Determinants of physical activity during cancer treatment: a longitudinal exploration of psycho-cognitive variables and physician counseling.

Individuals with cancer are recommended to engage in regular physical activity (PA) even during cancer therapy. The aim of this study was to explore how patient-reported physician PA counseling influences their PA intention and behavior in addition to psycho-cognitive determinants derived from the theory of planned behavior (TPB). A longitudinal study during cancer treatment was conducted among N = 115 patients with breast, prostate, or colorectal cancer (Mage = 58.0, SD = 11.5; 55.7% female). The median time since diagnosis was 2 months, and 19.1% were diagnosed with metastases. Participants provided information on PA counseling by their physicians and on psycho-cognitive variables of the TPB at three measurement points. Additionally, they wore accelerometers for seven days at baseline and three months later. Nearly half of participants (48%) reported basic PA counseling and 30% reported in-depth PA counseling. Patients in poorer health and with lower education reported significantly less in-depth counseling. In addition to patient self-efficacy in performing PA, only in-depth physician PA counseling, but not basic physician counseling, predicted intention for PA four weeks later. Patients' PA three months after baseline was predicted by patients' PA at baseline and their intention for PA. Overall, the PA level at baseline was identified as the most important predictor of PA three months later. Nevertheless, physicians seem to have the ability to increase their cancer patients' intention for PA by in-depth counseling.

A prospective study on inter-operator variability in semi-robotic software-based MRI/TRUS-fusion targeted prostate biopsies.

PURPOSE: Magnetic resonance imaging (MRI)/ultrasound-fusion prostate biopsy (FB) comprises multiple steps each of which can cause alterations in targeted biopsy (TB) accuracy leading to false-negative results. The aim was to assess the inter-operator variability of software-based fusion TB by targeting the same MRI-lesions by different urologists. METHODS: In this prospective study, 142 patients eligible for analysis underwent software-based FB. TB of all lesions (n = 172) were carried out by two different urologists per patient (n = 31 urologists). We analyzed the number of mismatches [overall prostate cancer (PCa), clinically significant PCa (csPCa) and non-significant PCa (nsPCa)] between both performed TB per patient. In addition we evaluated factors contributing to inter-operator variability by uni- and multivariable analyses. RESULTS: In 11.6% of all MRI-lesions (10.6% of all patients) there was a mismatch between TB1 and TB2 in terms of overall prostate cancer (PCa detection. Regarding csPCa, patient-based mismatch occurred in 14.8% (n = 21). Overall PCa and csPCa detection rate of TB1 and TB2 did not differ significantly on a per-patient and per-lesion level. Analyses revealed a smaller lesion size as predictive for mismatches (OR 9.19, 95% CI 2.02-41.83, p < 0.001). CONCLUSION: Reproducibility and precision of targeting particularly small lesions is still limited although using software-based FB. Further improvements in image-fusion, segmentation, needle-guidance, and automatization are necessary.

Onset and burden of lower limb lymphedema after radical prostatectomy: a cross-sectional study.

OBJECTIVES: To explore men's onset and burden of lower limb lymphedema (LLL) after radical prostatectomy (RP) with pelvic lymph node dissection (PLND). PATIENTS AND METHODS: A cross-sectional survey-based study was conducted nation-wide and web-based in Germany. Part 1 included 15 multidisciplinary compiled questions with three questions from the Short Form 12 Health Survey (SF-12) and the WHO activity recommendation and part 2 included the validated German Lymph-ICF-Questionnaire (Lymph-ICF-LL). Subgroup comparisons and simple regression analyses were used to identify factors associated with therapy and burden of LLL, followed by multiple regression analyses to explain variance in impairment in the patients' daily life. RESULTS: Fifty-four patients completed the survey. Median time of LLL-onset was reported with 2.0 (0.5-9.75) months after RP. Nineteen patients (35.2%) reported bilateral lymphedema, 28 (51.9%) the use of individually fitted compression stockings (CS), 25 (46.3%) of manual lymphatic drainage (LD), and 26 (48.1%) complete regression. The Lymph-ICF-LL revealed a higher total burden for patients with an active LLL compared to complete regression (total score: 25.5 vs. 11.9, p = 0.01) especially for "physical function" (28.3 vs. 12.9, p < 0.01) and "mental function" (26.2 vs. 6.7, p < 0.01). In multiple linear regression analysis, a higher BMI (ß = 0.28), lower subjective general health (ß = -0.48), and active lymphedema (ß = 0.28) were significant predictors of higher reported impairments in the Lymph-ICF-LL, accounting for 45.4% of variance. CONCLUSION: Men with LLL after RP with PLND report a significant burden in daily life. Basic therapy needs to be offered early. Postoperative onset of LLL is variable, which should be considered when assessing complications after RP.

