PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions.

PURPOSE: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy. METHODS: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings. RESULTS: A total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17-224.60; p = 0.038). CONCLUSION: Patients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.

Follow-up of vascular-targeted photodynamic therapy in a real-world setting.

PURPOSE: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). METHODS: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months. Functional outcome after 1 year was investigated by IIEF-5 and IPSS questionnaires. Progression was defined as the evidence3 of ISUP ≥ 2 PCa. RESULTS: At any control biopsy (n = 46) after VTP, only 37% of patients showed no evidence of PCa. Recurrence-free survival was 20 months (95% CI 4.9-45.5) and progression-free survival was 38.5 months (95% CI 33.5-43.6 months). In-field and out-field recurrent PCa occurs in 37% (55% ISUP ≥ 2 PCa) and 35% (56% ISUP ≥ 2 PCa). Seventy-nine percent of patients preserved erectile function, respectively. Ten percent of patients presented long-term bladder outlet obstruction. None of the patients presented incontinence. CONCLUSION: Due to the high-recurrence in- and out-field recurrence rate in a mainly low-risk prostate cancer cohort, VTP has to be regarded critically as a therapy option in these patients. Pre-interventional diagnostic evaluation is the main issue before focal therapy to reduce the risk of tumor recurrence and progression.

Treatment trends for undescended testis and impact of guideline changes a medical health care analysis of orchidopexy and cryptorchidism in Germany between 2006 und 2020.

BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Value of perilesional biopsies in multiparametric magnetic resonance imaging-targeted biopsy and systematic biopsy in detection of prostate cancer: results of a prospective, non-randomized, surgeon-blinded study.

PURPOSE: The goal of this study is to address if detection rates of clinically significant prostate cancer (csPCa) can be increased by additional perilesional biopsies (PB) in magnetic resonance (MR)/ultrasound fusion prostate biopsy in biopsy-naïve men. METHODS: This prospective, non-randomized, surgeon-blinded study was conducted between February 2020 and July 2022. Patients were included with PSA levels < 20 ng/ml and ≥ one PI-RADS lesion (grades 3-5) per prostate lobe. Prostate biopsy was performed by two urologists. The first performed the MR-fusion biopsy with 3-5 targeted biopsies (TB) and 6 PB in a standardized pattern. The second performed the systematic (12-fold) biopsy (SB) without knowledge of the MR images. Primary outcome of this study is absence or presence of csPCa (≥ ISUP grade 2) comparing TB, PB and SB, using McNemar test. RESULTS: Analyses were performed for each PI-RADS lesion (n = 218). There was a statistically significant difference in csPC detection rate of TB + SB between PI-RADS 3, 4 and 5 lesions (18.0% vs. 42.5% vs. 82.6%, p < 0.001) and TB + PB (19.7% vs. 29.1% vs. 78.3%). Comparing only maximum ISUP grade per lesion, even SB plus TB plus PB did not detect more csPCa compared to SB plus TB (41.3% vs. 39.9%, p > 0.05). CONCLUSION: We present prospective study data investigating the role of perilesional biopsy in detection of prostate cancer. We detected no statistically significant difference in the detection of csPCa by the addition of PB. Therefore, we recommend continuing 12-fold bilateral SB in addition to TB.

The Role of Multiparametric MRI (mpMRI) in the Prediction of Adverse Prostate Cancer Pathology in Radical Prostatectomy Specimen.

INTRODUCTION: Prostate cancer (PCa) risk stratification is essential in guiding therapeutic decision. Multiparametric magnetic resonance tomography (mpMRI) holds promise in the prediction of adverse pathologies (AP) after prostatectomy (RP). This study aims to identify clinical and imaging markers in the prediction of adverse pathology. METHODS: Patients with PCa, diagnosed by targeted biopsy after mpMRI and undergoing RP, were included. The predictive accuracy of mpMRI for extraprostatic extension (ECE), seminal vesicle infiltration (SVI), and lymph node positivity was calculated from the final histopathology. RESULTS: 846 patients were involved. Independent risk parameters include imaging findings such as ECE (OR 3.12), SVI (OR 2.55), and PI-RADS scoring (4: OR 2.01 and 5: OR 4.34). mpMRI parameters such as ECE, SVI, and lymph node metastases showed a high prognostic accuracy (73.28% vs. 95.35% vs. 93.38%) with moderate sensitivity compared to the final histopathology. The ROC analysis of our combined scoring system (D'Amico classification, PSA density, and MRI risk factors) improves the prediction of adverse pathology (AUC: 0.73 vs. 0.69). CONCLUSION: Our study supports the use of mpMRI for comprehensive pretreatment risk assessment in PCa. Due to the high accuracy of factors like ECE, SVI, and PI-RADS scoring, utilizing mpMRI data enabled accurate prediction of unfavorable pathology after RP.

