Carcinoma In Situ Research Articles

The impact of positive surgical margins after cystectomy on oncological outcomes: a nationwide study.

To evaluate whether surgical margin status, alongside existing postoperative risk indicators, improves the identification of bladder cancer patients who may benefit from adjuvant therapy following radical cystectomy (RC). In this nationwide cohort study, patients aged ≥18 years diagnosed with muscle-invasive bladder cancer(MIBC) without nodal or distant metastasis (cT2-4aN0/xM0) between November 2017 and December 2020 who underwent RC were selected from the Netherlands Cancer Registry. Detailed information on surgical margin status was obtained through linkage with the Dutch central pathology database, Palga. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to assess the independent prognostic effect of positive surgical margins (carcinoma in situ (CIS)] only or invasive carcinoma) on PFS and OS. We identified 1445 MIBC patients treated by RC (53% open, 47% robot-assisted), of whom 135 (9.3%) had positive surgical margins (10.7% in the open and 7.7% in the robot-assisted cohort). In the entire cohort, OS was 79% and 60% at 12 and 48 months after RC, respectively. PFS was 70% and 61% at 12 and 24 months, respectively. Multivariable Cox regression showed worse PFS (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.67-2.72) and OS (HR 2.02, 95% CI 1.58-2.58) in patients with surgical margins with invasive carcinoma vs patients with negative margins. Patients with only CIS in the margins also appeared to have worse PFS (HR 1.60, 95% CI 1.00-2.58) but these results were not statistically significant. No difference was found for OS (HR 1.30, 95% CI 0.80-2.12). Positive margins should be considered a 'high risk feature, as they result in increased risk of disease progression and impaired survival outcomes. These findings support further investigation of the potential efficacy of adjuvant therapy (i.e., radiotherapy and systemic therapy) among patients with positive surgical margins.

Deficient cell-cell cohesion is linked with lobular localization in simplified models of lobular carcinoma in situ (LCIS).

Lobular carcinoma in situ (LCIS) is a precursor of invasive lobular carcinoma of the breast. LCIS cells lack cell-cell cohesion due to the loss of E-cadherin. LCIS cells grow in mammary lobules rather than in ducts. The etiology of this pattern, especially its dependence on cellular cohesion, is incompletely understood. We simulated passive intra-glandular scattering of carcinoma in situ (CIS) cells in an ultra-simplified hollow mold tissue replica (HMTR) and a discrete-time mathematical model featuring particles of variable sizes representing single cells (LCIS-like particles) or groups of cohesive carcinoma cells (DCIS-like particles). The HMTR features structures reminiscent of a mammary duct with associated lobules. The discrete mathematical model characterizes spatial redistribution over time and includes transition probabilities between ductal or lobular localizations. Redistribution of particles converged toward an equilibrium depending on particle size. Strikingly, equilibrium proportions depended on particle properties, which we also confirm in a continuous-time mathematical model that considers controlling lobular properties such as crowding. Particles of increasing size, representing CIS cells with proficient cohesion, showed increasingly higher equilibrium ductal proportions. Our investigations represent two conceptual abstractions implying a link between loss of cell-cell cohesion and lobular localization of LCIS, which provide a much-needed logical foundation for studying the connections between collective cell behavior and cancer development in breast tissues. In light of the findings from our simplified modeling approach, we discuss multiple avenues for near-future research that can address and evaluate the redistribution hypothesis mathematically and empirically.

Comparing core needle biopsy and surgical excision in breast cancer diagnosis: implications for clinical practice from a retrospective cohort study.

