Soc. Int. Urol. J., Volume 4, Issue 4 (July 2023) – 16 articles , Pages 241-348

Introduction: Vibrational spectroscopy (VS) is a new and rapidly evolving technology in cancer diagnostics. Originating from analytical chemistry, VS evaluates vibrations of nuclei to produce a unique “biological fingerprint.” While multiple studies have been published on this technology and physician awareness has increased, no systematic review has evaluated the role of VS in bladder cancer (BCa) tissue diagnosis. Methods: To conduct this systematic review, we searched the MEDLINE, Embase, and Cochrane databases for studies that used Raman spectroscopy (RS), surface-enhanced RS (SERS), infrared spectroscopy (IR) or near-infrared spectroscopy (NIRS) to analyze human BCa specimens. Studies using animal tissue or liquid biopsies were excluded. We synthesized the evidence by comparing modalities, study design, data analysis techniques, and diagnostic accuracy. The quality of evidence was evaluated by the QUADAS-2 tool. Results: Out of 362 results, 20 studies met our inclusion criteria. There has been growing interest in VS use in BCa, with 50% of the studies published in the past 5 years. RS was the most commonly used modality (65%), followed by IR (20%) and SERS (10%). Only one study compared RS to IR (5%). The mean sample size was 44 patients (range, 6–214). To date, there have been only 2 in vivo studies, with the remaining ex vivo studies performed with large variation in tissue preparation, data analysis, and reporting. Advancements in fiber optic probes and machine-learning data analysis techniques, and increased computational power have improved diagnostic accuracy up to 98% sensitivity and 100% specificity. Conclusions: VS shows high potential for BCa diagnosis, but there is a need for uniform reporting methods and studies with adequate sample sizes to validate the models. RS has shown promising results, with ongoing improvements in fiber optic probes allowing its integration into conventional cystoscopes. While no single VS modality has proven to be perfect, a multimodal approach is likely required to establish its value in clinical practice. Full article

Objectives: To compare outcomes of laparoscopic versus open pyeloplasty for the management of pelvicoureteric junction obstruction (PUJO) using a systematic review and meta-analysis. In September 2022, electronic database searches were conducted using the Cochrane Library, the Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, clinical trial registries, and relevant conferences to identify relevant abstracts and presentations. Methods: Prospective randomized controlled trials comparing laparoscopic to open pyeloplasty for PUJO were included in the review. There were no restrictions on date or language. All populations were included. The authors performed data extraction and risk of bias assessment using the risk of bias tool. Meta-analysis was performed using RevMan software. Results: Six prospective randomized controlled trials involving 335 participants were included in the analysis. Six studies included data on the failure rate, with a slight favouring of open pyeloplasty compared to laparoscopic pyeloplasty, although this was not statistically significant (odds ratio [OR], 1.39; 95% confidence interval [CI] 0.50 to 3.83). Five studies compared operative time, with open pyeloplasty found to have shorter times across all studies (mean difference [MD], 54.97 minutes; 95% CI 47.08 to 62.85). Based on 5 studies, laparoscopic pyeloplasty has a shorter hospital stay (MD, 4.12 days; 95% CI 3.64 to 4.59). Two studies compared postoperative analgesia requirements, showing a lower diclofenac requirement in the laparoscopic group (MD, 330.08 mg; 95% CI 298.05 to 362.11 mg). One study compared blood loss intraoperatively and found no significant difference between the groups (MD, 8.52 mL; 95% CI -2.49 to 19.53). Based on 4 studies, laparoscopic pyeloplasty may result in slightly higher complication rates postoperatively (OR, 1.49; 95% CI 0.53 to 4.18); however, there was no statistically significant difference. No subgroup analyses were conducted. Conclusions: Limited, low-quality evidence from small-scale trials suggests that laparoscopic pyeloplasty has improved outcomes in terms of shorter hospital stays and reduced postoperative pain compared to open pyeloplasty. Open pyeloplasty, on the other hand, had a shorter operative time. Failure rate, complication rate, and blood loss were comparable between the 2 approaches. Full article

Bladder cancer has a significant impact on patients, in terms of both morbidity and financial burden. This is especially true for patients with nonmuscle-invasive bladder cancer, who undergo long-term surveillance via cystoscopy and imaging, resulting in significant costs and risks. To address this issue, urinary tumor DNA analysis, or “urinary liquid biopsy,” has emerged as a potential solution to reduce the testing burden and mitigate many of the costs and risks. Over time, urinary tumor DNA analysis has undergone several refinements. However, existing FDA-approved urinary biomarker assays currently lack the sensitivity and specificity to significantly impact clinical decision-making. Subsequent iterations of these technologies have attempted to bridge this gap by improving their diagnostic accuracy, and ultimately, clinical utility. Here, we discuss the current role as well as future directions of urinary tumor DNA analysis for the detection and long-term surveillance of nonmuscle-invasive bladder cancer. Full article

