Bladder Cancer, Version 3.2024.

Bladder cancer, the sixth most common cancer in the United States, is most commonly of the urothelial carcinoma histologic subtype. The clinical spectrum of bladder cancer is divided into 3 categories that differ in prognosis, management, and therapeutic aims: (1) non-muscle-invasive bladder cancer (NMIBC); (2) muscle invasive, nonmetastatic disease; and (3) metastatic bladder cancer. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Bladder Cancer, including changes in the fifth edition of the WHO Classification of Tumours: Urinary and Male Genital Tumours and how the NCCN Guidelines aligned with these updates; new and emerging treatment options for bacillus Calmette-Guérin (BCG)-unresponsive NMIBC; and updates to systemic therapy recommendations for advanced or metastatic disease.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

A Preliminary Diagnostic Model for Forward Head Posture among Adolescents Using Forward Neck Tilt Angle and Radiographic Sagittal Alignment Parameters.

Despite numerous attempts to correct forward head posture (FHP), definitive evidence-based screening and diagnostic methods remain elusive. This study proposes a preliminary diagnostic methodology for FHP, utilizing a noninvasive body angle measurement system as a screening test for FHP and incorporating radiological parameters for sagittal alignment. We enrolled 145 adolescents for FHP screening. The forward neck tilt angle (FNTA), defined as the angle between the vertical line and the line connecting the participant's acromion and tragus, was measured using the POM-Checker (a noninvasive depth sensor-based body angle measurement system). A whole-spine standing lateral radiograph was obtained, and eight sagittal alignment parameters were measured. Statistical analyses of the association between the FNTA and eight sagittal alignment parameters were conducted. We used 70% of the participant data to establish a preliminary diagnostic model for FHP based on FNTA and each sagittal alignment parameter. The accuracy of the model was evaluated using the remaining 30% of the participant data. All radiological parameters of sagittal alignment showed weak statistical significance with respect to FNTA (best case: r = 0.16, p = 0.0500; cranial tilt). The proposed preliminary diagnostic model for FHP demonstrated 95.35% agreement. Notably, the model using FNTA without radiological parameters accurately identified (100%) participants who required radiographic scanning for FHP diagnosis. Owing to the weak statistical significance of the association between radiological parameters and external body angle, both factors must be considered for accurate FHP diagnosis. When a clear and severe angle variation is observed in an external body angle check, medical professionals should perform radiographic scanning for an accurate FHP diagnosis. In conclusion, FNTA assessment of FNTA through the proposed preliminary diagnostic model is a significant screening factor for selecting participants who must undergo radiographic scanning so that a diagnosis of FHP can be obtained.

Predicting adequate segmental lordosis correction in lumbar spinal stenosis patients undergoing oblique lumbar interbody fusion: a focus on the discontinuous segment.

PURPOSE: To identify the factors associated with a correction of the segmental angle (SA) with a total change greater than 10° in each level following minimally invasive oblique lumbar interbody fusion (MIS-OLIF). METHODS: Patients with lumbar spinal stenosis who underwent single- or two-level MIS-OLIF were reviewed. Segments with adequate correction of the SA >10° after MIS-OLIF in immediate postoperative radiograph were categorized as discontinuous segments (D segments), whereas those without such improvement were assigned as continuous segments (C segments). Clinical and radiological parameters were compared, and multivariate logistic regression analysis was performed to identify factors associated with SA correction >10° after MIS-OLIF. RESULTS: Of 211 segments included, 38 segments (18.0%) were classified as D segments. Compared with C segments, D segments demonstrated a significantly smaller preoperative SA (mean ± standard deviation [SD], - 1.1° ± 6.7° vs. 6.6° ± 6.3°, p < 0.001), larger change of SA (mean ± SD, 13.5° ± 3.4° vs. 3.1° ± 3.9°, p < 0.001), and a higher rate of presence of facet effusion (76.3% vs. 48.6%, p = 0.002). Logistic regression revealed preoperative SA (odds ratio (OR) [95% confidence interval (CI)]:0.733 [0.639-0.840], p < 0.001) and facet effusion (OR [95% CI]:14.054 [1.758-112.377], p = 0.027) as significant predictors for >10° SA correction after MIS-OLIF. CONCLUSION: Preoperative kyphotic SA and facet effusion can predict SA correction >10° following MIS-OLIF. For patients with lordotic SA and no preoperative facet effusion, supplemental procedures, such as anterior column release or posterior osteotomy, should be prepared for additional lumbar lordosis correction required for remnant global sagittal imbalance after MIS-OLIF.

Quality of Life in the Phase 2/3 Trial of N-803 Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin‒Unresponsive Nonmuscle-Invasive Bladder Cancer.

