Distinct distribution patterns of exercise-induced natural killer cell mobilization into the circulation and tumor tissue of patients with prostate cancer.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

Treatment Failure in Vertebral Osteomyelitis: Is it All About Staphylococcus aureus ?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The aim was to compare the influence of 2 common vertebral osteomyelitis (VO) causing pathogens on treatment failure within the first year of diagnosis. SUMMARY OF BACKGROUND DATA: VO is mainly caused by Staphylococcus aureus (SA), while enterococci and streptococci (ENST) are also responsible for a significant proportion of VO, particularly in elderly patients. Data on VO caused by SA show a tendency for worse outcome, whereas data on VO caused by ENST are scarce. For this purpose, our study compares characteristics of patients with VO caused by SA or ENST in order to analyze risk factors for treatment failure. METHODS: We conducted a retrospective monocentric study including VO patients from 2008 to 2020. Primary outcome was treatment failure defined as death or relapse within 1 year (T1). We compared patients diagnosed with VO caused by Staphylococcus aureus including MRSA to patients diagnosed with VO caused by Enterococcus and Streptococcus species, which were combined into one group. Polymicrobial infections were excluded. We employed multiple logistic regression analysis to adjust for confounding. To account for moderation, the model was repeated with an included interaction term. RESULTS: Data of 130 VO patients (SA=95; ENST=35) were available at T1. Treatment failure occurred in 37% of SA patients and 23% of ENST patients. On multivariate analysis SA [odds ratio (OR): 3.12; 95% confidence interval (CI): 1.09-10.53; P =0.046], Charlson comorbidity index (OR: 1.31; 95% CI: 1.11-1.58; P =0.002) and infectious endocarditis (IE; OR: 4.29; 95% CI: 1.23-15.96; P =0.024) were identified as independent risk factors for treatment failure. CONCLUSION: In our cohort every third patient with VO caused by SA or ENST dies within 1 year. Our findings indicate that patients with VO caused by SA, concomitant IE and/or a high Charlson comorbidity index score may be at elevated risk for treatment failure. These findings can be used to individualize patient care and to direct clinical surveillance. This could include echocardiography evaluating for the presence of IE in patients with VO caused by gram-positive pathogens.

Perioperative Outcomes of Transurethral Resection, Open Prostatectomy, and Laser Therapy in the Surgical Treatment of Benign Prostatic Obstruction: A "Real-World" Data Analysis from the URO-Cert Prostate Centers.

INTRODUCTION: The aim of the study is to compare length of hospital stay, transfusion rates, and re-intervention rates during hospitalization for transurethral resection of the prostate (TUR-P), open prostatectomy (OP), and laser therapy (LT) for surgical treatment of benign prostatic obstruction (BPO). METHODS: URO-Cert is an organization, in which clinical data of prostatic diseases from 2 university, 19 public, and 3 private hospitals and 270 office-based urologists are collected in order to document treatment quality. Data on diagnostics, therapy, and course of disease are recorded web based. The analysis includes datasets from 2005 to 2017. RESULTS: Of 10,420 patients, 8,389 were treated with TUR-P, 1,334 with OP, and 697 with LT. Median length of hospital stay was 6 days (IQR: 4-7) for TUR-P, 9 days (IQR: 7-11) for OP, and 5 days (IQR: 4-6) for LT (p < 0.001). Risk for a hospital stay ≥7 days was higher for OP versus TUR-P (OR: 7.25; 95% CI = 6.27-8.36; p < 0.001) and LT (OR: 17.89; 95% CI = 14.12-22.65; p < 0.001) and higher for TUR-P versus LT (OR: 2.47; 95% CI = 2.03-3.01; p < 0.001). OP had a significantly higher risk for transfusions than TUR-P (OR: 2.44; 95% CI = 1.74-3.41; p < 0.001) and LT (OR: 3.32; 95% CI = 1.56-7.01; p < 0.001). Transfusion rates were not significantly different between TUR-P and LT (OR: 1.36; 95% CI = 0.66-2.79; p = 0.51). Risk of re-intervention was not different between all 3 approaches. CONCLUSION: OP was associated with higher transfusion rates and longer hospital stay than TUR-P and LT. Risk of transfusion was not different between TUR-P and LT, but TUR-P was inferior to LT concerning length of hospital stay. Re-intervention rates during hospitalization did not differ between the groups.