Accelerative Solid-State Oxidation Behaviour of Amorphous and Partially Crystalline Venetoclax.

There is a growing focus on solid-state degradation, especially for its relevance in understanding interactions with excipients. Performing a solid-state degradation of Venetoclax (VEN), we delve into VEN's stability in different solid-state oxidative stress conditions, utilizing Peroxydone™ complex and urea peroxide (UHP). The investigation extends beyond traditional forced degradation scenarios, providing insights into VEN's behavior over 32 h, considering temperature and crystallinity conditions. Distinct behaviors emerge in the cases of Peroxydone™ complex and UHP. The partially crystalline (PC-VEN) form proves more stable with Peroxydone™, while the amorphous form (A-VEN) shows enhanced stability with UHP. N-oxide VEN, a significant degradation product, varies between these cases, reflecting the impact of different oxidative stress conditions. Peroxydone™ complex demonstrates higher reproducibility and stability, making it a promising option for screening impurities in solid-state oxidative stress scenarios. This research not only contributes to the understanding of VEN's stability in solid-state but also aids formulators in anticipating excipient incompatibilities owing to presence of reactive impurities (peroxides) and oxidation in the final dosage form.

Single-center, prospective phase 2 trial of high-intensity focused ultrasound (HIFU) in patients with unilateral localized prostate cancer: good functional results but oncologically not as safe as expected.

PURPOSE: Focal therapy (FT) for localized prostate cancer (PCa) is only recommended within the context of clinical trials by international guidelines. We aimed to investigate oncological follow-up and safety data of focal high-intensity focused ultrasound (HIFU) treatment. METHODS: We conducted a single-center prospective study of 29 patients with PCa treated with (focal) HIFU between 2016 and 2021. Inclusion criteria were unilateral PCa detected by mpMRI-US-fusion prostate biopsy and maximum prostate specific antigen (PSA) of 15 ng/ml. Follow-up included mpMRI-US fusion-re-biopsies 12 and 24 months after HIFU. No re-treatment of HIFU was allowed. The primary endpoint was failure-free survival (FFS), defined as freedom from intervention due to cancer progression. RESULTS: Median follow-up of all patients was 23 months, median age was 67 years and median preoperative PSA was 6.8 ng/ml. One year after HIFU treatment PCa was still detected in 13/ 29 patients histologically (44.8%). Two years after HIFU another 7/29 patients (24.1%) were diagnosed with PCa. Until now, PCa recurrence was detected in 11/29 patients (37.93%) which represents an FFS rate of 62%.One patient developed local metastatic disease 2 years after focal HIFU. Adverse events (AE) were low with 70% of patients remaining with sufficient erectile function for intercourse and 97% reporting full maintenance of urinary continence. CONCLUSION: HIFU treatment in carefully selected patients is feasible. However, HIFU was oncologically not as safe as expected because of progression rates of 37.93% and risk of progression towards metastatic disease. Thus, we stopped usage of HIFU in our department.

Hospital rating websites play a minor role for uro-oncologic patients when choosing a hospital for major surgery: results of the German multicenter NAVIGATOR-study.

