High-risk Cancer Research Articles

Gender-specific differences in recurrence and progression following BCG instillation for NMIBC

Introduction: To assess gender-specific differences in recurrence-free (RFS), progression-free (PFS), cancer-specific survival (CSS) and overall survival (OS) among patients with intermediate or high-risk non-muscle invasive bladder cancer (NMIBC) receiving BCG is the primary aim of this systematic review and meta-analysis. Methods: In July 2023, we performed a literature search using MEDLINE, Embase and Cochrane Library. This study was prospectively registered at PROSPERO (CRD 2023443269). The detailed review protocol is accessible via CRD. Results: The systematic literature search identified 6,723 studies, of which 38 fulfilled the inclusion criteria. Random effect meta-analysis for RFS, based on data from 24 studies, revealed no statistically significant gender-specific difference (HR comparing males to females=0.9618, 95% CI: 0.8408-1.1003, p=0.5707). Similarly, for PFS, incorporating data from 14 studies, no statistically significant difference (HR =0.9540, 95% CI: 0.7709- 1.1805, p=0.6648), for CSS, analysis of data from three studies yielded no statistically significant difference (HR =0.9228, 95% CI: 0.6196-1.3743, p=0.6925), and for OS, based on data from two studies, no statistically significant difference was observed (HR = 1.1436, 95% CI: 0.5092-2.5684, p=0.7452). The risk of bias assessment indicated an overall moderate to high risk of bias. Conclusion: The findings indicate no association between gender and oncologic outcomes following BCG.

The Application of Mohs Micrographic Surgery in the Treatment of Acral Basal Cell Carcinoma: A Report of Two Cases

Background/Objectives: Mohs micrographic surgery (MMS) is a precise skin surgery technique that is particularly useful in the treatment of high-risk skin cancers and tumors located in challenging anatomical areas. Methods: we report two cases of basal cell carcinoma located in the acral areas effectively treated using MMS. Results: the presented cases demonstrate that MMS is an excellent surgical modality providing outstanding medical, cosmetic, and functional outcomes. Moreover, this study provides another dermoscopic presentation of acral basal cell carcinoma in a patient without the diagnosis of hereditary genetic syndromes associated with an increased risk of skin cancer. Conclusions: basal cell carcinoma located on hands and feet, albeit rare, should be included in the differential diagnosis of amelanotic skin tumors in acral areas.

Whole Exome-Wide Association Identifies Rare Variants in APC Associated with High-Risk Colorectal Cancer in the Middle East

Background: Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enriched in high-impact rare alleles, which might play a crucial role in the etiology and susceptibility of CRC. Methods: In this study, an exome-wide association analysis was performed in 146 patients with high-risk CRC in the Middle East and 1395 healthy controls. The aim was to identify rare germline variants in coding regions and their splicing sites associated with high-risk CRC in the Middle Eastern population. Results: Rare inactivating variants (RIVs) in APC had the strongest association with high-risk CRC (6/146 in cases vs. 1/1395 in controls, OR = 59.7, p = 5.13 × 10−12), whereas RIVs in RIMS1, an RAS superfamily member, were significantly associated with high-risk CRC (5/146 case vs. 2/1395 controls, OR = 24.7, p = 2.03 × 10−8). Rare damaging variants in 17 genes were associated with high-risk CRC at the exome-wide threshold (p < 2.5 × 10−6). Based on the sequence kernel association test, nonsynonymous variants in six genes (TNXB, TAP2, GPSM3, ADGRG4, TMEM229A, and ANKRD33B) had a significant association with high-risk CRC. RIVs in APC—the most common high-penetrance genetic factor—were associated with patients with high-risk CRC in the Middle East. Individuals who inherited APC RIVs had an approximate 60-fold increased risk of developing CRC and were likely to develop the disease earlier. Conclusions: We identified new potential CRC predisposition variants in other genes that could play a role in CRC inheritance. However, large collaborative studies are needed to confirm the association of these variants with high-risk CRC. These results provide information for counseling patients with high-risk CRC and their families in our population.