Non-invasive urine markers for the differentiation between RCCs and oncocytoma.

BACKGROUND: Recently, our group showed that Vim3 is overexpressed in tissue samples of renal oncocytomas and Mxi-2 in clear cell renal carcinoma (ccRCC). The mechanism leading to the truncation of both proteins is known and involves with two miRs, both detectable in urine. Since the analysis of miRs is time-consuming, our aim was to identify the truncated proteins in urine instead. Furthermore, urine samples from small renal masses (SRMs) (n = 45, <4 cm) were analyzed to get a pre-surgical differentiation of the cancer subtypes. METHODS: Urines were accessed from the urological biobank (n = 350). Proteins were isolated from urine samples, and Western blots were performed. Each sample was analyzed with ELISA for the expression of Vim3 and Mxi-2. A lateral flow assay was established. For the detection of SRMs, the miRs were isolated and qRT-PCR was performed. RESULTS: A significant increase of Vim3 in urines from patients with oncocytoma (n = 20) was detectable with ELISA compared to all other subtypes of RCCs (chromophobe (n = 50), papillary (n = 40), ccRCC (n = 200), and controls (n = 40) (***p < 0.0001)). Mxi-2 was predominantly overexpressed in ccRCCs (***p < 0.0001). Lateral flow assay of Vim3 and Mxi-2 shows two bands in the case of oncocytoma and ccRCC indicating the specificity of this test. For SRMs, an overexpression of miR-15a/Mxi2 was detectable in urine samples from ccRCC and chromoRCC patients. In contrast to that, miR-498/Vim3 were predominantly overexpressed in oncocytoma patients. CONCLUSION: Both proteins (Vim3 and Mxi-2) were detectable in patients' urines and can be used for the non-invasive differentiation of kidney cancers.

[Active surveillance-much safety, little recruitment : Is it possible to extend the indication for "intermediate-risk" prostate cancer?] / Active Surveillance ­ viel Sicherheit, wenig Rekrutierung : Ist eine Ausdehnung der Indikation auf das intermediäre Risiko möglich?

BACKGROUND: In contrast to North America or Sweden, active surveillance (AS) has not yet become established in our country for suitable prostate carcinomas (PCa). The strict entry criteria specified by the guideline are not likely to improve the acceptance in the near future. In early detection, prostate-specific antigen (PSA) testing leads to high numbers of overtreatment. There are various reasons for the continued preference for radical surgery. OBJECTIVES: The goal is to examine whether the heterogeneous group with intermediate-risk PCa contains tumors that may be eligible for AS. MATERIALS AND METHODS: In the HAROW trial, 52 AS patients with differently defined intermediate-risk PCa were followed for a median of 85.6 months. Oncologic outcomes are reported. RESULTS: Sixteen (30%) patients had a tumor of cT2b category, 21 (40%) had a Gleason score 3 + 4, 7 (14%) had ≥3 positive biopsy cores, 21 (40%) had a PSA >10 ng/ml, and 22 (42%) had a PSA density >0.2 ng/ml2. Carcinoma-specific and metastasis-free survival were 100% and 96%, respectively. Thirty four patients discontinued AS in favor of invasive treatment, and an additional eight men maintained a noninvasive approach by switching to watchful waiting. CONCLUSIONS: Efforts are under way to specify the criteria for patients with intermediate-risk PCa who may be eligible for AS. Tumors of cT2 category could be grouped together. The Gleason 4 fraction needs to be quantified because it determines the prognosis.

Stage and Grade Migration in Prostate Cancer Treated With Radical Prostatectomy in a Large German Multicenter Cohort.

