{"title":"Harmonizing biomarker testing in NSCLC: The critical role of cytopathology in delivering comprehensive biomarker testing for patients with NSCLC","authors":"Sinchita Roy-Chowdhuri MD PhD, Haresh Mani MD","doi":"10.1002/cncy.70139","DOIUrl":"10.1002/cncy.70139","url":null,"abstract":"<p>The era of precision oncology has transformed the management of non-small cell lung cancer (NSCLC). The discovery of actionable biomarkers and the development of targeted therapies, immune checkpoint inhibitor therapies, and antibody–drug conjugates have transformed the clinical management of patients with NSCLC.<span><sup>1</sup></span> Therapeutic decisions increasingly depend on comprehensive molecular profiling and biomarker assessment based on the testing recommendations from clinical practice guidelines.<span><sup>2</sup></span> In a recent article in <i>Cancer</i>,<span><sup>3</sup></span> Patel and colleagues present a timely analysis of biomarker testing recommendations across major professional society guidelines and highlight an often-overlooked challenge in clinical decision-making: variability in guideline interpretation and implementation despite broad agreement on fundamental principles. The work, conducted through the American Cancer Society National Lung Cancer Roundtable Biomarker Consensus Committee, highlights an issue of growing relevance as the number of actionable biomarkers continues to expand and the complexity of testing strategies increases.</p><p>Using a modified RAND Appropriateness Method, the authors compared recommendations from the National Comprehensive Cancer Network (NCCN), American Society of Clinical Oncology (ASCO), and CAP/IASLC/AMP molecular testing guidelines.<span><sup>4-6</sup></span> The clinical scenarios used in the guideline comparisons centered around <i>who to test</i>, <i>what to test</i>, and <i>how/where to test</i>. Their findings demonstrate that although substantial concordance exists among contemporary guidelines, particularly between NCCN and ASCO, important differences in wording, scope, and framing may lead to variability in clinical practice. The CAP/IASLC/AMP guidelines were included in the initial review by the panel; however, unlike the NCCN and ASCO guidelines, which are regularly updated, the CAP/IASLC/AMP guidelines have not been updated since 2018, causing significant discordance in specific areas (for instance, the CAP/IASLC/AMP guidelines recommend only <i>EGFR, ALK, ROS1</i> for testing, whereas NCCN and ASCO recommend broad panel-based testing for <i>BRAF, HER2, RET, MET</i> exon 14 skipping, <i>NTRK</i>, and <i>KRAS</i> alterations in addition to <i>EGFR, ALK,</i> and <i>ROS1</i>). The authors did note that the CAP/IASLC/AMP guidelines are currently being updated and a comparison with the updated guideline could have significant changes to their conclusions.</p><p>One of the key findings in this study by Patel and colleagues is that even though NCCN and ASCO recommendations were concordant in nearly 90% of evaluated clinical scenarios, consensus among expert reviewers was achieved in only approximately half of these scenarios. This highlights how subtle differences in language can influence clinical decision-making and that concordance between guidelines does not necessar","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Hasan Bilal MD, Joanna Gibson MD, PhD, David Kim MD, Angelique W. Levi MD, Aziza Nassar MD, MPH, MBA, Handy Oen MBA, CT (ASCP), MB, Valentina Robila MD, PhD, Mauro T. Saieg MD, PhD, FIAC, Qiuying Shi MD, MS, Vanda F. Torous MD, Akkus Zeynettin PhD, Melissa M. Zhao MD, MS, Oscar Lin MD, PhD
{"title":"Leveraging large language models to enhance cytopathology: Opportunities, challenges, and future directions; a practical review from the ASC Clinical Practice Committee","authors":"K. Hasan Bilal MD, Joanna Gibson MD, PhD, David Kim MD, Angelique W. Levi MD, Aziza Nassar MD, MPH, MBA, Handy Oen MBA, CT (ASCP), MB, Valentina Robila MD, PhD, Mauro T. Saieg MD, PhD, FIAC, Qiuying Shi MD, MS, Vanda F. Torous MD, Akkus Zeynettin PhD, Melissa M. Zhao MD, MS, Oscar Lin MD, PhD","doi":"10.1002/cncy.70134","DOIUrl":"10.1002/cncy.70134","url":null,"abstract":"<p>Large language models (LLMs) and vision-language models represent a fundamentally different category of artificial intelligence (AI) compared to prior image analysis approaches in digital pathology, which have largely been based on convolutional neural network architectures. This review from the American Society of Cytopathology Clinical Practice Committee examines the current evidence for LLM and vision-language model applications in cytopathology, including structured reporting, diagnostic assistance, quality control, education, and workflow integration. The distinction between applications with preliminary evidence and those that remain hypothetical is described. A detailed assessment of the challenges that must be addressed before clinical deployment, including hallucination risk, limited explainability, bias, data privacy, validation gaps, and infrastructure barriers is discussed. A review of the regulatory landscape in the United States and European Union as it applies to AI-enabled software as a medical device is provided. Recommendations addressing cytopathology-specific benchmarks, multi-institutional validation, transparent governance, and incremental deployment beginning with low-risk applications are suggested. In the current environment, LLMs have the potential to augment cytopathology practice, but responsible adoption requires rigorous validation and sustained collaboration among cytopathologists, AI researchers, and regulatory bodies.