PURPOSE: Hospital rating websites (HRW) offer decision support in hospital choice for patients. To investigate the impact of HRWs of uro-oncological patients undergoing elective surgery in Germany. METHODS: From 01/2020 to 04/2021, patients admitted for radical prostatectomy, radical cystectomy, or renal tumor surgery received a questionnaire on decision-making in hospital choice and the use of HRWs at 10 German urologic clinics. RESULTS: Our study includes n = 812 completed questionnaires (response rate 81.2%). The mean age was 65.2 ± 10.2 years; 16.5% were women. Patients were scheduled for prostatectomy in 49.1%, renal tumor surgery in 20.3%, and cystectomy in 13.5% (other 17.1%). Following sources of information influenced the decision process of hospital choice: urologists' recommendation (52.6%), previous experience in the hospital (20.3%), recommendations from social environment (17.6%), the hospital's website (10.8%) and 8.2% used other sources. Only 4.3% (n = 35) used a HRW for decision making. However, 29% changed their hospital choice due to the information provided HRW. The most frequently used platforms were Weisse-Liste.de (32%), the AOK-Krankenhausnavigator (13%) and Qualitaetskliniken.de (8%). On average, patients rated positively concerning satisfaction with the respective HRW on the Acceptability E-Scale (mean values of the individual items: 1.8-2.1). CONCLUSION: In Germany, HRWs play a minor role for uro-oncologic patients undergoing elective surgery. Instead, personal consultation of the treating urologist seems to be far more important. Although patients predominantly rated the provided information of the HRW as positive, only a quarter of users changed the initial choice of hospital.

Negative multiparametric magnetic resonance imaging for prostate cancer: further outcome and consequences.

PURPOSE: EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. METHODS: A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. RESULTS: 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02-1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01-1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1-2 lesion (OR 0.38 [0.15-0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. CONCLUSIONS: Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Increased Severe Adverse Outcomes and Decreased Emergency Room Visits for Pyelonephritis: First Report of Collateral Damage during COVID-19 Pandemic in Urology.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is disrupting urology health-care worldwide. Reduced emergency room visits resulting in adverse outcomes have most recently been reported in pediatrics and cardiology. We aimed to compare patients with emergency room visits for pyelonephritis in 2019 (pre-COVID-19 era) and within the first wave of pandemic in 2020 (COVID-19 era) with regard to the number of visits and severe adverse disease outcomes. METHODS: We performed a retrospective multicentre study comparing characteristics and outcomes of patients with pyelonephritis, excluding patients with hydronephrosis due to stone disease, in 10 urology departments in Germany during a 1-month time frame in March and April in each 2019 and 2020. RESULTS: The number of emergency room visits for pyelonephritis in the COVID-19 era was lower (44 patients, 37.0%) than in the pre-COVID-19 era (76 patients, 63.0%), reduction rate: 42.1% (p = 0.003). Severe adverse disease outcome was more frequent in the COVID-19 era (9/44 patients, 20.5%) than in the pre-COVID-19 era (5/76 patients, 6.6%, p = 0.046). In detail, 7 versus 3 patients needed monitoring (15.9 vs. 3.9%), 2 versus no patients needed intensive-care treatment (4.5 vs. 0%), 2 versus no patients needed drain placement (4.5 vs. 0%), 2 versus no patients had a nephrectomy (4.5 vs. 0%), and 2 versus 1 patient died (4.5 vs. 1.3%). CONCLUSION: This report of collateral damage during CO-VID-19 showed that emergency room visits were decreased, and severe adverse disease outcomes were increased for patients with pyelonephritis in the COVID-19 era. Health authorities should set up information campaign programs actively encouraging patients to utilize emergency room services in case of severe symptoms specifically during the actual second wave of pandemic.

Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles.

A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC®) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50-6.50 µg/mL (R2 = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.

Prostate cancer rates in patients with initially negative elastography-targeted biopsy vs. systematic biopsy.

PURPOSE: To assess whether real-time elastography-targeted biopsy (RTE-bx) is superior to the standard systematic transrectal ultrasound (TRUS)-guided biopsy in predicting subsequent prostate cancer (PCa) rates in patients with initially negative biopsy and to specifically reveal differences in the occurrence of high-grade (Gleason ≥ 4 + 3) PCa by comparing both biopsy methods. PATIENTS AND METHODS: Overall, 630 patients had an initially negative prostate biopsy between 2007 and 2015, either RTE targeted (n = 213) or systematically (n = 417). Follow-up data, ascertained by a questionnaire, of patients receiving RTE-bx were compared to data of patients receiving systematic biopsy (sbx) using Mann-Whitney-U test and Chi-square test. We performed logistic regression analyses to assess any association with PCa or high-grade PCa occurrence. RESULTS: In total, 258 (41%) patients were diagnosed with PCa at repeat biopsy whereof 54 (8.6%) harboured high-grade PCa. PCa occurred in 95 (44.6%) patients with initially negative RTE-bx and in 163 (39.1%) patients with initially negative sbx (p = 0.003). 24 (11.3%) patients receiving RTE-bx and 30 (7.2%) patients receiving sbx were diagnosed with high-grade PCa (p = 0.095). Logistic regression analyses showed that patients with the initial RTE-bx vs. those with the initial sbx neither resulted in a significant higher risk for PCa occurrence (OR 1.35 [CI 0.87-2.1]; p = 0.2) nor for high-grade PCa occurrence (OR 1.52 [CI 0.66-3.35]; p = 0.3). CONCLUSIONS: We found no statistically significant association of prior biopsy method to subsequent PCa or high-grade PCa occurrence. Referring to our analyses, RTE is not superior to sbx in predicting subsequent PCa rates and, therefore, not eligible to decide on repeat biopsy.

