The latest medical research on Urology

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Building Artificial Intelligence (AI) Based Personalized Predictive Models (PPM).

BJU International

Applications of artificial intelligence techniques (AI) to build personalized predictive models (PPM) are the means to an end for accurately predic...

Clinical determinants for successful circulating tumor DNA analysis in prostate cancer.


Plasma-based cell-free DNA is an attractive biospecimen for assessing somatic mutations due to minimally-invasive real-time sampling. However, next generation sequencing (NGS) of cell-free DNA (cfDNA) may not be appropriate for all patients with advanced prostate cancer (PC).

Blood was obtained from advanced PC patients for plasma-based sequencing. UW-OncoPlex, a ∼2 Mb multi-gene NGS panel performed in the CLIA/CAP environment, was optimized for detecting cfDNA mutations. Tumor tissue and germline samples were sequenced for comparative analyses. Multivariate logistic regression was performed to determine the clinical characteristic associated with the successful detection of somatic cfDNA alterations (ie detection of at least one clearly somatic PC mutation).

Plasma for cfDNA sequencing was obtained from 93 PC patients along with tumor tissue (N = 67) and germline (N = 93) controls. We included data from 76 patients (72 prostate adenocarcinoma; 4 variant histology PC) in the analysis. Somatic DNA aberrations were detected in 34 cfDNA samples from patients with prostate adenocarcinoma. High PSA level, high tumor volume, and castration-resistance were significantly associated with successful detection of somatic cfDNA alterations. Among samples with somatic mutations detected, the cfDNA assay detected 93/102 (91%) alterations found in tumor tissue, yielding a clustering-corrected sensitivity of 92% (95% confidence interval 88-97%). All germline pathogenic variants present in lymphocyte DNA were also detected in cfDNA (N = 12). Somatic mutations from cfDNA were detected in 30/33 (93%) instances when PSA was >10 ng/mL.

Disease burden, including a PSA >10 ng/mL, is strongly associated with detecting somatic mutations from cfDNA specimens.

Peyronie's disease and testosterone deficiency: Is there a link?

World Journal of Diabetes

Peyronie's disease (PD) and testosterone deficiency (TD) impact men at the same stage of life and can ultimately contribute to erectile dysfunction. There is speculation that low levels of testosterone (T) may predispose men to penile fibrosis; however, there is no published, up-to-date review summarizing the current evidence. Therefore, we conducted a narrative review of the literature exploring the relationship between PD and TD.

A comprehensive systematic search of existing literature of five online databases from June 1990 to June 2018 examining the relationship between PD and TD was conducted. The Cochrane risk-of-bias tool for randomized trials and the risk-of-bias assessment tool for cohort studies were used to evaluate the quality of studies.

Six studies were identified (n = 675). Overall, five studies supported the link between PD and TD by demonstrating relationships in PD patients with low total T, free T, bioavailable T, greater penile curvature, and plaque development. However, one study demonstrated no connection between the conditions. The literature is restricted by small studies with methodological flaws.

There are a number of mechanisms to support the link between TD and PD. The literature on the topic is limited by small studies which are overall conflicting. The findings of this work suggest the need for larger, prospective studies to clarify the role of TD in the development, evaluation, and treatment of PD. Establishing such a relationship could change management of PD as a diagnosis of PD may encourage clinicians to evaluate a patient's testosterone levels.

Smarter screening for prostate cancer.

World Journal of Diabetes

Prostate cancer is the second commonest cancer among men. In the large European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, prostate-specific antigen (PSA) screening has been shown to substantially reduce prostate cancer mortality. However, PSA screening is known to lead to more unnecessary prostate biopsies and over-diagnosis of clinically insignificant cancer. Therefore, it is imperative that smarter screening methods be developed to overcome the weaknesses of PSA screening. This review explores the novel screening tools that are available.

A comprehensive literature search was performed using PubMed regarding newer biomarkers, imaging techniques and risk-predicting models that are used to screen for prostate cancer in mainly biopsy-naïve men.

Novel serum-based models like 4Kscore® and prostate health index (PHI) are generally better than PSA alone in detecting clinically significant cancer. Similarly, urine-based biomarkers like prostate cancer antigen 3 (PCA3) and HOXC6/DLX1 have been shown to be more accurate than PSA screening. More recently, multiparametric magnetic resonance imaging (mpMRI) is gaining popularity for its ability to detect clinically significant cancer. There is also evidence that combining individual tests to develop prediction models can reliably predict high-risk prostate cancers while reducing the number of unnecessary biopsies. Combinations such as the Stockholm-3 model (STHLM3) and other novel combinations are presented in this review.

While we continue to find the smarter screening methods that are reliable, precise, and cost-effective, we continue to advocate shared decision-making in prostate cancer screening in order to work in our patients' best interests.

Metastasis-directed stereotactic radiotherapy for oligoprogressive castration-resistant prostate cancer: a multicenter study.

World Journal of Diabetes

Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC).

This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1-5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT.

Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4-91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5-19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8-25.8 months). One-year systemic treatment-free survival was 72.1%.

SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted.

Metastasectomy for visceral and skeletal oligorecurrent prostate cancer.

World Journal of Diabetes

Metastasis direct therapy (MDT) is a common practice in different fields of oncology. However, there is a lack of data on surgical MDT in visceral/skeletal oligometastatic prostate cancer (PCa). We aimed to assess the role of surgical excision of visceral and skeletal PCa recurrence.

Seventeen PCa patients experienced metachronous visceral or skeletal oligometastatic recurrence following maximal local treatment. Oligometastatic recurrence was defined as 1-3 lesions, detected with the best imaging technique available at the time of diagnosis. All patients underwent metastasectomy and were followed for a median of 43 months. Postoperative complications were graded using the Clavien-Dindo classification of surgical complications. Kaplan-Meier plots were used to assess overall survival.

Fourteen patients (82%) had visceral lesions, two had bone lesions (12%), and one had an abdominal wall metastasis (6%). Four patients (24%) were under active ADT at the time of metastasectomy. PSA decreased after metastasectomy in 16 (94%) patients. Ten (77%) of the 13 ADT-naïve patients had a PSA decrease of ≥ 50%. Following metastasectomy, 16 (94.1%) patients developed metastatic recurrence of which 11 (64.7%) were again oligometastatic, amenable for repeated MDT. The median time to metastatic recurrence was 14 months (range 6.4-40). We observed 8% Clavien-Dindo grade 3-4 complications in 21 procedures.

In this report, we analyzed the outcomes of surgical excision of visceral and skeletal PCa recurrence following primary treatment. We found that removing metastasis to the bone and viscera can be associated with long-term disease-free periods at a low rate of serious complications. These exploratory results should be confirmed in prospective studies.

The role of metastatic burden in cytoreductive/consolidative radical cystectomy.

World Journal of Diabetes

To describe our institutional experience with cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial carcinoma (UC) and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC.

We performed IRB-approved review of our cystectomy database, and identified 43 patients with metastatic UC who underwent CCRC. Baseline demographics, chemotherapy regimen, clinicopathologic features, and perioperative complications were collected. Progression-free survival (PFS) and CSS were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC.

Of the 43 patients, 32 (74.4%) had clinical evidence of distant metastases, while 11 harbored occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 30 patients. Solitary metastases were found in 22 patients (51.1%). Forty-one (95%) patients received chemotherapy prior to CCRC. Disease progression was detected in 35 patients after CCRC (median PFS 5.9 months), and 34 died of metastatic cancer (median CSS 12.3 months). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.62, 95% CI 1.16-5.90, p = 0.02), with median CSS of 26.0 months vs. 7.9 months (p < 0.001). Median postoperative length of stay was 10 days. Overall, 56% suffered postoperative complications, including one perioperative mortality.

CCRC is feasible in the setting of metastatic UC. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.

A randomized controlled comparison between periprostatic nerve block and pelvic plexus block at the base and apex of 14-core prostate biopsies.

World Journal of Diabetes

To compare the pain control efficacies of the pelvic plexus block (PPB), periprostatic nerve block (PNB), and controls during a 14-core basal and apical core prostate biopsy.

This randomized controlled study, performed between January 2015 and January 2016, included patients with an abnormal serum prostate-specific antigen (PSA > 3 ng/mL) level or a palpable nodule on digital rectal examination. The enrolled patients were randomized into three groups: Group 1, intrarectal local anesthesia (IRLA, 10 mL of 2% lidocaine jelly) and PPB with 3.0 mL of 2% lidocaine injected at the bilateral pelvic plexus; Group 2, IRLA and PNB with 3.0 mL of 2% lidocaine injected at both periprostatic nerves; and Group 3, only IRLA. Patients answered the visual analog scale (VAS) questionnaire at 6 time points.

This study consisted of 163 patients (Group 1 = 55, Group 2 = 55, and Group 3 = 53). Pain at the apical biopsy location was less in Groups 1 and 2 than in Group 3 (p < 0.001, p < 0.001) and between the two local anesthetic groups (PNB + IRLA vs PPB + IRLA). Group 2 patients reported less pain than Group 1 patients (p = 0.022). Pain during the basal core biopsy was significantly less in Groups 1 and 2 than in Group 3 (p = 0.002, p < 0.001), but there were no significant differences in pain control between the two methods (PNB + IRLA vs PPB + IRLA, p = 0.054) during basal core biopsy.

PNB + IRLA is an effective local anesthetic method for reducing pain when performing apical biopsies compared with PPB + IRLA or IRLA alone.

Male CP/CPPS: where do we stand?

World Journal of Diabetes

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), commonly encountered in urologic practice, carries with it a stigma of poor understanding, ineffective treatment, and significant financial and quality of life burden.

This clinically practical review is based on the authors' personal clinical experience in interpretation and application of currently available evidence.