Treatment decision satisfaction and regret after focal HIFU for localized prostate cancer.

PURPOSE: Focal therapies (FTs) are investigated within prospective studies on selected patients treated for localized prostate cancer (PCa). Benefits are preservation of genitourinary function and reduced complications, but follow-up is elaborate and is associated with uncertainty as cancer-free survival appears to be lower compared to standard radical treatments. The aim of this study was to analyse patient-reported acceptance of FT and evaluate factors associated with treatment decision regret. METHODS: 52 patients who received focal high-intensity focused ultrasound for low- to intermediate-risk PCa between 2014 and 2019 within two prospective trials were eligible for a survey regarding PCa-related treatment regret and quality-of-life (Clark's scale) and the following potential predictors: sociodemographic variables, Charlson Comorbidity Index, subjective aging (AARC-10 SF), and general health-related quality-of-life (SF-12). Cancer persistence/recurrence (multiparametric MRI and fusion biopsy after 12 months) and functional outcomes (EPIC-26 UI/UIO/S) data were also included in this study. RESULTS: The overall survey response rate was 92.3% (48/52 patients). Median follow-up was 38 months (interquartile range = 25-50 months). In total, ten patients (20.8%) reported treatment decision regret. In univariable analyses, a clinically meaningful increase in urinary incontinence showed a significant association (OR 4.43; 95% CI 0.99-20.53; p = 0.049) with regret. Cancer recurrence (OR 12.31; 95% CI 1.78-159.26; p = 0.023) and general health worry as a domain of Clark's scale (OR 1.07; 95% CI 1.03-1.14; p < 0.01) were predictors of regret in a multivariable logistic regression model (AUC = 0.892). CONCLUSION: Acceptance of FT is comparable to standard treatments. Extensive follow-up including regular PSA testing does not cause additional regret but careful patient selection and information before FT is crucial.

Triggers and oncologic outcome of salvage radical prostatectomy, salvage radiotherapy and active surveillance after focal therapy of prostate cancer.

PURPOSE: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. METHODS: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan-Meier curves were generated to determine oncological outcomes. RESULTS: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9-16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35-4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. CONCLUSION: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

[MRI-guided minimally invasive treatment of prostate cancer]. / MRT-gestützte minimal-invasive Therapie des Prostatakarzinoms.

CLINICAL/METHODOLOGICAL ISSUE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate plays a crucial role in the diagnosis and local staging of primary prostate cancer. STANDARD RADIOLOGICAL METHODS: Image-guided biopsy techniques such as MRI-ultrasound fusion not only allow guidance for targeted tissue sampling of index lesions for diagnostic confirmation, but also improve the detection of clinically significant prostate cancer. METHODOLOGICAL INNOVATIONS: Minimally invasive, focal therapies of localized prostate cancer complement the treatment spectrum, especially for low- and intermediate-risk patients. PERFORMANCE: In patients of low and intermediate risk, MR-guided, minimally invasive therapies could enable local tumor control, improved functional outcomes and possible subsequent therapy escalation. Further study results related to multimodal approaches and the application of artificial intelligence (AI) by machine and deep learning algorithms will help to leverage the full potential of focal therapies for prostate cancer in the upcoming era of precision medicine. ACHIEVEMENTS: Completion of ongoing randomized trials comparing each minimally invasive therapy approach with established whole-gland procedures is needed before minimally invasive therapies can be implemented into existing treatment guidelines. PRACTICAL RECOMMENDATIONS: This review article highlights minimally invasive therapies of prostate cancer and the key role of mpMRI for planning and conducting these therapies.

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy.

BACKGROUND: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. MATERIAL AND METHODS: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). RESULTS: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. CONCLUSION: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.

Prospective Feasibility Study of Single-Shot Antibiotic Prophylaxis in Transrectal Focal Ablation of Prostate Cancer.

