The Rho-kinase inhibitor Y27632 promotes ureteral relaxation in an in vivo rat model for partial ureteral obstruction.

PURPOSE: Aim of this study was to evaluate the effect of intravenous Y27632 (a ROK inhibitor) on intra-ureteral pressures and on blood pressure in an in vivo rat model for unilateral partial ureteral obstruction (PUO). METHODS: 15 Male Sprague Dawley rats were used. Under isofluran anesthesia, saline was continuously infused via polyethylene (PE)-10 catheters inserted in the ureters beneath the kidney pelvis. Left psoas muscle was sutured around the distal left ureter to create a partial obstruction. Carotid artery and femoral vein were cannulated with PE catheters for registration of mean arterial blood pressure (MAP) and for administration of drugs. Left and right ureter pressures and MAP were simultaneously recorded. Y27632 (0.03 and 0.1 mg/kg each n = 6-7) was given intravenously. T-test was used for comparisons. RESULTS: Spontaneous peristaltic pressure waves were recorded at baseline for both ureters. After the obstruction, Y27632 reduced maximum pressure (MaxP) by 10.5 ± 1.9% (0.03 mg/kg; p = 0.004) and 29.1 ± 4.8% (0.1 mg/kg; p < 0.001), minimum pressure (MinP) by 5.2 ± 2.3% (0.03 mg/kg; p = 0.02) and 12.2 ± 3.4% (0.1 mg/kg; p = 0.009), the area under the curve (AUC) by 7.8 ± 2.4% (0.03 mg/kg; p = 0.008) and 16.5 ± 3.7% (0.1 mg/kg;p = 0.007), the waves amplitude by 23.4 ± 11.3% (0.03 mg/kg; p = 0.098) and 38.7 ± 7.5% (0.1 mg/kg; p < 0.001), with no effect on contraction frequency. During simultaneous recordings from the normal ureter at the investigated doses, Y27632 reduced MaxP, MinP, AUC and waves amplitude by 1-7%. The MAP was reduced by 12.5 ± 5.3% (0.03 mg/kg; p = 0.07) and 15.8 ± 1.8% (0.1 mg/kg; p < 0.001). CONCLUSIONS: Y27632 decreased intra-ureteral pressures of a partially obstructed ureter with limited effect on blood pressure in an animal model of unilateral PUO.

A review on pharmacological options for the treatment of erectile dysfunction: state of the art and new strategies.

INTRODUCTION: Erectile dysfunction (ED) affects between 12.9% and 28.1% of men worldwide, presenting a strong aged-correlated prevalence. Several pharmacological treatments are currently available for ED, which can be classified into oral, injection, and topical/intraurethral therapies. AREAS COVERED: Extensive research on PubMed/MEDLINE until February 2023 was performed. For each of the aforementioned drug classes, available molecules, and formulations, their efficacy and most common adverse events as well as general guidelines on prescription were investigated and extensively described. A glimpse into future directions regarding ED pharmacotherapy is also present. EXPERT OPINION: In recent years, there have been significant developments in pharmacological treatments for ED. It is essential for physicians to identify the best treatment option for patients based on their preferences and sexual habits. The treatment approach for ED has shifted from a sequential to a parallel paradigm, where all treatment options are available as first-line therapies. While there are promising regenerative therapies for ED, such as shockwaves and platelet-rich plasma injections, pharmacological treatment is still the most effective option for most patients.

Predicting global QoL after orthotopic neobladder or ileal conduit diversion: nomogram development.

