Search Results (1,316)

Background and Clinical Significance: Lymph node metastases from carcinoma of unknown primary origin (CUP) are a rare and diagnostically challenging entity, particularly when arising from thoracic malignancies with atypical clinical presentations. This study aims to illustrate the essential nature of multidisciplinary integration, with a particular emphasis on the role of the pathologist in identifying occult thoracic tumors. Case Presentation: We report three cases of patients presenting with cervical or systemic lymphadenopathy as the initial clinical manifestation. Comprehensive diagnostic workups included advanced imaging (CT, MRI, and PET), comprehensive histopathological analysis, and next-generation sequencing of circulating tumor DNA. Case one and case two were diagnosed as occult primary non-mucinous lung adenocarcinomas, based on the integration of morphological features and immunohistochemical co-expression of TTF-1 and Napsin A, despite the absence of identifiable lung lesions. One case harbored an ALK rearrangement, guiding effective targeted therapy with alectinib. Case three involved metastatic pleural epithelioid mesothelioma, which presented with systemic lymphadenopathy and was initially misclassified as metastatic adenocarcinoma. Diagnosis was confirmed by the loss of BAP1 expression by immunohistochemistry and the detection of a BAP1 S160fs*1 mutation, emphasizing the role of molecular pathology. Conclusions: Lymphadenopathy as the first manifestation of thoracic malignancy is a rare but clinically significant occurrence. In such atypical presentations, pathologists play a pivotal role in diagnosis, often leading the process when clinical or radiological clues are minimal or absent. Accurate histopathological assessment is essential to establish a correct diagnosis and guide appropriate therapy. A multidisciplinary approach remains the cornerstone of diagnostic precision in CUP cases. Full article

Background and Objectives: Positron emission tomography with 18F-FDG (PET-CT) provides a quantitative measure of tumor metabolic activity through the maximum standardized uptake value (SUVmax) of lung tumors—a measure of metabolic activity that may have prognostic value in non-small cell lung cancer (NSCLC). This study evaluated whether preoperative tumor SUVmax predicts outcomes in resected NSCLC. Materials and Methods: This single-center retrospective study included 209 consecutive patients with resected NSCLC who had preoperative FDG PET-CT. SUVmax of the primary tumor was recorded, and patients were stratified into low- and high-SUVmax groups to evaluate survival outcomes. Results: Median age was 62 years and 77% were male. Histologic subtypes were adenocarcinoma (44%), squamous carcinoma (43%), and others (13%), with stage I–III distribution of 39.7%, 33.5%, and 26.8%, respectively. SUVmax demonstrated moderate discrimination for mortality (AUC = 0.652), with an optimal cutoff of 11.14. Patients with SUVmax ≥ 11.14 had significantly worse OS and DFS. However, on multivariate analysis, SUVmax was not an independent predictor of outcomes, while extracapsular invasion (OS) and adjuvant chemotherapy (DFS) remained significant. Conclusions: In this cohort of resected NSCLC, high preoperative SUVmax (≥11.14) was associated with more advanced tumor stage and worse OS/DFS but was not an independent prognostic factor after accounting for other variables. Tumor invasiveness and use of adjuvant therapy were stronger outcome predictors. Preoperative SUVmax may help identify high-risk patients when considered alongside established clinicopathologic factors. Full article

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. App^NL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD. Full article

