Previous
Axillary staging has traditionally been performed routinely in early breast cancer to provide prognostic information and guide adjuvant therapy. In the era of targeted anti-tumor therapy and biology-driven treatment selection, however, the therapeutic relevance of nodal status has diminished in selected patients with clinically node-negative disease. Recent randomized trials, including Sentinel node vs. Observation after axillary UltraSouND (SOUND), INtergroup SEntinel MAmma trial (INSEMA), and Dutch Breast Cancer Research Group (BOrstkanker Onderzoek Groep; BOOG) 2013-08, have demonstrated that omission of sentinel lymph node biopsy (SLNB) in carefully selected patients undergoing breast-conserving surgery with planned whole-breast radiotherapy (WBRT) does not compromise local or distant disease control and rarely alters adjuvant systemic or radiotherapy management. The most robust evidence applies to postmenopausal women aged ≥ 50 years with ductal tumors ≤ 2 cm, grade 1–2, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and clinically node-negative disease. In this biologically favorable population, the therapeutic impact of nodal findings is limited as systemic therapy and radiotherapy decisions are predominantly driven by tumor subtype and genomic risk stratification rather than minimal nodal involvement. Based on evidence from recent randomized trials and current guidelines, this position paper proposes a practical four-step framework for decision-making regarding omission of SLNB. Redefining the axilla in this context represents a precision-oncology approach to surgical de-escalation, aligning local treatment intensity with biological risk while preserving oncologic safety.
Axillary staging has traditionally been performed routinely in early breast cancer to provide prognostic information and guide adjuvant therapy. In the era of targeted anti-tumor therapy and biology-driven treatment selection, however, the therapeutic relevance of nodal status has diminished in selected patients with clinically node-negative disease. Recent randomized trials, including Sentinel node vs. Observation after axillary UltraSouND (SOUND), INtergroup SEntinel MAmma trial (INSEMA), and Dutch Breast Cancer Research Group (BOrstkanker Onderzoek Groep; BOOG) 2013-08, have demonstrated that omission of sentinel lymph node biopsy (SLNB) in carefully selected patients undergoing breast-conserving surgery with planned whole-breast radiotherapy (WBRT) does not compromise local or distant disease control and rarely alters adjuvant systemic or radiotherapy management. The most robust evidence applies to postmenopausal women aged ≥ 50 years with ductal tumors ≤ 2 cm, grade 1–2, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative and clinically node-negative disease. In this biologically favorable population, the therapeutic impact of nodal findings is limited as systemic therapy and radiotherapy decisions are predominantly driven by tumor subtype and genomic risk stratification rather than minimal nodal involvement. Based on evidence from recent randomized trials and current guidelines, this position paper proposes a practical four-step framework for decision-making regarding omission of SLNB. Redefining the axilla in this context represents a precision-oncology approach to surgical de-escalation, aligning local treatment intensity with biological risk while preserving oncologic safety.
DOI: https://doi.org/10.37349/etat.2026.1002404
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Background:
Preliminary findings from this study were previously published as a conference abstract (https://doi.org/10.1158/2326-6074.IO2025-B039). Immune checkpoint inhibitors (ICIs) have shown activity in nasopharyngeal carcinoma (NPC), but their efficacy and safety when integrated with standard chemoradiotherapy (CRT) for locally advanced NPC remain under investigation. We performed a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy and safety of integrating ICIs with standard CRT-based treatment in patients with locally advanced NPC.
Methods:
MEDLINE and EMBASE were searched from inception through September 1, 2025, for English-language phase II or III randomized controlled trials evaluating ICIs plus standard therapy. Eligible studies reported efficacy outcomes, including progression-free/event-free survival (PFS/EFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS), and/or safety outcomes. Hazard ratios (HRs) were pooled using the generic inverse variance method, and risk ratios (RRs) for adverse events were pooled using the Mantel-Haenszel method. Fixed-effect models were used, with heterogeneity assessed using I2 statistics.
Results:
Three trials randomized 1,022 patients: CONTINUUM (n = 423), DIPPER (n = 450), and a phase II toripalimab trial (n = 149). The pooled safety population included 998 patients. ICIs significantly improved PFS/EFS [HR 0.54; 95% confidence interval (CI): 0.40–0.72; P < 0.0001], DMFS (HR 0.52; 95% CI: 0.36–0.75; P = 0.0005), and LRFS (HR 0.47; 95% CI: 0.31–0.71; P = 0.0003). OS favored the ICI arm but was not statistically significant (HR 0.77; 95% CI: 0.49–1.20; P = 0.24). ICIs increased immune related adverse events, whereas most CRT-associated locoregional and hematologic toxicities were not significantly increased.
Discussion:
Adding ICIs to standard CRT based therapy significantly improved disease control outcomes, including PFS/EFS, DMFS, and LRFS, without broadly worsening the overall CRT associated toxicity profile. Longer follow up is needed to determine whether these early disease control benefits translate into a statistically significant OS advantage.
Background:
Preliminary findings from this study were previously published as a conference abstract (https://doi.org/10.1158/2326-6074.IO2025-B039). Immune checkpoint inhibitors (ICIs) have shown activity in nasopharyngeal carcinoma (NPC), but their efficacy and safety when integrated with standard chemoradiotherapy (CRT) for locally advanced NPC remain under investigation. We performed a systematic review and meta-analysis of randomized controlled trials evaluating the efficacy and safety of integrating ICIs with standard CRT-based treatment in patients with locally advanced NPC.
Methods:
MEDLINE and EMBASE were searched from inception through September 1, 2025, for English-language phase II or III randomized controlled trials evaluating ICIs plus standard therapy. Eligible studies reported efficacy outcomes, including progression-free/event-free survival (PFS/EFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS), and/or safety outcomes. Hazard ratios (HRs) were pooled using the generic inverse variance method, and risk ratios (RRs) for adverse events were pooled using the Mantel-Haenszel method. Fixed-effect models were used, with heterogeneity assessed using I2 statistics.
Results:
Three trials randomized 1,022 patients: CONTINUUM (n = 423), DIPPER (n = 450), and a phase II toripalimab trial (n = 149). The pooled safety population included 998 patients. ICIs significantly improved PFS/EFS [HR 0.54; 95% confidence interval (CI): 0.40–0.72; P < 0.0001], DMFS (HR 0.52; 95% CI: 0.36–0.75; P = 0.0005), and LRFS (HR 0.47; 95% CI: 0.31–0.71; P = 0.0003). OS favored the ICI arm but was not statistically significant (HR 0.77; 95% CI: 0.49–1.20; P = 0.24). ICIs increased immune related adverse events, whereas most CRT-associated locoregional and hematologic toxicities were not significantly increased.
Discussion:
Adding ICIs to standard CRT based therapy significantly improved disease control outcomes, including PFS/EFS, DMFS, and LRFS, without broadly worsening the overall CRT associated toxicity profile. Longer follow up is needed to determine whether these early disease control benefits translate into a statistically significant OS advantage.
DOI: https://doi.org/10.37349/etat.2026.1002403
Aim:
Treatment approaches for biliary tract cancer (BTC) vary widely. Genomic profiling through next-generation sequencing (NGS) has made it possible to apply precision medicine in the management of BTC. This retrospective observational study aimed to evaluate the implementation of treatments based on identified genomic mutations and their clinical significance in patients with BTC in Japan, where NGS is covered by health insurance.