Introduction: Quality of life (QoL) outcomes in patients undergoing radical cystectomy (RC) with orthotopic neobladder (ONB) or ileal conduit (IC) have been extensively investigated. However, a general lack of consensus on QoL's predictive factors exists. The aim of the study was to develop a nomogram using preoperative parameters to predict global QoL outcome in patients with localized muscle-invasive bladder cancer (MIBC) undergoing RC with ONB or IC urinary diversion (UD). Methods: A cohort of 319 patients who underwent RC and ONB or IC were retrospectively enrolled. Multivariable linear regression analyses were used to predict the global QoL score of the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), according to the patient characteristics and UD. A nomogram was developed and internally validated. Results: Patients' data in the two study groups significantly differed with regard to comorbidity profiles (chronic cardiac failure, p < 0.001; chronic kidney disease, p < 0.01; hypertension, p < 0.03; diabetic disease, p = 0.02; chronic arthritis, p = 0.02). A multivariable model that included patient age at surgery, UD, chronic cardiac disease, and peripheral vascular disease represented the basis for the nomogram. The calibration plot of the prediction model showed a systematic overestimation of the predicted global QoL score over the observed scores, with a slight underestimation for observed global QoL scores between 57 and 72. After performing leave-one-out cross-validation, the root mean square error (RMSE) emerged as 24.0. Discussion/conclusion: A novel nomogram based completely on known preoperative factors was developed for patients with MIBC undergoing RC to predict a mid-term QoL outcome.

Is Active Surveillance an Option for the Management of Men with Low-grade Prostate Cancer and a Positive Family History? Results from a Large, Single-institution Series.

BACKGROUND: Family history (FH) of prostate cancer (PCa) is associated with an increased risk of PCa and adverse disease features. However, whether patients with localized PCa and FH could be considered for active surveillance (AS) remains controversial. OBJECTIVE: To assess the association between FH and reclassification of AS candidates, and to define predictors of adverse outcomes in men with positive FH. DESIGN, SETTING, AND PARTICIPANTS: Overall, 656 patients with grade group (GG) 1 PCa included in an AS protocol at a single institution were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analyses assessed the time to reclassification (GG ≥2 and GG ≥3 at follow-up biopsies) overall and according to FH status. Multivariable Cox regression tested the impact of FH on reclassification and identified the predictors among men with FH. Men treated with delayed radical prostatectomy (n = 197) or external-beam radiation therapy (n = 64) were identified, and the impact of FH on oncologic outcomes was assessed. RESULTS AND LIMITATIONS: Overall, 119 men (18%) had FH. The median follow-up was 54 mo (interquartile range 29-84 mo), and 264 patients experienced reclassification. The 5-yr reclassification-free survival rate was 39% versus 57% for FH versus no FH (p = 0.006), and FH was associated with reclassification to GG ≥2 (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.19-2.15, p = 0.002). In men with FH, the strongest predictors of reclassification were prostate-specific antigen (PSA) density (PSAD), high-volume GG 1 (≥33% of cores involved or ≥50% of any core involved), and suspicious magnetic resonance imaging (MRI) of the prostate (HRs 2.87, 3.04, and 3.87, respectively; all p < 0.05). No association between FH, adverse pathologic features, and biochemical recurrence was observed (all p > 0.05). CONCLUSIONS: Patients with FH on AS are at an increased risk of reclassification. Negative MRI, low disease volume, and low PSAD identify men with FH and a low risk of reclassification. Nonetheless, sample size and wide CIs entail caution in drawing conclusions based on these results. PATIENT SUMMARY: We tested the impact of family history in men on active surveillance for localized prostate cancer. A significant risk of reclassification, but not adverse oncologic outcomes after deferred treatment, prompts the need for cautious discussion with these patients, without precluding initial expectant management.

The Complex Interplay between Serum Testosterone and the Clinical Course of Coronavirus Disease 19 Pandemic: A Systematic Review of Clinical and Preclinical Evidence.

