Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in theASCO Guidelines Methodology Manual. ASCO Living Guidelines follow theASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only). Updates are published regularly and can be found athttps://ascopubs.org/nsclc-da-living-guideline.

Living guidelines are developed for selected topic areas with rapidly evolving evidence that drives frequent change in recommended clinical practice. Living guidelines are updated on a regular schedule by a standing expert panel that systematically reviews the health literature on a continuous basis, as described in theASCO Guidelines Methodology Manual. ASCO Living Guidelines follow theASCO Conflict of Interest Policy Implementation for Clinical Practice Guidelines. Living Guidelines and updates are not intended to substitute for independent professional judgment of the treating clinician and do not account for individual variation among patients. See appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only). Updates are published regularly and can be found athttps://ascopubs.org/nsclc-non-da-living-guideline.

The authors present the guidelines of the REFCOR (French Rare Head-and-Neck Cancer Expert Network) for sinonasal mucosal melanoma.

With the approval of PARP inhibitors (PARPi), both as monotherapy and in combination with androgen receptor signalling inhibitors (ARSi), for metastatic castration-resistant prostate cancer (mCRPC) and their rapid development in earlier disease settings, there is an urgent need to integrate homologous recombination repair (HRR) testing into daily clinical practice to identify patients who may benefit from these therapies and to improve patient management. Alterations in HRR genes are found in approximately 15-30% of patients with mCRPC and are associated with poor prognosis. In addition, some alterations are hereditary; therefore, testing also has implications for the identification of hereditary cancer risk. The successful implementation of HRR gene testing depends not only on access to sequencing technologies but also on the establishment of a comprehensive pre- and post-analytical framework. The aim of this document is to establish a multidisciplinary expert opinion consensus on the optimisation of molecular assessment of BRCA1/2 and other HRR gene alterations in metastatic prostate cancer to support implementation in clinical practice.

Hairy cell leukemia (HCL) and HCL variant (HCLv) are distinct, rare, and chronic splenic B-cell lymphomas/leukemias that partially overlap in clinicopathologic presentation but differ in genetic basis, prognosis, and management. HCL is caused by the BRAF-V600E kinase-activating mutation in >95% of the patients, usually has excellent responses to chemotherapy with purine analogues, and is also amenable to BRAF inhibitor-based targeted treatments. In contrast, HCLv lacks BRAFV600E mutation, requires combined therapy with purine analogues in addition to rituximab, and generally shows less durable responses. Here, an international team of hematologists, experts on these rare diseases, was convened by the Hairy Cell Leukemia Foundation to update the previous guidelines (published in 2017) by providing a summary of current methods to diagnose and manage patients with HCL and HCLv as well as a prospective on newer targeted therapies to further improve outcomes.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumors that appear as metastases for which a standard diagnostic work-up fails to identify the tissue of origin. There is now high-level evidence showing that actionable genomic alterations should be routinely determined in patients with CUP to enable molecularly guided therapy as appropriate. In this guideline (updated in 2025), we summarize diagnostic processes and therapeutic options for CUP, as well as new developments in molecular medicine that will help to improve the poor outcomes associated with this unique disease entity.

Management of chronic lymphocytic leukemia/ small lymphocytic lymphoma. (CLL/SLL) has undergone a significant paradigm shift, with chemo immunotherapy being virtually abandoned in favor of targeted agents. A panel of CLL/SLL experts from Tuscany proposes an updated real-life diagnostic and therapeutic approach that integrates genomic and somatic prognostic factors into routine risk stratification and treatment decisions. While the safety and efficacy of new agents are well-established in both clinical trials and real-world series, the rapid introduction of second-generation BTK inhibitors and BCL-2 antagonists necessitates a uniform and shared approach for daily clinical practice. This updated consensus reinforces the essential role of FISH for 17p deletion and TP53 mutational status before every treatment line, while IGHV mutation status should be performed for initial risk assessment. Reflecting current evidence, the proposal emphasizes a comprehensive pretreatment workup, with a particular focus on cardio-oncological screening and monitoring according to recent ESC guidelines to mitigate risks associated with BTKIs. The consensus reaffirms abdominal and superficial lymph node ultrasound as the gold standard radiological investigation for both diagnosis and response evaluation in CLL, offering a practical and radiation-free tool for longitudinal monitoring. Treatment selection is tailored based on age, genetic risk, and comorbidities, prioritizing zanubrutinib, acalabrutinib, and venetoclax-based regimens to prevent unnecessary toxicities. Furthermore, the consensus addresses the management of high-risk scenarios, including Richter transformation and the emerging role of pirtobrutinib and BTK degraders. By combining the latest clinical evidence with extensive daily experience, this updated Tuscany consensus provides a practical framework for optimized, personalized management of CLL/SLL patients in the modern therapeutic era.