Liquid biopsy has demonstrated success as a diagnostic, prognostic, and therapy response monitoring tool in various cancers and could represent a rapid and minimally invasive alternative or complementary test for testicular germ cell tumors (GCTs). This article aims to review the current state of the research into circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA) in testicular GCTs. Studies have confirmed the presence of ctDNA and cfDNA can be identified in peripheral blood samples of patients with testicular GCTs. Further research has attempted to optimize the methods for ctDNA detection in plasma to improve the sensitivity of these tests; however, a single method with high sensitivity and reliability has yet to be established. Previous studies have employes different methods for detecting cfDNA, including spectrophotometry, capillary electrophoresis, quantitative polymerase chain reaction (PCR), reverse transcription-polymerase chain reaction (RT-PCR), and whole genome sequencing. These studies have various elements of cfDNA examined such as total cfDNA quantity, methylation patterns, and specific mutations. Additional studies have investigated the efficacy of cfDNA detection in combination with other tests including miRNA analysis. The application of cfDNA as a biomarker has been rapidly expanding in several malignancies. However, there is a relative paucity of research on the clinical utility of cfDNA in testicular cancer, and many questions remain about the significance and feasibility of this biomarker in GCTs. Cell-free DNA shows promise as a biomarker to enhance detection and disease monitoring in testicular cancer, but robust studies are needed to develop an optimal and reproducible method for cfDNA detection in order to determine its clinical application in testicular cancer. Full article

Circulating tumor DNA (ctDNA) has been investigated as a potential noninvasive biomarker for disease prognostication, monitoring, and treatment selection in various tumor types, including renal cell carcinoma (RCC). In this narrative review, we explore the current methods of ctDNA analysis and the use of ctDNA in both localized and metastatic RCC, focusing on plasma and urine samples. Additionally, we discuss several ongoing as well as upcoming clinical trials that incorporate ctDNA analyses into their study designs and outcomes. Despite the exciting potential of ctDNA in RCC, current assays still face significant limitations in sensitivity and detection limits. Full article

The treatment landscape for metastatic prostate cancer has undergone significant changes in recent years. The availability of next-generation imaging techniques and the emergence of novel therapies have led to earlier and more aggressive treatment approaches for patients. However, despite these advancements, drug resistance and progression to castration-resistant disease remain inevitable. Understanding the molecular landscape of advanced prostate cancer lies at the forefront of being able to deliver personalized therapies and more robustly risk-stratify patients, when combined with clinical factors. Advanced prostate cancer is characterized by inter- and intratumoral heterogeneity, posing challenges in comprehensively analyzing the genomic tumor profile using a solitary tissue sample. Additionally, the disease often manifests as bone-predominant metastatic tumors, making biopsies impractical in many cases. Moreover, archival tissue samples from a prostatectomy specimen may not accurately represent the current state of the tumor. To overcome these limitations, liquid biopsies using plasma samples have emerged as a minimally invasive surrogate approach to obtain real-time information on the genomic tumor profile. Growing evidence confirms the excellent concordance of liquid biopsies with tissue samples, making them an attractive alternative to traditional tissue biopsies. These assays can provide predictive and prognostic information that may enhance patient discussions and influence treatment decisions. This review focuses on the evolution and utility of circulating tumor-derived DNA (ctDNA) liquid biopsy assays in metastatic prostate cancer. Full article

Objective: To quantify changes in the burden of bladder cancer (BC) inpatient health care in Chile between 2001 and 2019, focusing on the impact of public policies and the type of medical insurance (public or private) held by patients. Methods: We retrospectively collected national data on hospital discharges and calculated raw and adjusted hospitalization rates for the period of 2001 to 2019 categorized by sex and age. Additionally, we analyzed length of hospital stays, outcomes of surgical interventions, and discharge conditions based on the type of medical insurance — public: FONASA; private: ISAPRE. We also evaluated the impact of public policies such as the GES (“garantías explícitas en salud”) program, which ensures opportunities and access to medical attention, financial protection, and quality of care for a subset of diseases. Results: A total of 34,100 hospital discharges were analyzed. Most patients were men (71%), and median age was 69 years. Of the patients, 91.3% had some kind of medical insurance, either private or public. Within this subset, 71.3% had public medical insurance (FONASA) and 23.2% had private medical insurance (ISAPRE). Patients on FONASA had significantly higher levels of overall surgery-related mortality (0.83% vs. 0.2%) and significantly longer median hospital stays (4 days vs. 2 days) compared to patients on ISAPRE. Following the implementation of the GES program in 2013, we observed an increase in transurethral resections and a reduction in radical cystectomies among publicly insured patients. Conclusions: The type of medical insurance has a significant impact on the burden of BC-related inpatient health care in Chile, reflecting a significant disparity in terms of health care. The implementation of public policies such as the GES program can play a key role in reducing this gap between public and private medical insurance systems, especially in underdeveloped countries. Full article