Since the beginning of the coronavirus disease 19 (COVID-19) pandemic, efforts in defining risk factors and associations between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinical, and molecular features have initiated. After three years of pandemic, it became evident that men have higher risk of adverse outcomes. Such evidence provided the impetus for defining the biological fundaments of such a gender disparity. Our objective was to analyze the most recent literature with the aim of defining the relationship between COVID-19 and fertility, in particular, we assessed the interplay between SARS-CoV-2 and testosterone in a systematic review of literature from December 2019 (first evidence of a novel coronavirus in the Hubei province) until March 2022. As a fundamental basis for understanding, articles pertaining preclinical aspects explaining the gender disparity (n=9) were included. The main review categories analyzed the risk of being infected with SARS-CoV-2 according to testosterone levels (n=5), the impact of serum testosterone on outcomes of COVID-19 (n=23), and the impact SARS-CoV-2 on testosterone levels after infection (n=19). Preclinical studies mainly evaluated the relation between angiotensin-converting enzyme 2 (ACE2) and its androgen-mediated regulation, articles exploring the risk of COVID-19 according to testosterone levels were few. Although most publications evaluating the effect of COVID-19 on fertility found low testosterone levels after the infection, follow-up was short, with some also suggesting no alterations during recovery. More conclusive findings were observed in men with low testosterone levels, that were generally at higher risk of experiencing worse outcomes (i.e., admission to intensive care units, longer hospitalization, and death). Interestingly, an inverse relationship was observed in women, where higher levels of testosterone were associated to worse outcomes. Our finding may provide meaningful insights to better patient counselling and individualization of care pathways in men with testosterone levels suggesting hypogonadism.

Peyronie's disease development and management in diabetic men.

BACKGROUND: Peyronie's disease (PD) is a fibrosing disorder of the penis resulting in plaque formation and penile deformity that negatively affect sexual and psychosocial function of patients. A multifactorial etiology of PD is assumed with diabetes mellitus (DM) being a potential risk factor. OBJECTIVES: The aim of this narrative review was to investigate diabetes role in PD pathophysiology, diagnosis, and treatment. MATERIALS AND METHODS: A non-systematic narrative review of original articles, meta-analyses, and randomized trials was conducted, including articles in the pre-clinical setting to support relevant findings. RESULTS: Diabetes is one of the most common comorbidity observed in PD patients, with a prevalence of about 11% and a strong association with erectile dysfunction (ED). DM is associated with both a higher risk of developing PD and has also an impact on the outcomes of PD's treatments. DISCUSSION: Evidence from literature underlines that metabolic alterations typical of DM are pivotal factors in the development of PD and resistance to its medical treatment. CONCLUSION: The role of DM in development of PD is still debated, while its role in PD development is not completely clear, there is a clear impact of DM on PD treatment outcomes.

The Impact of SARS-CoV-2 Pandemic on Time to Primary, Secondary Resection and Adjuvant Intravesical Therapy in Patients with High-Risk Non-Muscle Invasive Bladder Cancer: A Retrospective Multi-Institutional Cohort Analysis.

BACKGROUND: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). METHODS: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. RESULTS: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p < 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p < 0.0001). CONCLUSIONS: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.

Prediction of the Need for an Extended Lymphadenectomy at the Time of Radical Cystectomy in Patients with Bladder Cancer.

BACKGROUND: A prospective randomized trial (LEA AUO AB 25/02) found no survival benefit in extended compared with limited pelvic lymph node dissection (PLND) templates in bladder cancer (BCa) patients treated with radical cystectomy (RC). However, the rate of lymph node invasion (LNI) in the standard and extended templates was lower than estimated. OBJECTIVE: To assess the accuracy of preoperative clinical and pathological parameters to predict LNI and to develop a model to preoperatively select candidates for the extended PLND templates. DESIGN, SETTING, AND PARTICIPANTS: A total of 903 BCa patients treated at a single institution were retrospectively identified. The primary outcome was to identify preoperatively the risk of LNI to tailor the type of PLND. The extended PLND templates consisted in the removal of pelvic lymph nodes together with the common iliac, presacral, para-aortocaval, interaortocaval, and paracaval sites up to the inferior mesenteric artery. INTERVENTION: A total of 903 BCa patients were treated with RC and bilateral extended PLND templates. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Several models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses. A nomogram predicting LNI in the extended pattern was developed and validated internally. RESULTS AND LIMITATIONS: Overall, 55 patients (6.1%) had LNI in the extended PLND templates at RC. The median number of nodes removed was 19 (interquartile range: 13-26). A model including age, clinical T stage, clinical node stage, lymphovascular invasion, and presence of carcinoma in situ at the last transurethral resection before RC was developed. The AUC of this model is 73%. Using a cutoff of 3%, 108 extended PLNDs (12%) would be spared and only two LNIs (3%) would be missed. The main limitations of our model are the retrospective nature of the data, lack of external validation, and low rate of LNI. CONCLUSIONS: This is the first proposed model to predict LNI in the extended PLND templates. This model might help urologists identify which patients might benefit from an extended PLND at the time of RC, reserving a standard PLND for all the others. PATIENT SUMMARY: We developed the first nomogram to predict lymph node invasion (LNI) in the extended pelvic lymph node dissection templates in bladder cancer patients treated with radical cystectomy. The adoption of our model to identify candidates for the extended pelvic lymph node dissection templates could avoid up to 12% of these procedures at the cost of missing only 3% of patients with LNI.

