Genomic testing has the potential to transform cancer care across the patient pathway. However, its benefits remain unevenly realised across populations and health systems. Precision oncology is characterised by a strong promissory discourse, with expectations of improved outcomes and cost-effectiveness, yet real-world implementation remains variable and context dependent. This review examines how patient and public awareness interacts with, and is constrained by, structural, organisational and political-economic factors that shape equitable access to genomically driven cancer care across five themes: (1) the power of patient and public advocacy; (2) learning from the patient perspective; (3) culturally responsive communication; (4) structural and personal barriers and facilitators and (5) political economy of health. Examples are mapped across global regions to highlight how health system, structural and societal factors continue to limit the universal realisation of genomic medicine’s benefits. We present four recommendations to strengthen the translation of awareness into equitable access and clinical impact: (1) expand and adequately power genomic studies in underserved populations; (2) improve risk communication and decision-making across the cancer pathway; (3) equitable validation and interpretation of emerging genomic technologies and (4) generate real-world evidence on access, uptake and outcomes of genome-matched therapies. Embedding awareness, trust, access and equity in future initiatives is imperative to realise the promise of precision medicine for all patients.
Cancer treatment has dramatically improved with the introduction of immune checkpoint inhibitors (ICIs). They are now common treatments for individuals of reproductive age, an important consideration when treating pregnant patients. Cancer in pregnancy is rare and guidelines available for ICI use during gestation are based on pre-clinical studies, single human case reports and spontaneous report databases. The immune pathways including PD-1 and PD-L1/PD-L2 and CTLA-4 provide critical immune inhibitory checkpoints at the maternal-fetal interface. These pathways support immune tolerance during implantation and the development of the placenta. Experimental animal studies demonstrated that inhibiting these immune pathways will result in increased frequency of adverse events such as spontaneous abortions and premature births. Human placental transfer of ICIs across the placenta is minimal in early gestation and increases in later gestation, coinciding with less exposure to developing organs during organogenesis and more exposure closer to term. There are now seventeen documented cases in the literature describing pregnant patients treated with ICIs. Most neonates developed normally in infancy, while there are a few documented cases of suspected neonatal immune-mediated complications. Experts including regulatory agencies and oncology professional organisations advise against the use of ICIs in pregnancy unless their use is critical to the survival of the patient and there is no safer alternative. Patient counselling regarding the risks of using ICIs during pregnancy, postpartum or both, involves a multidisciplinary team and requires shared decision making regarding maternal health, infant follow-up and standardised documentation for understanding potential delayed effects on neonate immunity as well as providing accurate information for future counselling.
Cancer is a genomic disease caused by variants in genes that impact on the regulation of cell division, cell growth and cell death. While the majority of cancers are caused by acquired genomic variation, a significant minority are influenced by inherited genetic variation which can increase the chance of a person developing cancer in their lifetime. Inherited genetic factors can be monogenic or polygenic and also interact with other cancer risk factors to create an individualised risk profile. Understanding personalised cancer risk can facilitate precision screening, prevention and early detection strategies. In this review, we give an overview of constitutional genetic susceptibility to cancer, how to assess and identify enhanced susceptibility and exemplars of how this influences precision management.
Radiotheranostics is reshaping precision oncology by integrating molecular imaging with targeted radionuclide therapy through matched diagnostic-therapeutic radiopharmaceutical pairs. Landmark clinical successes, including Lutetium-177-DOTATATE (177Lu-DOTATATE) and 177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617), have validated this approach and accelerated the shift from empiric dosing towards evidence-based practice supported by randomised trials. Beyond established somatostatin receptor and PSMA paradigms, emerging platforms targeting tumour-stroma and lineage-associated biology, such as fibroblast activation protein and other receptor systems, are broadening applications across diverse malignancies. In parallel, advances in radionuclide science, including next-generation β-emitters and targeted α-particle therapies, are enabling strategies with higher biological effectiveness and potential advantages in small-volume and micrometastatic disease. Innovations in ligand and vector engineering (including half-life extension and multivalent constructs) aim to improve tumour retention and therapeutic index. Finally, quantitative imaging, personalised dosimetry (from organ-based to voxel-level approaches) and artificial intelligence (AI)-enabled workflows are laying the foundation for scalable, individualised treatment planning and response assessment. This review synthesises key developments in molecular targeting, radiochemistry, dosimetry, AI and combination strategies, outlining the priorities required to translate next-generation radiotheranostics into durable, multidisciplinary cancer care.