INTRODUCTION: In the phase 2/3 study QUILT-3.032 (NCT03022825), the ability of the IL-15RαFc superagonist N-803 (nogapendekin alfa inbakicept) plus bacillus Calmette-Guérin (BCG) to elicit durable complete responses in patients with BCG-unresponsive nonmuscle-invasive bladder cancer (NMIBC) was demonstrated. As a secondary end point, patient-reported outcomes (PROs) were assessed. METHODS: Both cohort A patients with carcinoma in situ with or without Ta/T1 disease and cohort B patients with high-grade Ta/T1 papillary disease who received N-803 plus BCG therapy completed the EORTC (European Organization for Research and Treatment of Cancer) Core 30 and Quality of Life NMIBC-Specific 24 questionnaires at baseline and months 6, 12, 18, and 24 on study. Scores were analyzed using descriptive statistics, and multivariable analyses were performed to identify baseline variables associated with PROs. RESULTS: On study, mean physical function (PF) and global health (GH) scores remained relatively stable from baseline for cohorts A (n = 86) and B (n = 78). At month 6, cohort A patients with a complete response reported higher PF scores than those without (P = .0659); at month 12, > 3 as compared with ≤ 3 prior transurethral resections of bladder tumor was associated (P = .0729) with lower GH scores. In cohort B, baseline disease type was associated (P = .0738) with PF and race was significantly associated (P = .0478) with GH at month 6. NMIBC-Specific 24 summary scores also remained stable on study for both cohorts. CONCLUSIONS: The overall stability of PROs scores, taken together with the efficacy findings, indicates a favorable risk-benefit ratio and quality of life following N-803 plus BCG.

Relationships between protein and other chemical composition and texture of tofu made from soybeans grown in different locations.

Understanding quantitative relationships between protein and other chemical components in diverse soybean genotypes (lines) grown in different locations and the firmness of tofu can provide scientific insight for selecting soybean suitable for tofu making. Locations showed significant effects on seed components, including total protein, major storage proteins, subunits and polypeptides of the major storage proteins, and calcium, but not magnesium or phytic acid. Results showed that 11S content, but not 11S/7S ratio, was only correlated with filled tofu firmness when analyzed over all locations. A strong and positive correlation between firmness and A3 polypeptide of the 11S protein content was found for both pressed tofu (r = 0.80, p < 0.001) and filled tofu (r = 0.76, p < 0.001) over three locations (overall pooled data) and within most individual locations. The correlation of filled tofu firmness and A3 polypeptide was significant for each of the three individual locations. However, the correlation of pressed tofu firmness and A3 polypeptide content was significant at two of three locations. Mean calcium content was positively correlated with mean pressed and filled tofu firmness over all locations, but calcium was not correlated with pressed tofu firmness at any individual location, and only one location showed a significant correlation of calcium and filled tofu firmness. In addition, pressed tofu firmness was found to be negatively correlated with tofu yield. The findings that A3 polypeptide's strong relationship with tofu firmness within certain locations may be used by the food industry to select proper soybean for manufacturing tofu and to facilitate tofu soybean breeding for tofu making.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment.

PURPOSE: The purpose of this American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In 2023, the NMIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from July 2019 to May 2023. This review identified 1918 abstracts, of which 75 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) in support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on variant histologies, urine markers after diagnosis of bladder cancer, intravesical therapy, BCG maintenance, enhanced cystoscopy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Efficacy of Total En Bloc Spondylectomy versus Stereotactic Ablative Radiotherapy for Single Spinal Metastasis.

To compare total en bloc spondylectomy (TES) with stereotactic ablative radiotherapy (SABR) for single spinal metastasis, we undertook a single center retrospective study. We identified patients who had undergone TES or SABR for a single spinal metastasis between 2000 and 2019. Medical records and images were reviewed for patient and tumor characteristics, and oncologic outcomes. Patients who received TES were matched to those who received SABR to compare local control and survival. A total of 89 patients were identified, of whom 20 and 69 received TES and SABR, respectively. A total of 38 matched patients were analyzed (19 TES and 19 SABR). The median follow-up period was 54.4 (TES) and 26.1 months (SABR) for matched patients. Two-year progression-free survival (PFS) and overall survival (OS) rates were 66.7% and 72.2% in the TES and 38.9% and 50.7% in the SABR group, respectively. At the final follow-up of the matched cohorts, no significant differences were noted in OS (p = 0.554), PFS (p = 0.345) or local progression (p = 0.133). The rate of major complications was higher in the TES than in the SABR group (21.1% vs. 10.5%, p = 0.660). These findings suggest that SABR leads to fewer complications compared to TES, while TES exhibits better mid-term control of metastatic tumors.

The Fate of Pre-Existing L5-S1 Degeneration following Oblique Lumbar Interbody Fusion of L4-L5 and Above.