Genomic technologies including next-generation sequencing (NGS) and arrays for cytogenetic anomalies are now standard of care in England for the diagnostic evaluation of patients with suspected haematological malignancies. Challenges remain in the management of potential germline findings as a result of NGS panels and copy number variant analyses in haemato-oncology pathways. The first national consensus meeting in April 2022 organised by the UK Cancer Genetics Group (UKCGGG), in collaboration with the CanGene-CanVar research programme and the NHS England haemato-oncology working group led to published best practice recommendations on laboratory and clinical pathways where there was potential to identify germline predisposition to haematological malignancies. On 3 and 4 April 2025, a second national meeting was held to address further challenges in these pathways and review updates in the national landscape subsequent to the 2022 recommendations. The meeting specifically focussed on TP53, DDX41, myeloproliferative neoplasm driver genes, non-single nucleotide variation and identification of gene carriers for addition to the National Inherited Cancer Predisposition Register (NICPR) through the National Disease Registration Service (NDRS). Using the format of a pre-workshop survey followed by structured discussion and in-meeting polling, high-level consensus was achieved for UK best practice across these areas.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate are intended to serve as a resource for health care providers to identify individuals who may benefit from cancer risk assessment and genetic counseling and testing; help guide decisions related to genetic testing; and facilitate a multidisciplinary approach in the comprehensive care of individuals at increased risk for hereditary breast, ovarian, pancreatic, and prostate cancer. The current guidelines focus primarily on assessment of pathogenic and likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants associated with increased risk of these cancers. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding screening for prostate cancer and pancreas cancer, as well as testing criteria for nonepithelial ovarian cancer.

The evolution of serous high grade ovarian cancer management is characterized by a more regulated patients' journey on the one hand and the development of new therapeutic options on the other hand, the selection of which is guided by tumor molecular characteristics. Surgery remains the cornerstone of treatment. It can be performed only in authorized expert sites that can demonstrate sufficient experience from highly skilled surgical teams, and quality criteria including prehabilitation and rehabilitation programs. The diagnostic step is crucial; it comprises multiple biopsies that allow reliable pathological and molecular analyses, and a comprehensive surgical staging. Determination of BRCA1/2 mutation and homologous recombination deficiency statuses by validated methods guide maintenance therapy at advanced stages and referring to oncogenetic consultation if appropriate. For these advanced diseases, the two main questions for surgical strategy are the feasibility of complete resection (without residual disease, CC-0), assessed during surgical exploration of pelvis and abdomen, and the optimal timing of this surgery (upfront or after neoadjuvant chemotherapy). In recurrent diseases, surgery remains a main piece of treatment in case of late relapse and medical treatment depends on drugs used in the first line; in early platinum resistant relapse, a new therapeutic option is available with mirvétuximab soravtansine.

Histomolecular diagnosis of endometrial cancer systematically includes the evaluation of hormonal receptors, P53 and MMR statutes (determination of PD-L1 and HRD statutes is not required). Therapeutic progress in advanced endometrial cancer is mainly related to the first-line utilization of immunotherapy associated with chemotherapy, a strategy assessed in five randomized controlled trials, although at the moment, only dostarlimab is available in France. Immunotherapy administration requires specific pretherapeutic workup and monitoring. Hormone therapy remains an option in non-aggressive, low grade endometrioid cancer, expressing hormone receptors. Treatment choice is based on clinical situation (upfront metastatic disease or relapse after adjuvant therapy, and duration of platinum-free interval in case of adjuvant therapy), disease aggressivity, molecular status (in particular, MMR status) and patients' comorbidities. PARP inhibitors are not recommended as maintenance therapy. In second line, the combination of pembrolizumab and lenvatinib is the standard treatment if chemoimmunotherapy has not been used previously. If it has been, therapeutic strategy depends on the duration of platinum-free interval. Inclusion in a clinical trial should always be considered when the patient's performance status makes it possible. The choice of the trial is guided by HER2 status in immunohistochemistry and results of new generation sequencing when available. The current trend towards the development of personalized medicine highlights the importance of pathological and molecular characterization of the tumor.