Screening for Breast Cancer Risk: An Analysis of Under-recognized Risk Factors and Comparison of Interventions.

Recognition of patients at high risk (HR) for breast cancer allows earlier screening and opportunities for risk reduction. We compare patients referred to our breast clinic as HR vs referrals for other reason (ROR) and found to be HR. We evaluate under-recognized factors and treatment differences. A retrospective chart review of patients found to be HR but referred for any reason to our breast clinic from July 2012 to December 2022 was performed. Referral reason, demographics, hormonal history, family history, and other risk factors were evaluated and compared (HR vs ROR). While other risk models were used for screening, Gail and Tyrer-Cuzick version 7 (TCv7) were used for comparison. Breast imaging received, hormonal therapy, and genetics referral evaluations were compared. 195 patients were referred to our breast team, 113 (58%) were referred as HR while 82 (42%) were ROR. Average age was 47 years old. 175 (91%) were Caucasian. 74 (65.5%) were referred for genetic testing, and 32 (26%) tested positive for a genetic mutation (n = 10, 12% ROR). 67 (35%) were recommended chemoprevention (n = 32, 16.4% took chemoprevention). 6 (3.1%) underwent prophylactic mastectomies and 163 (85%) had supplemental breast imaging. Comparison of HR vs ROR did not show significant differences in hormonal factors or treatments received; however, TCv7 was higher in the group referred as HR (P < .001). Our study showed that HR patients are more commonly referred secondary to family history but undergo similar treatments as those ROR. Accessibility to screening tools and education of risk factors, especially in minorities and those not otherwise being screened, may help better recognize HR.

Multidimensional Healthcare Access Barriers to Prostate-Specific Antigen Testing: A Nation-Wide Panel Study in the United States From 2006 to 2020.

Rising metastatic prostate cancer incidence has renewed debate regarding benefits of prostate-specific antigen (PSA) screening. Identifying barriers to accessing screening for individuals at high risk of lethal prostate cancer may slow this rise. We examined associations of access barriers with receipt of PSA testing, stratified by sociodemographic factors. We pooled data from male respondents to Behavior Risk Factor Surveillance Systems (BRFSS) surveys from 2006 to 2020. Questions related to affordability (insurance, cost of visits) and accommodation (regular primary care provider (PCP), physician recommending a PSA test) were considered as individual-level barriers. For availability, we linked provider density from the 2012 Area Health Resource File and estimated driving times to closest health facility within Micropolitan and Metropolitan Statistical Area (MMSA) using Google Earth Engine. These measures were used to compute a spatial accessibility index. We fit survey-weighted, covariate-adjusted logistic regression models to estimate associations of barriers with receipt of PSA within the past 2 years and examined effect modification by sociodemographic factors. There were 185,643 participants, of whom 73% were White, 11% were Black, 4% were Asian, and 11% were Hispanic. Physician recommendation was the strongest predictor of having a PSA test (aOR: 14.5, 95% CI: 13.6, 15.6). Not having a regular PCP (aOR: 0.29, 95% CI: 0.27, 0.31), insurance (aOR: 0.64, 95% CI: 0.58, 0.71), and prohibitive cost of care (aOR: 0.82, 95% CI: 0.75, 0.90) were associated with lower PSA testing. Access barriers were stronger predictors of PSA testing for Asian and White participants compared to other groups (Phet < 0.004 for insurance and regular PCP) and for those with college education compared to those without (Phet < 0.05 for insurance, perceived unaffordability). Physician recommendation was the strongest predictor of receipt of PSA testing, regardless of sociodemographic grouping. Future studies should consider access barriers jointly and across sociodemographic strata.

Human papillomavirus-based cervical screening and long-term cervical cancer risk: a randomised health-care policy trial in Sweden.