Preoperative ultrasound-guided core needle biopsy (CNB) is currently the standard procedure for managing breast illnesses. However, the differences in outcomes between CNB and surgical excision (SE) have not been thoroughly assessed. This study aimed to explore the disparities in pathological outcomes between these two procedures, using a large sample dataset. This retrospective study consecutively included patients who underwent CNB and SE at Shenzhen People's Hospital from May 2016 to June 2023. Immunohistochemistry (IHC) was utilized to determine the status of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor-2 (HER2), and Ki-67. Patients presenting with HER2 IHC 2+ underwent additional fluorescence in situ hybridization (FISH) examination. The cutoff value for high Ki-67 expression was established at 14%. Molecular subtypes were classified into four groups (Luminal A, Luminal B, Triple-negative, and HER2-positive) and five groups [Luminal A, Luminal B+ (HER2-positive), Luminal B- (HER2-negative), Triple-negative, and HER2-positive], based on different criteria. A total of 4,209 patients were included in this study. Post-surgical confirmation revealed 2,410 cases as benign and 1,799 as malignant. Among the malignant cases, 334 were excluded due to either not having undergone direct surgery or having incomplete IHC results. The remaining 1,465 cases underwent IHC testing. CNB demonstrated a 97% concordance rate (CR) in diagnosing benign cases. The CRs for diagnosing invasive breast cancer (IBC) and carcinoma in situ (CIS) were 92% and 54%, respectively. ER, PgR, HER2, and Ki-67 exhibited CRs of 94%, 91%, 98%, and 84%, respectively. In the four-group classification, the overall diagnostic CR was 82%, with CRs for Luminal A, Luminal B, HER2-positive, and triple-negative breast cancer (TNBC) being 84%, 82%, 78%, and 85%, respectively. Under the five-group classification, the overall diagnostic CR was also 82%, with CRs for Luminal A, Luminal B+, Luminal B-, HER2-positive, and TNBC being 86%, 85%, 94%, 88%, and 92%, respectively. This study demonstrates that CNB is highly accurate in differentiating benign from malignant breast lesions, particularly showing significant consistency in the diagnosis of molecular subtypes, providing a reliable reference for clinical diagnosis.

Characterization of A Bronchoscopically Induced Transgenic Lung Cancer Pig Model for Human Translatability.

There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs have high impact on humans due to similar anatomy and physiology. We present the characterization of a bronchoscopically-induced LC model in Oncopigs carrying inducible KRAS G12D and TP53 R167H mutations. Twelve Oncopigs underwent 29 injections via flexible bronchoscopy. Eighteen Adenovirus-Cre recombinase gene (AdCre) inductions were performed endobronchially (n=6) and transbronchially with a needle (n=12). Eleven control injections were performed without AdCre. Oncopigs underwent serial contrast-enhanced chest CT with clinical follow-up for 29 weeks. Following autopsy, lung and organ tissues underwent histopathology, immunohistochemistry, and RNA-sequencing with comparative analysis with The Cancer Genome Atlas (TCGA) human LC data. All 18 sites of AdCre injections had lung consolidations on CT imaging. Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ (CIS) in 11/12 (91.7%), and invasive cancer (excluding CIS) in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed expression of Pan-CK+/epithelial cancer cells, with macrophages and T cells infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC (TCGA), in contrast to 29.88% overlap of KRAS-mutant mouse LC with human LC. The transgenic and immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. Overlap of the Oncopig LC transcriptome with human LC transcriptome was noted. This pig model is expected to have high clinical translatability to the human LC patient.

Adherence to First-Line Intravesical Bacillus Calmette-Guérin Therapy in the Context of Guideline Recommendations for US Patients With High-Risk Non-muscle Invasive Bladder Cancer.

