethral fistula repair alters the results of fistula closure.Methods: A retrospective cohort study, included were all children who underwent local fistula closure following hypospadias repair between 2006 and 2017. Patients who underwent reoperative urethroplasty were excluded. Data were extracted from electronic records, and missing data were supplied by telephone interviews. Characteristics of patients and fistulas were compared between children who underwent fistula closure only and those who underwent meatoplasty for meatal stenosis during the same surgery. The primary endpoint was fistula recurrence.Results: In total, 106 local repairs of urethrocutaneous fistulas were performed during the study period, and 25 of them included concomitant meatoplasty for meatal stenosis. There was no difference in terms of location, size, and number of fistulas or the number of recurrent fistulas between the 81 patients who underwent fistula closure only and the 25 who underwent concomitant meatoplasty. The fistula recurrence rate was 17 per 81 (21%) for the fistula only group and 5 per 25 (20%) for the fistula and meatoplasty group after a median follow-up of 7 and 8 years, respectively. Meatoplasty was required in a subsequent procedure in 5 of 81 in the former group vs 3 of 25 patients in the latter group.Conclusion: The presence and repair of meatal stenosis does not alter the recurrence rate of urethrocutaneous fistulas repaired concomitantly following hypospadias repair. [ABSTRACT FROM AUTHOR]

Objectives: To study the effect of central tumor location on the glomerular filtration rate (GFR) after partial nephrectomy for renal cortical tumor. Methods: We reviewed our institutional database to identify patients who had undergone partial nephrectomy from January 1995 to July 2005. Central tumors were defined as those encroaching on the collecting system or renal sinus or that did not distort the renal contour; all others were categorized as peripheral on preoperative abdominal imaging. We calculated the GFR preoperatively, during the hospital stay, and at 1 and 12 months after surgery. Linear regression models were fit to determine the association of tumor location with the changes in GFR at each period, after controlling for age, sex, operative and ischemic times, comorbidities, and blood loss. Results: A total of 248 central and 333 peripheral tumors were available for analysis. Patients with central tumors were younger than those with peripheral tumors (62 versus 59 years, P = 0.014) and experienced longer intraoperative renal ischemia times (40 versus 29 minutes, P <0.001) and longer operations (195 versus 179 minutes, P = 0.004). On multivariate analysis, tumor location was not significantly associated with the change in GFR at any of the intervals, after adjusting for the covariates. Conclusions: The results of our study have indicated that tumor location does not appear to affect long-term renal function. Thus, partial nephrectomy should not be withheld from this subset of patients. [Copyright &y& Elsevier]

• 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]

Objective: To assess patient adherence to intravesical instillation therapy for nonmuscle invasive urothelial carcinoma outside of clinical trials.Materials and Methods: We reviewed the records of patients from 2000 to 2013 who received intravesical therapy for nonmuscle invasive urothelial carcinoma. Patients with evidence of tumor recurrence or progression were excluded. We performed univariable and multivariable regression analyses to predict adherence to intravesical therapy.Results: A total of 729 patients started 861 induction cycles, 63% with bacillus Calmette-Guèrin (BCG) and 37% with mitomycin C (MMC). The rate of completion of 6 weeks induction therapy with BCG and MMC was similar (86% and 87%, respectively). Within the BCG cohort, 161 (35%) patients commenced the Southwest Oncology Group (SWOG) maintenance protocol after induction and 16 (10%) completed all 21 treatments. A monthly protocol for BCG was started by 87 patients (19%) and 48 (55%) completed all 9 treatments. MMC therapy was started in 270 patients, 97 of whom (36%) commenced monthly maintenance treatment, and 46 (47%) completed treatments. Median number of instillations was 7 for patients undergoing monthly maintenance therapy (MMC or BCG) and 9 for patients allocated to 3 years BCG. On multivariable analysis, recurrence after prior treatment of urothelial carcinoma was predictive of patients' adherence to treatment.Conclusion: Compliance with intravesical therapy is low in clinical practice, notably for longer treatment schedules. [ABSTRACT FROM AUTHOR]