Objective:To compare the real-world effectiveness and recorded safety of first-line liposomal irinotecan+oxaliplatin+fluorouracil+leucovorin (NALIRIFOX), modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (Gem/NabP) in treatment-naïve patients with advanced pancreatic ductal adenocarcinoma (PDAC) in Thailand. Methods and analysis:This retrospective, multicentre cohort study included adult patients with unresectable locally advanced or metastatic PDAC who initiated first-line NALIRIFOX, mFOLFIRINOX or Gem/NabP across 10 major Thai cancer centres between January 2021 and July 2024. Propensity score matching was performed to reduce treatment selection bias using age, sex, Eastern Cooperative Oncology Group performance status, metastatic burden, primary tumour location and baseline albumin. Overall survival (OS) and progression-free survival (PFS) were the primary outcomes. Secondary outcomes were objective response rate (ORR) and grade ≥3 treatment-related adverse events. Safety analyses were limited to matched patients with sufficient follow-up documentation to assess toxicity retrospectively. Results:Of 513 eligible patients, 199 were included in the matched cohort: 52 received NALIRIFOX, 105 mFOLFIRINOX and 42 Gem/NabP. Median OS was 10.4 months for NALIRIFOX, 9.6 months for mFOLFIRINOX and 6.0 months for Gem/NabP. NALIRIFOX was associated with similar OS to mFOLFIRINOX (HR 1.09, 95% CI 0.72 to 1.67; p=0.68) and longer OS than Gem/NabP (HR 1.68, 95% CI 1.03 to 2.75; p=0.04). Median PFS was 5.0 months for both NALIRIFOX and mFOLFIRINOX and 4.3 months for Gem/NabP; NALIRIFOX showed longer PFS than Gem/NabP (HR 1.63, 95% CI 1.05 to 2.50; p=0.03), while PFS was similar between NALIRIFOX and mFOLFIRINOX. ORR was 37.5% for NALIRIFOX, 23.8% for mFOLFIRINOX and 40.5% for Gem/NabP. Recorded grade ≥3 toxicities appeared lower with NALIRIFOX, although cross-regimen safety comparisons were limited by retrospective toxicity ascertainment and likely differential reporting. Baseline carbohydrate antigen 19-9 remained imbalanced after matching because it was not included in the propensity model. Conclusion:In this multicentre real-world matched cohort of advanced PDAC, NALIRIFOX and mFOLFIRINOX were associated with comparable survival outcomes, and both were associated with more favourable survival than Gem/NabP. Recorded grade ≥3 toxicities appeared lower with NALIRIFOX, but safety findings should be interpreted cautiously because of retrospective toxicity capture and residual confounding. Prospective studies are needed to validate these findings.
Artificial intelligence (AI) has been rapidly integrated into radiation oncology workflows, with the most visible successes occurring in auto-segmentation of target volumes and organs at risk. While these advances have delivered meaningful efficiency gains and improved standardisation, their impact on clinical outcomes in head and neck cancer remains indirect. In head and neck radiotherapy, long-term toxicity and quality of life are influenced not only by contouring accuracy but more directly by nuanced dosimetric trade-offs during treatment planning. This narrative review synthesises the current landscape of AI applications in head and neck radiotherapy planning and highlights the limitations of a segmentation-dominated paradigm. We review the evolution of planning AI from knowledge-based statistical models to deep learning-based dose prediction and emerging reasoning-driven frameworks. We also aim to discuss how these approaches may function as complementary components of a broader planning intelligence ecosystem. In addition to potential patient-level benefits, we examine the system-level implications of planning and dosimetry AI. Finally, we outline key considerations for the safe evaluation and deployment of planning AI. Together, this review positions planning and dosimetry AI as an enabling infrastructure for predictive, adaptive and equitable head and neck radiotherapy.
The rising incidence of oropharyngeal cancer (OPC), primarily driven by human papillomavirus (HPV), presents a significant public health challenge. Given the markedly better prognosis associated with HPV-positive OPC, there is a compelling need to balance oncologic efficacy and reduce treatment morbidity. Although early de-escalation trials did not change standards, selective, biomarker-informed strategies show promise. This review synthesises evidence across transoral robotic surgery (TORS), reductions in RT dose and elective volumes, systemic therapy modification and the integration of circulating HPV DNA, immune profiling and functional imaging to guide truly personalised de-escalation. Ultimately, successful deintensification will require integration of biomarkers, multidisciplinary collaboration and patient-centred decision-making, moving beyond stage and HPV status alone.