INTRODUCTION: Urinary tract infections (UTI) represent the most frequent complications after transrectal focal ablation of prostate cancer. Single-shot antibiotic prophylaxis for prevention has not yet been described. METHODS: In this cohort study of patients who received a high-intensity focused ultrasound (HIFU) ablation of prostate cancer within a registered prospective single-arm trial, we analyzed posttreatment UTI (≤30 days after HIFU) related to perioperative antibiotic management in an exploratory analysis: single-shot prophylaxis or targeted treatment for bacteriuria. Potential risk factors associated with UTI were evaluated by uni- and multivariate regression analyses. RESULTS: In total, 55 patients were eligible for analysis. Of these, 76.4% received antibiotic single-shot prophylaxis. UTI occurred in 10.7% of all patients, 5.4% developed fever, 3.6% required hospitalization. An antibiotic single-shot prophylaxis helped to protect 90.5% of men from infectious complications. Estimated effects indicate that a longer posttreatment catheterization (OR 3.38, 95% CI 0.47-27.08) and larger ablation volume (OR 4.85, 95% CI 0.61-107.49) might be associated with the highest risk for UTI after treatment. CONCLUSION: Single-shot antibiotic prophylaxis compared to a targeted antibiotic treatment showed a similar effectivity to prevent patients from infectious complications and should be considered as an element of antibiotic stewardship. Further research on risk factors and antibiotic strategies is required.

Phosphodiesterase SMPDL3B Gene Expression as Independent Outcome Prediction Marker in Localized Prostate Cancer.

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.

Association of training level and outcome of software-based image fusion-guided targeted prostate biopsies.

PURPOSE: The aim of this study was to assess the impact of experience on the outcome of image fusion-guided prostate biopsies performed by urologists working at a high-volume medical center. METHODS: The first 210 consecutive fusion biopsies were analyzed following installation of the software-based biopsy platform Artemis™ (Eigen, USA). The impact of training was measured in terms of changes in prostate cancer detection rates and biopsy duration over time. We sought to identify a threshold of experience for urologists, which predicts higher detection rates of targeted biopsies. The influence of various factors on prostate cancer detection rates was evaluated using bi- and multivariate analysis. RESULTS: Twenty-two urologists (n = 9 senior urologists, n = 13 urological residents) performed targeted biopsies followed by systematic 12-core biopsies. Overall, targeted biopsies yielded a positive result in 39.6% of 260 suspicious MRI lesions. A subgroup analysis of the six urologists who performed more than ten biopsies was then conducted, and their level of experience (i.e., performance of more than eight biopsies) was found to be associated with higher detection rates than those with less experience (49.0% and 23.0%, respectively; p < 0.001) in the targeted biopsies. Experience was likewise a significant and independent predictor of a cancer-positive targeted biopsy (p = 0.002). Experienced senior physicians did not outperform residents in their targeted biopsy results. Further, biopsy duration correlated negatively (r = - 0.5931, p < 0.001) with the total number of biopsies performed for all subgroups during the period of assessment. CONCLUSIONS: Experience is an important predictor of the rate of detection in targeted biopsies using software-based biopsy platforms with semi-robotic assistance. Moreover, the performance of just a few procedures appears sufficient to increase biopsy effectiveness significantly. Lastly, supervision by experts is recommended during the training phase.

Defining the target prior to prostate fusion biopsy: the effect of MRI reporting on cancer detection.

PURPOSE: Definition of targets in multiparametric MRI (mpMRI) prior to MRI/TRUS fusion prostate biopsy either by urologist or radiologist, as a prose report or by illustration is crucial for accurate targeted biopsies (TB). The objective was to analyze the effect of MRI reporting on target definition and cancer detection. METHODS: 202 patients underwent MRI/TRUS fusion biopsy with Artemis™ (Eigen, USA). mpMRI results were submitted in written form to urologists, who marked the targets in the proprietary software. An expert uroradiologist reviewed and marked mpMRI targets blinded to biopsy data. We compared number, localization and volume of targets between the observers and analyzed whether variations impaired TB results by bivariate and logistic regression models. RESULTS: Interobserver variability was moderate regarding number and low regarding localization of targets. Urologists overestimated target volumes significantly compared to radiologists (p = 0.045) and matching target volume between both observers was only 43.9%. Overall cancer detection rate was 69.8 and 52.0% by TB. A higher matching target volume was a significant predictor of cancer in TB (p < 0.001). Logistic regression revealed prostate volume and PI-RADS as independent predictors. Defining targets in incorrect T2w slices in the cranio-caudal axis are one presumable reason for missing cancer in TB. CONCLUSIONS: A high concordance of the target definition between radiologist and urologist is mandatory for accurate TB. Optimized ROI definition is recommended to improve TB results, preferably as contouring in MRI sequences by the radiologist or, if not feasible, by precise MRI reports including specific localization in sequence and slice as well as an illustration. High prostate volume and low PI-RADS score have to be considered as limiting factors for target definition.

Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker.

In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer.Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized (n = 58; 42 with Gleason score 6-7, 16 with Gleason score ≥8) and metastatic prostate cancer (n = 11) compared with patients with benign prostatic hyperplasia (n = 15) and healthy individuals (n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups (p = 0.004). CLDN3 levels were higher in patients with Gleason ≥8 tumors compared with patients with benign prostatic hyperplasia (p = 0.012) and Gleason 6-7 tumors (p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score ≥ 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA.By using the described workflow claudin 3 was identified and validated as a potential blood-based biomarker in prostate cancer. Furthermore this workflow could serve as a template to be used in other cancer entities.

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine.

Urothelial carcinoma (UC) is one of the most common cancers and survival rates are low in metastatic disease with currently established first-line platinum-based chemotherapies. Unlike in many other cancers, no clinically established molecular targeted therapies exist for the treatment of this malignancy. Here we present a case of complete tumor remission following third-line treatment with trastuzumab and gemcitabine in a patient with human epidermal growth factor receptor 2 (HER2)-positive UC after progression under cisplatin and vinflunine chemotherapies. This case shows the potential significance of anti-HER2 therapy in selected patients with molecularly characterized UC. Clinical trials so far show inconclusive outcomes of anti-HER2 therapies in UC, indicating further need for both basic research and clinical studies for the identification of resistance factors and improved patient selection.

The EEF1A2 gene expression as risk predictor in localized prostate cancer.

BACKGROUND: Besides clinical stage and Gleason score, risk-stratification of prostate cancer in the pretherapeutic setting mainly relies on the serum PSA level. Yet, this is associated with many uncertainties. With regard to therapy decision-making, additional markers are needed to allow an exact risk prediction. Eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was previously suggested as driver of tumor progression and potential biomarker. In the present study its functional and prognostic relevance in prostate cancer was investigated. METHODS: EEF1A2 expression was analyzed in two cohorts of patients (n = 40 and n = 59) with localized PCa. Additionally data from two large expression dataset (MSKCC, Cell, 2010 with n = 131 localized, n = 19 metastatic PCa and TCGA provisional data, n = 499) of PCa patients were reanalyzed. The expression of EEF1A2 was correlated with histopathology features and biochemical recurrence (BCR). To evaluate the influence of EEF1A2 on proliferation and migration of metastatic PC3 cells, siRNA interference was used. Statistical significance was tested with t-test, Mann-Whitney-test, Pearson correlation and log-rank test. RESULTS: qRT-PCR revealed EEF1A2 to be significantly overexpressed in PCa tissue, with an increase according to tumor stage in one cohort (p = 0.0443). In silico analyses in the MSKCC cohort confirmed the overexpression of EEF1A2 in localized PCa with high Gleason score (p = 0.0142) and in metastatic lesions (p = 0.0038). Patients with EEF1A2 overexpression had a significantly shorter BCR-free survival (p = 0.0028). EEF1A2 expression was not correlated with serum PSA levels. Similar results were seen in the TCGA cohort, where EEF1A2 overexpression only occurred in tumors with Gleason 7 or higher. Patients with elevated EEF1A2 expression had a significantly shorter BCR-free survival (p = 0.043). EEF1A2 knockdown significantly impaired the migration, but not the proliferation of metastatic PC3 cells. CONCLUSION: The overexpression of EEF1A2 is a frequent event in localized PCa and is associated with histopathology features and a shorter biochemical recurrence-free survival. Due to its independence from serum PSA levels, EEF1A2 could serve as valuable biomarker in risk-stratification of localized PCa.

Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review.