Human papillomavirus (HPV)-based cervical screening is a globally recommended public health policy. Randomised clinical trials find superior performance of primary HPV-based screening compared with cytology for preventing cervical cancer. However, additional evidence from real-world public health policies is needed. In preplanned secondary analysis of a randomised health-care policy trial in Sweden we aimed to evaluate which policy provided better protection against invasive cervical cancer, after two full rounds of screening. The organised cervical screening programme in the capital region of Sweden invited all women aged 30-64 years and eligible for screening to a randomised health-care policy trial of HPV-based versus cytology-based screening. During 2014-16, 395 725 eligible women were randomly assigned (non-concealed) to either policy and the invasive cervical cancer incidences over 8 years of follow-up were compared. Intention-to-screen analyses included all invited women and per-protocol analyses the women that attended baseline screening according to protocol. This trial is registered with ClinicalTrials.gov, NCT01511328. Women invited to HPV-based cervical screening had a 17% lower invasive cervical cancer risk compared with women invited to cytology (hazard ratio [HR] 0·83, 95% CI 0·70-0·98). Women participating in HPV-based screening had a 28% lower invasive cervical cancer risk compared with women participating with cytology (HR 0·72, 95% CI 0·54-0·95). Adverse events were a higher number of referrals to colposcopy with biopsy in the HPV policy (15 832 [7·5%] of 212 199 in intention to screen analyses and 9968 [9·0%] of 110 176 per protocol at baseline) than in the cytology policy (12 650 [6·9%] of 183 120 in intention to screen analyses, and 7179 [7·9%] of 90 821 per protocol at baseline). Women who were HPV-negative at baseline had invasive cervical cancer risks of 1·3 (95% CI 0·6-2·4) per 100 000 person-years, whereas the risk for women with normal cytology was 9·1 (6·7-11·8) per 100 000 person-years. HPV-positive women with negative cytology triage had invasive cervical cancer risks of 79·2 per 100 000 person-years and HPV 16 or HPV 18-positive women with negative cytology triage had risks of 318·2 per 100 000 person-years. This randomised policy trial found HPV-based screening to be superior for preventing invasive cervical cancer in the real-world setting. A single baseline HPV-negative test was associated with a very low invasive cervical cancer risk after 8 years. However, HPV positivity with negative cytology triage was associated with high invasive cervical cancer risks. Region Stockholm, Swedish Cancer Society, and European Union Horizon 2020.

High-risk histology endometrial cancer and mismatch repair status: The impact of histologic subtype and MLH1 hypermethylation on outcomes

High-risk histology endometrial cancer and mismatch repair status: The impact of histologic subtype and MLH1 hypermethylation on outcomes

Treatment patterns and outcomes of patients with stage I, high-risk endometrial cancer histologies

Treatment patterns and outcomes of patients with stage I, high-risk endometrial cancer histologies

Impact of the 2023 FIGO staging on a high-risk endometrial cancer cohort

Impact of the 2023 FIGO staging on a high-risk endometrial cancer cohort

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

Disease-free survival as a predictor of overall survival in patients with high-risk endometrial cancer receiving adjuvant therapy

Cancer and mortality risks among people with multiple sclerosis: A population-based study in Isfahan, Iran.