Significant progress has been made in terms of classification and evaluation of the disease, leading to encouraging improvements in treatment outcomes. The Chronic Prostatitis Symptom Index (CPSI) is a helpful tool in clinical evaluation and has proven invaluable for research purposes, while UPOINT has demonstrated the heterogeneity of the disease and provides physicians with a uniquely patient-centered approach to treatment. The importance of the microbiome in the evaluation of CP/CPPS patients has yet to be fully appreciated. While personalized, multi-modal therapy appears to be the key to treatment, the addition of pelvic floor physiotherapy (PFPT) with injection of trigger points, and psychosocial therapies to the multi-modal approach armamentarium are promising advances. Innovative interventional approaches are encouraging but require study.

While encouraging therapies have been added to personalized, multi-modal treatment strategies, newer innovative therapies appear promising for improved treatment of CP/CPPS patients.

Sacral neuromodulation in congenital lumbo-sacral and traumatic spinal cord defects with neurogenic lower urinary tract symptoms: a single-center experience in children and adolescents.

World Journal of Diabetes

This study evaluated sacral neuromodulation's effectiveness for managing refractory neuropathic lower urinary tract dysfunction in children and adolescents.

Twenty-five children and adolescents underwent peripheral nerve evaluation test phase of sacral neuromodulation at our center. Thirteen (seven boys and six girls) cases suffered from neuropathic lower urinary tract dysfunction refractory to the maximum medical treatment. The test was done with temporary wire in all patients. Patients with more than 50% improvement in symptoms were chosen for the second stage of implantation of quadripolar tined lead and implantable pulse generator. Bowel transit symptoms were recorded before and after the surgery.

Eight patients (61.53%; five boys and three girls) had positive responses to the peripheral nerve evaluation test phase. They underwent implantation of permanent quadripolar tined lead and implantable pulse generator. The etiologies were lumbosacral myelomeningocele, occult spina bifida, partial sacral agenesis and incomplete spinal cord injury. Positive clinical response (> 50% improvement in symptoms) was achieved in seven (85%) at a mean follow-up of 14.25 months. Three patients became capable to stop clean intermittent catheterization (P =0.125). The 24-h pad test decreased from 484 to 78 g from before to after the surgery (P =0.043).

This clinical study on a small sample size of children and adolescents demonstrates positive results in short-term follow-up. However, as the procedure is still not approved officially, multicenter studies with more patients can prove the safety and efficacy of sacral neuromodulation in long term among this special group of patients.

CD163+ macrophages predict a poor prognosis in patients with primary T1 high-grade urothelial carcinoma of the bladder.

World Journal of Diabetes

Macrophages are a major cell type that can infiltrate solid tumors and exhibit distinct phenotypes in different tumor microenvironments. This study investigates the prognostic value of tumor-infiltrated CD163+ macrophages in patients with T1 high-grade (T1HG) bladder cancer.

CD163+ macrophages were assessed by immunohistochemistry in 94 T1HG bladder cancer samples. Kaplan-Meier analyses and Cox proportional hazards' regression models were applied to evaluate recurrence-free survival, progression-free survival and disease-specific survival.

With a median follow-up of 60 months, 37 (39.4%) patients experienced disease recurrence, 14 (14.9%) progression, 11 (11.7%) disease-specific mortality. High CD163+ macrophages were associated with higher risk of disease recurrence and progression (P < 0.05, for both). In multivariate Cox proportional hazards regression analysis, high CD163+ macrophages were a significant negative predictor of recurrence-free survival, progression-free survival and disease-specific survival (P < 0.05 for all).

CD163+ macrophages are a poor prognostic factor in T1HG bladder cancer. This finding provide the ground for further testing it in predicting the outcome of this challenging disease.

Multivariate risk prediction tools including MRI for individualized biopsy decision in prostate cancer diagnosis: current status and future directions.

World Journal of Diabetes

Individualized risk-adapted algorithms in prostate cancer (PCa) diagnosis using predictive prebiopsy variables in addition to prostate-specific antigen value may result in a considerable reduction of unnecessary systematic biopsies. Multi-parametric magnetic resonance imaging (mpMRI) has emerged as a secondary prediction tool that can further improve the detection of clinically significant prostate cancer (csPCa). This review explores the performance of new MRI risk models for indicating a biopsy for prostate cancer diagnosis.

The area under the receiver-operating characteristic curve for detecting csPCa varies between 0.64 and 0.91 in biopsy-naïve men, and between 0.78 and 0.93 in men with a previous negative biopsy. The utility of multivariate risk prediction tools including MRI suspicion scores as an extra input parameter has the potential to avoid a notable number of biopsies and detection of clinically insignificant PCa at a low price of missing some csPCa. The trade-off depends on the risk threshold that is chosen. In biopsy-naïve men a net benefit was obtained at a risk threshold of above 10% for csPCa in most MRI risk prediction models. All constructed MRI risk models used (referral) patient cohorts with high prevalence of csPCa. Using more representative cohorts from daily clinical screening, net benefit may attenuate at lower risk thresholds. Strengths and limitations of these models are discussed.

To assess their wider applicability, in-depth analysis of mpMRI predictive qualities should be further investigated, in combination with required external validation of these models in a multicenter setting with large prospective datasets.