BACKGROUND: Limited data are available for the use of agents in metastatic castration-resistant prostate cancer (mCRPC) beyond the third-line. We provide data during treatment with cabazitaxel (CAB), helping to improve the informed-consent process. PATIENTS AND METHODS: We retrospectively reviewed patients treated with fourth-line or beyond CAB for mCRPC after failure of previous therapies with docetaxel, abiraterone acetate, enzalutamide and/or radium-223. The progression-free survival (PFS) and the overall survival (OS) were estimated using the Kaplan-Meier method and compared to published data based on a structured literature review. The hospitalization rate was recorded. Factors influencing 6-months OS were analyzed. RESULTS: Fifteen patients were identified at 4 institutions and included in the analysis. The median PFS was 104 days (range 47-397 days). The median time to death was 10 months (range 2-16). PFS and OS data are in accordance with 17 published patients so far. During the therapy, eleven (73%) of the patients were hospitalized. Prostate-specific antigen (PSA, 500 units; hazards ratio [HR] 1.491, 95% CI 1.000-2.0175), white blood cell count (HR 0.425, 95% CI 0.108-0.952), hemoglobin (HR 0.6014, 95% CI 0.2942-1.0758), and alkaline phosphatase (100 units; HR 1.0964, 95% CI 1.000-1.2859) correlate with 6-months OS. CONCLUSIONS: CAB beyond the third-line is often accompanied by hospitalization. PFS is a significant proportion of the median time of OS. The baseline laboratory might be a good indicator for the decision between CAB and best-supportive care.

Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer.

BACKGROUND: Abiraterone Acetate (AA) represents a highly effective androgen-receptor (AR) axis targeted agent. Treatment with AA in castration-resistant prostate cancer (CRPC) may partly mediate neuroendocrine differentiation (NED) as an escape mechanism, which may have implications for the choice of sequential therapy in CRPC. We evaluated how treatment with AA influences circulating neuromediators chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (Pro-GRP) in chemotherapy-naïve CRPC patients. METHODS: We conducted an analysis in chemotherapy-naïve CRPC patients with clinical or radiographic progression of disease. A total of 35 patients were included at five institutions between February 2013 and December 2014. Sixteen of them had received AA. Serum samples were obtained before a docetaxel-based chemotherapy and analyzed in a reference laboratory. Univariable and multivariable analyses were performed to test the influence of AA treatment, its duration of treatment, and other clinicopathological variables on circulating neuromediators. RESULTS: CGA and NSE levels were above the upper limit of normal (ULN) in n = 20 (57.1%) and n = 13 (37.1%), respectively. Treatment with AA and duration of treatment were not associated with levels above the ULN (CGA and NSE) or higher levels (Pro-GRP) of neuromediators. CGA levels were associated with age (P = 0.092), lymph node metastasis (P = 0.014), duration of androgen deprivation therapy (ADT; P = 0.083), and intake of proton pump inhibitors (P = 0.069). Pro-GRP levels were significantly associated with PSA levels (P = 0.002). On multivariate analysis, CGA levels above the ULN were significantly correlated with ADT (P = 0.01) and intake of proton pump inhibitors (P = 0.03). CONCLUSIONS: Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.

Peritoneal Flap for Lymphocele Prophylaxis Following Robotic-assisted Radical Prostatectomy with Lymph Node Dissection: The Randomised Controlled Phase 3 PELYCAN Trial.