Background/Objectives: Small-cell prostate cancer (SCPC) is a rare, aggressive variant of prostate cancer with poor prognosis, arising “de novo” or through lineage plasticity from conventional adenocarcinoma under androgen receptor-targeted therapies. Characterized by low PSA levels despite high tumor burden and visceral metastases, SCPC poses diagnostic challenges with conventional and PSMA-targeted imaging due to variable tracer uptake. This narrative review aims to evaluate the role of PET/CT tracers in clinical and preclinical settings for SCPC diagnosis, staging, and management. Methods: A systematic literature search was conducted on PubMed and Scopus up to December 2025 using terms “PET OR positron emission tomography AND prostate OR prostatic AND small-cell NOT non-small-cell”. Eight studies (five clinical, three preclinical) on the role of PET/CT imaging in SCPC were included and analyzed for study design, population, tracers, and findings, with comparative evaluation of diagnostic performance across PET tracers. Results: Clinical studies showed that ¹¹C-choline detects progression at low PSA but misses SCPC; ¹⁸F-FDG exhibited a high SUVmax value for distinguishing SCPC from adenocarcinomas with neuroendocrine differentiation, predicting poor survival; ⁶⁸Ga-DOTATATE identified NEPC/SCPC with promising prognostic/therapeutic value for selected cases. Preclinical models evaluated ⁸⁹Zr-tracers targeting DLL3 or CDCP1 (an antigen expressed in aggressive neuroendocrine tumours) and ¹⁸F-BnTP (a target of mitochondrial activity) in SCPC subtypes, focusing on translational imaging. Conclusions: From this review, although still based on limited literature evidence and mostly derived from retrospective and small SCPC sub-cohorts,¹⁸F-FDG PET/CT currently appears as the most reliable tracer for SCPC, aiding tumor detection and prognostication when PSMA/choline imaging fails. In the preclinical setting, DLL3/CDCP1-targeted agents emerge as promising theranostics tools. Multimodal imaging approach and prospective trials are needed for standardization and patient-based SCPC management. Full article

Background and Clinical Significance: Histiocytic sarcoma is a rare and aggressive hematopoietic malignancy, which is particularly uncommon in the head and neck region and exceedingly rare within lymph nodes associated with salivary glands. The present study aims to describe the clinical, radiologic, histopathologic, and immunophenotypic features of a primary histiocytic sarcoma, arising in a lymph node within the submandibular gland, and to highlight the diagnostic challenges and management considerations through a correlation with the existing literature. Case presentation: This case report was conducted according to the CARE guidelines. A 93-year-old male presented with a progressively enlarging mass at the right submandibular region. Clinical examination, magnetic resonance imaging, and fine-needle aspiration cytology were performed, raising suspicion for a malignancy. The patient underwent surgical excision of the right submandibular gland with limited level I_b lymph node dissection. Histopathological evaluation combined with an extensive immunohistochemical panel established the diagnosis of histiocytic sarcoma. The tumor was composed of pleomorphic epithelioid and spindle-shaped cells with marked cytologic atypia and high mitotic activity. Immunohistochemistry demonstrated strong positivity for histiocytic markers (CD163, CD68, CD14) and negativity for epithelial, lymphoid, and dendritic cell markers, allowing for the exclusion of major differential diagnoses. The proliferative index (Ki-67) was approximately 90%, indicating aggressive biological potential. FDG PET-CT performed two months after surgery showed no evidence of residual, regional, or distant disease. Considering the localized presentation and the patient’s advanced age, no adjuvant therapy was administered. During follow-up, no evidence of recurrence or disease progression was observed. Conclusions: Primary histiocytic sarcoma involving a lymph node within the submandibular gland is extremely rare and may clinically and cytologically mimic other malignancies. Accurate diagnosis relies on comprehensive immunohistochemical evaluation and exclusion of phenotypic mimickers. A review of previously reported cases of cervical lymph node histiocytic sarcoma demonstrated an age range from 35 to 80 years, with a male predominance and a higher incidence in Asian countries. Most cases presented with localized cervical lymph node disease. Surgical excision was the most commonly applied treatment, and was frequently associated with favorable outcomes, with several patients remaining disease-free during follow-up periods ranging from 24 to 48 months. The accumulation of additional well-documented cases is essential to improve diagnostic accuracy and guide evidence-based treatment strategies for this uncommon entity. Full article