INTRODUCTION: Overdiagnosis and overtherapy in prostate cancer (PCa) treatment should be avoided, which has led to an awareness of the need to decrease treatment in cases of low-risk PCa with radical prostatectomy (RP). Simultaneously, prostate-specific antigen testing has become less popular in the last few years, which has resulted in higher cancer grade and stage at diagnosis. We evaluated stage and grade migration in the disease of patients treated with RP in a large German cohort. PATIENTS AND METHODS: Overall, 4842 patients undergoing RP between 2000 and 2019 were included. Age, prostate-specific antigen level, biopsy, and pathologic Gleason score as well as clinical and pathologic stage were collected. D'Amico risk groups and Gleason score were evaluated over different time points. RESULTS: We detected a significant grade migration toward higher grade. The proportion of biopsy Gleason sum ≤ 6 dropped from 45.8% to 20.6% between ≤ 2010 and 2017-2019. Further, the proportion of patients with low D'Amico risk scores also decreased by almost 50% (20.8% vs 12.2%). Finally, the proportion of non-organ-confined PCa increased over time, and the proportion of postoperative Gleason sum ≤ 6 decreased from 20% to 10% over time. CONCLUSION: Taken together, data indicate a significant preoperative grade and stage migration toward disease of higher grade in RP-treated PCa. Between the years 2000 and 2019, the proportion of biopsy Gleason sum ≤ 6 and the proportions of D'Amico low risk disease decreased by approximately 50% (respectively, 45% to 20% and 20.8% to 12.2%). This might indicate better patient selection for RP, but might also be a telltale sign of the rising mortality and morbidity of PCa.

Active Surveillance for Incidental (cT1a/b) Prostate Cancer: Long-Term Outcomes of the Prospective Noninterventional HAROW Study.

INTRODUCTION: Optimal treatment for incidental prostate cancer (IPC) after surgical treatment for benign prostate obstruction is still debatable. We report on long-term outcomes of IPC patients managed with active surveillance (AS) in a German multicenter study. METHODS: HAROW (2008-2013) was designed as a noninterventional, prospective, health-service research study for patients with localized prostate cancer (≤cT2), including patients with IPC (cT1a/b). A follow-up examination of all patients treated with AS was carried out. Overall, cancer-specific, and metastasis-free survival and discontinuation rates were determined. RESULTS: Of 210 IPC patients, 68 opted for AS and were available for evaluation. Fifty-four patients had cT1a category and 14 cT1b category. Median follow-up was 7.7 years (IQR: 5.7-9.1). Eight patients died of which 6 were still under AS or watchful waiting (WW). No PCa-specific death could be observed. One patient developed metastasis. Twenty-three patients (33.8%) discontinued AS changing to invasive treatment: 12 chose radical prostatectomy, 7 radiotherapy, and 4 hormonal treatment. Another 19 patients switched to WW. The Kaplan-Meier estimated 10-year overall, cancer-specific, metastasis-free, and intervention-free survival was 83.8% (95% CI: 72.2-95.3), 100%, 98.4% (95% CI: 95.3-99.9), and 61.0% (95% CI: 47.7-74.3), respectively. In multivariable analysis, age (RR: 0.97; p < 0.001), PSA density ≥0.2 ng/mL2 (RR: 13.23; p < 0.001), and PSA ≥1.0 ng/mL after surgery (RR: 5.19; p = 0.016) were significantly predictive for receiving an invasive treatment. CONCLUSION: In comparison with other AS series with a general low-risk prostate cancer population, our study confirmed the promising survival outcomes for IPC patients, whereas discontinuation rates seem to be lower for IPC. Thus, IPC patients at low risk of progression may be good candidates for AS.

EBV induced loss of sperm quality.

OBJECTIVE: To analyze the presence of Epstein-Barr-virus (EBV) in sperm samples from patients diagnosed with some impairment of the fertility parameters evaluated using seminogram and to observe if there is any difference with the normozoospermic samples. We hypothesize that an EBV infection is responsible for the upregulation of the miRNA 199-3p, which binds to the 3'UTR of endothelin-1 (ET-1). ET-1 is a key factor to produce Vimentin (Vim3), and therefore, it influences the expression of Vim3. Since Vim3 is predominantly detectable in sperms without any structural defects, the newly identified regulation mechanism can be responsible for the loss of sperm quality. MATERIAL AND METHODS: This study was performed from January 2017 to December 2020 and included 27 patients who provided ejaculated samples obtained by masturbation. Ejaculates were evaluated according to the Word Health Organization's criteria. Posteriorly, the samples were sorted according to the seminogram diagnosis and further analyzed using different enzyme-linked absorbed immune assays to determine the level or concentration of Epstein-Barr nuclear antigen (EBNA), ET-1, and Vim3. RESULTS: All sperm samples with the impairment of fertility parameters contained the EBNA and presented a downregulation of ET-1 and Vim3. In addition, sperms located in the swim ups are also partially positive for the EBV virus in different clinical aspects. CONCLUSION: Based on the regulation mechanism here presented, it seems that the EBV induces changes at the miRNA level, which are responsible for the decreasing of sperm quality.