BACKGROUND: Symptomatic lymphoceles (SLCs) after transperitoneal robotic-assisted radical prostatectomy with pelvic lymph node dissection (PLND) are common. Evidence from randomised controlled trials (RCTs) on the impact of peritoneal flaps (PFs) on lymphocele (LC) reduction is inconclusive. OBJECTIVE: To show that addition of PFs leads to a reduction of postoperative SLCs. DESIGN, SETTING, AND PARTICIPANTS: An investigator-initiated, prospective, parallel, double-blinded, adaptive, phase 3 RCT was conducted. Recruitment took place from September 2019 until December 2021; 6-month written survey-based follow-up was recorded. Stratification was carried out according to potential LC risk factors (extended PLND, diabetes mellitus, and anticoagulation) and surgeons; 1:1 block randomisation was used. Surgeons were informed about allocation after completion of the last surgical step. INTERVENTION: To create PFs, the ventral peritoneum was incised bilaterally and fixated to the pelvic floor. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was SLCs. Secondary endpoints included asymptomatic lymphoceles (ALCs), perioperative parameters, and postoperative complications. RESULTS AND LIMITATIONS: In total, 860 men were screened and 551 randomised. Significant reductions of SLCs (from 9.1% to 3.7%, p = 0.005) and ALCs (27.2% to 10.3%, p < 0.001) over the follow-up period of 6 mo were observed in the intention-to-treat analysis. Operating time was 11 min longer (p < 0.001) in the intervention group; no significant differences in amount (80 vs 103, p = 0.879) and severity (p = 0.182) of postoperative complications (excluding LCs) were observed. The survey-based follow-up might be a limitation. CONCLUSIONS: This is the largest RCT evaluating PF creation for LC prevention and met its primary endpoint, the reduction of SLCs. The results were consistent among all subgroup analyses including ALCs. Owing to the subsequent reduction of burden for patients and the healthcare system, establishing PFs should become the new standard of care. PATIENT SUMMARY: A new technique-creation of bilateral peritoneal flaps-was added to the standard procedure of robotic-assisted prostatectomy for lymph node removal. It was safe and decreased lymphocele development, a common postoperative complication and morbidity. Hence, it should become a standard procedure.

Perioperative Outcomes and Complication Rates in Holmium Laser Enucleation of the Prostate Patients After Prior Prostate Biopsy-Does It Really Make a Difference? A Propensity Score Matched Analysis.

Introduction: Before holmium laser enucleation of the prostate (HoLEP), many patients have undergone short-term prostate biopsy (PB) to rule out the presence of prostate cancer. The aim of this study is to determine whether a short-term PB before HoLEP has an impact on the perioperative outcomes or complications of HoLEP. Methods: In total, 734 consecutive patients treated with HoLEP at a tertiary care university hospital between January 2021 and July 2023 were retrospectively enrolled. Patients who had PB within 6 months before HoLEP were matched to patients who underwent PB more than 6 months or had no PB before HoLEP using propensity score matching (PSM) based on age, prostate volume (PV), prostate-specific antigen (PSA), preoperative urinary tract infection (UTI), and surgeon. Perioperative parameters, such as operation time (OT), enucleation efficiency (EF), as well as complications according to the Satava classification, the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI) were evaluated. Results: In total, 206 patients were matched. Age, PV, PSA, as well as the presence of a preoperative UTI and surgeons did not differ significantly between both groups after PSM. There were no significant differences in mean OT (75 vs. 81 minutes, p = 0.28) and EF (2.13 vs. 2.13 g/min, p = 0.99). No differences were noted regarding intraoperative (16 vs. 25, p = 0.16) or postoperative complications graded by CDC (p = 0.53) and CCI (p = 0.92). Conclusion: PB within 6 months preoperatively before HoLEP showed no effect on perioperative outcomes or intra- and postoperative complications.

Emerged or imposed: a theory on the role of physical templates and self-organisation for vegetation patchiness.

In this article, we develop a unifying framework for the understanding of spatial vegetation patterns in heterogeneous landscapes. While much recent research has focused on self-organised vegetation the prevailing view is still that biological patchiness is mostly due to top-down control by the physical landscape template, disturbances or predators. We suggest that vegetation patchiness in real landscapes is controlled both by the physical template and by self-organisation simultaneously, and introduce a conceptual model for the relative roles of the two mechanisms. The model considers four factors that control whether vegetation patchiness is emerged or imposed: soil patch size, plant size, resource input and resource availability. The last three factors determine the plant-patch size, and the plant-to-soil patch size ratio determines the impact of self-organisation, which becomes important when this ratio is sufficiently small. A field study and numerical simulations of a mathematical model support the conceptual model and give further insight by providing examples of self-organised and template-controlled vegetation patterns co-occurring in the same landscape. We conclude that real landscapes are generally mixtures of template-induced and self-organised patchiness. Patchiness variability increases due to source-sink resource relations, and decreases for species of larger patch sizes.

Spatial instabilities untie the exclusion-principle constraint on species coexistence.

Using a spatially explicit mathematical model for water-limited vegetation we show that spatial instabilities of uniform states can lead to species coexistence under conditions where uniformly distributed species competitively exclude one another. Coexistence is made possible when water-rich patches formed by a pattern forming species provide habitats for a highly dispersive species that is a better competitor in uniform settings.