Objective: To compare the incidence rate of urinary tract infections (UTIs) and associated pathogens between patients with ileal conduit and patients with orthotopic neobladder urinary diversion.Patients and Methods: The medical records of 179 patients treated with radical cystectomy between 2006 and 2011 were reviewed and data pertaining to postoperative UTI were collected. UTI incidence was reported at 3 months' intervals and compared by diversion type. Preoperative predictors of UTI were evaluated with Cox regression analyses.Results: The study cohort included 130 patients with ileal conduit and 49 patients with orthotopic neobladder. Patients with a neobladder were younger (P <.001). Median follow-up was 38 months (IQR [interquartile range], 11-63). Median time from surgery to first infection was 1.5 months (IQR, 1-12.5) for patients with a neobladder and 11 months (IQR, 2.5-27) for patients with a conduit (P = .04). During the first 3 months after surgery, 29% of the patients with a neobladder and 8% of the patients with ileal conduit had a UTI episode (P = .001). Rates of UTI did not differ during subsequent follow-up. Diversion type was not associated with UTI on multivariable analysis. Escherichia coli was the most common pathogen in patients with a conduit (58%), and Klebsiella spp. in patients with a neobladder (29%).Conclusion: The risk of UTI is significantly higher in patients with a neobladder during the first 3 months after surgery and comparable to patients with ileal conduit during subsequent follow-up. These findings may facilitate preoperative counseling regarding the expected risk of UTI after urinary diversion. [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]

Abstract: Context: The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011. Objective: Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management. Evidence acquisition: The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles. Evidence synthesis: Once a non–muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guérin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion. Conclusions: These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients. [Copyright &y& Elsevier]

Abstract: Background: Cancer often involves inflammatory processes. We hypothesized that immune mediators in urine may serve as biomarkers for bladder cancer (BCa). Objective: To investigate whether BCa might be marked by urinary levels of heat shock proteins (HSPs; HSP60, HSP70, or HSP90) or cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, tumor growth factor [TGF]-β, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, or IL-13). Design, setting, and participants: This was a case–control study with a discovery and validation phase. We examined urine from 106 consecutive patients: healthy controls (n =18); hematuria with no evidence of BCa (n =20); non–muscle-invasive BCa (n =50); and muscle-invasive BCa (n =18). The concentrations of HSPs and cytokines were assessed by enzyme-linked immunosorbent assay. In the validation phase, independent urine samples from 40 patients were analyzed (controls [n =19] and BCa [n =21]). Measurements: We used the area under the curve (AUC) of a receiver operating characteristic analysis to determine the ability of HSPs and cytokines to mark BCa and applied a multivariate logistic regression to create a formula able to diagnose BCa. The formula was applied to the validation set without recalculation, and positive and negative predictive values were calculated. Results and limitations: Urinary concentrations of IL-8, IL-10, and IL-13 were significantly elevated in BCa; IL-13 was the most prominent marker (AUC: 0.93; 95% confidence interval [CI], 0.85–0.99). The multivariate regression analysis highlighted HSP60 (odds ratio [OR]: 1.206; 95% CI, 1.041–1.397, p =0.003) and IL-13 (OR: 1.020; 95% CI: 1.007–1.033, p =0.012). The validation assay was performed using HSP60 and IL-13. The overall positive predictive value was 74% (95% CI, 64–84%); and the negative predictive value was 76% (95% CI, 66–86%). Since we examined a small number of patients, the results need to be confirmed in a larger cohort. Conclusions: These results suggest that it might be possible to develop a urinary biomarker for BCa and raise the possibility that expression of anti-inflammatory cytokines and HSPs might allow BCa to evade immune surveillance. [Copyright &y& Elsevier]

OBJECTIVE: To evaluate the effect of baseline renal function and comorbidity index on survival in patients with renal tumors. PATIENTS AND METHODS: We retrieved demographic, clinico-pathologic, body mass index (BMI), and comorbidity data (assessed by Charison-Romano index and hypertension) for 1479 patients who underwent partial or radical nephrectomy between January 4, 1995, and June 9, 2005, for localized renal tumors. We used the abbreviated Modified Diet and Renal Disease equation to estimate giomerular filtration rate (eGFR) using the last preoperative serum creatinine measurement. Body mass index and eGFR time trends were analyzed with linear regression. The effect of BMI, comorbidity, and baseline eGER on disease-free and overall survival was studied using Cox regression controlling for pathologic stage, nodal status, and metastasis. RESULTS: Over a 10-year interval, median BMI increased from 27 (interquartile range [IQR], 24-31) to 28 (IQR, 25-31; P=.004), and median baseline eGFR decreased from 70 (IQR, 58-80) to 63 mL/min per 1.73 m² (IQR, 57-78; P.<.001). Multivariate regression demonstrated an association between year of surgery and baseline eGFR (P<.001) even after adjusting for age, sex, comorbidity, BMI, and tumor size. We repeated the analysis for patients aged 18 to 70 years, and this association persisted (P<.001). Baseline eGFR, BMI, and comorbidity were not associated with disease-free survival after controlling for stage. However, moderately reduced baseline eGFR (45-60 mL/min per 1.73 m²) and severely reduced eGFR (<45 mL/min per 1.73 m²) were significantly associated with overall survival (hazard ratio, 1.5; P<003; and hazard ratio, 2.8; P<.001; respectively). [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]