Methods:
We conducted a retrospective analysis of 65 patients with unresectable or recurrent BTC who underwent comprehensive genomic profiling at a single institution between November 2019 and October 2024. Genomic mutations were classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) scale. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test.
Results:
Among the 65 patients, clinically relevant genomic mutations classified using the ESCAT scale were identified in 47 patients, and clinically treatable genomic mutations were identified in 13 patients. Six patients ultimately received mutation-guided therapy, including fibroblast growth factor receptor inhibitors and pembrolizumab. The median time from specimen submission to review by the expert panel was 26 (range, 16–40) days. No significant difference in OS was observed based on the site of the primary tumor (log-rank test, P = 0.5804).
Conclusions:
Although clinically actionable genomic mutations were identified in one-fifth of patients, < 10% ultimately received treatment based on those findings, highlighting a gap between genomic profiling and treatment implementation. In contrast, with the increasing number of available therapies, access to precision treatment for patients with BTC may improve in the future through a combination of early adoption of NGS and the complementary use of liquid biopsy when tissue is unavailable.
Aim:
Treatment approaches for biliary tract cancer (BTC) vary widely. Genomic profiling through next-generation sequencing (NGS) has made it possible to apply precision medicine in the management of BTC. This retrospective observational study aimed to evaluate the implementation of treatments based on identified genomic mutations and their clinical significance in patients with BTC in Japan, where NGS is covered by health insurance.
Methods:
We conducted a retrospective analysis of 65 patients with unresectable or recurrent BTC who underwent comprehensive genomic profiling at a single institution between November 2019 and October 2024. Genomic mutations were classified according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT) scale. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test.
Results:
Among the 65 patients, clinically relevant genomic mutations classified using the ESCAT scale were identified in 47 patients, and clinically treatable genomic mutations were identified in 13 patients. Six patients ultimately received mutation-guided therapy, including fibroblast growth factor receptor inhibitors and pembrolizumab. The median time from specimen submission to review by the expert panel was 26 (range, 16–40) days. No significant difference in OS was observed based on the site of the primary tumor (log-rank test, P = 0.5804).
Conclusions:
Although clinically actionable genomic mutations were identified in one-fifth of patients, < 10% ultimately received treatment based on those findings, highlighting a gap between genomic profiling and treatment implementation. In contrast, with the increasing number of available therapies, access to precision treatment for patients with BTC may improve in the future through a combination of early adoption of NGS and the complementary use of liquid biopsy when tissue is unavailable.
DOI: https://doi.org/10.37349/etat.2026.1002402
This article belongs to the special issue Targeted and Precision Therapy for Adult Hepatopancreatobiliary Cancers and Liver Metastases
With national breast cancer screening programs leading to earlier diagnosis and improved treatments, more women are achieving long-term remission. However, this has resulted in rising rates of cardiotoxicity in breast cancer survivors consequent to their cancer therapies. Anthracyclines, a cornerstone treatment in breast cancer, carry a significant risk of short- and long-term cardiotoxicity through inhibition of topoisomerase II, preventing DNA repair and increasing oxidative stress. This most commonly manifests in the form of left ventricular (LV) systolic dysfunction or heart failure, and in severe cases, death. Many of the other treatments, including taxanes, cyclophosphamide, human epidermal growth factor receptor 2 inhibitors, immunotherapies, hormone therapies, and radiotherapy, also carry a risk of cardiac injury in the form of heart failure, arrhythmias, myocarditis, and pericardial disease. Surveillance has traditionally been performed by monitoring LV ejection fraction by transthoracic echocardiography. However, this has been found to be a late marker of cardiotoxicity, with damage potentially irreversible, and may reflect a missed opportunity for early intervention. Research has focused on identifying cardiac biomarkers and advanced imaging techniques, including strain analysis, to detect subclinical myocardial injury or dysfunction prior to irreversible damage, with LV global longitudinal strain a sensitive marker of subclinical LV systolic dysfunction and superior predictor of future cardiovascular events. Further research is needed to establish standardized guidelines on surveillance and management of this vulnerable patient cohort.
With national breast cancer screening programs leading to earlier diagnosis and improved treatments, more women are achieving long-term remission. However, this has resulted in rising rates of cardiotoxicity in breast cancer survivors consequent to their cancer therapies. Anthracyclines, a cornerstone treatment in breast cancer, carry a significant risk of short- and long-term cardiotoxicity through inhibition of topoisomerase II, preventing DNA repair and increasing oxidative stress. This most commonly manifests in the form of left ventricular (LV) systolic dysfunction or heart failure, and in severe cases, death. Many of the other treatments, including taxanes, cyclophosphamide, human epidermal growth factor receptor 2 inhibitors, immunotherapies, hormone therapies, and radiotherapy, also carry a risk of cardiac injury in the form of heart failure, arrhythmias, myocarditis, and pericardial disease. Surveillance has traditionally been performed by monitoring LV ejection fraction by transthoracic echocardiography. However, this has been found to be a late marker of cardiotoxicity, with damage potentially irreversible, and may reflect a missed opportunity for early intervention. Research has focused on identifying cardiac biomarkers and advanced imaging techniques, including strain analysis, to detect subclinical myocardial injury or dysfunction prior to irreversible damage, with LV global longitudinal strain a sensitive marker of subclinical LV systolic dysfunction and superior predictor of future cardiovascular events. Further research is needed to establish standardized guidelines on surveillance and management of this vulnerable patient cohort.
DOI: https://doi.org/10.37349/etat.2026.1002401
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Endocrine treatment in combination with CDK4/6 inhibitors represents the mainstay of first-line palliative treatment in HR+/HER2– breast cancer. The treatment landscape after progression on CDK4/6 inhibitors has evolved into a complex and rapidly evolving field, driven by novel endocrine and targeted agents, new combination therapies, and increasing implementation of biomarker-directed approaches. Recent randomized trials have shown that new therapeutic strategies significantly prolong progression-free survival in this setting, with some treatments reaching notable numerical improvements. Translating these options into routine clinical practice remains challenging due to heterogeneous trial designs, lack of head-to-head comparisons, suboptimal comparator treatments, and limited overall survival data. While the increasing implementation of biomarkers holds the potential for more personalized treatments, their clinical utility depends on their mechanistic and contextual biological relevance, methodological reliability of detection, and proven predictive value in clinical trials. Based on the current evidence, optimal treatment selection and sequencing in the post-CDK4/6 inhibitor setting remain insufficiently defined, and optimization of biomarker-guided treatment requires further mechanistic understanding and methodological refinement. This narrative review provides an overview of the most recent randomized clinical trial evidence shaping current clinical practice and discusses persistent uncertainties regarding its implementation in routine care.