Multiple sclerosis (MS) and cancer present substantial global health challenges. Understanding cancer patterns among people with MS (PwMS) is crucial due to potential variations across demographics and geographic regions. Isfahan province in Iran, known for its high MS incidence ratio, offers a significant population for comprehensive studies on MS. In this study, we aim to investigate the association between risk of cancer and MS. Data on PwMS were collected utilizing the National Multiple Sclerosis Registry System of Iran (NMSRI), with diagnoses confirmed using McDonald criteria by neurologists specialized in MS. Cancer incidence was investigated using the Iranian National Population-Based Cancer Registry (INPCR) data, collected following international protocols. Descriptive statistics and regression analyses were employed to assess factors associated with cancer and mortality risks among PwMS. Survival analysis was conducted using Kaplan-Meier curves. Out of 10,049 PwMS, 123 were diagnosed with cancer, with an mean age at the time of cancer diagnosis being 40.41 years and a mean MS duration of 6.76 years. The majority had relapsing-remitting MS (81.2%), and Interferon-β was the most common disease-modifying therapy (DMT) (42.4%). Cancer incidence was 125.6 per 100,000 person-years, peaking at ages 60-64 (677.9 per 100,000 person-years). Receiving monoclonal antibody medications and older age were significantly associated with higher cancer risk (OR:1.542 (1.009-2.357), OR:1.033 (1.015-1.051), respectively). Female breast cancer had the highest incidence ratio among PwMS (40.17 per 100,000 person-years), followed by thyroid (18.38 per 100,000 person-years) and digestive system cancers (17.36 per 100,000 person-years). Breast cancer was the predominant cancer in women, while digestive system cancers were most common among men. Being male and having longer MS duration were linked to higher cancer mortality risk (HR: 2.683, 1.087, respectively). Cancer incidence among 10,049 people with multiple sclerosis was significant, especially in older individuals, with breast cancer being the most common. Male gender and longer MS duration were linked to higher cancer mortality risk.

Advancing prostate cancer detection: High-accuracy urine test distinguishes between high and low-risk cancers

Prostate cancer remains one of the leading causes of cancer-related deaths among men. The standard method for early detection involves measuring Prostate-specific antigen (PSA) levels in the blood, with elevated PSA levels prompting further diagnostic procedures, such as a prostate biopsy. While effective, biopsies can be painful and carry risks of complications such as fever and urinary tract infections. To reduce unnecessary biopsies, researchers have sought alternative diagnostic methods. In recent years, a urine test was developed for early-stage prostate cancer detection. However, this test struggled to differentiate between aggressive and slow-growing cancers, the latter of which often require minimal treatment and are managed through active surveillance. To address this limitation, scientists at Wunderkind University have significantly enhanced the urine test. By analysing the genomes of thousands of prostate cancer patients, they identified a panel of 16 genes detectable in urine that can effectively distinguish between high-risk and low-risk cancers. When applied to individuals with elevated PSA levels, this improved test demonstrated an impressive 97% accuracy in identifying advanced prostate cancer. This advancement holds great promise for reducing unnecessary biopsies and improving patient outcomes by accurately identifying those needing aggressive treatment versus those suitable for observation. This review paper will explore the development, validation, and clinical implications of this novel urine test, highlighting its potential to transform prostate cancer diagnostics and patient management.

Comprehensive Analysis of Prognostic Alternative Splicing Signatures in Tumor Immune Infiltration in Bladder Cancer.

Bladder cancer exhibits substantial heterogeneity encompassing genetic expressions and histological features. This heterogeneity is predominantly attributed to alternative splicing (AS) and AS-regulated splicing factors (SFs), which, in turn, influence bladder cancer development, progression, and response to treatment. This study aimed to explore the immune landscape of aberrant AS in bladder cancer and establish the prognostic signatures for survival prediction. Bladder cancer-related RNA-Seq, transcriptome, and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA). Gene set enrichment analysis (GSEA) was used to identify significantly enriched pathways of cancer-related AS events. The underlying interactions among differentially expressed genes (DEGs) and cancer-related AS events were assessed by a protein-protein interaction network. Univariate and multivariate Cox regression analyses were performed to identify crucial prognostic DEGs that co-occurred with cancer-related AS events (DEGAS) for overall survival. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was used to assess the efficiency of the prognostic signatures. The CIBERSORT algorithm was used to explore the abundance of immune infiltrating cells. A total of 3755 cancer-related AS events and 3110 DEGs in bladder cancer were identified. Among them, 379 DEGs co-occurred with cancer-related AS events (DEGAS), of which 102 DEGAS were associated with 14 dysregulated SFs. GSEA and KEGG analysis showed that cancer-related AS events were predominantly enriched in pathways related to immunity, tumorigenesis, and treatment difficulties of bladder cancer. Multivariate Cox regression analysis identified 8 DEGAS (CABP1, KCNN2, TNFRSF13B, PCDH7, SNRPA1, APOLD1, CX3CL1, and DENND5A) significantly associated with OS, and they were further integrated into the prediction model with good AUCs at 3-year, 5-year and 7-year ROC curves (all>0.7). Immune infiltration analysis revealed the significant enrichment of three immune cell types (B cells naïve, dendritic cells resting, and dendritic cell activated) in high-risk bladder cancer patients. This study not only unveiled comprehensive prognostic signatures of AS events in bladder cancer but also established a robust prognostic model based on survival-related DEGAS. These aberrant AS events, dysregulated SFs, and the identified 8 DEGAS may have significant clinical potential as therapeutic targets for bladder cancer.