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148721207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic performance of artificial intelligence models trained on scattered single-cell images is not preserved for hyperchromatic crowded cell groups in cervical cytology","authors":"Shinichi Tanaka CT, PhD, Yudai Yamamoto CT, Konatsu Yokota MT, Tamami Yamamoto CT, Norihiro Teramoto MD, PhD","doi":"10.1002/cncy.70140","DOIUrl":"10.1002/cncy.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Deep learning has shown promising performance in cervical cytology; however, many studies have relied on presegmented single-cell images rather than the more complex morphologic patterns encountered in routine practice. Here, scattered cells were defined as isolated or dissociated, nonoverlapping single cells. This study quantified the performance loss when artificial intelligence (AI) models trained on these cells were applied to hyperchromatic crowded cell groups (HCGs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Binary convolutional neural network models were developed to differentiate between negative for intraepithelial lesion or malignancy cases and high-grade squamous intraepithelial lesion cases via a scattered cell data set composed of institutional and public liquid-based cytology images. The scattered cell data set comprised 101 cases, with 1062 images; the independent HCG data set comprised 48 cases, with 330 images. ResNet-50, ResNeXt-50, ConvNeXt-Tiny, EfficientNet-B3, VGG-19, and GoogLeNet were trained on scattered cell images, and then directly applied to HCGs without retraining or threshold recalibration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All models showed high performance on the scattered cell data set, with the area under the receiver operating characteristic curve (AUC) ranging from 0.950 to 0.996. When directly applied to HCGs, performance declined across all architectures, with the AUC ranging from 0.385 to 0.683. ConvNeXt-Tiny showed the highest AUC on HCGs (0.683); however, this remained substantially lower than its performance on scattered cells (0.996). For all architectures, the AUC was significantly lower on HCGs than on the scattered cell data set.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Binary AI models trained on scattered cell images achieved excellent discrimination in the original setting but their performance was not preserved when directly applied to HCGs. These findings underscore the need for direct validation and HCG-aware model design in cervical cytology AI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Feasibility of routine clinical liquid-based cytology for lung cancer compact panel testing","authors":"Yoshiki Shinomiya PhD, Kanako C. Hatanaka MD, PhD, Asami Okumura MS, Ayae Nange MS, Mamiko Yamamoto MS, Manabu Azuma, Katsuji Marukawa PhD, Yuko Ishida, Tomohiro Shimizu MS, Ryoko Watanabe, Yamato Hashimoto, Mitsuharu Abiko, Yoshiharu Sato PhD, Jun Sakakibara-Konishi MD, PhD, Tatsuya Kato MD, PhD, Shinya Tanaka MD, PhD, Yutaka Hatanaka PhD","doi":"10.1002/cncy.70135","DOIUrl":"10.1002/cncy.70135","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The Lung Cancer Compact Panel (cPANEL) is a recently approved highly sensitive multiplex gene panel in Japan that supports both DNA- and RNA-based next-generation sequencing. Although cytological specimens are acceptable for cPANEL, unfixed cell pellets or dedicated preservation tubes are typically recommended. However, evidence remains limited regarding whether residual liquid-based cytology (LBC) cell suspensions prepared for routine cytological diagnosis can be used directly for cPANEL testing without dedicated molecular preservation or additional preanalytical processing. In this study, we evaluated the feasibility of applying LBC specimens that are widely used in contemporary clinical practice to cPANEL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed DNA and RNA quality in 69 clinical LBC specimens. Among these, 51 specimens containing non-small cell lung cancer cells with previously determined driver alteration status were subjected to cPANEL testing to evaluate assay concordance with clinical companion diagnostic results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DNA integrity was generally well preserved (DNA Integrity Number [DIN]: 6.2 ± 1.5). In contrast, RNA integrity showed greater variability (DV200: 16.4 ± 12.1%). ThinPrep-fixed specimens demonstrated lower DIN and DV200 values compared with CytoRich Red-fixed specimens. Although all samples successfully passed the DNA-based cPANEL assay, six cases (11.8%) failed the RNA-based assay, with RNA yield being a major contributing factor. Among the 46 evaluable specimens, concordance was 95.7% and sensitivity was 92.3%, or 88.9% including RNA module failures as cPANEL-negative.