Endocrine treatment in combination with CDK4/6 inhibitors represents the mainstay of first-line palliative treatment in HR+/HER2– breast cancer. The treatment landscape after progression on CDK4/6 inhibitors has evolved into a complex and rapidly evolving field, driven by novel endocrine and targeted agents, new combination therapies, and increasing implementation of biomarker-directed approaches. Recent randomized trials have shown that new therapeutic strategies significantly prolong progression-free survival in this setting, with some treatments reaching notable numerical improvements. Translating these options into routine clinical practice remains challenging due to heterogeneous trial designs, lack of head-to-head comparisons, suboptimal comparator treatments, and limited overall survival data. While the increasing implementation of biomarkers holds the potential for more personalized treatments, their clinical utility depends on their mechanistic and contextual biological relevance, methodological reliability of detection, and proven predictive value in clinical trials. Based on the current evidence, optimal treatment selection and sequencing in the post-CDK4/6 inhibitor setting remain insufficiently defined, and optimization of biomarker-guided treatment requires further mechanistic understanding and methodological refinement. This narrative review provides an overview of the most recent randomized clinical trial evidence shaping current clinical practice and discusses persistent uncertainties regarding its implementation in routine care.
DOI: https://doi.org/10.37349/etat.2026.1002400
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
A functional immune system is a key antagonist of cancer cell growth. Cytokines such as interferons (IFNs) promote the onset of inflammation, turn cells into an anti-viral state, and shape the dynamic tumor-immune cell interactome. Recent work illustrates how type I IFNs contribute to the resolution of inflammatory conditions. This involves macrophage-mediated efferocytosis for the clearance of apoptotic cells and the intrinsic capacity of type I IFNs to restrict their own autocrine signaling loops via the IFN-stimulated gene 15 (ISG15) protein. We discuss how this may affect tumor cells and how acetylation-dependent processes can affect the phosphorylation-dependent signaling cascades that augment IFN-dependent gene expression.
A functional immune system is a key antagonist of cancer cell growth. Cytokines such as interferons (IFNs) promote the onset of inflammation, turn cells into an anti-viral state, and shape the dynamic tumor-immune cell interactome. Recent work illustrates how type I IFNs contribute to the resolution of inflammatory conditions. This involves macrophage-mediated efferocytosis for the clearance of apoptotic cells and the intrinsic capacity of type I IFNs to restrict their own autocrine signaling loops via the IFN-stimulated gene 15 (ISG15) protein. We discuss how this may affect tumor cells and how acetylation-dependent processes can affect the phosphorylation-dependent signaling cascades that augment IFN-dependent gene expression.
DOI: https://doi.org/10.37349/etat.2026.1002399
Breast cancer management increasingly hinges on decisions made in “grey zones” where tissue sampling is scarce, and tumour biology evolves under therapeutic pressure. This narrative review synthesises evidence on how whole-body imaging biomarkers and circulating tumour DNA (ctDNA) can support response-adaptive pathways at the interface of surgical and systemic care. Four clinically actionable domains are discussed. (a) 16α-[18F]fluoro-17β-estradiol ([18F]FES) positron emission tomography/computed tomography (PET/CT) enables non-invasive, whole-body mapping of functional oestrogen receptor (ER) expression to address receptor discordance, heterogeneous metastases, and selection of endocrine-based strategies. (b) Human epidermal growth factor receptor 2 (HER2)-targeted PET (notably 89Zr-trastuzumab, with emerging alternatives) provides whole-body receptor assessment to uncover actionable HER2-positive disease despite HER2-negative primaries, informing anti-HER2 treatment selection when repeat biopsy is infeasible. (c) In triple-negative breast cancer treated with immune checkpoint inhibitors, 18F-fluorodeoxyglucose (18F-FDG) PET/CT offers quantitative response and whole-body burden assessment but requires immunotherapy-aware interpretation (e.g., confirmation strategies for apparent early progression) to mitigate pseudoprogression and dissociated responses, while simultaneously visualising immune-related adverse events. (d) Pairing early metabolic change on FDG PET/CT with ctDNA kinetics is presented as a biologically complementary approach for response monitoring and risk stratification, with potential to inform trial-embedded response-adaptive hypotheses, with ctDNA offering a rapid systemic trajectory and PET providing lesion-level localisation in heterogeneous or oligoprogressive disease. Overall, these tools add value only when linked to prespecified clinical questions and consensus actions; prospective studies are needed to validate standardised, outcome-improving response-adaptive algorithms that integrate imaging and liquid biopsy. Key implementation challenges include tracer availability, harmonised acquisition/reconstruction, threshold definition, and avoiding overtesting. Near-term impact may be greatest in problem-solving and in trial-embedded decision rules that operationalise biomarker-guided care.
Breast cancer management increasingly hinges on decisions made in “grey zones” where tissue sampling is scarce, and tumour biology evolves under therapeutic pressure. This narrative review synthesises evidence on how whole-body imaging biomarkers and circulating tumour DNA (ctDNA) can support response-adaptive pathways at the interface of surgical and systemic care. Four clinically actionable domains are discussed. (a) 16α-[18F]fluoro-17β-estradiol ([18F]FES) positron emission tomography/computed tomography (PET/CT) enables non-invasive, whole-body mapping of functional oestrogen receptor (ER) expression to address receptor discordance, heterogeneous metastases, and selection of endocrine-based strategies. (b) Human epidermal growth factor receptor 2 (HER2)-targeted PET (notably 89Zr-trastuzumab, with emerging alternatives) provides whole-body receptor assessment to uncover actionable HER2-positive disease despite HER2-negative primaries, informing anti-HER2 treatment selection when repeat biopsy is infeasible. (c) In triple-negative breast cancer treated with immune checkpoint inhibitors, 18F-fluorodeoxyglucose (18F-FDG) PET/CT offers quantitative response and whole-body burden assessment but requires immunotherapy-aware interpretation (e.g., confirmation strategies for apparent early progression) to mitigate pseudoprogression and dissociated responses, while simultaneously visualising immune-related adverse events. (d) Pairing early metabolic change on FDG PET/CT with ctDNA kinetics is presented as a biologically complementary approach for response monitoring and risk stratification, with potential to inform trial-embedded response-adaptive hypotheses, with ctDNA offering a rapid systemic trajectory and PET providing lesion-level localisation in heterogeneous or oligoprogressive disease. Overall, these tools add value only when linked to prespecified clinical questions and consensus actions; prospective studies are needed to validate standardised, outcome-improving response-adaptive algorithms that integrate imaging and liquid biopsy. Key implementation challenges include tracer availability, harmonised acquisition/reconstruction, threshold definition, and avoiding overtesting. Near-term impact may be greatest in problem-solving and in trial-embedded decision rules that operationalise biomarker-guided care.
DOI: https://doi.org/10.37349/etat.2026.1002398
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Four major analytical themes were identified: 1) The innovation paradox and financial toxicity, where prohibitive pricing (exceeding 100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure deficits and epistemic injustice, highlighted by a 9.4% access rate to next-generation sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The judicialization dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.