Objectives Newer cancer treatments, such as small molecule tyrosine kinase inhibitors and monoclonal antibodies that restore anti-tumour immunity, lead to improved survival when delivered as adjuvant or neoadjuvant treatments with surgery or chemoradiotherapy for early and locally advanced non-small cell lung cancer (NSCLC). However, these novel drugs are costly, posing a funding challenge for most health systems. A Markov modelling-based cost–utility analysis was conducted to determine its cost-effectiveness in Sri Lanka from a health system perspective.Design A decision-analytic model was developed to evaluate the incremental costs and quality-adjusted life-years (QALYs) associated with treating patients diagnosed with stage II-III NSCLC for the following treatments: adjuvant osimertinib following surgery and after curative chemoradiotherapy, adjuvant alectinib after surgery, neoadjuvant nivolumab prior to surgery, adjuvant pembrolizumab and atezolizumab after surgery, perioperative durvalumab and pembrolizumab and consolidation durvalumab after chemoradiotherapy. The study employed 1-month simulation cycles over a lifetime. Sex-specific analyses were conducted and parameter uncertainty was addressed using probabilistic analysis. A willingness-to-pay threshold of US$6700 per QALY was applied. A 5-year budget impact analysis was performed for therapies identified as cost-effective.Results At the primary threshold, adjuvant osimertinib after surgery and after curative chemoradiotherapy, adjuvant alectinib after surgery and neoadjuvant nivolumab were cost-effective in both males and females. However, conclusions were sensitive to lower opportunity-cost-informed thresholds. At US$3000 per QALY, only osimertinib-based strategies remained robustly cost-effective. Other therapies were not cost-effective at current prices and would require substantial price reductions. The 5-year cumulative budget impact of adopting cost-effective therapies under full implementation was approximately US$11.8 million.Conclusions Using a common modelling approach and Sri Lanka-specific costing assumptions, we present comparative cost-effectiveness results across multiple novel perioperative, adjuvant and neoadjuvant strategies for stage II–III NSCLC. These findings are intended to support prioritisation of which therapies could be considered first for public funding and to indicate the price reductions required for other agents to represent value for money.
Penile cancer (PeCa) is a rare malignancy with substantial global variation in clinical presentation, staging practices and treatment approaches. This scoping review synthesises current evidence across key domains of PeCa management, including tumour classification, human papillomavirus (HPV) integration, organ preservation, nodal staging, systemic therapy and survivorship care. Despite recent updates in the American Joint Committee on Cancer staging system, limitations persist, particularly the absence of biologically relevant factors such as HPV status. While HPV-associated tumours may exhibit different responses to radiotherapy and systemic treatments, routine HPV testing and serotyping are not yet standardised in clinical practice. Early-stage PeCa remains amenable to organ-sparing approaches—including brachytherapy and reconstructive surgery—yet access to these modalities varies widely. Nodal management remains an area of controversy, with global inconsistencies in surgical templates and staging algorithms. Dynamic sentinel lymph node biopsy is emerging as a minimally invasive alternative but remains underused outside of high-volume centres. For node-positive disease, there is growing support for treatment intensification with chemotherapy and radiotherapy; however, prospective evidence is limited. Survivorship issues, particularly regarding psychosocial support and functional outcomes, remain poorly addressed in both research and routine care. This review identifies persistent gaps in the literature and highlights the need for international consensus-building, longitudinal data collection and equitable access to multidisciplinary care through collaborative efforts.