Objectives: Testicular torsion is a time-critical, organ-threatening diagnosis requiring prompt surgical intervention for successful salvage of the organ. In Australia, 28% of individuals live in rural and remote areas and face barriers to health care such as greater distance, lower socioeconomic status, (SES), and limited health infrastructure. We hypothesize that these barriers would delay intervention and access to surgical care, and lead to higher orchidectomy rates. Objectives: A 12-year retrospective audit was conducted at a large rural referral center in Australia, focusing on patients undergoing scrotal exploration for testicular torsion. Primary outcomes were orchidectomy rate, time to operation, and ultrasound (US) and their relationship with patient distance, SES, age, and peripheral hospital attendance. Data on SES for geographic postcodes was obtained from the Australian Government Socio-Economic Indexes for Areas 2016. Statistical analysis was performed using IBM SPSS Statistics software, and a P value < 0.05 was considered significant. Results: The study involved 107 patients, of whom 46% had left-sided pathology. The median age of the patients was 14 years. Median SES was in the 37% to 41% centile range, median distance from travelled was 62 kilometers, and median time to operation from triage was 194 minutes. Of the patients, 34 attended a peripheral hospital. No significant risk factors for orchidectomy were identified. US was used in 65% of cases, with torsion detected in 50% of those cases, and orchidectomy performed in 11 patients. US had a sensitivity of 86.1% and specificity of 52.9%. Conclusion: Despite significant differences in geographical distance, SES, age, and access to health care, patients in rural and remote areas of Australia experienced equivalent outcomes in testicular torsion management. Testicular torsion was safely managed at a central referral center using a peripheral hospital catchment in rural and remote areas of Australia, despite significant time delays due to greater distance or lower SES. Full article

Objective: To assess the ability of cell-free urinary and plasma tumor DNA (cfDNA) to predict pathologic stage at radical cystectomy for patients with clinical muscle-invasive bladder cancer. Methods: A total of 25 patients with clinical muscle-invasive bladder cancer were enrolled before undergoing radical cystectomy. Blood and urine were collected before surgery. The 600-gene PredicineATLAS panel was used to sequence blood buffy-coat germline DNA, plasma cfDNA, and urine cfDNA samples. Low-pass whole genome sequencing was performed on plasma- and urine-derived cfDNA. CfDNA tumor fraction (TF), genome-wide copy number burden (CNB), and estimated tumor mutational burden (TMB) were measured in both plasma and urine samples and their correlation with pathologic T-stage was examined. Results: Three of 25 plasma samples had insufficient cfDNA. In 22 of 22 plasma samples and 24 of 25 urine samples, at least one nonsynonymous somatic variant was detected. Across the cohort, 44% of plasma variants were concordant with paired urine variants. The mean number of variants did not differ between noninvasive (< pT1/pN0) and invasive disease (≥ pT1 or N+) for both plasma (8 vs. 9.5 variants; P = 0.85) and urine (33.7 vs. 30 variants; P = 0.45). A strong correlation was observed between urine TF and urine CNB score within patients (rv = 0.92). Plasma TF (r = 0.38), urine TF (r = 0.21), and urine CNB score (r = 0.16) exhibited positive correlations with pT stage. Patients with carcinoma in situ (CIS) had higher mean urine TF and CNB scores (P = 0.07 and P = 0.05, respectively). Plasma TF and CNB score did not correlate with the presence of CIS. Conclusions: Combining plasma- and urine-based cfDNA analysis may help identify patients with residual disease at radical, although we were unable to predict pathologic T-stage based on these metrics.The presence of CIS may contribute to greater urinary CNB and TF levels. Considering CIS in the analysis may improve the ability to correlate tumor metrics with pathologic stage. Low-pass whole genome sequencing–derived urinary CNB correlates strongly with urinary TF and may provide a less resource-intensive method for future longitudinal disease monitoring. Full article