Antimicrobial lubricant reduces rectal bacteria at transrectal prostate biopsy: results from a prospective randomized trial.

PURPOSE: Antibiotic resistance may lead to increasing infection rates at transrectal prostate biopsy. Local antimicrobial agents might help to reduce bacterial load. The aim of this study was to test the potency of antimicrobial lubricants to reduce local bacterial loads and specifically fluoroquinolone-resistant strains. PATIENTS AND METHODS: Overall, 384 prostate biopsy (PBx) patients of a larger prospective randomized trial (n = 1000) were included. Patients were randomized for biopsy with pre-interventional instillation of an antimicrobial lubricant (intervention group n = 256) or with the standard lubricant (control group n = 128). Bacteria were recovered on pre- and post-biopsy rectal swab cultures from both patient groups. Bacterial colonization was semi-quantitatively recorded and analyzed for the presence of ciprofloxacin-resistant isolates. RESULTS: Within the intervention group, where antimicrobial lubricant was instilled for PBx, the post-biopsy bacterial count was statistically significantly lower compared to prior biopsy bacterial count (p < 0.001), while in the control group, no statistically significant difference was shown. Moreover, our results demonstrated the tendency for reduction in ciprofloxacin-resistant bacteria growth when instillation of antimicrobial lubricant was used (9.4% versus 5.9%, p = 0.5 prior- and post-biopsy). No reduction in ciprofloxacin-resistant bacterial growth was demonstrated for the control group. Ciprofloxacin-resistance was shown in overall 30 (7.8%) patients. CONCLUSION: Our data demonstrated that the antimicrobial lubricant prior biopsy leads to reduced bacterial load. Moreover, our data show the tendency for reduced ciprofloxacin-resistant bacteria growth when antimicrobial lubricant was instilled prior biopsy. However, the incidence of ciprofloxacin-resistant bacteria is low in our patient population. Rectal swabs should assess fluoroquinolone-resistance rates at prostate biopsy.

Mapping the landscape of urology: A new media-based cross-sectional analysis of public versus academic interest.

OBJECTIVES: To quantify public and academic interest in the urological field using a novel new media-based methodology. METHODS: We systematically measured public and academic interest in 56 urological keywords and combined in nine subspecialties. Public interest was quantified as video views on YouTube. Academic interest was quantified as article citations using Microsoft Academic Search. The public-to-academic interest ratio was calculated for a comparison of subspecialties as well as for diseases and treatments. RESULTS: For the selected 56 urological keywords, we found 226 617 591 video views on YouTube and 2 146 287 citations in the academic literature. The public-to-academic interest ratio was highest for the subspecialties robotic urology (ratio 6.3) and andrological urology (ratio 4.6). Prostate cancer was the central urological disease combining both a high public (20% of all video views) and academic interest (26% of all citations, ratio 0.8). Further diseases/treatments of high public interest were premature ejaculation (ratio 54.4), testicular cancer (ratio 11.4), erectile dysfunction (ratio 5.5) and kidney transplant (ratio 3.7). Urological treatments had a higher public-to-academic interest ratio (median ratio 0.25) than diseases (median ratio 0.05; P = 0.029). CONCLUSIONS: A quantification of academic and public interest in the urological field is feasible using a novel new media-based methodology. We found several mismatches in public versus academic interest in urological diseases and treatments, which has implications for research strategies, conference planning and patient information projects. Regular re-assessments of the public and academic interest landscape can contribute to detecting and proving trends in the field of urology.