Comparative small molecule screening of primary human acute leukemias, engineered human leukemia and leukemia cell lines.

Targeted therapeutics for high-risk cancers remain an unmet medical need. Here we report the results of a large-scale screen of over 11,000 molecules for their ability to inhibit the survival and growth in vitro of human leukemic cells from multiple sources including patient samples, de novo generated human leukemia models, and established human leukemic cell lines. The responses of cells from de novo models were most similar to those of patient samples, both of which showed striking differences from the cell-line responses. Analysis of differences in subtype-specific therapeutic vulnerabilities made possible by the scale of this screen enabled the identification of new specific modulators of apoptosis, while also highlighting the complex polypharmacology of anti-leukemic small molecules such as shikonin. These findings introduce a new platform for uncovering new therapeutic options for high-risk human leukemia, in addition to reinforcing the importance of the test sample choice for effective drug discovery.

The association between heart failure diagnosis and the incidence of cancer: a longitudinal analysis of the United Kingdom Biobank

Abstract Background Heart failure (HF) and cancer represent prevalent chronic conditions with a high burden of disease worldwide. Several studies have shown a high frequency of coexistence of these two entities, highlighting a potential bidirectional association. However, few longitudinal studies have explored whether patients with HF have a significantly increased risk of cancer and if comorbidity profiles affect this risk. Purpose To explore the association between incident HF diagnosis and cancer development in UK Biobank participants after adjustment by potential confounders. Methods We conducted a retrospective cohort study in UK Biobank. HF and cancer diagnoses were determined using diagnoses and patient reports. We evaluated breast, liver, lung, prostate, colorectal, uterus, and hematological cancer. Individuals with a history of HF or cancer diagnosed before the baseline assessment were excluded. The primary exposure was incident HF diagnosis after enrollment, and the primary outcome was incident cancer during follow-up. Multivariate Cox proportional hazard regression models using time-varying covariates were used to calculate hazard ratios (HR) for the explored associations with overall cancer and by major cancer type. A Bonferroni-corrected p-value &amp;lt; 0.003 was considered statistically significant to control for family-wise error rate. Results 476,652 patients were analyzed (mean age: 56.3 years; 57.8% females). Over a median follow-up of 13.7 years, 12,461 (2.6%) developed HF, and 34,452 (7.2%) were diagnosed with cancer. Incident HF was significantly associated with increased overall cancer risk (HR 1.34, 95% CI 1.22–1.48. p&amp;lt;0.001), as well as lung (HR 1.30, 95% CI 1.18–1.43), and hematological cancers (HR 1.54, 95% CI 1.25–1.91. p&amp;lt;0.001) (Figure). Conclusion Despite sharing multiple comorbidities and risk factors, incident HF remained significantly associated with a higher cancer risk even after multivariable adjustment by relevant confounders. Nevertheless, confounding bias and especially detection bias, cannot be ruled out in the present analysis. Further research is necessary to validate these findings and elucidate the mechanisms underlying this association.Figure

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.