Precision oncology has revolutionized cancer care in high-income countries, but its implementation in Latin American low-resource settings faces profound bioethical dilemmas. This study analyzes these challenges through the lens of social justice and equity. An integrative review was conducted following the Whittemore and Knafl framework. A systematic search was performed across PubMed, Scopus, SciELO, and LILACS (2015–2025). Thematic synthesis was applied to integrate empirical data with normative bioethical theories. Four major analytical themes were identified: 1) The innovation paradox and financial toxicity, where prohibitive pricing (exceeding 100,000 USD/year) violates distributive justice and leads to a biological penalty in survival; 2) Infrastructure deficits and epistemic injustice, highlighted by a 9.4% access rate to next-generation sequencing (NGS) and the risks of applying Eurocentric genomic data to admixed LA populations; 3) Research vulnerability, where clinical trials serve as survival strategies, compromising autonomy and informed consent; and 4) The judicialization dilemma, where individual court orders for high-cost drugs threaten systemic sustainability and equity. To prevent a genomic apartheid, Latin America must transition toward genomic sovereignty and frugal precision oncology. Bioethical frameworks in the region must prioritize protection ethics and social justice to ensure that scientific innovation does not exacerbate existing health inequities.
DOI: https://doi.org/10.37349/etat.2026.1002397
Primary bone sarcomas are rare and biologically heterogeneous malignancies for which therapeutic progress remains limited, particularly in metastatic and recurrent disease. Advances in genomic and molecular profiling have revealed substantial inter- and intratumoral heterogeneity across the major subtypes, including osteosarcoma, Ewing sarcoma and chondrosarcoma, challenging conventional histology-driven treatment strategies. Precision medicine approaches are being increasingly explored to better capture this biological complexity and guide individualized therapeutic decision-making. This review examines emerging precision oncology strategies in bone sarcomas, including molecular diagnostics, targeted therapeutic approaches, three-dimensional functional modeling systems, and liquid biopsy technologies for dynamic disease monitoring. Together, these platforms provide biologically informed frameworks for patient-specific treatment and longitudinal assessment of tumor evolution. However, clinical implementation remains limited by genomic complexity, small patient cohorts, and methodological variability across experimental platforms. The integration of multi-layered precision models combining genomic stratification, functional drug sensitivity testing and circulating biomarker monitoring may enable more adaptive and individualized management strategies. Such approaches have the potential to improve therapeutic selection and ultimately advance outcomes for patients with primary bone sarcomas.
Primary bone sarcomas are rare and biologically heterogeneous malignancies for which therapeutic progress remains limited, particularly in metastatic and recurrent disease. Advances in genomic and molecular profiling have revealed substantial inter- and intratumoral heterogeneity across the major subtypes, including osteosarcoma, Ewing sarcoma and chondrosarcoma, challenging conventional histology-driven treatment strategies. Precision medicine approaches are being increasingly explored to better capture this biological complexity and guide individualized therapeutic decision-making. This review examines emerging precision oncology strategies in bone sarcomas, including molecular diagnostics, targeted therapeutic approaches, three-dimensional functional modeling systems, and liquid biopsy technologies for dynamic disease monitoring. Together, these platforms provide biologically informed frameworks for patient-specific treatment and longitudinal assessment of tumor evolution. However, clinical implementation remains limited by genomic complexity, small patient cohorts, and methodological variability across experimental platforms. The integration of multi-layered precision models combining genomic stratification, functional drug sensitivity testing and circulating biomarker monitoring may enable more adaptive and individualized management strategies. Such approaches have the potential to improve therapeutic selection and ultimately advance outcomes for patients with primary bone sarcomas.
DOI: https://doi.org/10.37349/etat.2026.1002396
This article belongs to the special issue Precision Oncology: Molecular Classification, Efficacy Prediction, and Treatment Decision-Making
Aim:
The aim of our study was to evaluate the safety and efficacy of delivering systemic treatments concurrently with whole-brain radiotherapy (WBRT).
Methods:
A single-institution, prospective observational study was conducted in Athens, Greece, including 99 patients treated with WBRT for brain metastases from September 2017 until October 2019, and with a follow-up period extending to March 2025. The study endpoints included overall survival (OS) for all causes of death, time to intracranial progression (TTICP), and serious acute toxicities.
Results:
The median OS from all causes of death was 6 months [95% confidence interval (CI): 4.7–7.3]. Concomitant systemic therapy reduced the risk of death (p = 0.005), and the presence of systemic metastases (p = 0.009) increased the risk of death for patients with brain metastases treated with whole brain radiotherapy. The median TTICP was 10 months (95% CI: 3.3–16.6), with a more protracted fractionation and a larger number of brain metastases being prognostic of an increase in the TTICP. Acute severe toxicity was observed in 16.2% of patients, with no statistically significant difference between concurrent and no systemic therapy groups, and with no treatment interruptions in patients treated concurrently.
Conclusions:
This study showed that there is no serious toxicity from the combination of systemic therapy with WBRT, and that the OS and the TTICP are not compromised with their concurrent delivery.
Aim:
The aim of our study was to evaluate the safety and efficacy of delivering systemic treatments concurrently with whole-brain radiotherapy (WBRT).
Methods:
A single-institution, prospective observational study was conducted in Athens, Greece, including 99 patients treated with WBRT for brain metastases from September 2017 until October 2019, and with a follow-up period extending to March 2025. The study endpoints included overall survival (OS) for all causes of death, time to intracranial progression (TTICP), and serious acute toxicities.
Results:
The median OS from all causes of death was 6 months [95% confidence interval (CI): 4.7–7.3]. Concomitant systemic therapy reduced the risk of death (p = 0.005), and the presence of systemic metastases (p = 0.009) increased the risk of death for patients with brain metastases treated with whole brain radiotherapy. The median TTICP was 10 months (95% CI: 3.3–16.6), with a more protracted fractionation and a larger number of brain metastases being prognostic of an increase in the TTICP. Acute severe toxicity was observed in 16.2% of patients, with no statistically significant difference between concurrent and no systemic therapy groups, and with no treatment interruptions in patients treated concurrently.
Conclusions:
This study showed that there is no serious toxicity from the combination of systemic therapy with WBRT, and that the OS and the TTICP are not compromised with their concurrent delivery.
DOI: https://doi.org/10.37349/etat.2026.1002395
Breast cancer remains one of the leading causes of cancer-related mortality worldwide, and despite considerable advances in therapeutic strategies, the absence of reliable, minimally invasive diagnostic tools continues to limit early detection and real-time disease monitoring. Liquid biopsy has emerged as a transformative paradigm in oncology, offering the capacity to integrate tumor biology through the analysis of tumor-derived materials that circulate in peripheral blood and other biofluids. This review provides a comprehensive overview of the key analytes employed in liquid biopsy, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), extracellular vesicles (EVs), and protein biomarkers with particular emphasis on their translational relevance in breast cancer. Drawing on landmark clinical trials and foundational molecular studies, we highlight how these biomarkers capture spatial and temporal tumor heterogeneity in ways that conventional tissue biopsy cannot. Finally, we address the technical, clinical, and ethical challenges that still impede widespread adoption of liquid biopsy, and we outline a forward-looking research agenda oriented toward multi-omics integration and point-of-care diagnostics. Taken together, this review underscores the potential of liquid biopsy to complement existing diagnostic standards and improve how we screen for, monitor, and treat breast cancer across disease stages.