Cell-based immunotherapies require noninvasive tools that can quantify the migration, biodistribution, and persistence of administered immune cells. This review focuses primarily on oncologic immune cell therapy, while also considering selected inflammatory disease models in which immune-cell trafficking is biologically relevant. We critically compare direct radionuclide labeling, sodium iodide symporter (NIS)-based reporter gene imaging, radionuclide-integrated nanoplatforms, and Cerenkov-based hybrid optical conversion strategies. Direct labeling with agents such as [⁸⁹Zr]Zr-oxine, [¹¹¹In]In-oxine, and [⁹⁹ᵐTc]Tc-HMPAO enables early positron emission tomography (PET)/single-photon emission computed tomography (SPECT) biodistribution assessment, usually within hours to several days after cell administration. NIS reporter imaging with [¹²⁴I]NaI, [¹²³I]NaI, [⁹⁹ᵐTc]TcO₄⁻, or [¹⁸F]TFB supports repeated viability-dependent imaging, because signal generation depends on active transporter expression in living engineered cells. Radionuclide-integrated gold nanoplatforms can improve intracellular retention and offer theranostic potential through combined imaging, photothermal, radiotherapeutic, or immunomodulatory functions. We further discuss PET/SPECT balance, radiopharmaceutical nomenclature, nanoparticle stabilization, ethical aspects of genetic modification, tumor-on-a-chip systems for preclinical testing, and limitations of narrative evidence synthesis. Together, these platforms provide complementary strategies for image-guided immune cell therapy, with translational relevance for patient selection, treatment optimization, safety monitoring, and oncology practice. In conclusion, NIS-centered nuclear imaging and radionuclide-integrated nanoplatforms represent complementary, clinically actionable tools for quantitative immune-cell tracking, therapeutic optimization, and safety monitoring in translational oncology and inflammatory disease research. Full article

Background: Accurate staging is vital for optimizing outcomes in pediatric rhabdomyosarcoma (RMS). While [¹⁸F]-FDG PET/CT is increasingly utilized, its specific impact on clinical management and its prognostic value compared to conventional imaging (CI) require further evaluation. Methods: In this retrospective single-center study, we reviewed 56 pediatric patients with RMS who underwent [¹⁸F]-FDG PET/CT at our center. Imaging findings were compared with CI (CT/MRI) and correlated with clinical management and survival outcomes. Results: In the total cohort (n = 56), PET/CT demonstrated high concordance with CI for nodal assessment, with an apparent sensitivity of 89.5% and specificity of 94.6%. PET/CT identified skeletal metastases in 5 patients (8.9%) and correctly characterized suspicious pulmonary nodules in one case, though it failed to detect a 0.6 cm lung nodule visualized on chest CT. Notably, PET/CT findings directly altered clinical management in 16.1% of patients (n = 9), primarily through radiotherapy adjustments, including field expansions (n = 4), field reductions (n = 3), and the initiation of previously unplanned radiotherapy (n = 2). At a median follow-up of 33.3 months, an exploratory analysis showed that patients with an SUVmax ≥3.6 had a lower 3-year EFS (57.6% vs. 71.6%; p = 0.51) and OS (60.4% vs. 71.6%; p = 0.63); neither comparison reached statistical significance. Conclusion: [¹⁸F]-FDG PET/CT is a powerful adjunct in pediatric RMS staging, particularly for nodal and skeletal evaluation. Its ability to refine radiotherapy planning in nearly one-sixth of cases underscores its clinical utility. SUVmax is not a validated prognostic or predictive biomarker in pediatric RMS; prospective, adequately powered multicenter studies, ideally incorporating volumetric PET parameters, are needed before any role in risk-stratified therapy can be defined. Full article