Long-term outcomes of active surveillance for clinically localized prostate cancer in a community-based setting: results from a prospective non-interventional study.

PURPOSE: To report on long-term outcomes of patients treated with active surveillance (AS) for localized prostate cancer (PCa) in the daily routine setting. METHODS: HAROW (2008-2013) was a non-interventional, health service research study about the management of localized PCa in the community setting, with 86% of the study centers being office-based urologists. A follow-up examination of all patients who opted for AS as primary treatment was carried out. Overall, cancer-specific, and metastasis-free survival, as well as discontinuation rates, were determined. RESULTS: Of 329 patients, 62.9% had very-low- and 21.3% low-risk tumours. The median follow-up was 7.7 years (IQR 4.7-9.1). Twenty-eight patients (8.5%) died unrelated to PCa, of whom 19 were under AS or watchful waiting (WW). Additionally, seven patients (2.1%) developed metastasis. The estimated 10-year overall and metastasis-free survival was 86% (95% CI 81.7-90.3) and 97% (95% CI 94.6-99.3), respectively. One hundred eighty-seven patients (56.8%) discontinued AS changing to invasive treatment: 104 radical prostatectomies (RP), 55 radiotherapies (RT), and 28 hormonal treatments (HT). Another 50 patients switched to WW. Finally, 37.4% remained alive without invasive therapy (22.2% AS and 15.2% WW). Intervention-free survival differed between the risk groups: 47.8% in the very-low-, 33.8% in the low- and 34.6% in the intermediate-/high-risk-group (p = 0.008). On multivariable analysis, PSA-density ≥ 0.2 ng/ml2 was significantly predictive for receiving invasive treatment (HR 2.55; p = 0.001). CONCLUSION: Even in routine care, AS can be considered a safe treatment option. Our results might encourage office-based urologists regarding the implementation of AS and to counteract possible concerns against this treatment option.

Effect of a Single Bout of Aerobic Exercise on Kynurenine Pathway Metabolites and Inflammatory Markers in Prostate Cancer Patients-A Pilot Randomized Controlled Trial.

The kynurenine (KYN) pathway gains growing research interest concerning the genesis, progression and therapy of solid tumors. Previous studies showed exercise-induced effects on metabolite levels along the KYN pathway. Modulations of the KYN pathway might be involved in the positive impact of exercise on prostate cancer progression and mortality. The objective of this trial was to investigate whether a single-physical exercise alters tryptophan (TRP) metabolism and related inflammatory markers in this population. We conducted a randomized controlled trial with 24 patients suffering from prostate cancer. While the control group remained inactive, the intervention group performed a 30-min aerobic exercise on a bicycle ergometer at 75% of individual VO2peak. Before (t0) and directly after the exercise intervention (t1) KYN, TRP, kynurenic acid, quinolinic acid as well as various inflammation markers (IL6, TNF-α, TGF-ß) were measured in blood serum. At baseline, the present sample showed robust correlations between TRP, KYN, quinolinic acid and inflammatory markers. Regarding the exercise intervention, interaction effects for TRP, the KYN/TRP ratio and TGF-ß were observed. The results show for the first time that acute physical exercise impacts TRP metabolism in prostate cancer patients. Moreover, baseline associations underline the relationship between inflammation and the KYN pathway in prostate cancer.

[Noninvasive treatment of organ-confined prostate cancer in elderly patients-results of the HAROW study]. / Die nichtinvasive Therapie des organbegrenzten Prostatakarzinoms im Alter ­ Ergebnisse der HAROW-Studie.