Breast cancer remains one of the leading causes of cancer-related mortality worldwide, and despite considerable advances in therapeutic strategies, the absence of reliable, minimally invasive diagnostic tools continues to limit early detection and real-time disease monitoring. Liquid biopsy has emerged as a transformative paradigm in oncology, offering the capacity to integrate tumor biology through the analysis of tumor-derived materials that circulate in peripheral blood and other biofluids. This review provides a comprehensive overview of the key analytes employed in liquid biopsy, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), extracellular vesicles (EVs), and protein biomarkers with particular emphasis on their translational relevance in breast cancer. Drawing on landmark clinical trials and foundational molecular studies, we highlight how these biomarkers capture spatial and temporal tumor heterogeneity in ways that conventional tissue biopsy cannot. Finally, we address the technical, clinical, and ethical challenges that still impede widespread adoption of liquid biopsy, and we outline a forward-looking research agenda oriented toward multi-omics integration and point-of-care diagnostics. Taken together, this review underscores the potential of liquid biopsy to complement existing diagnostic standards and improve how we screen for, monitor, and treat breast cancer across disease stages.
DOI: https://doi.org/10.37349/etat.2026.1002394
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Aim:
Breast cancer remains a major cause of cancer-related mortality in women, particularly in advanced stages where therapeutic options are limited. While immune checkpoint inhibitors (ICIs) have improved outcomes in a subset of patients, many do not respond, highlighting the need for alternative immunotherapeutic strategies. This study evaluated the effect of dendritic cell (DC)-based immunotherapy on tumor growth and on the inflammatory profile of peritoneal myeloid cells in a 4T1 murine breast cancer model.
Methods:
BALB/c mice bearing 4T1 breast tumors were treated with bone marrow-derived DC-based immunotherapy. Tumor volume was monitored over time, and CD14+ cells obtained from peritoneal lavage were analyzed by flow cytometry for the cytokines IL-12, IL-17, and TNF-α and the transcription factors RORγT and GATA3.
Results:
DC-based immunotherapy was associated with a non-significant trend toward reduced tumor volume and a marked suppression of key proinflammatory cytokines: IL-12 (P < 0.0005), IL-17 (P < 0.0001), and TNF-α (P < 0.0001). Expression of the transcription factors RORγT and GATA3, associated with Th17 and Th2 differentiation, was also downregulated (P < 0.0001). These immunological effects were observed in CD14+ myeloid cells from the peritoneal compartment.
Conclusions:
DC-based immunotherapy modulates the systemic/peritoneal inflammatory profile and attenuates tumor-promoting inflammation. This strategy may offer therapeutic benefit for patients with breast cancer who are unresponsive to conventional or ICI-based treatments and supports its further evaluation in translational studies.
Aim:
Breast cancer remains a major cause of cancer-related mortality in women, particularly in advanced stages where therapeutic options are limited. While immune checkpoint inhibitors (ICIs) have improved outcomes in a subset of patients, many do not respond, highlighting the need for alternative immunotherapeutic strategies. This study evaluated the effect of dendritic cell (DC)-based immunotherapy on tumor growth and on the inflammatory profile of peritoneal myeloid cells in a 4T1 murine breast cancer model.
Methods:
BALB/c mice bearing 4T1 breast tumors were treated with bone marrow-derived DC-based immunotherapy. Tumor volume was monitored over time, and CD14+ cells obtained from peritoneal lavage were analyzed by flow cytometry for the cytokines IL-12, IL-17, and TNF-α and the transcription factors RORγT and GATA3.
Results:
DC-based immunotherapy was associated with a non-significant trend toward reduced tumor volume and a marked suppression of key proinflammatory cytokines: IL-12 (P < 0.0005), IL-17 (P < 0.0001), and TNF-α (P < 0.0001). Expression of the transcription factors RORγT and GATA3, associated with Th17 and Th2 differentiation, was also downregulated (P < 0.0001). These immunological effects were observed in CD14+ myeloid cells from the peritoneal compartment.
Conclusions:
DC-based immunotherapy modulates the systemic/peritoneal inflammatory profile and attenuates tumor-promoting inflammation. This strategy may offer therapeutic benefit for patients with breast cancer who are unresponsive to conventional or ICI-based treatments and supports its further evaluation in translational studies.
DOI: https://doi.org/10.37349/etat.2026.1002393
Aim:
Oligoprogressive disease (OPD) has emerged as a clinically relevant and common scenario in oncology, reflecting progression in a limited number of metastatic sites while systemic therapy continues to control the majority of disease. Despite its increasing recognition, the definition, diagnostic approach, and management of OPD remain poorly standardized.
Methods:
A multidisciplinary expert panel from Kazakhstan and international faculty, including ten medical oncologists, radiation, and surgical oncologists, participated in a structured survey. The questionnaire consisted of 15 items divided into three domains: definition of OPD, diagnostic evaluation, and treatment strategies. Responses were analyzed, and consensus was defined as ≥ 70% agreement, relative agreement as 50–69%, and lack of consensus as < 50%.
Results:
Consensus was reached that OPD is defined as progression in a limited number of lesions while other sites remain controlled, regardless of lesion size or localization. No consensus was achieved regarding the maximum number of progressive lesions, with experts divided between “≤ 5 lesions” and “any number amenable to local therapy.” Imaging with CT or PET-CT was considered sufficient. Biopsy and molecular testing were recommended only in selected contexts. Systemic therapy continuation during OPD was endorsed if effective, with strong support for local therapy, particularly stereotactic ablative radiotherapy (SBRT/SABR). Divergence remained regarding the management of repeat OPD.
Conclusions:
This Kazakhstan Cancer Society consensus defines the fundamental clinical features of OPD and provides practical recommendations for diagnosis and treatment. Comparison with international guidelines reveals broad alignment on systemic continuation and local therapy, as well as persistent variation regarding lesion number, biopsy, and repeat OPD management.
Aim:
Oligoprogressive disease (OPD) has emerged as a clinically relevant and common scenario in oncology, reflecting progression in a limited number of metastatic sites while systemic therapy continues to control the majority of disease. Despite its increasing recognition, the definition, diagnostic approach, and management of OPD remain poorly standardized.
Methods:
A multidisciplinary expert panel from Kazakhstan and international faculty, including ten medical oncologists, radiation, and surgical oncologists, participated in a structured survey. The questionnaire consisted of 15 items divided into three domains: definition of OPD, diagnostic evaluation, and treatment strategies. Responses were analyzed, and consensus was defined as ≥ 70% agreement, relative agreement as 50–69%, and lack of consensus as < 50%.
Results:
Consensus was reached that OPD is defined as progression in a limited number of lesions while other sites remain controlled, regardless of lesion size or localization. No consensus was achieved regarding the maximum number of progressive lesions, with experts divided between “≤ 5 lesions” and “any number amenable to local therapy.” Imaging with CT or PET-CT was considered sufficient. Biopsy and molecular testing were recommended only in selected contexts. Systemic therapy continuation during OPD was endorsed if effective, with strong support for local therapy, particularly stereotactic ablative radiotherapy (SBRT/SABR). Divergence remained regarding the management of repeat OPD.
Conclusions:
This Kazakhstan Cancer Society consensus defines the fundamental clinical features of OPD and provides practical recommendations for diagnosis and treatment. Comparison with international guidelines reveals broad alignment on systemic continuation and local therapy, as well as persistent variation regarding lesion number, biopsy, and repeat OPD management.