Cancer predisposition syndromes (CPSs), including genetic tumour risk syndromes (genturis), are a heterogeneous group of genetic disorders characterised by an increased risk of developing tumours compared to the general population. CPSs raise reproductive issues for affected individuals because of the risk of passing the disease-causing genetic alterations on to offspring. The demand for reproductive counselling is often unmet due to the lack of sufficient healthcare professionals with the specialised knowledge, experience and skill. Based on a comprehensive literature review of 851 publications and expert consensus (multidisciplinary medical experts and patient representatives), the European Reference Network on genetic tumour risk syndromes (ERN GENTURIS) developed a guideline providing 16 recommendations for reproductive counselling in CPSs. The central recommendation is to offer reproductive counselling proactively to all individuals with a CPS and their relevant family members, together with psychological support and in multidisciplinary collaborations. This guideline aims to standardize the offer of reproductive counselling for individuals with a CPS across Europe, empowers healthcare professionals for their specific tasks, and helps patients dealing with their own challenges.

Measurable residual disease (MRD) monitoring has become a critical component in the management of acute myeloid leukemia (AML), to inform prognosis, guide therapy, and serve as a key end point in clinical trials. The 2025 update of the MRD guideline provides a comprehensive and refined framework for MRD assessment, aligned with the European LeukemiaNet (ELN) 2022 genetic risk classification. Developed by members of the ELN AML MRD Working Party, the guidelines incorporate expert consensus determined through a 2-stage Delphi round. They address the clinical implementation of MRD methodologies, technical considerations, integration into clinical trials, and future directions. Importantly, MRD recommendations are tailored to individual prognostic and genetic subgroups. A new qualitative MRD response category, designated as optimal, warning, or high risk of treatment failure, has been introduced to facilitate contextual interpretation of the MRD burden and its clinical relevance. Notably, ultrahigh-sensitivity next-generation sequencing-based MRD assessment is now recommended for FLT3 internal tandem duplication-mutated AML after intensive chemotherapy and before allogeneic hematopoietic cell transplantation. A total of 56 recommendations were formulated, with 53 achieving a high level of consensus (≥90%). These updated guidelines represent a major step forward toward harmonizing MRD assessments in AML and enhancing its clinical utility across diverse treatment settings.

Waldenström's macroglobulinemia (WM) is a rare, indolent B-cell lymphoma that predominantly affects older adults. In recent years, significant progress has been made in understanding its pathogenesis, identifying relevant biomarkers, and developing novel therapeutic approaches to complement traditional chemoimmunotherapy-collectively reshaping the management landscape of WM. In this article, we provide comprehensive, evidence-based recommendations for the diagnosis, molecular evaluation, and treatment of WM, including strategies for both frontline and relapsed disease. These guidelines are informed by the latest clinical research, expert consensus, and current practice standards, with the goal of equipping clinicians with a practical and effective framework for delivering optimal care to patients with WM.

It has been five years since the last version of the clinical practice guidelines for the management of adult diffuse gliomas was published by the Asian Glioma Genome Atlas (AGGA). Significant progress and revisions have occurred in the diagnosis and treatment of adult diffuse gliomas in recent years. In response to these updates, the joint guideline committee of the Chinese Glioma Cooperative Group (CGCG), the Society for Neuro-Oncology of China (SNO-China), and the Chinese Brain Cancer Association (CBCA) has revised the clinical practice guidelines. This updated guideline emphasizes molecular and pathological diagnostics, as well as the primary treatment modalities of surgery, radiotherapy, chemotherapy, and targeted therapy. Additionally, we have incorporated findings from recent clinical trials of new therapies to align with cutting-edge treatment strategies. This guideline is designed to serve as a practical resource for all professionals involved in managing adult diffuse glioma patients, while also providing valuable information for insurance companies and other institutions responsible for regulating cancer care costs in China and beyond.

Approximately 5% of all colorectal cancers have a strong genetic component and are classified as hereditary colorectal cancer (HCRC). Some of the unique features commonly seen in HCRC cases include early age of onset, synchronous/metachronous cancer occurrence, and multiple cancers in other organs. These characteristics require different management approaches, including diagnosis, treatment or surveillance, from those used in the management of sporadic colorectal cancer. Accurate diagnosis of HCRC is essential because it enables targeted surveillance and risk reduction strategies that improve patient outcomes. Recent genetic advances revealed several causative genes for polyposis and non-polyposis syndromes. The Japanese Society for Cancer of the Colon and Rectum (JSCCR) first published guidelines for the management of HCRC in 2012, with subsequent revisions every 4 years. The 2024 update to the JSCCR guidelines for HCRC was developed by meticulously reviewing evidence from systematic reviews and the consensus of the JSCCR HCRC Guidelines Committee, which includes representatives from patient advocacy groups for FAP and Lynch syndrome. These guidelines provide an up-to-date summary of HCRC, along with clinical recommendations for managing FAP and Lynch syndrome.