BACKGROUND: Previous studies have identified various risk factors for adjacent segment disease (ASD) at the L5-S1 level after fusion surgery, including preoperative sagittal imbalance, longer fusion, and preoperative disc degeneration. However, only a few studies have explored the risk factors for ASD at the L5-S1 level after oblique lumbar interbody fusion (OLIF) at the L4-L5 level and above. This study aimed to identify the risk factors for symptomatic ASD at the L5-S1 level in patients with pre-existing degeneration after OLIF at L4-L5 and above. METHODS: We retrospectively reviewed the data of patients who underwent OLIF at L4-L5 and above, with a minimum follow-up period of 2 years. Patients with central stenosis or Lee grade 2 or 3 foraminal stenosis at L5-S1 preoperatively were excluded. Patients were divided into ASD and non-ASD groups based on the occurrence of new-onset L5 or S1 radicular pain requiring epidural steroid injection (ESI). The clinical and radiological factors were analyzed. Logistic regression was used to identify the risk factors for ASD of L5-S1. RESULTS: A total of 191 patients with a mean age ± standard deviation of 68.6 ± 8.3 years were included. Thirty-four (21.7%) patients underwent ESI at the L5 root after OLIF. In the logistic regression analyses, severe disc degeneration (OR (95% confidence interval (CI)): 2.65 (1.16-6.09)), the presence of facet effusion (OR (95% CI): 2.55 (1.05-6.23)), and severe paraspinal muscle fatty degeneration (OR (95% CI): 4.47 (1.53-13.05)) were significant risk factors for ASD in L5-S1. CONCLUSIONS: In this study, the presence of facet effusion, severe disc degeneration, and severe paraspinal muscle fatty degeneration at the L5-S1 level were associated with the development of ASD at L5-S1 following OLIF at L4-L5 and above. For patients with these conditions, surgeons could consider including L5-S1 in the fusion when considering OLIF at the L4-L5 level and above.

Enhancing the image quality of blue light cystoscopy through green-hue correction and fogginess removal.

Blue light cystoscopy (BLC) is a guideline-recommended endoscopic tool to detect bladder cancer with high sensitivity. Having clear, high-quality images during cystoscopy is crucial to the sensitive, efficient detection of bladder tumors; yet, important diagnostic information is often missed or poorly visualized in images containing illumination artifacts or impacted by impurities in the bladder. In this study, we introduce computational methods to remove two common artifacts in images from BLC videos: green hue and fogginess. We also evaluate the effect of artifact removal on the perceptual quality of the BLC images through a survey study and computation of Blind/Referenceless Image Spatial Quality Evaluator scores on the original and enhanced images. We show that corrections and enhancements made to cystoscopy images resulted in a better viewing experience for clinicians during BLC imaging and reliably restored lost tissue features that were important for diagnostics. Incorporating these enhancements during clinical and OR procedures may lead to more comprehensive tumor detection, fewer missed tumors during TURBT procedures, more complete tumor resection and shorter procedure time. When used in off-line review of cystoscopy videos, it may also better guide surgical planning and allow more accurate assessment and diagnosis.

Innovative Developments in Lumbar Interbody Cage Materials and Design: A Comprehensive Narrative Review.

This narrative review comprehensively examines the evolution and current state of the interbody cage technology for lumbar interbody fusion (LIF). This review highlights the biomechanical and clinical implications of transition from traditional static cage designs to advanced expandable variants for spinal surgery. The review begins by exploring the early developments in cage materials, highlighting the roles of titanium and polyetheretherketone in advancing LIF techniques. It discusses the strengths and limitations of these materials, leading to innovations in surface modifications and the introduction of novel materials, such as tantalum, as an alternative material. Advancements in three-dimensional printing and surface modification technologies form a significant part of this review, emphasizing the role of these technologies in enhancing the biomechanical compatibility and osseointegration of interbody cages. This review also explores the rise of biodegradable and composite materials such as polylactic acid and polycaprolactone, addressing their potential to mitigate long-term implant-related complications. A critical evaluation of static and expandable cages is presented in this review, including their respective clinical and radiological outcomes. While static cages have been a mainstay of LIF, expandable cages are noted for their ability to adapt to the patient's anatomy, potentially reducing complications such as cage subsidence. However, this review highlights the ongoing debate and the lack of conclusive evidence regarding the superiority of either cage type in terms of clinical outcomes. Finally, this review proposes future directions for cage technology, focusing on the integration of bioactive substances and multifunctional coatings and development of patient-specific implants. These advancements aim to further enhance the efficacy, safety, and personalized approach of spinal fusion surgeries. This review offers a nuanced understanding of the evolving landscape of cage technology in LIF and provides insights into the current practices and future possibilities in spinal surgery.