DOI: https://doi.org/10.37349/etat.2026.1002392
Aim:
Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigate viral activity in breast tissues. Among high-risk HPV types, HPV16 is one of the most prevalent and exhibits the highest carcinogenic potential. Therefore, this study aimed to evaluate the expression of HPV16 oncogenes E5, E6, and E7 in breast tumors, as well as the modulation of the PI3K/AKT/mTOR signaling pathway associated with viral activity.
Methods:
A total of 92 breast cancer patients were included after Ethics Committee approval. Clinical data were obtained from medical records. RNA was extracted from formalin-fixed, paraffin-embedded tissues and reverse-transcribed into cDNA. Transcripts of HPV oncogenes (E5, E6, and E7), components of the PI3K/AKT/mTOR pathway, and regulatory genes (EGFR and PTEN) were quantified by RT-qPCR. Gene expression levels were calculated using the ΔCt method.
Results:
Forty-eight samples met RNA quality criteria and were included in the expression analysis. Among these, 77.08% showed expression of at least one viral oncogene, with E5 being the most frequently expressed. The PI3K/AKT/mTOR pathway was modulated in HPV-positive samples, with increased PI3K expression and decreased mTOR expression. Notably, the high expression of E5—associated with immune evasion—combined with reduced mTOR expression suggests that HPV16 status may influence therapeutic response in breast cancer patients.
Conclusions:
These findings reinforce the importance of further studies investigating HPV activity in breast tumors to better understand its biological and clinical impact.
Aim:
Breast cancer is the most prevalent malignant tumor among women. Human papillomavirus (HPV) has been detected in breast tumors since the 1990s, and beyond its oncogenic potential, therapy resistance driven by viral immune evasion in non-anogenital tumors, such as oropharyngeal cancers, highlights the need to investigate viral activity in breast tissues. Among high-risk HPV types, HPV16 is one of the most prevalent and exhibits the highest carcinogenic potential. Therefore, this study aimed to evaluate the expression of HPV16 oncogenes E5, E6, and E7 in breast tumors, as well as the modulation of the PI3K/AKT/mTOR signaling pathway associated with viral activity.
Methods:
A total of 92 breast cancer patients were included after Ethics Committee approval. Clinical data were obtained from medical records. RNA was extracted from formalin-fixed, paraffin-embedded tissues and reverse-transcribed into cDNA. Transcripts of HPV oncogenes (E5, E6, and E7), components of the PI3K/AKT/mTOR pathway, and regulatory genes (EGFR and PTEN) were quantified by RT-qPCR. Gene expression levels were calculated using the ΔCt method.
Results:
Forty-eight samples met RNA quality criteria and were included in the expression analysis. Among these, 77.08% showed expression of at least one viral oncogene, with E5 being the most frequently expressed. The PI3K/AKT/mTOR pathway was modulated in HPV-positive samples, with increased PI3K expression and decreased mTOR expression. Notably, the high expression of E5—associated with immune evasion—combined with reduced mTOR expression suggests that HPV16 status may influence therapeutic response in breast cancer patients.
Conclusions:
These findings reinforce the importance of further studies investigating HPV activity in breast tumors to better understand its biological and clinical impact.
DOI: https://doi.org/10.37349/etat.2026.1002391
This article belongs to the special issue Breaking Boundaries in Breast Cancer Care: Emerging Controversies and Innovation in Surgical and Medical Approaches
Tumor heterogeneity and cellular plasticity are major drivers of therapeutic failure across many cancer types. While precision oncology has largely focused on static genomic alterations, growing evidence indicates that tumors behave as dynamic biological systems that continuously adapt during treatment. Tumor cell populations can transition between distinct functional states under therapeutic pressure, including transient drug-tolerant phenotypes that may precede stabilization of genetically or epigenetically resistant clones. These transitions are shaped by mechanisms such as epigenetic reprogramming, stress-response signaling, metabolic rewiring, and microenvironmental interactions. This review synthesizes findings from tumor plasticity, drug-tolerant persister biology, therapy-induced vulnerabilities, clonal evolution, and adaptive therapy to examine how temporal tumor dynamics influence treatment response. Emerging evidence suggests that some tumors may pass through short-lived phases of cellular instability during therapy in which molecular dependencies, stress-response programs, or adaptive survival states are altered before resistance becomes genetically or epigenetically stabilized. However, such transition states should be considered therapeutically actionable only when linked to functional evidence of altered drug sensitivity, pathway dependence, immune susceptibility, or clinical response. Advances in single-cell transcriptomics, epigenomic profiling, serial circulating tumor deoxyribonucleic acid (ctDNA)/cfDNA analysis, multi-omics integration, and dynamic imaging are enabling longitudinal monitoring of tumor state transitions and may facilitate identification of transient biological states preceding stable resistance. Integrating temporal tumor biology with therapeutic sequencing strategies, adaptive treatment schedules, and biomarker-guided monitoring may therefore help test whether specific adaptive states can be therapeutically exploited and may refine precision oncology approaches.
Tumor heterogeneity and cellular plasticity are major drivers of therapeutic failure across many cancer types. While precision oncology has largely focused on static genomic alterations, growing evidence indicates that tumors behave as dynamic biological systems that continuously adapt during treatment. Tumor cell populations can transition between distinct functional states under therapeutic pressure, including transient drug-tolerant phenotypes that may precede stabilization of genetically or epigenetically resistant clones. These transitions are shaped by mechanisms such as epigenetic reprogramming, stress-response signaling, metabolic rewiring, and microenvironmental interactions. This review synthesizes findings from tumor plasticity, drug-tolerant persister biology, therapy-induced vulnerabilities, clonal evolution, and adaptive therapy to examine how temporal tumor dynamics influence treatment response. Emerging evidence suggests that some tumors may pass through short-lived phases of cellular instability during therapy in which molecular dependencies, stress-response programs, or adaptive survival states are altered before resistance becomes genetically or epigenetically stabilized. However, such transition states should be considered therapeutically actionable only when linked to functional evidence of altered drug sensitivity, pathway dependence, immune susceptibility, or clinical response. Advances in single-cell transcriptomics, epigenomic profiling, serial circulating tumor deoxyribonucleic acid (ctDNA)/cfDNA analysis, multi-omics integration, and dynamic imaging are enabling longitudinal monitoring of tumor state transitions and may facilitate identification of transient biological states preceding stable resistance. Integrating temporal tumor biology with therapeutic sequencing strategies, adaptive treatment schedules, and biomarker-guided monitoring may therefore help test whether specific adaptive states can be therapeutically exploited and may refine precision oncology approaches.
DOI: https://doi.org/10.37349/etat.2026.1002390
Aim:
Minimally invasive approaches for radical cystectomy (RC) have been increasingly adopted; however, comparative evidence regarding surgical quality and perioperative outcomes among open (ORC), laparoscopic (LRC), and robot-assisted RC (RARC) remains limited. This study evaluated these three modalities using standardized composite metrics, trifecta and pentafecta, and inverse probability of treatment weighting.
Methods:
We retrospectively analyzed 192 patients who underwent RC with ileal conduit or neobladder reconstruction between 2006 and 2023. Inverse probability of treatment weighting was applied using comprehensive clinicopathological covariates. Trifecta and pentafecta achievements, perioperative parameters, and postoperative complications were compared among the ORC (n = 110), LRC (n = 38), and RARC (n = 44) groups.