Factors associated with actinic keratoses in people with albinism in the Albivoire program

Abstract Background People with albinism (PWA) face health inequalities partly due to barriers in accessing health care, consequently delaying the diagnosis of skin precancerous and cancerous lesions. Actinic keratoses (AK), are common precancerous lesions, indicating a high risk of skin cancer. Given the scarcity of research on skin cancer prevention among PWA in Africa, this study aimed to determine the prevalence and factors associated with AK in PWA followed in the Albivoire program. Methods This cross-sectional analytical study was conducted within the ongoing Albivoire program in Ivory Cost. Initiated in Ivory Coast in 2021, Albivoire is the largest comprehensive preventive and care initiative with and for PWA, offering medical consultation campaigns in dermatology, ophthalmology, and psychology. Dermatological records of consenting patients were analyzed. The prevalence (95%CI) of AK was estimated, and the associated factors assessed using logistic model. Results To date, a total of 1978 PWA received care across four regions (Abidjan, Bouaké, Korhogo and Man). Available data from 475 PWA were analyzed, among whom 247 (52%) were women. The median age was 14 years (interquartile range [IQR]: 7-25). Of these, 181 individuals (38.1%, 95% CI [33.7 - 42.6]) presented with actinic keratoses (AK). The median age of PWA with AK was 22 years (vs 11 years for without AK (p &amp;lt; 0.001). Among PWA with AK, 87.8% were daily exposed to sun (vs 12.2% for those exposed occasionally, p = 0.026). In the multivariate analysis, factors significantly associated with AK included age 22 years or older (vs age &amp;lt; 22 years, aOR=4.83, p &amp;lt; 0.001), the presence of ephelides (vs absence; aOR=2.08, p = 0.003) and presence of xerosis (vs absence aOR=4.88, p &amp;lt; 0.001). Conclusions This study highlights the high prevalence of AK in PWA in Ivory Cost, and identifies specific modifiable associated factors which should be targeted in global health strategies to prevent skin cancer among this vulnerable population. Key messages • Prevalence of skin precancerous lesions (actinic keratoses) in people with albinism in Ivory Cost is high (38%) and associated with modifiable risk factors. • Tailored public health interventions needed to prevent skin cancers in vulnerable populations, targeting lesions like xerosis, ephelides, and actinic keratoses through skin protection.

Application of classification tree to construct a predictive model for screening compliance among populations at high risk for early cancer in the upper digestive tract

Application of classification tree to construct a predictive model for screening compliance among populations at high risk for early cancer in the upper digestive tract

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.

Clinical Significance of Talin-1 and HER-2 Status in Different Types of Gastric Carcinoma

Background Talin-1 (TLN1) is crucial in cell migration, metastasis, and cancer development. This study evaluated Talin-1 expression and its clinical significance in gastric cancer (GC), along with human epidermal growth factor receptor-2 (HER-2) expression and its correlation with Talin-1. Methods Bioinformatics analysis assessed the potential prognostic value of Talin-1 and HER-2 in GC patients. The study included 223 GC patients (Signet Ring Cells and Intestinal subtypes) and 29 non-malignant tissue samples. Immunohistochemistry (IHC) on tissue microarray slides evaluated Talin-1 and HER-2 expression and clinical significance. Receiver operating characteristic (ROC) curves assessed their diagnostic value. Results Bioinformatics identified Talin-1 as a potential prognostic factor and HER-2 as an oncogene in GC. Talin-1 and HER-2 expression increased in SRC-type GC samples compared to non-malignant tissues. High cytoplasmic Talin-1 expression inversely correlated with tumor expansion and invasion in SRC-type GC. Increased HER-2 expression positively correlated with metastasis. ROC curves showed significant diagnostic values for both proteins. Conclusions Higher cytoplasmic Talin-1 expression is associated with less invasive tumor behavior, while increased membranous HER-2 expression is associated with metastasis in SRC-type GC. These findings suggest potential use in assessing diagnosis and screening high-risk cancer patients, particularly those with SRC-type GC.