Defining the Most Informative Intermediate Clinical Endpoints for Predicting Overall Survival in Patients Treated with Radical Prostatectomy for High-risk Prostate Cancer.

BACKGROUND: Given the prolonged natural history of clinically localized, high-risk prostate cancer, there is a need for the identification of intermediate clinical endpoints (ICEs) to predict long-term overall survival (OS). OBJECTIVE: To explore the role of novel potential ICEs based on clinical follow-up to predict long-term survival in patients with high-risk prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Overall, 3507 patients treated at 12 tertiary referral centers between 1988 and 2016 were evaluated. INTERVENTION: Radical prostatectomy (RP) with extended pelvic lymph node dissection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The impact of biochemical recurrence (BCR) and clinical recurrence (CR) within 1, 3, 5, and 7yr after surgery on the risk of OS was evaluated in multivariable Cox regression analyses. In patients with BCR, the impact of progression to CR within 6mo and 1, 3, and 5yr on long-term OS was investigated. Discrimination was assessed using Harrell's c index. RESULTS AND LIMITATIONS: Median follow-up for survivors was 76mo. The 5- and 10-yr OS and cancer-specific survival rates were 94% and 81% versus 98% and 95%, respectively. On a time-varying multivariable analysis, BCR (hazard ratio [HR]: 1.02; 95% confidence interval [CI]: 1.00, 1.04) and CR (HR: 1.05; 95% CI: 1.03-1.07) emerged as predictors of OS (p<0.001). The development of CR within 5yr after surgery was the most informative ICE for predicting OS (c index: 0.74). In patients with BCR, progression to CR within 12mo represented the most informative predictor for the subsequent risk of dying from all causes. Patients who developed BCR within 5yr after RP and progressed to CR within 12mo had a 10-yr OS rate of 47%. These results require prospective validation. CONCLUSIONS: When predicting long-term survival in surgically treated high-risk patients, progression to CR within 5yr of RP confers the highest discrimination with respect to other landmark points. In men experiencing BCR, progression to CR within the subsequent 12mo achieved the highest discrimination. Further studies are needed to validate our findings. PATIENT SUMMARY: We investigated the most informative intermediate clinical endpoints for predicting overall survival (OS). Occurrence of clinical recurrence within 5yr after radical prostatectomy confers the highest discrimination to a model predicting OS.

The effect of age and comorbidities on early postoperative complications after radical cystectomy: A contemporary population-based analysis.