BACKGROUND: Noninvasive treatment options such as active surveillance (AS), watchful waiting (WW), and hormone deprivation therapy (HT) are particularly important in elderly patients with localized prostate cancer (PCa). OBJECTIVES: We examine the use of these noninvasive treatment options in the everyday care in a cohort of patients ≥70 years old. MATERIALS AND METHODS: In the HAROW study, the treatment of localized PCa under everyday conditions is investigated. The only inclusion criterion was newly diagnosed organ-confined PCa (≤cT2c). In AS, WW, and HT patients, we compared initial tumor and patient characteristics, follow-up examinations and changes of therapy. RESULTS: Of 457 patients ≥70 years, 210 chose AS, 160 HT, and 87 WW. Observation times were 6.3 years (AS), 7.5 years (HT), and 7.0 years (WW). AS patients (73.2 years) were younger than WW (76.0 years) and HT patients (76.9 years) and had a higher proportion of low-risk tumors (80%) versus WW (31%) and HT (19%). A change of therapy was observed in 47.1% of AS, 17.2% of WW and 13.1% of HT patients. Metastasis occurred in 1.0% of AS, 4.6% of WW, and 6.9% of HT patients. Overall survival was 94.3% for AS, 90.8% for WW and 81.9% for HT. Within the first 28.4 months, the mean number of PSA determinations did not differ between AS and WW (6.1 vs. 5.2; p = 0.09); a rebiopsy was performed in 37.6% of AS, 11.4% of WW, and 17% of HT patients. CONCLUSIONS: The allocation to curative and palliative strategies should be made according to patient and tumor characteristics by definition. Palliative procedures may represent concepts in older patients who initially chose a curative AS strategy.

Vimentin 3 Allows Differentiation between Normozoospermia and Oligoasthenoteratozoospermia.

Vimentin is a structural protein predominantly located in the head of sperms. The function and localization of the previously identified truncated version, Vimentin 3 (Vim3), are still unknown. To investigate whether the expression of Vim3 can be used as a reliable marker for the differentiation of sperm quality, we analyzed ejaculates from patients with oligoasthenoteratozoospermia (OAT) syndrome and normozoospermia. We identified sperms with head, neck, and tail changes, which were less positive for Vim3 in OAT syndrome compared to normozoospermia. The expression of Vim3 was significantly downregulated in patients with OAT syndrome compared to sperms from patients with normozoospermia (∗∗ p < 0.01). The ELISA analysis showed similar results as ejaculates from normozoospermic patients showed a significantly higher Vim3 concentration than patients with OAT syndrome (∗∗∗ p < 0.001). This study demonstrates that Vim3 is more highly expressed in ejaculates from patients with normozoospermia compared to ejaculates from patients with OAT syndrome. Therefore, we postulate that Vim3 can be used to determine ejaculate quality. Furthermore, we identified the marker, Vim3, to differentiate between mature sperms with no morphological changes and sperms with head, neck, and tail changes. A lateral flow assay that allows quick analysis is currently under development.

Prostate-specific health-related quality of life and patient-physician communication - A 3.5-year follow-up.

OBJECTIVE: The aim of this study is to examine associations between prostate-specific health-related quality of life (HRQOL) and aspects of patient-physician communication in localized prostate cancer treatment. METHODS: Data of patients with localized prostate cancer were collected at 6-month intervals over a 3.5-year period within a prospective, observational study (HAROW). Data collection comprised D'Amico risk categories, the Charlson Comorbidity Index, patient-physician communication (information, shared decision making, support, devotion), and prostate-specific HRQOL (incontinence aid, urinary symptoms, bowel symptoms, hormonal treatment-related symptoms, sexual functioning, sexual activity). Data of N = 1722 patients undergoing radical prostatectomy were analyzed by longitudinal multilevel analysis. RESULTS: The mean patient age was 65 years; 31% had a low risk and 38% an intermediate risk of cancer growth and spread; 73% had a Charlson Comorbidity Index of 0. Significant associations were found between prostate-specific HRQOL and shared decision making, support and devotion. Patient information was not significantly associated with aspects of prostate-specific HRQOL. CONCLUSION: Patient reported long term outcomes are associated with aspects of patient-physician communication in prostate cancer patients. Patients feeling involved by their urologists experience less side effects of (surgical) treatment. PRACTICE IMPLICATIONS: Special communication training programmes should be developed and implemented for urologists.

Low-dose computed tomography of urolithiasis in obese patients: a feasibility study to evaluate image reconstruction algorithms.