Autonomic Nervous System Activity for Risk Stratification of Emergency Patients With Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) causes appreciable morbidity and mortality in adults, especially in those ≥65 years of age. At hospital admission, an immediate and reliable risk assessment is necessary to detect patients with possible fatal outcome. OBJECTIVE: We aimed to evaluate markers of the autonomic nervous system based on an electrocardiogram to predict mortality in patients with CAP. METHODS: For this purpose, the deceleration capacity (DC) of heart rate was calculated in 253 patients who presented to the emergency department with CAP. The 30-day mortality rate was defined as the primary endpoint (PEP). The secondary endpoint was the total mortality within 180 days. RESULTS: PEP was reached in 33 patients (13%). The DC, measured in milliseconds, was significantly lower in patients who reached the PEP than in those who did not (2.3 ± 1.5 ms vs. 3.6 ± 2.3 ms, p = 0.004). The DC was also significantly lower in nonsurvivors than in survivors at the time of the secondary endpoint (2.3 ± 1.5 ms vs. 3.7 ± 2.4 ms, p < 0.001). Our results indicate that DC is an independent predictor of 30- and 180-day mortality. CONCLUSION: DC was independently associated with death from CAP in our study. As a practical consequence, DC could be useful in triage decisions. Patients with certain high risks could benefit from adjuvant treatment and special medical attention.

The Impact of Repeat Prostate Biopsies on Oncologic, Pathological and Perioperative Outcomes after Radical Prostatectomy.

PURPOSE: The impact of repeat biopsy sessions on radical prostatectomy remains controversial regarding perioperative, pathological and oncologic outcome. MATERIALS AND METHODS: We analyzed the records of 12,624 patients who underwent radical prostatectomy from 2007 to 2013. The association of the number of biopsy sessions (range 1 to 3 or more) with pathological outcomes and perioperative complications was analyzed using the Wilcoxon matched pair test. To test the association between biopsy sessions and biochemical recurrence-free survival we used Kaplan-Meier curves and multivariable Cox regression analysis. RESULTS: Of the patients 89.2% had 1 biopsy session, 7.4% had 2 sessions and 3.4% had 3 or more sessions. Median followup was 36.6 months. In patients with 1, 2 and 3 or more biopsy sessions prostate volume (38, 44 and 45 ml) and prostate specific antigen (6.7, 7.6 and 10.1 ng/ml, respectively) were greater (each p <0.001). The perioperative outcome was more favorable. Patients with 1, 2 and 3 or more biopsy sessions more often had organ confined tumors (67.6%, 72.1% and 72.9%, p = 0.003) and higher tumor volume (3.1, 3.0 and 3.6 ml, p <0.001) but a lower tumor percent (7.5%, 3.7% and 2.4%, respectively, p <0.001). More biopsy sessions were associated with fewer lymph node metastases (1, 2 and 3 sessions 0.23, 0.13 and 0.17, respectively, p <0.001). Gleason score and surgical margin status did not differ. The overall biochemical recurrence rate was 18.9% and it was comparable among the biopsy groups. No association was found between the number of biopsies and biochemical recurrence. CONCLUSIONS: Patients with multiple biopsy sessions experience a slightly more favorable pathological outcome without an impact on the oncologic outcome. The perioperative outcome was more favorable in patients with multiple biopsies.

Impact of preoperative risk on metastatic progression and cancer-specific mortality in patients with adverse pathology at radical prostatectomy.