Background: Bacillus Calmette-Guérin (BCG) can reduce recurrence and delay progression among patients with high-risk non-muscle invasive bladder cancer (NMIBC), but is associated with a substantial emotional, physical, and social burden. Objectives: This study evaluated the adequacy of first-line intravesical BCG treatment among high-risk NMIBC patients in the United States, including the subgroup with carcinoma in situ (CIS) of the bladder. Methods: Adults with high-risk NMIBC treated with BCG were selected from de-identified MarketScan® Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Adequacy of BCG induction and maintenance was evaluated from the first BCG claim until the end of the patient's observation, using a previously published claims-based algorithm (induction: ≥5 instillations within 70 days; induction and maintenance: ≥7 instillations within 274 days of first instillation) and a definition based on the landmark Southwest Oncology Group (SWOG) trial (induction: ≥5 instillations without gaps >7 days; followed by ≥2 instillations at month 3, 6, and every 6 months thereafter). Proportions of patients with adequate BCG induction and maintenance were reported overall and compared between those with and without CIS. Results: Of 5803 high-risk NMIBC patients treated with first-line BCG (mean age, 67.3 years; 20.6% female), 930 (16.0%) had CIS. After first-line BCG, 56.6% received another treatment. Although 86.9% had adequate BCG induction based on the claims-based algorithm (SWOG, 73.6%), only 41.5% had adequate BCG induction and maintenance (SWOG, 1.6%). Similar trends were observed for patients with and without CIS, with higher adherence to guidelines for patients with CIS (adequate induction using claims-based algorithm: 90.3% vs 86.2%; adequate induction and maintenance: 50.8% vs 39.7%, all P < .001). A greater proportion of CIS patients than non-CIS patients had cystectomy (CIS, 14.4%, non-CIS, 8.5%; P < .001) after first-line BCG. Discussion: Among patients with NMIBC treated with first-line intravesical BCG, most received adequate BCG induction but less than half had adequate BCG maintenance. BCG treatment was also inadequate for patients with CIS, with only half of patients receiving adequate BCG maintenance and a higher proportion undergoing cystectomy following first-line BCG. Conclusions: Results emphasize the need for additional treatment options for patients with NMIBC.

Adherence to First-Line Intravesical Bacillus Calmette-Guérin Therapy in the Context of Guideline Recommendations for US Patients With High-Risk Non-muscle Invasive Bladder Cancer

Background: Bacillus Calmette-Guérin (BCG) can reduce recurrence and delay progression among patients with high-risk non–muscle invasive bladder cancer (NMIBC), but is associated with a substantial emotional, physical, and social burden. Objectives: This study evaluated the adequacy of first-line intravesical BCG treatment among high-risk NMIBC patients in the United States, including the subgroup with carcinoma in situ (CIS) of the bladder. Methods: Adults with high-risk NMIBC treated with BCG were selected from de-identified MarketScan® Commercial, Medicare, and Medicaid Databases (1/1/2010-2/28/2021). Adequacy of BCG induction and maintenance was evaluated from the first BCG claim until the end of the patient’s observation, using a previously published claims-based algorithm (induction: ≥5 instillations within 70 days; induction and maintenance: ≥7 instillations within 274 days of first instillation) and a definition based on the landmark Southwest Oncology Group (SWOG) trial (induction: ≥5 instillations without gaps &gt;7 days; followed by ≥2 instillations at month 3, 6, and every 6 months thereafter). Proportions of patients with adequate BCG induction and maintenance were reported overall and compared between those with and without CIS. Results: Of 5803 high-risk NMIBC patients treated with first-line BCG (mean age, 67.3 years; 20.6% female), 930 (16.0%) had CIS. After first-line BCG, 56.6% received another treatment. Although 86.9% had adequate BCG induction based on the claims-based algorithm (SWOG, 73.6%), only 41.5% had adequate BCG induction and maintenance (SWOG, 1.6%). Similar trends were observed for patients with and without CIS, with higher adherence to guidelines for patients with CIS (adequate induction using claims-based algorithm: 90.3% vs 86.2%; adequate induction and maintenance: 50.8% vs 39.7%, all P &lt; .001). A greater proportion of CIS patients than non-CIS patients had cystectomy (CIS, 14.4%, non-CIS, 8.5%; P &lt; .001) after first-line BCG. Discussion: Among patients with NMIBC treated with first-line intravesical BCG, most received adequate BCG induction but less than half had adequate BCG maintenance. BCG treatment was also inadequate for patients with CIS, with only half of patients receiving adequate BCG maintenance and a higher proportion undergoing cystectomy following first-line BCG. Conclusions: Results emphasize the need for additional treatment options for patients with NMIBC.

Unveiling the Clinical Path of Microinvasive Breast Cancer: A Comparative Study With Tis-T1 Breast Cancer.