Purpose: Retrospective evaluation and comparison of image quality generated by low-dose computed tomography (LDCT) from obese patients with urolithiasis using alternative reconstruction algorithms. Materials and methods: Twenty-five obese patients (body mass index [BMI]>25 kg/m2) underwent LDCT scans for suspected urolithiasis. The scans were recompiled using filtered-back projection (FBP), statistical iterative reconstruction (iDose) and iterative model-based reconstruction (IMR). Dose-length product (DLP) and patient details were obtained from the CT dose report and clinical charts, respectively. Objective image noise was assessed by measuring the SD of Hounsfield units (HUs) in defined locations. Additionally, subjective image evaluation was independently performed by two radiologists using a 3-point Likert scale. The inter-reviewer agreement of image quality was calculated. Results: Ureteral concretions were observed in all CT scans, two of which revealed bilateral stones. The assessed patients' mean BMI was 29.29±3.74 kg/m2, and the DLP of the CT scans was 100.04±10.00 mGy*cm. All scans were rated diagnostic with the iDose and iterative model-based reconstructions, whereas 41% of the scans performed with FBP reconstruction were nondiagnostic. With respect to image quality, IMR was superior to iDose and FBP, both in the objective (P<0.001) and overall subjective (P≤0.008) evaluation of the respective data sets. The inter-reviewer agreement for overall image quality was "almost perfect" for IMR, "substantial" for iDose and "moderate" for FBP (κ values of 1.0, 0.6 and 0.46, respectively). Conclusion: Using iterative image reconstruction algorithms, LDCT of urolithiasis is feasible in overweight patients with a BMI between 25 and 35 kg/m2. Due to higher image quality, IMR is the preferred algorithm for scan reconstruction as it may help to avoid repeated examinations due to initial nondiagnostic scans.

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia.

BACKGROUND: The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT). OBJECTIVES: To analyse the use of tamoxifen in iOAT. METHOD: Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment. RESULTS: After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7-4.8] vs. 5.3 [3.1-7.1]; p = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9-11.5] vs. 15.9 mIU/mL [8.4-19.9]; p = 0.003) and luteinizing hormone (4.5 [3.3-6.6] vs. 7.6 mIU/mL [4.8-10.7]; p = 0.007) significantly increased. At a cut-off of >8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068-0.773]; p  = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of <82 ng/L (OR 18.0 [95% CI 1.267-255.744]; p = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events. CONCLUSIONS: Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.

Predictive value of the UICC and AJCC 8th edition tumor-nodes-metastasis (TNM) classification for patients treated with radical prostatectomy.

BACKGROUND: According to the 8th-edition of the tumor-nodes-metastasis-classification localized prostate cancer (PCa) can be divided into two categories (cT1,cT2), two stages (SI,SII), and, by incorporating prostate-specific-antigen (PSA) and WHO-grade (Gleason-Score), into prognostic stage groups (PSG I,IIA,IIB,IIC,III). We examined the predictive value of these systems for an organ-confined disease (pT≤2), favorable WHO-grade ≤2 (Gleason-score ≤7a), and biochemical-free-survival (BFS) after radical prostatectomy (RP). METHODS: Data were collected in a prospective, non-interventional, multicenter health-service-research study for the treatment of localized PCa (HAROW) with 687 patients receiving RP. Mean Follow-up was 31.7 months. RESULTS: Organ-confined disease was present in 76.5% and 63.6% of cT1 and cT2 patients, 75.7% and 59.6% of SI and SII, and 84.6%, 81.6%, 72.8% and 42.5% of PSG I, IIA, IIB and ≥ IIC (p = 0.001). Favorable WHO-grade (Gleason-Score) was present in 75.4% and 60.7% of cT1 and cT2 patients, 74.3% and 56.5% of SI and SII patients, and 86.1%,85.6%,73.3% and 29.5% of PSG I, IIA, IIB and ≥ IIC (p = 0.001). Probability of BFS was 92.0% and 91.5% for cT1 and cT2 (p = 0.990), 91.1% and 94.2% for SI and S II (p = 0.286) and 96.6%,95.1%,91.4% and 78.8% for PSG I,IIA,IIB and ≥ IIC (p = 0.001). CONCLUSIONS: CT 1/cT2 and S I/II subgrouping is feasible to predict a different pT-category and a favorable WHO-grade (Gleason-Score) after RP, but failed to predict a different BFS. With the additional information of WHO-grade (Gleason-Score) and PSA, the PSG represents an approach for the prediction of all examined endpoints which is a useful tool to help clinicians to advise their patients.

MicroRNAs as Urinary Biomarker for Oncocytoma.