BACKGROUND: Analyzing the relationship between perioperative outcomes and age in urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC) in a continuous fashion may provide detailed information on the increased risk of complications in older patients, even after accounting for different comorbidity profiles. Given the limited data available in the literature, we tested these relationships within a large scale, population-based database. MATERIALS AND METHODS: Within the NIS database (2003-2015), we identified patients who underwent RC for UCB. Multivariable logistic regression (MLoR) and Poisson regression (MPR) models were used after adjustment for clustering and stratification for comorbidity profiles. RESULTS: Overall, 20,144 patients underwent RC with a median age of 70 years (interquartile range: 62-77). In MLoR models, continuously coded age represented an independent predictor of overall (odds ratio [OR]: 1.008, 95%-confidence interval [CI]: 1.005-1.012), cardiac (OR: 1.042, 95%-CI: 1.035-1.049), vascular (OR: 1.024, 95%-CI: 1.014-1.034), respiratory (OR: 1.016, 95%-CI 1.009-1.022), miscellaneous medical (OR: 1.013, 95%-CI: 1.009-1.017), infectious (OR: 1.012, 95%-CI 1.004-1.019), transfusions (OR: 1.011, 95%-CI 1.007-1.015) and bowel obstruction (OR: 1.009, 95%-CI 1.004-1.013) complications, and in-hospital mortality (OR: 1.057, 95%-CI 1.039-1.075). Conversely, patients age did not predict intraoperative (p = 0.7), genitourinary (p = 0.9), operative wound (p = 0.2) and miscellaneous surgical complications (p = 0.1). In MPR models, patients age predicted longer LOS (relative risk [RR]: 1.002, 95%-CI 1.001-1.003). Finally, a decreasing effect of age was observed in patients low vs high comorbidity burden for cardiac, respiratory and overall complications. CONCLUSIONS: Most of early postoperative RC complications are related to patients age, but its impact varies according to comorbidity profile. Further studies are needed to validate our findings that may be then considered for individual counselling and informed consent, as well as for health expenditure planning.

Evaluation of Cause of Death After Radical Cystectomy for Patients With Bladder Cancer: The Impact of Age at the Time of Surgery.

INTRODUCTION: Patients with bladder cancer treated with radical cystectomy (RC) have heterogeneous results in term of cancer-specific (CSM) and other cause mortality (OCM). Our aim is to assess the impact of age on cause of death after RC. PATIENTS AND METHODS: We retrospectively analyzed the data of 1222 patients treated with RC and bilateral pelvic lymph node dissection owing to nonmetastatic bladder cancer between 1990 and 2013. Patients were stratified according to age (< 59 vs. 60-69 vs. 70-79 vs. ≥ 80 years), tumor T stage at RC (pT0-T2 vs. pT3-T4), and tumor N stage at RC (pN+ vs. pN0). Competing-risks survival analyses were used to estimate CSM and OCM rates. RESULTS: With a median follow up of 6 years, 92 (7.5%) and 385 (31.5%) OCM and CSM were recorded. The 5-year CSM and OCM rates were 40% and 8.8%, respectively. After stratification according to disease stage and patient age, CSM emerged as the main cause of mortality in all patient subgroups. The 5-year OCM was 4.6%, 4.8%, 11%, and 32% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. The 5-years CSM was 34%, 45%, 35%, and 56% for patients aged < 60 years versus 60 to 69 years versus 70 to 79 years versus ≥ 80 years, respectively. Similar findings were observed stratifying the population according to pathologic T and N stage. CONCLUSION: CSM is the preponderant cause of death for all the patients, regardless of age or stage. In this regard, RC also seems to be a reasonable approach for octogenarians.

Radical Cystectomy in Pathological T4a and T4b Bladder Cancer Patients: Is There Any Space for Sub Stratification?

INTRODUCTION: According to TNM staging, pathological T4ab are comprehensive of the invasion of prostate, seminal vesicles, uterus or vagina and pelvic or abdominal wall. However, few data are available on the perioperative and oncological outcomes of specific organ invasion. MATERIALS AND METHODS: A total of 917 consecutive bladder cancer (BCa) patients treated with radical cystectomy (RC) at a single institution between 1990 and 2015 were studies. Cox regression analyses were used to stratify pT4ab according to the site of invasion and survival. RESULTS: Overall, 176 (19.2%) and 40 (4.4%) patients harbored pT4a or pT4b disease. Specifically, 84 (9.2%) patients reported prostate and/or SVI invasion, 62 (6.8%) prostate only, 16 (1.7%) uterus, 14 (1.5%) vaginal, 24 (2.6%) pelvic wall, and 16 (1.7%) abdominal wall invasion. The median follow-up in pT4 patients was 48 months. The 1-year cancer-specific mortality (CSM) rates were 71, 65, 24, 50, 50, and 72%, for vaginal, uterus, prostate only, prostate and/or seminal vesicles, pelvic wall, and abdominal wall invasions, respectively. At multivariable Cox regression, the invasion of prostate only (hazard ratio [HR] 3.53), prostate and/or SVI (HR 4.98), uterus (HR 7.16), vagina (HR 6.12), pelvic (HR 11.81), abdominal (8.36) were associated with adverse CSM. CONCLUSIONS: Our study described the differences in survival related to invasion site in pT4 patients, confirming poor survival expectancies in this subgroup. Patients with prostate invasion only seem to be associated with better survival than those affected by concomitant invasion of seminal vesicles. Uterus and vaginal invasions were associated with poor survival outcomes. Patients Summary: In this study, we looked at the outcome of locally advanced invasive BCa (stage pT4) in patients treated with RC at a tertiary referral hospital. We analyzed the differences in survival related to the specific organ invasion. We confirmed poor survival in this subgroup of patients. Only patients who had prostate invasion only seem to have a better survival.