Results:
RARC achieved the most favorable perioperative and surgical outcomes. Specifically, RARC showed significantly higher rates of several trifecta and pentafecta components than ORC, including fewer positive soft tissue surgical margins (0.0% vs. 5.2%, P < 0.01), reduced major complication rates within 90 days (16.1% vs. 44%, P < 0.05), and fewer urinary diversion–related sequelae within 12 months (1.5% vs. 13.5%, P < 0.05). RARC was also associated with significantly lower blood loss than ORC (380 ± 513 mL vs. 2,913 ± 2,997 mL, P < 0.01), as well as lower rates of pelvic abscess, gastrointestinal anastomotic leakage, and obstructive ileus (all P < 0.01) than ORC. In contrast, LRC was not superior to ORC in terms of major complications or diversion-related outcomes. Local pelvic recurrence within 12 months did not differ significantly among the three modalities.
Conclusions:
RARC may be a favorable surgical option for reducing perioperative morbidity in patients with high-grade bladder cancer, with comparable 12-month local recurrence rates among surgical approaches.
Aim:
Minimally invasive approaches for radical cystectomy (RC) have been increasingly adopted; however, comparative evidence regarding surgical quality and perioperative outcomes among open (ORC), laparoscopic (LRC), and robot-assisted RC (RARC) remains limited. This study evaluated these three modalities using standardized composite metrics, trifecta and pentafecta, and inverse probability of treatment weighting.
Methods:
We retrospectively analyzed 192 patients who underwent RC with ileal conduit or neobladder reconstruction between 2006 and 2023. Inverse probability of treatment weighting was applied using comprehensive clinicopathological covariates. Trifecta and pentafecta achievements, perioperative parameters, and postoperative complications were compared among the ORC (n = 110), LRC (n = 38), and RARC (n = 44) groups.
Results:
RARC achieved the most favorable perioperative and surgical outcomes. Specifically, RARC showed significantly higher rates of several trifecta and pentafecta components than ORC, including fewer positive soft tissue surgical margins (0.0% vs. 5.2%, P < 0.01), reduced major complication rates within 90 days (16.1% vs. 44%, P < 0.05), and fewer urinary diversion–related sequelae within 12 months (1.5% vs. 13.5%, P < 0.05). RARC was also associated with significantly lower blood loss than ORC (380 ± 513 mL vs. 2,913 ± 2,997 mL, P < 0.01), as well as lower rates of pelvic abscess, gastrointestinal anastomotic leakage, and obstructive ileus (all P < 0.01) than ORC. In contrast, LRC was not superior to ORC in terms of major complications or diversion-related outcomes. Local pelvic recurrence within 12 months did not differ significantly among the three modalities.
Conclusions:
RARC may be a favorable surgical option for reducing perioperative morbidity in patients with high-grade bladder cancer, with comparable 12-month local recurrence rates among surgical approaches.
DOI: https://doi.org/10.37349/etat.2026.1002389
Aim:
Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/– ICI may be a feasible choice.
Methods:
We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/– ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
Results:
There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1–14) of TC over median 12 weeks (range 3–53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist’s discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7–10.4), median PFS of 4.6 months (IQR 3.3–10.2), and median OS of 9.4 months (IQR 6.3–15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/– ICI was overall well tolerated with expected type and severity of adverse events.
Conclusions:
Strategies to overcome ICI resistance are needed, and TC +/– ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.
Aim:
Despite advances with immune checkpoint inhibitor (ICI)-based regimens in the past decade, patients with metastatic urothelial cancer (mUC) face a poor prognosis with few approved options. Platinum-based chemotherapy with paclitaxel and carboplatin (TC) +/– ICI may be a feasible choice.
Methods:
We generated an IRB-approved, HIPAA-compliant retrospective database of patients at Mayo Clinic Cancer Center with mUC who started TC +/– ICI after disease progression on ICI from January 2018 through December 2024. Baseline demographics, clinicopathologic features, and treatment outcomes were extracted from the electronic health record. Kaplan-Meier method was used to calculate median duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
Results:
There were 32 patients who fit inclusion criteria, including 31 patients who had disease progression on ICI in the metastatic setting and 1 patient who developed metastatic disease on adjuvant nivolumab. Patients received a median of 4 cycles (range 1–14) of TC over median 12 weeks (range 3–53). Overall, 81% of patients received TC concurrently with an ICI, and 28% continued maintenance ICI after TC discontinuation (at the treating oncologist’s discretion due to adequate response or toxicity). The best objective response rate was 41% and disease control rate was 75%, with median DOR of 4.8 months (IQR 2.7–10.4), median PFS of 4.6 months (IQR 3.3–10.2), and median OS of 9.4 months (IQR 6.3–15.9). Some patients in this series had very durable responses with PFS > 12 months and OS > 24 months. TC +/– ICI was overall well tolerated with expected type and severity of adverse events.
Conclusions:
Strategies to overcome ICI resistance are needed, and TC +/– ICI after disease progression on an ICI shows promising tolerability and efficacy in this setting for patients with mUC. Our series was notable for some patients having a durable response. Validation in larger cohorts is warranted.
DOI: https://doi.org/10.37349/etat.2026.1002387
This article belongs to the special issue Emerging Innovation in Surgical and Medical Approaches on the Horizon for Urogenital Malignancies
Aim:
The aim was to determine the transcriptomic features of tumor and stromal cells in direct contact within tumor nodules in luminal and triple-negative breast cancer.
Methods:
Spatial transcriptomic profiling was performed using the Visium 10x platform on FFPE tumor tissue sections from 10 patients with luminal breast cancer and 9 patients with triple-negative breast cancer. Manual morphological annotation of spots and evaluation of differentially expressed genes (DEGs) in identified spot clusters were performed using Loupe Browser v8.0.0 (10X Genomics, USA). Activated biological processes were assessed using the Enrichr online resource and the GO Biological Process 2025 database. Ligand-receptor pairs were identified using the CellChat package (v2.0) in R (v4.4.2).
Results:
In luminal breast cancer, mixed cluster (tumor cells colocalized with stromal cells) was characterized by overexpression of genes encoding S100A family Ca2+-binding proteins (S100A4, S100A8, S100A9), matrix metalloproteinases (MMP2, MMP7, MMP14), cytokeratins (KRT5, KRT7, KRT15, KRT23, KRT81), the mesenchymal marker VIM, and epithelial-mesenchymal transition (EMT)-associated genes (ICAM1, PRRX1) compared to tumor-only cluster. In triple-negative breast cancer, mixed cluster showed overexpression of S100A2, S100A8, S100A9, the epithelial gene KRT6B, the cancer stem cell marker CD44, and NOTCH2, which is associated with negative regulation of EMT. In both breast cancer subtypes, mixed cluster showed transcriptomic enrichment of gene sets associated with regulation of the ERK/MAPK cascade, apoptosis, and cell adhesion and migration. Ligand-receptor pairs associated with cell-cell contact, EMT, and immune response were also detected in colocalized cells, with a broader spectrum of these pairs observed in luminal breast cancer.
Conclusions:
This study assessed the transcriptomic characteristics of directly contacting tumor and stromal cells and identified the spectrum of ligand-receptor pairs mediating their interactions. Characterizing the properties of cells at the tumor-stroma interface helps unravel mechanisms of breast cancer progression and identify novel diagnostic markers and therapeutic targets.