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>With appropriate fixative selection and adequate cellularity, cPANEL using clinical LBC specimens may serve as a practical diagnostic platform. We demonstrated that routine LBC specimens can be directly applied to cPANEL without special preanalytical processing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 9","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13444665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Screening efficiency over experience: Rapid target detection in low-power field as a modifiable cognitive biomarker for diagnostic accuracy in digital cytology","authors":"Naoya Abe CT, PhD, Yukari Nishimura CT, PhD, Kazuya Yamashita CT, PhD, Takushi Kawamorita PhD, Yusuke Takatori PhD, Yoshiki Murakumo MD, PhD, Reiko Furuta CT, PhD","doi":"10.1002/cncy.70132","DOIUrl":"10.1002/cncy.70132","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Traditionally, cytology expertise has been equated with professional experience. However, the transition to whole-slide imaging and artificial intelligence (AI) necessitates a shift from exhaustive screening to rapid verification. The goal of this study was to identify cognitive biomarkers associated with diagnostic accuracy and evaluate their modifiability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In phase 1, 100 cytotechnologists with 1–40 years of experience diagnosed 30 digital cytology images using eye-tracking. Gaze metrics across areas of interest were analyzed via nominal logistic regression. In phase 2, 28 students completed a 3-month cytotechnology training program. Pre- and post-training metrics were compared using Wilcoxon signed-rank tests and effect sizes (<i>r</i>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Years of experience showed no significant correlation with diagnostic accuracy (<i>r</i> = 0.189, <i>p</i> > .05). Multivariate analysis identified shorter total fixation duration on the “low-power field (LPF) main object” as the sole independent predictor of high accuracy (<i>p</i> = .045), suggesting a “pop-out” detection mechanism. Experience correlated only with attention to sample information. Post-training (phase 2), students' time to first target fixation decreased substantially (<i>r</i> = 0.62–0.86), whereas their attention to normal backgrounds decreased (<i>r</i> = 0.71). This demonstrates the rapid acquisition of expert-like selective attention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Efficiency in LPF target detection is a better predictor of diagnostic accuracy than professional experience. This study identifies LPF efficiency as a modifiable cognitive biomarker that can be acquired through standard education. Quantifying these gaze metrics provides an objective means of evaluating skill development and readiness for the AI era.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Much promise, scant evidence for multicancer early detection tests","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70128","DOIUrl":"10.1002/cncy.70128","url":null,"abstract":"<p>In a provocative ad that debuted during last February’s Super Bowl, San Francisco–based telehealth company Hims & Hers asserted, “Rich people live longer,” and then suggested how everyone else might “get the best of everything” to boost their own longevity. Among the company’s products, the ad pitched “early cancer detection through a simple blood test” and showed an African American man receiving a smartphone notification—“No cancer signal detected”—and then leaning his head back with a smile of evident relief. Less than 2 weeks later, however, the maker of that aggressively marketed multicancer early detection (MCED) test reported far less reassuring news: It had failed to achieve its primary endpoint of shifting detection away from late-stage cancer diagnoses in a randomized controlled clinical trial in the United Kingdom.<span><sup>1</sup></span></p><p>The $949 MCED test, which is called Galleri and was developed by Menlo Park, California–based health care company GRAIL, is designed to detect more than 50 cancers by identifying circulating cancer-specific biomarkers on bits of cell-free DNA. From the biomarker data, proprietary machine learning algorithms indicate the likely tissue of origin or cancer signal of origin. At the annual meeting of the American Society of Clinical Oncology in May, leaders of the large Galleri trial pointed to several bright spots, including a shift away from later diagnoses as the trial progressed, including a 14% reduction in stage IV diagnoses for a subset of 12 preselected cancers after 3 years of screening.