Are the Results of the Prostate Testing for Cancer and Treatment Trial Applicable to Contemporary Prostate Cancer Patients Treated with Radical Prostatectomy? Results from Two High-volume European Institutions.

The Prostate Testing for Cancer and Treatment (ProtecT) trial reported excellent outcomes for patients with localized prostate cancer (PCa) managed with radical prostatectomy (RP), radiotherapy, or active monitoring. We aimed at assessing the generalizability of the ProtecT trial to contemporary patients undergoing RP at two high-volume institutions. Overall, 29147 PCa patients treated with RP between 1999 and 2016 were included. We evaluated changes in disease characteristics over time. Competing-risk analyses estimated the 10-yr cancer-specific mortality (CSM) and other-cause mortality (OCM) rates. Overall, 20598 (71%) patients were eligible for the ProtecT trial, ranging from 76% in 1999-2005 to 67% in 2014-2016. The proportion of prostate-specific antigen (PSA) ≥20ng/ml, biopsy grade group 4-5, and high-risk disease increased over time (all p<0.001). Among men potentially eligible for the ProtecT trial included in our study, median PSA and grade group 4-5 were higher as compared with the ProtecT trial (6.5 vs 4.7ng/ml and 9% vs 2%), especially in individuals treated in more recent years (7.1ng/ml and 16% for 2014-2016). Median follow-up was 50 mo. When considering patients eligible for the ProtecT trial, the 10-yr OCM rate exceeded the CSM rate (7% vs 2%). Conversely, when focusing on patients not eligible due to disease aggressiveness, the risk of CSM exceeded that of OCM (10% vs 7%). Clinicians should carefully consider the inverse stage migration toward more aggressive disease among surgical candidates in more recent years. Individuals not eligible for the ProtecT trial are more likely to die from PCa than from OCM, thus being the optimal candidates for testing the role of primary treatments. PATIENT SUMMARY: Contemporary prostate cancer surgery candidates harbor more aggressive disease features at presentation as compared with men included in the Prostate Testing for Cancer and Treatment (ProtecT) trial and are, in turn, at an increased risk of progression and mortality. Clinicians should take this into consideration when generalizing the results of the ProtecT trial with a particular emphasis on the oncologic safety of active monitoring in contemporary patients not included in structured prostate-specific antigen-based screening programs.

Assessment of Oncological Outcomes After Radical Prostatectomy According to Preoperative and Postoperative Cancer of the Prostate Risk Assessment Scores: Results from a Large, Two-center Experience.