Aim:
The aim was to determine the transcriptomic features of tumor and stromal cells in direct contact within tumor nodules in luminal and triple-negative breast cancer.
Methods:
Spatial transcriptomic profiling was performed using the Visium 10x platform on FFPE tumor tissue sections from 10 patients with luminal breast cancer and 9 patients with triple-negative breast cancer. Manual morphological annotation of spots and evaluation of differentially expressed genes (DEGs) in identified spot clusters were performed using Loupe Browser v8.0.0 (10X Genomics, USA). Activated biological processes were assessed using the Enrichr online resource and the GO Biological Process 2025 database. Ligand-receptor pairs were identified using the CellChat package (v2.0) in R (v4.4.2).
Results:
In luminal breast cancer, mixed cluster (tumor cells colocalized with stromal cells) was characterized by overexpression of genes encoding S100A family Ca2+-binding proteins (S100A4, S100A8, S100A9), matrix metalloproteinases (MMP2, MMP7, MMP14), cytokeratins (KRT5, KRT7, KRT15, KRT23, KRT81), the mesenchymal marker VIM, and epithelial-mesenchymal transition (EMT)-associated genes (ICAM1, PRRX1) compared to tumor-only cluster. In triple-negative breast cancer, mixed cluster showed overexpression of S100A2, S100A8, S100A9, the epithelial gene KRT6B, the cancer stem cell marker CD44, and NOTCH2, which is associated with negative regulation of EMT. In both breast cancer subtypes, mixed cluster showed transcriptomic enrichment of gene sets associated with regulation of the ERK/MAPK cascade, apoptosis, and cell adhesion and migration. Ligand-receptor pairs associated with cell-cell contact, EMT, and immune response were also detected in colocalized cells, with a broader spectrum of these pairs observed in luminal breast cancer.
Conclusions:
This study assessed the transcriptomic characteristics of directly contacting tumor and stromal cells and identified the spectrum of ligand-receptor pairs mediating their interactions. Characterizing the properties of cells at the tumor-stroma interface helps unravel mechanisms of breast cancer progression and identify novel diagnostic markers and therapeutic targets.
DOI: https://doi.org/10.37349/etat.2026.1002388
We aimed to evaluate the suitability of archival ureteroscopic (URS) biopsy specimens for fibroblast growth factor receptor 3 (FGFR3) biomarker analysis in upper urinary tract urothelial carcinoma. Thirty-six patients with upper urinary tract urothelial carcinoma who underwent diagnostic URS and radical nephroureterectomy (RNU) were included. Among the 36 RNU-derived tissue specimens, 33 (92%) yielded valid FGFR3 RNA test results; the remaining three (8.3%) showed test failure because of undetectable amplification by reverse transcriptase-polymerase chain reaction. Of the 33 RNU specimens with valid amplification, eight (24%) had FGFR3 alterations. Of these eight specimens, two (25%) were valid for FGFR3 RNA testing; one showed positive concordance with the paired RNU specimen, whereas the other did not. The remaining six specimens (75%) showed test failure. Correlation analysis of FGFR3 immunohistochemical staining scores demonstrated a moderate positive correlation between RNU and paired URS specimens (Spearman’s ρ = 0.47, P = 0.004). Our findings indicate that URS biopsy specimens are unsuitable for FGFR3 RNA testing but may be useful for protein-based biomarker analysis when RNU specimens are unavailable.
We aimed to evaluate the suitability of archival ureteroscopic (URS) biopsy specimens for fibroblast growth factor receptor 3 (FGFR3) biomarker analysis in upper urinary tract urothelial carcinoma. Thirty-six patients with upper urinary tract urothelial carcinoma who underwent diagnostic URS and radical nephroureterectomy (RNU) were included. Among the 36 RNU-derived tissue specimens, 33 (92%) yielded valid FGFR3 RNA test results; the remaining three (8.3%) showed test failure because of undetectable amplification by reverse transcriptase-polymerase chain reaction. Of the 33 RNU specimens with valid amplification, eight (24%) had FGFR3 alterations. Of these eight specimens, two (25%) were valid for FGFR3 RNA testing; one showed positive concordance with the paired RNU specimen, whereas the other did not. The remaining six specimens (75%) showed test failure. Correlation analysis of FGFR3 immunohistochemical staining scores demonstrated a moderate positive correlation between RNU and paired URS specimens (Spearman’s ρ = 0.47, P = 0.004). Our findings indicate that URS biopsy specimens are unsuitable for FGFR3 RNA testing but may be useful for protein-based biomarker analysis when RNU specimens are unavailable.
DOI: https://doi.org/10.37349/etat.2026.1002385
This article belongs to the special issue Emerging Innovation in Surgical and Medical Approaches on the Horizon for Urogenital Malignancies
Aim:
Transurethral laser ablation (TULA) for recurrent bladder cancer is a less invasive treatment method for patients. We report here our initial clinical experience with TULA for recurrent bladder cancer.
Methods:
This retrospective study analyzed 48 patients. Twenty-four cases were treated with TULA and another 24 cases were treated with transurethral resection of bladder tumor (TURBT) from Feb 2024 to Mar 2025 at Kochi Medical School Hospital. Intraoperative and postoperative outcomes and recurrence-free survival (RFS) were analyzed between TULA and TURBT.
Results:
This study showed that TULA using a 980-nm diode laser was significantly shorter than TURBT in terms of perioperative results: operative time, hospital stay, catheterization, bladder irrigation, and postoperative hospital stay. Regarding the occurrence of complications, TULA was observed to be less prevalent than TURBT in all cases. Kaplan-Meier curves showed that TULA was significantly associated with longer RFS compared to TURBT (hazard ratio 4.739; 95% confidence interval, 1.272–17.65; p = 0.02039).
Conclusions:
Our preliminary results showed that TULA for recurrent bladder cancer is feasible and safe.
Aim:
Transurethral laser ablation (TULA) for recurrent bladder cancer is a less invasive treatment method for patients. We report here our initial clinical experience with TULA for recurrent bladder cancer.
Methods:
This retrospective study analyzed 48 patients. Twenty-four cases were treated with TULA and another 24 cases were treated with transurethral resection of bladder tumor (TURBT) from Feb 2024 to Mar 2025 at Kochi Medical School Hospital. Intraoperative and postoperative outcomes and recurrence-free survival (RFS) were analyzed between TULA and TURBT.
Results:
This study showed that TULA using a 980-nm diode laser was significantly shorter than TURBT in terms of perioperative results: operative time, hospital stay, catheterization, bladder irrigation, and postoperative hospital stay. Regarding the occurrence of complications, TULA was observed to be less prevalent than TURBT in all cases. Kaplan-Meier curves showed that TULA was significantly associated with longer RFS compared to TURBT (hazard ratio 4.739; 95% confidence interval, 1.272–17.65; p = 0.02039).
Conclusions:
Our preliminary results showed that TULA for recurrent bladder cancer is feasible and safe.
DOI: https://doi.org/10.37349/etat.2026.1002386
This article belongs to the special issue Emerging Innovation in Surgical and Medical Approaches on the Horizon for Urogenital Malignancies