<span><sup>2</sup></span> Even so, the disappointing overall results raised new questions about a rapidly emerging kind of liquid biopsy sold under a regulatory loophole that does not require the laboratory-developed tests to be reviewed by the US Food and Drug Administration.</p><p>Many cancer researchers agree that the MCED tests, if proven, could help to fill a huge blind spot in cancer screening. “Despite the limitations, the promise is really great,” says Carmen Guerra, MD, MSCE, a professor of medicine and of biostatistics and epidemiology at the University of Pennsylvania in Philadelphia. The challenge has been establishing the tests’ bona fides <i>after</i> they have been on the market (Galleri has been sold since 2021) amid uncertainty over the clinical significance of some trial measures as well as <i>how</i> the tests are performed. “The big concern from primary care is we don’t know if these work,” says Richard Hoffman, MD, MPH, an emeritus professor of medicine at the University of Iowa in Iowa City. “So you’re going to be spending a lot of money going down these pathways of diagnostic testing and treatment without knowing that there’ll be any benefit.”</p><p>The current cancer screening paradigm, Dr Guerra says, suffers from a lack of established tests for the vast majority of cancer types. Identifying them through more swabs, scans, x-rays, or other traditional methods is not feasible o","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Standardizing the unstandardized: The international system reaches the cerebrospinal fluid","authors":"Ashish Chandra MD","doi":"10.1002/cncy.70133","DOIUrl":"10.1002/cncy.70133","url":null,"abstract":"<div>\u0000 \u0000 <p>Two new studies now make the most substantial case yet that the framework of the International System for Reporting Serous Fluid Cytopathology can be carried across the biologic boundary to include cerebrospinal fluid, and current work on the second edition of the system will address cerebrospinal fluid for the first time as a special category of body fluid—an expansion the international community has explicitly endorsed. The contributions of these authors will stand among the empirical foundations on which a coherent, cerebrospinal fluid–specific—and, ultimately, fluid-agnostic—reporting standard can be built.</p>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Implementation and impact of primary HPV testing in cervical cancer screening: Historical perspectives and institutional experience at a large academic medical center","authors":"Rebecca A. Yoda MD, Eric C. Huang MD, PhD","doi":"10.1002/cncy.70129","DOIUrl":"https://doi.org/10.1002/cncy.70129","url":null,"abstract":"<p>Recognition of high-risk human papillomavirus (HPV) as the etiologic agent in nearly all cervical cancers has fundamentally reshaped screening strategies, driving the development and adoption of highly sensitive molecular HPV assays. Over the past several decades, cervical cancer screening guidelines have shifted from primarily cytology-based approaches toward HPV-based modalities, with primary HPV testing now recommended as the preferred method by the American Cancer Society and anticipated to be similarly endorsed by the United States Preventive Services Task Force. This article traces the evolution of cervical cancer screening, from the original Papanicolaou test to current guideline recommendations, and discusses the logistical requirements for transitioning to a primary HPV screening system, including triage strategies for HPV-positive cases. The authors additionally present an institutional experience of initiating primary HPV testing, highlighting its impact on cytopathology laboratory workflow and specimen volumes.</p>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148534274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gregor Barth MD, Stefan Koch MD, Thorsten H. Ecke MD
{"title":"Keratin 17 immunocytochemistry in urine cytology for urothelial carcinoma detection: Diagnostic performance and interobserver agreement in a prospective real-world cohort","authors":"Gregor Barth MD, Stefan Koch MD, Thorsten H. Ecke MD","doi":"10.1002/cncy.70130","DOIUrl":"10.1002/cncy.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Urine cytology is recommended for noninvasive detection of urothelial carcinoma (UC) but shows limited sensitivity, particularly in low-grade disease. Keratin 17 (K17) has emerged as a promising immunocytochemical marker. This study evaluated the diagnostic performance and interobserver agreement of K17 in a routine setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This prospective cross-sectional study included 184 urine samples from patients undergoing diagnostic evaluation for suspected UC. K17 immunocytochemistry was performed with a fully automated platform and independently evaluated by two blinded raters. Cytology was classified according to The Paris System for Reporting Urinary Cytology. UC status was determined by histology when available or by follow-up and multidisciplinary assessment. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analysis; interobserver reliability was assessed with the Cohen κ and intraclass correlation coefficient (ICC). Multivariable logistic regression evaluated combined diagnostic approaches.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>K17 expression was significantly higher in UC than in non-UC samples (<i>p</i> < .001). Across raters, area under the ROC curve (AUC) values ranged from 0.68 to 0.71. Sensitivity was 52.9%–65.9%, with a specificity of 73.7%–82.8%. Sensitivity ranged from 45.5% to 54.5% for low-grade tumors and from 57.7% to 73.1% for high-grade tumors. In stage-based analyses, sensitivity was 49.2%–61.5% for non–muscle-invasive UC and 65%–80% for muscle-invasive UC. Combining K17 with cytology numerically improved diagnostic discrimination (AUC value, 0.76; 95% CI, 0.69–0.83). Interobserver agreement was moderate to substantial (κ = 0.684; ICC, 0.653). Limitations included single-center design, partial histological verification (81%), and post hoc optimized cutoffs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>K17 immunocytochemistry is a reproducible adjunct to urine cytology, with moderate diagnostic performance. It may warrant further evaluation as an adjunctive marker, particularly in low-grade and cytologically equivocal cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 8","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148410463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New progress in addressing cancer pain","authors":"Bryn Nelson PhD, William Faquin MD, PhD","doi":"10.1002/cncy.70118","DOIUrl":"10.1002/cncy.70118","url":null,"abstract":"<p>Although pain has long been recognized as a common feature of both cancer and cancer treatments, efforts to recognize and resolve it have faltered in part because of fragmented care, a lack of objective measurements, and limited options for mitigating moderate to severe pain. Recent studies have provided reason for optimism by reframing cancer pain as a dynamic, multifactorial phenomenon with diverse and potentially modifiable contributors; by clarifying some of its mechanistic causes; and by expanding the palette of possible interventions.</p><p>The traditional touch-a-hot-stove understanding of pain viewed the sensation as a warning: a protective mechanism to discourage pain-causing actions. Subsequent research, however, determined that this view of pain, called nociceptive, is fundamentally different from a second type, neuropathic, in which damage or disease results in malfunctioning nerves and a pain sensation often described as burning or tingling. Although opioid drugs are often effective in treating nociceptive pain, they are far less useful for treating neuropathic pain.</p><p>Recent studies have added further nuance with the recognition that biological, psychological, and social factors can influence pain perception; this observation has led to what is called the biopsychosocial model of pain. “I think we really started to recognize then that there are all of these different influences in the way that we experience pain, both in its intensity and also in its functional impairments, like how it affects our lives,” says Hailey Bulls, PhD, an assistant professor of anesthesiology and perioperative medicine at the University of Alabama at Birmingham.</p><p>Even so, she says that the multifactorial model does not always take into account the timing and ebb and flow of cancer pain–influencing factors. To help to fill the gaps, Dr Bulls and her collaborators created a new model for conceptualizing cancer pain through three interconnected phases: “predisposing factors that increase cancer pain risk, precipitating factors that trigger cancer pain onset, and perpetuating factors that sustain or exacerbate cancer pain over time.”<span><sup>1</sup></span> The new 3P-CP model, the researchers suggest, “has the potential to guide comprehensive assessment, risk mitigation, prevention, and intervention strategies—supporting efforts to deliver the right targeted and tailored treatments, to the right patients, at the right time.”</p><p>Newly diagnosed patients, for example, may have predisposing factors such as physical or mental health conditions that could increase their pain. Cancer is a major precipitating factor for pain, of course, but so are many cancer treatments—particularly ones with higher doses or longer durations. Physical inactivity, sleep disturbances, and medication dependencies, among other contributors, can all act as perpetuating factors that worsen the intensity of pain or prolong it.</p><p>The shift in how to think about cancer pa","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"134 7","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}