The prognosis of microinvasive breast cancer (MIBC) is controversial, with a high reported rate of local recurrence (LR). This study aimed to evaluate the characteristics, treatments, and prognosis of patients with MIBC compared to those with carcinoma insitu (CIS) or early invasive cancer. Patients who diagnosed with CIS or stage I breast cancer were retrospectively enrolled. Using the Kaplan-Meier method, local recurrence-free survival (LRFS), systemic recurrence-free survival (SRFS), and cancer-specific survival (CSS) were compared according to T stage. The prognostic factors associated with LRFS were identified using the Cox proportional hazards model. According to T stage, 517 (21.6%), 200 (8.4%), 207 (8.7%), 363 (15.2%), and 1101 (46.1%) patients had Tis, T1mi, T1a, T1b, and T1c tumors, respectively. The proportion of human epidermal growth factor receptor 2-positive tumors was significantly higher in patients with MIBC (p < 0.0001). The administered adjuvant treatments also showed differences according to T stage (p < 0.0001). During the 73-month median follow-up period, patients with MIBC showed significantly worse LRFS than those with T1a or T1c tumors (p = 0.002). There was no significant difference in SRFS and CSS. In the Cox regression analysis, tumor multiplicity (p = 0.017), Ki-67 (p = 0.025), cancer subtype (p = 0.034), adjuvant endocrine therapy (p = 0.003), and adjuvant radiation therapy (p < 0.0001) were significant prognostic factors associated with LRFS. The risk of LR was higher in patients with MIBC than in those with small invasive breast cancer. Therefore, if indicated, adjuvant endocrine and radiation therapies should be administered to prevent undertreatment in patients with MIBC.

Molecular Detection by Rolling Circle Amplification Combined with Deep Sequencing of Mixed Infection by Bovine Papillomaviruses 2 and 4 in Carcinoma In Situ of the Bovine Esophageal Mucosa.

Papillomaviruses (PVs) are oncogenic and infect the skin and mucosa of various host species. Considering the recent advances in research on PVs using rolling circle amplification (RCA) followed by high-throughput sequencing (HTS), in this study, we aimed to investigate the bovine papillomavirus (BPV) types associated with proliferative lesions in the upper alimentary tract of an affected bull and characterize the viral strains through complete genome sequencing using this strategy. We analyzed the PV strains associated with two hyperplastic esophageal lesions through PCR using degenerate primer pairs and RCA, followed by HTS. HTS of the libraries generated using RCA products provided the whole genome sequence of BPV4 present in squamous papilloma, whereas the complete genome sequence of BPV2 and subgenomic fragments of BPV4 were identified in carcinoma in situ (CIS). For the first time, we have sequenced BPV2 identified from the CIS of the bovine upper alimentary canal. Additionally, RCA followed by HTS allowed characterization of the mixed infection by BPV2 and BPV4 in this lesion. These data reveal that BPV4 is not the only BPV type present in CIS of the esophageal mucous membrane; moreover, a mixed infection caused by BPV2 and BPV4 at the tested anatomical site was demonstrated.

Follow-up strategies after trimodal treatment for muscle-invasive bladder cancer: a systematic review

PurposeOptimal follow-up strategies following trimodal treatment for muscle invasive bladder cancer play a crucial role in detecting and managing relapse and side-effects. This article provides a comprehensive summary of the patterns and risk factors of relapse, functional outcomes, and follow-up protocols.MethodsA systematic literature search on PubMed and review of current guidelines and institutional follow-up protocols after trimodal therapy were conducted.ResultsOut of 200 identified publications, 43 studies (28 retrospective, 15 prospective) were selected, encompassing 7447 patients (study sizes from 24 to 728 patients). Recurrence rates in the urinary bladder varied between 14–52%; 3–16% were muscle-invasive while 11–36% were non-muscle invasive. Nodal recurrence occurred at 13–16% and distant metastases at 15–35%. After 5 and 10 years of follow-up, around 60–85% and 45–75% of patients could preserve their bladder, respectively. Various prognostic risk factors associated with relapse and inferior survival were proposed, including higher disease stage (> c/pT2), presence of extensive/multifocal carcinoma in situ (CIS), hydronephrosis, multifocality, histological subtypes, incomplete transurethral resection of bladder tumor (TURBT) and incomplete response to radio-chemotherapy. The analyzed follow-up guidelines varied slightly in terms of the number, timing, and types of investigations, but overall, the recommendations were similar.ConclusionRandomized prospective studies should focus on evaluating the impact of specific follow-up protocols on oncological and functional outcomes following trimodal treatment for muscle-invasive bladder cancer. It is crucial to evaluate personalized adaption of follow-up protocols based on established risk factors, as there is potential for improved patient outcomes and resource allocation.