Cardiovascular toxicity has emerged as a major determinant of long-term outcomes in cancer survivors as advances in oncologic therapies continue to improve survival. Conventional cardiac surveillance strategies predominantly rely on functional and structural changes, often identifying myocardial injury after clinically significant damage has occurred. The aim of this narrative review is to critically evaluate the role of nuclear imaging in advancing precision cardio-oncology by enabling earlier, mechanism-based detection and characterization of cancer therapy-related cardiotoxicity. We summarize current clinical applications of PET- and SPECT-based imaging, examine molecular and tracer-level innovations, and discuss emerging hybrid imaging and analytic approaches relevant to individualized cardiovascular risk stratification. Current literature indicates that nuclear imaging provides unique insights into myocardial perfusion, metabolism, inflammation, and microvascular dysfunction, facilitating detection of subclinical injury across diverse anticancer therapies, including anthracyclines, targeted agents, and immune checkpoint inhibitors. By integrating molecular imaging with conventional modalities, nuclear techniques support more personalized surveillance and management strategies. This narrative review highlights nuclear imaging as an emerging complementary modality within precision cardio-oncology supporting earlier detection and risk stratification, and outlines future directions required to optimize its clinical integration and impact on cardiovascular outcomes across the cancer care continuum. Full article

Prostate cancer (PCa) progression and treatment resistance are driven by tumor-intrinsic mechanisms and adaptive remodeling of the tumor microenvironment, in which cancer-associated fibroblasts (CAFs) play a crucial role. Although CAF biology is increasingly recognized, a major translational gap remains: CAFs are highly heterogeneous, and comprise distinct functional states with divergent effects on disease progression, immune regulation, and therapeutic resistance. To bridge this gap, we synthesize evidence from single-cell and spatial transcriptomic studies, tissue-based pathology, liquid biopsy assays, and molecular imaging to construct an evidence-tiered, decision-oriented translational framework that connects stromal mechanisms, translational measurement strategies, and therapeutic interventions in PCa. Single-cell and spatial transcriptomic analyses have consistently identified multiple CAF programs, including matrix-remodeling, inflammatory, immunoregulatory, antigen-presenting, and therapy-imprinted states, each with distinct functional outputs and clinical correlates. Tissue-based readouts, including reactive stromal grade (RSG) and fibroblast activation protein (FAP) immunohistochemistry, provide practical proxies for stromal activation and correlate with disease-specific mortality and imaging phenotypes. Circulating CAFs (cCAFs) represent an emerging liquid biopsy modality for longitudinal stromal monitoring, although technical standardization is required before clinical implementation. FAP-targeted PET imaging and emerging dual prostate-specific membrane antigen (PSMA)/FAP-targeted theranostic strategies provide noninvasive tools for patient selection and response assessment, particularly in PSMA-discordant or tracer-heterogeneous disease. Androgen receptor (AR)-targeted therapy can reprogram stromal states toward resistance-promoting circuits, highlighting the dynamic and plastic nature of the CAF compartment. A state-based CAF framework organizes stromal biology into testable translational hypotheses rather than immediate clinical standards. RSG and FAP-based tissue or imaging readouts are practical markers of stromal activation, whereas spatial CAF-immune signatures and cCAF assays remain investigational and require assay harmonization and prospective validation. Future trials should pre-specify stromal biomarkers as enrichment or pharmacodynamic variables when matched to the intervention and should avoid treating CAFs as a uniform therapeutic target. Full article

Animal-assisted interventions can support emotional well-being and social engagement, but their use may be limited by allergies, infection risks, and animal-handling requirements. As a scalable alternative, artificial intelligence-based pet therapy, including socially assistive and robotic pets, has been introduced in health care and community settings. This systematic review, conducted in accordance with PRISMA guidelines, searched PubMed, CINAHL Ultimate/MEDLINE, Scopus, Web of Science, and SAGE for studies published between 2014 and 2025 that evaluated the reported effects of AI-based pet therapy on patient outcomes. Of the 584 records identified, 27 studies met the inclusion criteria after duplicate removal and screening. Most studies involved older adults with dementia, although children, veterans, and community-dwelling adults were also represented. Across studies, AI-based pet therapy was associated with reduced agitation, anxiety, stress, and pain, as well as improved mood, communication, and social engagement. PARO was the most frequently studied robotic pet, and interventions were typically delivered 1–3 times weekly for 30–60 min over 4–12 weeks. Overall, AI-based pet therapy appears to be a promising complementary non-pharmacological approach, particularly for people with dementia and hospitalized children, although stronger evidence from larger, more standardized, and longer-term studies is still needed. Full article