OBJECTIVE: To evaluate the impact of preoperative risk category on metastatic disease and prostate cancer-specific mortality (CSM) in patients with prostate cancer (PCa) with adverse pathology at radical prostatectomy (RP). PATIENTS AND METHODS: The records of 6 943 patients who underwent RP at a European tertiary centre were analysed. Biochemical recurrence (BCR), metastatic disease and CSM were assessed for patients with adverse pathology at RP, and stratified according to preoperative low- vs intermediate-/high-risk PCa groups. Kaplan-Meier, cumulative incidence, Cox regression and competing risk regression analyses were performed. RESULTS: In patients with extracapsular extension, the metastatic disease rate was 1.6% vs 8% (P < 0.001) and the CSM rate was 2% vs 5% (P = 0.041) for low vs intermediate-/high-risk patients, respectively, at 10 years. In patients with pathological Gleason score ≥3+4, the metastatic disease rate was 3.0% vs 12% (P < 0.001) and the CSM rate was 3% vs 8%, respectively (P < 0.001). In patients with positive surgical margins (PSMs), the metastatic disease rate was 2.9% vs 15% (P < 0.001) and the CSM rate was 4% vs 10%, respectively (P = 0.0001). Low-risk status was a predictive factor for metastatic disease in patients with pathological Gleason score ≥3+4 (hazard ratio [HR] 0.51), pathological Gleason score ≥4+3 (HR 0.41) and PSMs (HR 0.46) and was a predictive factor for CSM risk in patients with pathological Gleason score ≥3+4 (HR 0.62). CONCLUSIONS: Patients with low-risk PCa were at significantly lower risk of metastatic disease and CSM than their intermediate-/high-risk counterparts, when adverse pathological features were identified at RP. This should be emphasized in the decision-making process after RP.

Comorbidity and age cannot explain variation in life expectancy associated with treatment of non-metastatic prostate cancer.

INTRODUCTION: Age and Charlson comorbidity index (CCI) affect life expectancy (LE) and other-cause mortality (OCM) in non-metastatic prostate cancer (nmPCa) patients. We examined their ability to predict OCM in individuals treated with radical prostatectomy (RP), brachytherapy (BT), external beam radiation (EBRT) androgen deprivation (ADT) or observation. We postulated that these variables are not sufficient to explain OCM and LE patterns according to different treatment types. PATIENTS AND METHODS: We relied on the SEER-Medicare database from 1991 to 2009. Overall, 283,125 patients with non-metastatic prostate cancer aged ≥66 years were treated with RP (15.5%), BT (13.9%), EBRT (21.4%), ADT alone (16.3%) or observation (32.8%). Cumulative incidence of OCM and LE was stratified by treatment type and adjusted for age and CCI. Competing risks regression was also used. RESULTS: OCM rates vary according to treatment, despite age and CCI adjustment. In RP or BT patients, LE exceeds 10 years, regardless of age and CCI. Conversely, a 10-year LE is not reached by patients >74 years treated with observation or ADT. In OCM competing risks regression, age, CCI and treatment type achieved independent predictor status (all p < 0.001). CONCLUSION: In patients with nmPCa, neither age nor CCI can accurately estimate OCM or LE in excess of 10 years. Primary treatment assignment is a strong determinant of OCM and LE, where RP and BT patients enjoy better OCM and LE rates than observation ADT or EBRT patients. In consequence, better clinical tools are needed to accurately assess OCM and LE in those settings.

Tumor volume improves the long-term prediction of biochemical recurrence-free survival after radical prostatectomy for localized prostate cancer with positive surgical margins.

PURPOSE: To develop a novel application evaluating the effect of tumor volume (TV) and percentage of high-grade tumor volume (%HGTV) on long-term biochemical recurrence-free survival rate (BCRFS) after radical prostatectomy (RP) in patients with pT2 PCa. METHODS: Retrospective analysis of 903 men with pT2 PCa between 1992 and 2004 at a single European tertiary care center was performed. Cox regression models identified risk factors for BCR. A nomogram was developed to predict the BCRFS at 5, 10 and 15 years after RP. Decision curve analyses were performed to identify the net increase in cases identified by the full model. RESULTS: BCR-free survival rates at 5, 10 and 15 years were 94, 90 and 86 %. In Cox regression analyses, TV, %HGTV and positive surgical margin status (SM) were independent predictors of BCR. Predictive accuracies (PA) at 5, 10 and 15 years of the base model (PSA, Gleason score, SM) were 76.8 % (95 % CI 67.9-78.2 %), 70.5 % (95 % CI 64.9-75.0 %) and 68.1 % (95 % CI 60.6-73.5 %). The full model, including TV and %HGTV, achieved 76.9, 72.4 and 70.7 %. These PA differences were statistically significant at 10 and 15 years (p < 0.001). CONCLUSIONS: TV and %HGTV could potentially serve as valuable measures to stratify patients at high risk of BCR. The use of our nomogram should be considered to counsel patients with pT2 disease and SM and to design appropriate follow-up or treatment regimens.