Differences in Clinical Outcomes and Survival Among Primary, Secondary, and Concomitant Carcinoma In Situ of the Bladder.

Carcinoma in situ (CIS) is a flat, high-grade, and aggressive form of urothelial carcinoma with a high risk of progression to muscle-invasive disease and metastasis. This study aimed to investigate differences in clinical outcomes and survival among patients with primary, secondary, and concomitant CIS of the bladder. A total of 209 patients diagnosed with CIS between 2010 and 2022 in our department with a minimum follow-up of 12 months were retrospectively analyzed. Patients with muscle-invasive cancer at diagnosis, those with recurrence within one month after diagnosis, and those with primary malignant melanoma were excluded. The recurrence, progression, and cancer-specific mortality rates of patients receiving Bacillus Calmette-Guérin therapy for CIS were analyzed. A total of 96 patients with primary (n = 18), secondary (n = 29), and concomitant CIS (n = 49) were included in the analysis. The median follow-up was 52.2 months. Patients with secondary CIS had a significantly higher recurrence rate than those with concomitant CIS (58.6% vs. 32.7%, p = 0.016). However, no significant difference in progression rates was observed among the three groups. Furthermore, no significant association was observed between CIS subtypes and recurrence-free survival (RFS) (HR = 1.45, 95% CI 0.96-2.46, p = 0.16) or progression-free survival (PFS) (HR = 2.20, 95% CI 0.99-4.87, p = 0.054). Secondary CIS had a significantly higher recurrence rate than concomitant CIS. However, no statistically significant association was observed between CIS subtypes and RFS or PFS.

The Simultaneous Use of Bladder Epicheck® and Urinary Cytology Can Improve the Sensitivity and Specificity of Diagnostic Follow-Up of Urothelial Lesions: Up-to-Date Data from a Multi-Institutional Cohort.

Background/Objectives: Bladder cancer is a prevalent urinary system malignancy and urinary cytology is widely used for its screening and follow-up. A novel diagnostic tool called Bladder Epicheck® (BE) is increasingly being used for monitoring the recurrence of non-muscle-invasive bladder cancer (NMIBC). The simultaneous use of BE and urinary cytology can increase the diagnostic performances in the follow-up of bladder neoplasms. Methods: In this multicenter study, we retrospectively evaluated the data of 322 patients in follow-up for a high-grade bladder carcinoma over a six-year period (from January 2018 to March 2024). The diagnostic performances of both cytology and BE and their combination were calculated using histology as gold standard. Results: Recurrences were diagnosed as high-grade urothelial carcinoma NMIBC in 18 cases, low-grade papillary NMIBC in 8 cases, and carcinoma in situ (CIS) in 4 cases. Cytological analysis correctly identified 26 out of 30 carcinomas, while 286 were correctly diagnosed as negative results. BE correctly identified 25 out of 30 carcinomas, 285 were correctly diagnosed as negative results. The combination of BE and urinary cytology correctly identified 29 out of 30 carcinomas, while 289 were correctly diagnosed as negative results. Conclusions: The combination of BE and cytology could be the most effective approach for follow-up diagnosis in patients with high-grade NMIBC, reducing unnecessary invasive procedures.

2023TiP A phase I/II study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients (pts) with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

2023TiP A phase I/II study of EG-70 (detalimogene voraplasmid) intravesical monotherapy for patients (pts) with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS)

Does radical cystectomy still have a role in BCG-unresponsive nonmuscle invasive bladder cancer?

Several novel therapies approved by the Food and Drug Administration (FDA) and explosion of clinical trials have changed the landscape Bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC). Given the recent advancements in bladder sparing options, the role of radical cystectomy (RC) in BCG-unresponsive NMIBC remains a subject of debate. All three novel agents currently approved by the FDA for BCG-unresponsive NMIBC have strict indication [carcinoma in situ (CIS)], low response rate, and short response duration. Some promising new agents are awaiting results and/or FDA approval. RC still provides the best oncologic control and acceptable quality of life, and potentially represents the most cost-effective option. It is an exciting time for the urologic oncology community to see the FDA approvals of some of the novel bladder sparing therapies and expansion of ongoing clinical trials. Yet, RC should still be considered as the gold standard of BCG-unresponsive NMIBC. We also must be cautious and selective in recommending bladder sparing options for patients with BCG-unresponsive NMIBC.