The evaluation of therapeutic response is essential in disease monitoring both for disease status and treatment efficacy in inflammatory bowel disease. Here, we focused on the use of positron emission tomography directed towards granzyme B, a serine protease released by activated cytotoxic T cells and natural killer cells, to evaluate the dynamics of therapeutic response in a colitis model. The goal was to explore the use of granzyme B positron emission tomography as a non-invasive biomarker to monitor disease activity and therapeutic response across several treatments in a dextran sulfate sodium-induced colitis model. C57BL/6 interleukin-10 knockout mice were divided into five groups, including a negative control, positive control and three treatment arms (antitumor necrosis factor, prednisolone, and anti-interleukin-23). The negative control group received regular water, while all other groups were induced with colitis via 3% DSS water for 1 week followed by normal water. Treatments were initiated after colitis was induced (anti-TNF antibody, prednisolone, or anti-IL-23 antibody). Positron emission tomography/computed tomography imaging with 68Ga-NOTA-GZP was performed at baseline (after colitis induction, before therapy), and at 1 and 2 weeks after treatment initiation. Histological analyses were also performed at 1 and 2 weeks after treatment initiation. Gzmb expression and histological changes were also assessed with immunofluorescence staining and bulk ribonucleic acid sequencing. Gzmb-targeted PET imaging revealed distinct longitudinal patterns of colonic tracer uptake related to treatment response. In positive control mice with DSS colitis (no treatment), bowel uptake of ⁶⁸Ga-NOTA-GZP increased significantly from baseline to week 2. Anti-TNF treatment reduced granzyme B positron emission tomography uptake significantly at week 2, approaching levels seen in negative controls. In prednisolone-treated mice, ⁶⁸Ga-NOTA-GZP uptake decreased at week 1 but rose significantly by week 2 but still was in normal range. Anti-IL-23 therapy produced a significantly elevated Gzmb PET signal at week 1, followed by a significant decline by week 2 of treatment. The imaging trends were corroborated by tissue analyses and IF staining for Gzmb, which revealed no colonic expression in negative controls and strong Gzmb elevation in positive controls and the prednisolone group but a decreased Gzmb signal in the anti-TNF and late anti-IL-23 groups. Bulk RNA sequencing also supported these findings, with Gzmb gene expression tracking with inflammation severity and NK/T cell abundance and decreasing after effective therapy. Gzmb-targeted PET/CT allows for dynamic and non-invasive assessment of intestinal immune compartment activity and an assessment of therapy in colitis. Gzmb PET was able to detect initial treatment responses of anti-TNF, steroid and anti-IL-23 based on changes in the Gzmb PET signal. This suggests that clinical Gzmb PET imaging may serve as precision imaging for monitoring disease activity with treatment in IBD and help improve patient care by identifying responders and non-responders in real time. Full article

Preoperative sarcopenia has emerged as an important determinant of adverse postoperative and long-term outcomes in patients with resectable non-small cell lung cancer (NSCLC). Its frequent coexistence with systemic inflammation may further worsen survival outcomes. At the same time, neoadjuvant chemotherapy and chemoimmunotherapy have substantially improved pathological response and survival in resectable NSCLC. However, their interaction with host-related factors such as sarcopenia and systemic inflammatory status remains insufficiently characterized. This narrative review aims to synthesize current evidence regarding the interplay between preoperative sarcopenia, systemic inflammation, and neoadjuvant therapy in resectable NSCLC and evaluates their potential combined impact on surgical and oncological outcomes. A narrative synthesis of 20 studies involving patients undergoing lung cancer resection was performed. Sarcopenia was primarily assessed using computed tomography or PET-CT-derived skeletal muscle indices, most commonly the skeletal muscle index, whereas systemic inflammation was evaluated using biochemical inflammatory markers. The available evidence consistently indicates that preoperative sarcopenia is associated with poorer long-term survival, and this adverse effect appears to be amplified in the presence of systemic inflammation. Although neoadjuvant chemoimmunotherapy has improved tumor response and survival outcomes, it may also act as a systemic stressor capable of aggravating muscle loss. Importantly, no study to date has simultaneously evaluated sarcopenia, systemic inflammation, and neoadjuvant therapy within a unified analytical framework. Most available studies focus primarily on sarcopenia, while inflammatory or treatment-related parameters are typically analyzed separately. Overall, while sarcopenia and systemic inflammation are recognized predictors of adverse outcomes in resectable NSCLC, robust evidence integrating them with neoadjuvant therapy is lacking. Clarifying their potential interaction may improve risk stratification and help to optimize perioperative management strategies in the era of neoadjuvant therapy. Full article