Breast cancer is one of the most common malignancies among women in China. According to GLOBOCAN 2022, more than 350,000 new breast cancer cases were diagnosed in China, ranking second among all newly diagnosed cancers in women. Although breast cancer has entered an era of chronic disease management and overall survival has improved substantially, the prognosis of metastatic breast cancer (MBC) remains unsatisfactory. The genome of MBC is characterized by spatiotemporal heterogeneity and may undergo dynamic evolution. With the continuous identification of actionable alterations, targeted therapies guided by genomic testing have emerged as an important approach to improving patient outcomes. Therefore, the implementation of standardized genomic testing in clinical practice has become an urgent priority. While several international and domestic guidelines have recommended genomic testing for MBC, China still lacks detailed technical specifications and clinical pathways tailored to advanced disease in the local healthcare context. Accordingly, it is imperative to establish a guideline for genomic testing in advanced breast cancer that reflects national realities, ensures strong clinical operability, unifies testing standards, and optimizes workflows, thereby expanding access to precision therapy and improving patient prognosis. Against this background, the Breast Cancer Committee of the Chinese Anti-Cancer Association convened a multidisciplinary working group experts. Following predefined methodological procedures-including clinical question prioritization, systematic evidence retrieval, graded evaluation, and formulation of recommendations-the guideline was developed. It integrates the latest evidence with multidisciplinary expert consensus, providing specific recommendations on key aspects of genomic testing for MBC, including patient eligibility, specimen selection, testing methodologies, and prioritization of target genes. In addition, the guideline systematically summarizes available targeted therapeutic strategies for different genomic alterations, and provides graded recommendations based on both levels of evidence and drug accessibility, thereby ensuring clarity and facilitating clinical implementation. This guideline is closely aligned with the realities of clinical practice and drug accessibility in China, with a strong emphasis on the feasibility of testing and the actionability of results. It establishes a multidisciplinary consensus on standardized pathways for genomic testing in patients with MBC, aiming to bridge precision diagnostics and individualized targeted therapy, and to provide practical guidance for improving the standardization of advanced breast cancer care nationwide.

Breast cancer is one of the most prevalent malignancies among women globally and ranks second in the incidence of malignant tumors among Chinese women. It has become a significant public health issue that seriously threatens women's health, highlighting the urgent need to establish a precision prevention and treatment system. Currently, the diagnosis and treatment of breast cancer have transitioned from traditional histological classification to a precision medicine phase centered on molecular characteristics, significantly enhancing the specificity and effectiveness of clinical treatments. With the rapid development of molecular biology techniques, the continuous discovery and application of new biomarkers have fueled the growing demand for molecular pathological testing in clinical settings. The widespread use of various molecular testing platforms has driven clinical decision-making from population-based and standardized approaches to individualized and refined strategies. This shift enables clinicians to more accurately assess patient prognosis and predict treatment responses, thereby formulating more appropriate treatment plans. However, the emergence of new technologies and biomarkers has also increased the requirements for standardization, normalization of testing procedures, and the establishment of quality control. While this trend brings new opportunities for precision diagnosis and treatment of breast cancer, it also poses higher demands on clinical and pathological practices, necessitating the establishment of unified precision diagnosis and treatment pathways and consensus. The "Guidelines on clinical practice of molecular tests in breast cancer in China (2025 edition)" was developed through a multidisciplinary collaboration among experts in molecular pathology and breast oncology, integrating domestic clinical realities with international advancements. We systematically evaluated evidence quality (GRADE criteria) and recommendation strength based on global clinical studies and practical experiences. The guideline aims to harmonize localized molecular diagnostic expertise with global insights, addressing critical needs in precision therapeutics, hereditary susceptibility assessment, and prognostic recurrence risk stratification. It proposes optimized clinical testing algorithms, emphasizes multidisciplinary integration, and establishes standardized protocols to ensure robust implementation of molecular diagnostics in China. This document serves as an authoritative reference for clinicians and pathologists to refine individualized patient management and jointly promotes the realization of the "Healthy China 2030" strategic goal.

RAD51C, RAD51D, and BRIP1 germline pathogenic variants (GPVs) are associated with increased lifetime risks of tubo-ovarian cancer. Resources for managing RAD51C, RAD51D, and BRIP1 heterozygotes in clinical practice are limited.

To formulate standardized recommendations for recognizing and managing the genetic risk of breast cancer, based on the latest scientific evidence and clinical experience.