Prospective evaluation of surgical margins in non-muscle invasive bladder cancer following primary transurethral resection

PurposeNon-muscle invasive bladder cancers (NMIBC) constitute approximately 75% of bladder cancer cases. Primary transurethral resection (TUR) plays a pivotal role in both diagnosis and treatment. However, despite initial resection, tumors are often missed, leaving behind microscopic residual tumors. This study aims to prospectively investigate the surgical margins of tumors, which may serve as a potential source of residual tumors. Materials and methodsSeventy patients diagnosed with NMIBC who underwent primary TUR were enrolled in this study. Following initial resection, samples were collected from the normal-appearing mucosa extending 1cm beyond the surgical margins. Lesions were categorized as ‘healthy margins’ for benign lesions, ‘tumoral margins’ for urothelial cancer, and ‘dysplastic margins’ for urothelial dysplasia. Clinical and pathological features of these groups were compared, and risk factors for detecting transitional cell carcinoma (TCC) in the normal-looking mucosa were analyzed. ResultsThe tumoral margins group showed a significantly higher rate of T1 stage tumors compared to the healthy margins group, and a significantly higher rate of high-grade (HG) tumors compared to the dysplastic margins group. Moreover, the tumoral margins group had a significantly higher proportion of high-risk patients (85.7%) compared to the other groups, while the healthy margins group had a significantly higher proportion of low-risk patients (35.3%) compared to the tumoral margins group (0.0%). Additionally, the tumoral margins group demonstrated a significantly higher rate of carcinoma in situ (CIS) compared to the healthy margins group (35.7% vs. 5.9%). Detection of urothelial cancer at the margins was associated with T1 stage, HG stage, and the presence of CIS based on univariate analyses. ConclusionTo minimize residual tumors and prevent recurrence in patients undergoing primary TUR, we advocate for the resection of macroscopically visible tumors with nearly 2cm of intact bladder tissue, thereby enhancing the quality of TUR. Level of evidenceThis study provides Level II evidence, based on its design as a prospective observational study. The findings are derived from well-designed cohort analyses, providing significant associations and insights into the factors affecting surgical margins in NMIBC patients.

Digital volumetric assessment of CIS and tumor mass compliments conventional histopathological assessment in muscle-invasive urothelial bladder cancer.

Carcinoma in situ (CIS) of the bladder is a known parameter regarding the prognosis and recurrence tendency of urothelial carcinomas. Nevertheless, there is little evidence whether the amount of CIS or other precursor lesions, as well as the quantified tumor mass of muscle-invasive urothelial carcinoma, has an influence on the survival or recurrence rate of affected patients. From 80 patients with muscle invasive urothelial bladder cancer and radical cystectomy, 23 samples each were obtained as part of a whole organ mapping in a single institution study, in which the precursor lesions and tumor area were digitally measured and further correlated to pathological standard parameters, patient survival, molecular luminal and basal subtypes, and immune infiltration. Significant correlations were found between tumor mass and surface lining CIS amount for pT-stage, lymphovascular invasion, and perineural infiltration. Furthermore, an increased tumor mass as well as an increased amount of CIS combined with an increased tumor mass showed a significantly reduced survival rate in multivariable analysis (HR = 2.75; P = 0.019 vs. HR = 3.54; P = 0.002) as well as a significantly increased recurrence. No correlations could be found with molecular subtypes and immune infiltration. The exact measurement of the tumor mass with and without the CIS surface area, whether manually or, more specifically, digitally, could be incorporated into routine diagnostics and implemented as an independent predictor for patient post-surgical outcomes. It can therefore serve as an additional predictor for risk stratification and, if necessary, intensified follow-up care or therapy.