The identification of benign renal oncocytoma, its differentiation from malignant renal tumors, and their eosinophilic variants are a continuous challenge, influencing preoperative planning and being an unnecessary stress factor for patients. Regressive changes enhance the diagnostic dilemma, making evaluations by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs (miRs) have been proposed as novel biomarkers to differentiate renal tumor subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines based on mechanisms known in oncocytomas has not been exploited. We used urines from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell, papillary, chromophobe) and with other urogenital lesions. miRs were extracted and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs preidentified by microarray after endothelin-1 stimulation of renal epithelial cells. Four miRs are proposed as presurgical urinary biomarkers due to their known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma-specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO2 levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon, shown previously).

Health-related quality of life in active surveillance and radical prostatectomy for low-risk prostate cancer: a prospective observational study (HAROW - Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting).

OBJECTIVES: To compare health-related quality of life (HRQOL) between patients with localised prostate cancer in an active surveillance (AS) group and a radical prostatectomy (RP) group, as evidence shows that both groups have similar oncological outcomes. Thus, comparative findings on the patients' HRQOL are becoming even more important to allow for informed treatment decision-making. PATIENTS AND METHODS: The Hormonal therapy, Active Surveillance, Radiation, Operation, Watchful Waiting (HAROW) study is a prospective, observational study designed to collect data for different treatment options for newly diagnosed patients with localised prostate cancer under real-life conditions. At 6-month intervals, clinical data (D'Amico risk categories, Charlson Comorbidity Index) and HRQOL (European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core questionnaire) were collected. Data were analysed by longitudinal multilevel analysis for patients with localised prostate cancer under AS and RP. RESULTS: Data from 961 patients (556 RP, 405 AS) were considered. The follow-up was 3.5 years (median 2 years). The results reveal significant, but not clinically relevant advantages for patients with low-risk prostate cancer managed with AS in contrast to RP concerning global HRQOL as well as role, emotional and social functioning over time, after controlling for age, comorbidities, and partnership status. In some, but not all HRQOL scales, RP patients start with a slightly lower HRQOL and recover up to the level of AS patients within 1-2 years after diagnosis. CONCLUSION: HRQOL is an important aspect in the decision-making and advising process for patients with prostate cancer. In many aspects of HRQOL, AS is associated with more favourable outcomes than RP within the first 1-2 years after diagnosis in our observational design, although the differences were not clinically significant. The result that HRQOL in AS patients is at least as high as in RP patients should be considered when advising patients about the different treatment options for low-risk localised prostate cancer.

Utilization of Active Surveillance and Watchful Waiting for localized prostate cancer in the daily practice.

PURPOSE: To analyze the utilization of Active Surveillance (AS) and Watchful Waiting (WW) in the daily routine setting, since both are non-invasive treatment options for localized prostate cancer (PCa), which are used in a curative (AS) or palliative (WW) setting. Since differentiation of both strategies is not always clear, patients were compared with respect to the inclusion criteria, frequency of follow-up examinations (Prostate Specific Antigen = PSA tests, rebiopsies), and initiation of a deferred treatment. METHODS: HAROW is a non-interventional, health-service research study on the management of localized PCa in the community setting. Of 3169 patients, prospectively enrolled from 2008 to 2013 with a mean follow-up of 28.2 months, 468 chose AS and 126 WW. Treating urologists reported clinical variables, information on therapy and clinical course of disease. RESULTS: AS patients were significantly younger and had more low-risk tumors. No differences were seen in the number of PSA tests during follow-up: mean number of PSA tests was 6.08 for AS- and 5.18 for WW patients, more than four PSA tests were reported in 63.9% AS- and 59.5% WW patients (p = 0.136). At least one re-biopsy was performed in 39.7% AS- and 9.5% WW patients (p < 0.001). Discontinuation rates were 23.9% (n = 112) for AS and 11.9% (n = 15) for WW. Most of the AS patients opted for a curative treatment (prostatectomy = 65, radiotherapy = 30), whereas 12 WW patients received a palliative hormone therapy and three patients received radiotherapy. CONCLUSIONS: Physicians seem to distinguish clearly between AS and WW in terms of inclusion criteria and deferred therapy, whereas this differentiation tends to become indistinct in terms of follow-up examinations.