BACKGROUND: Among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) and with virtually identical unfavorable pathological characteristics, those deemed at low risk (LR) preoperatively had better oncological outcomes than those with intermediate (IR) or high risk (HR) preoperatively. OBJECTIVE: To examine if this phenomenon still applies when preoperative Cancer of the Prostate Risk Assessment (CAPRA) scores are compared to postoperative scores (CAPRA-S) in RP patients. DESIGN, SETTING, AND PARTICIPANTS: We evaluated 10 290 PCa patients who underwent RP at tertiary care centers in Hamburg (Germany) and Milan (Italy) during 1991-2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: All patients were classified as CAPRA/CAPRA-S LR, IR, or HR (≤2, 3-5, and ≥6 points, respectively). Kaplan-Meier and Cox regression analyses were performed to assess the risk of biochemical recurrence (BCR) and metastatic disease (metD). RESULTS AND LIMITATIONS: Overall, 59.6%, 29.3%, and 11.1% patients were CAPRA-S LR, IR, and HR respectively. For CAPRA-S LR patients, 5-yr BCR-free and metD-free rates for preoperative CAPRA LR versus IR/HR patients were 93.1% versus 85.7% (p<0.001) and 99.7% versus 98.9% (p=0.017), respectively. For CAPRA-S IR/HR patients, the corresponding rates were 69.9% versus 57.2% and 98.2 versus 93.7% (both p<0.001). On multivariable Cox regression analyses, a combination of CAPRA-S and preoperative CAPRA resulted in increases in predictive accuracy for BCR (from 76.0% to 78.3%) and metD (from 82.0% to 84.0%). Specifically, biopsy Gleason patterns and the percentage of positive cores added information to the CAPRA-S score. Long-term follow-up is needed to discern clinical metD differences between preoperative CAPRA risk groups. CONCLUSIONS: CAPRA-S LR patients in the CAPRA IR/HR group had higher BCR/metD risk. Conversely, CAPRA-S IR/HR patients in the CAPRA LR group had lower BCR/metD risk. Future tools should incorporate better tumor and Gleason quantification to optimize prediction. PATIENT SUMMARY: We demonstrated that among 10290 European patients with prostate cancer who underwent radical prostatectomy, those deemed at low risk preoperatively had better oncological outcomes than their peers with intermediate or high risk, despite virtually identical unfavorable pathological characteristics.

A Multi-Institutional Validation of Gleason Score Derived from Tissue Microarray Cores.

To test the agreement between high-grade PCa at RP and TMA, and the ability of TMA to predict BCR. Validation of concordance between tissue microarray (TMA) and radical prostatectomy (RP) high-grade prostate cancer (PCa) is crucial because latter determines the treated natural history of PCa. We hypothesized that TMA Gleason score is in agreement with RP pathology and capable of accurately predicting biochemical recurrence (BCR). Data were provided from a multi-institutional Canadian sample of 1333 TMA and RP specimens with complete clinicopathological data. First, rate of agreement between TMA and high-grade Gleason at RP or biopsy and RP was tested. Second, ability of RP, TMA and biopsy to predict BCR was compared. Multivariable (MVA) Cox regression models were fitted and BCR rates were illustrated with Kaplan-Meier plots. Agreement between RP and TMA and between RP and biopsy was 72.6% (95% CI:69.7-75.5) and 60.4% (95% CI:57.2-63.6), respectively. In MVA predicting BCR, the accuracy for RP, TMA and biopsy was 0.73, 0.72 and 0.68, respectively. TMA added discriminatory ability among exclusively low-grade Gleason RP patients (p = 0.02), but did not improve BCR discrimination in exclusive high-grade PCa RP patients (p = 0.8). TMA Gleason grade accurately reflects presence of high-grade Gleason in RP specimen, accurately predicts BCR rates after RP and improves prediction of BCR in low-grade Gleason patients at RP.

The effect of androgen deprivation treatment on subsequent risk of bladder cancer diagnosis in male patients treated for prostate cancer.

INTRODUCTION: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). METHODS: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. RESULTS: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29-95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83-2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). CONCLUSION: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.

Inverse stage migration patterns in North American patients undergoing local prostate cancer treatment: a contemporary population-based update in light of the 2012 USPSTF recommendations.