Role of confocal laser endomicroscopy compared to high definition i- scan video bronchoscopy in patients with suspected lung cancer

Abstract Background Lung cancer is the leading cause of cancer-related mortality worldwide. Overall 5-year survival is poor at 15% with little improvement over the last twenty years (1.59 million deaths). Besides effective prevention strategies against the commonest risk factor; tobacco smoking, lung cancer mortality can be reduced if cases are detected and treated early. It is important to detect bronchial carcinoma in situ (CIS) since over 40% of these can develop into invasive cancer. Screening tests using sputum cytology and chest radiograph have been used with limited success Objective to study the diagnostic performance of confocal laser endomicroscopy in comparison to high definition i-scan videobronchoscopy in patients with suspected lung cancer. Patients and Methods The study was performed at Pulmonary diseases hospital in Kobry Elkobba military complex for 2 years since January 2018 to December 2019. The study included 25 patients all had chest CT findings suspicious of lung cancer. Results i-scan findings showed 68% accuracy and 73.3% specificity, and findings of confocal laser endomicroscopy were 92% accuracy and 90% specificity. Conclusion This was the preliminary study establishing patient characteristics in Egypt in the form of a comparison between tow methods of diagnosis of lung cancer. The study showed the higher sensitivity of confocal laser endomicroscopy in the diagnosis of lung cancer approved by the results of the pathological specimens optioned under the visual of confocal laser endomicroscopy in comparison to I-scan method.

N-803 Plus BCG Treatment for BCG-Naïve or -Unresponsive Non-Muscle Invasive Bladder Cancer: A Plain Language Review.

This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC).One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCGunresponsive). In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400μg N-803 along with a standard 50mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400μg N-803 plus 50mg BCG. There was also a cohort C that received only 400μg N-803. Treatments were delivered directly into the bladder once a week for 6weeks in a row. N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease.Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).

Nogapendekin alfa Inbakicept: First Approval.

Nogapendekin alfa inbakicept (ANKTIVA®; nogapendekin alfa inbakicept-pmln) is a recombinant interleukin-15 (IL-15) superagonist protein complex being developed by Altor BioScience, LLC, an indirect wholly owned subsidiary of ImmunityBio, Inc., for the treatment of solid and haematological cancers and HIV infection. In April 2024, nogapendekin alfa inbakicept was approved for use with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumours in the USA. This article summarizes the milestones in the development of nogapendekin alfa inbakicept leading to this first approval for the treatment of cancer.

365 Completion Mastectomy After Wide Local Excision (Wle) and Sentinel Lymph Node Biopsy (Slnb) for Ductal Carcinoma Insitu (Dcis), Local Data from the Countess of Chester Hospital

365 Completion Mastectomy After Wide Local Excision (Wle) and Sentinel Lymph Node Biopsy (Slnb) for Ductal Carcinoma Insitu (Dcis), Local Data from the Countess of Chester Hospital

Intravesical Gemcitabine and Docetaxel Therapy for BCG-Naïve Patients: A Promising Approach to Non-Muscle Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle invasive bladder cancer (NMIBC) faces limitations in efficacy and significant side effects, aggravated by a recent global shortage. In this prospective clinical study, we report the outcomes of sequential intravesical administration of gemcitabine and docetaxel (Gem/Doce) as a first-line treatment for BCG-naïve patients with high-risk NMIBC (HR NMIBC). From October 2019 until April 2022, we enrolled 52 patients and followed the treatment protocol set forth by the University of Iowa. Follow-up assessments were conducted every 3 months. In this cohort, 25 (48.1%) patients were diagnosed with high-grade T1 (T1HG) bladder cancer, 10 (19.2%) patients had carcinoma in situ (CIS), and 17 (32.7%) patients had a combination of T1HG+CIS. The median time to first recurrence in the T1HG, CIS, and T1HG+CIS groups was 11, 10.5, and 8.8 months, respectively. The recurrence-free survival was 98.1%, 94.2%, and 80.8% at 6, 9, and 12 months, respectively. The rate of progression-free survival was 100%, 98.1%, and 92.3% at 6, 9, and 12 months, respectively. We demonstrated the safety and efficacy of Gem/Doce therapy in BCG-naïve patients with HR NMIBC during a one-year follow-up. Further research with extended follow-ups, as well as direct comparisons of Gem/Doce with other anticancer agents, is essential.