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations. Full article

Diffuse midline gliomas (DMGs) are rare but highly aggressive central nervous system (CNS) tumors that can present in both pediatric and adult populations. These tumors were redefined in the 2016 WHO classification of CNS tumors based on integrated histopathological and molecular features, and were initially designated as “DMG, H3 K27M-mutant”. In the 2021 WHO update, DMGs were incorporated into the newly defined category of primarily pediatric-type diffuse high-grade gliomas, and nomenclature was changed to “DMG, H3 K27-altered” to encompass additional molecular drivers beyond the canonical H3 K27M mutation. Clinically, DMGs arise as expansile, infiltrating tumors within midline structures and may present as non-enhancing or enhancing lesions on imaging. Diagnosis is based on neuroimaging and molecular confirmation by immunohistochemistry or sequencing when tissue is available. DMGs are categorized as WHO grade 4 malignant tumors due to their aggressive biology leading to rapid and infiltrative growth. Owing to their deep and midline location, surgical resection is typically not feasible. Radiation therapy is the backbone of treatment, but there is no standard regimen of chemotherapy that has demonstrated durable efficacy. Recent progress in therapeutic approaches has led to a major breakthrough on 6 August 2025 when the U.S. Food and Drug Administration granted the accelerated approval of dordaviprone (ONC201), marking it as the first systemic therapy for progressive DMG harboring H3 K27M mutation. Other novel approaches, including chimeric antigen receptor (CAR) T-cell directed therapies and convection-enhanced delivery, are actively under investigation. We aim to comprehensively review DMGs, including the recent insights into their biology, the evolving therapeutic landscape, and the opportunities to fuel this new momentum against one of the most formidable gliomas. Full article

Background/Objectives: Outcome prediction in patients with estrogen (ER)-positive metastatic breast cancer (MBC) remains challenging. We investigated whether circulating tumor cell (CTC) count adds prognostic value in ER-positive MBC using immunohistochemical (IHC) or 16α-[¹⁸F]-fluoro-17β-estradiol (FES)-PET imaging. Methods: Patients with newly diagnosed non-rapidly progressive MBC receiving first-line endocrine monotherapy, with ER-positive IHC (biopsy) or FES-PET and available CTC count, were included. Associations of CTC count and CTC-ER status based on ESR1 mRNA expression with progression-free survival (PFS) and overall survival (OS) were analyzed, and the added prognostic value of CTC count (<5 vs. ≥5/7.5 mL) beyond a positive ER result was assessed. Results: In patients with ER-positive IHC (n = 98) or FES-PET (n = 99) out of 106 endocrine-treated patients, ≥5 CTCs were associated with shorter PFS (HR 1.86; p = 0.0047 and 1.75; p = 0.011) and OS (HR 3.19 and 3.22; both p < 0.01), respectively, compared with <5 CTCs. Adding CTC count to ER-positive IHC or FES-PET improved prognostic accuracy for PFS (p = 0.006 and 0.012) and OS (both p < 0.001). CTC-ER status (ESR1 RNA) was not associated with outcomes. Conclusions: CTC count adds prognostic value to PET- or biopsy-based ER analysis in endocrine-treated MBC. Full article