PURPOSE: Recent studies demonstrated ongoing inverse stage migration in prostate cancer (PCa) patients towards more advanced and unfavorable tumors. The USPSTF grade D recommendation may impact this trend in North American patients. We assessed contemporary stage migration and treatment trends in a large North American cohort diagnosed with PCa 2009-2014. METHODS: Time-trend analyses were performed in patients within the Surveillance, Epidemiology, and End Results database, with complete data of clinical tumor stage, biopsy Gleason score, and validated PSA values, resulting in 211,645 assessable patients. Patients were stratified according to their different treatment methods [radical prostatectomy (RP), radiotherapy (RT), and no local treatment (NLT)] and according to clinical and pathological risk stratification (D'Amico and CAPRA-S score). RESULTS: Over time, proportions of D'Amico low-risk (LR) decreased, with an increase in intermediate-to-high-risk (IR/HR) patients. These trends were more distinct in men ≥ 70 years. NLT proportions increased, most notably in D'Amico LR and/or older patients. Conversely, RP proportions remained stable in younger HR and increased in older HR patients. Similar patterns were demonstrated in the RP-treated subgroup: D'Amico HR, pT3, and/or lymph-node invasion or CAPRA-S HR proportions increased from 23.5 to 30.8, 24.3 to 32.9, and 10.7 to 16.3% (each p ≤ 0.015). CONCLUSIONS: Inverse stage migration with increase of unfavorable PCa continues in most contemporary North American patients. However, a paradigm shift to treat LR patients with less invasive methods (NLT) was demonstrated. Contrary, HR patients increasingly undergo LT. Future studies with long-term follow-up might answer if inverse stage migration vs. treatment trends translate into different PCa metastases/mortality rates vs. proposed NLT benefits, particularly related to USPSTF-recommended reduced PSA screening.

Impact of multiparametric MRI and MRI-targeted biopsy on pre-therapeutic risk assessment in prostate cancer patients candidate for radical prostatectomy.

PURPOSE: To assess the current status and future potential of multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TBx) on the pretherapeutic risk assessment in prostate cancer patients' candidates for radical prostatectomy. METHODS: A literature search of the MEDLINE/PubMed and Scopus database was performed. English-language original and review articles were analyzed and summarized after an interactive peer-review process of the panel. RESULTS: Pretherapeutic risk assessment tools should be based on target plus systematic biopsies, where the addition of systematic biopsy (TRUS-Bx) to the mpMRI-target cores is associated with a lower rate of upgrading at final pathology. The combination of mpMRI findings with clinical parameters outperforms models based on clinical parameters alone in the prediction of adverse pathological outcomes and oncological results. This is particularly true when a specialized radiologist is present. CONCLUSION: The combination of mpMRI findings and clinical parameters should be considered to improve patient stratification in the pretherapeutic risk assessment. There is an urgent need to develop or include MRI data and MRI-TBx findings in available preoperative risk tools. This will allow improving the pretherapeutic risk assessment, providing important additional information for patient-tailored treatment planning and optimizing outcomes.

Prediction of Complications in Radical Prostatectomy Prostate Cancer Patients: Simulated Annealing versus Co-Morbidity Indexes.

BACKGROUND: The Deyo/Charlson co-morbidity index (CCI) and Klabunde co-morbidity index (KCI) co-morbidity indexes represent outdated indexes when the endpoint of complications after radical prostatectomy (RP) is considered. A novel group of co-morbidities derived from International Classification of Diseases-9 diagnostic codes in a contemporary RP database could provide better accuracy. Research Design, Subjects and Measures: We relied on 20,484 patients with clinically localized non-metastatic prostate cancer treated with RP between 2000 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked database. We examined 2 endpoints, namely, 90-day medical complication rate and 90-day surgical complication rate after RP. Simulated annealing (SA) was used to develop a novel co-morbidity index. Finally, the newly identified groups of co-morbid conditions were compared with the CCI and Klabunde indexes. RESULTS: Our SA identified 10 and 7 individual co-morbid conditions able to predict 90-day medical and surgical complications respectively. This novel model showed improved predictive accuracy over CCI and KCI for the 2 endpoints considered (respectively: 59.4 vs. 58.1 and 58.0% for medical complications, 58.0 vs. 56.8 and 56.7% for surgical complications). CONCLUSIONS: The newly defined groupings of co-morbid conditions resulted in better ability to predict the 2 endpoints of interest compared to CCI and KCI. However, the gain was marginal. This implies that better tools should be defined to more accurately predict these outcomes.