Cervical cancer is a largely preventable disease, yet over 90% of its global mortality occurs in low and middle income countries(LMICs), reflecting profound inequities in access to screening and treatment. Traditional multivisit cervical cancer prevention models have been inadequate in these settings, largely due to high rates of loss to follow-up and insufficient health system infrastructure. In response, the WHO recommends the screen-and-treat (SAT) approach, which offers treatment based on a positive screening result, without requiring histological confirmation, preferably within a single visit. This narrative review synthesises evidence on the clinical effectiveness and operational feasibility of SAT in resource-constrained settings, with a focus on screening modalities, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) testing and treatment options including cryotherapy, thermal ablation (TA) and large-loop excision of the transformation zone (LLETZ). While VIA is low-cost and provides immediate results, its accuracy is limited by provider-dependent subjectivity. HPV testing, particularly through point-of-care platforms and self-sampling, offers higher sensitivity and improved acceptability and is now the WHO-recommended primary screening modality. For treatment, portable TA devices have emerged as a logistically superior alternative to cryotherapy in LMICs, eliminating the need for compressed gas while maintaining comparable efficacy. Recent evidence further confirms that TA is non-inferior to LLETZ in real-world SAT settings, challenging the long-held perception that ablative therapies are clinically inferior. Concerns about overtreatment persist but must be weighed against the considerably greater risk of undertreatment in fragmented health systems. Women living with HIV require particular attention, given higher HPV prevalence, lower test specificity, more rapid disease progression and substantially lower post-treatment cure rates, necessitating tailored management protocols. The SAT approach represents a pragmatic, evidence-based strategy for achieving cervical cancer elimination in LMICs, but its effectiveness will depend on contextually appropriate implementation, integration within existing primary healthcare services and dedicated strategies for high-risk populations.
The oligometastatic paradigm has expanded the use of stereotactic ablative radiotherapy (SABR) and local consolidative therapy (LCT) in metastatic non-small cell lung cancer (NSCLC), but accumulating evidence suggests that ‘oligometastatic NSCLC’ is not a single clinical entity. As systemic therapy has advanced—particularly third-generation EGFR tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors—both the intent and the incremental value of local therapy have diverged by molecular subtype, metastatic tempo and treatment setting. In EGFR-mutated disease, multiple prospective studies now support LCT as a strategy to extend durable benefit from TKIs by ablating limited sites of disease, with contemporary randomised data emerging in the osimertinib era and ongoing trials addressing optimal timing and completeness of consolidation. In driver-negative, immunotherapy-treated NSCLC, early phase and real-world series suggest that carefully selected patients can achieve durable control within multimodality pathways, but the most practice-defining randomised evidence to date has not supported routine consolidation for all non-progressing patients and highlights pneumonitis risk, reinforcing the need for stringent staging and selection. Management of EGFR-mutated small and non-symptomatic brain metastases has similarly evolved towards systemic-first sequencing with selective stereotactic radiosurgery for high-risk lesions or focal central nervous system escape, informed by emerging randomised data. Across settings, lesion count alone is an imperfect surrogate for biology; metastatic tempo, molecular drivers and treatment response patterns are increasingly relevant to deciding when SABR should be comprehensive, selective or deferred. Ongoing trials in targeted and immunotherapy eras will determine when LCT should be integrated as standard care versus an optimisation strategy for a minority. We propose a pragmatic framework centred on treatment intent—comprehensive ablation for potentially curable limited disease versus focal ablation to maintain an effective systemic agent—aimed at supporting multidisciplinary decision-making as the evidence base evolves.
Objectives In the last decades, artificial intelligence has made tremendous steps in supporting decision-making in healthcare. Bayesian networks (BNs) have emerged as powerful tools for probabilistic modelling and offer important advantages compared with regression-based models. This systematic review identifies the available literature on BNs for prognostication in oncology, evaluates their performance and discusses how BNs can overcome limitations of traditional prediction models.Design, setting, participants The systematic review was performed according to the Cochrane guidance and reported according to the guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). The protocol was registered in PROSPERO. Studies identified in MEDLINE and EMBASE were included.Main outcome measures Eligible studies investigated BNs as prognostication or predictive tools within oncology (solid or haematological malignancies).Results A total of 52 studies were included, with a median construction cohort size of 438 patients. More than half of studies harboured unclear or high concerns about bias. Most studies used score-based structure learning approaches to construct the BNs. External validation was applied in a minority of studies and showed excellent performance metrics when hybrid techniques (integration of machine-learning and expert knowledge) were applied. Studies comparing BN validation with Cox regression validation showed better performance for BNs in most studies.Conclusions When constructed with hybrid techniques, BNs offer great potential to support decision-making in clinical oncology. Advantages include their ability to estimate treatment effects with non-randomised data, to model causal relationships, to apply counterfactual reasoning and to work with missing variables. To be implemented into clinical practice, hybrid construction techniques, high-quality external validation, prospective evaluation with a health technology assessment and adequate postmarketing surveillance and maintenance are essential.PROSPERO registration number CRD420251140130.
Despite revolutionary advances in genomic technologies, a persistent disconnect exists between research discoveries and clinical implementation. This translational gap stems from misaligned incentive and funding structures: researchers prioritise publications over clinical uptake, with funding ending at proof-of-concept; clinicians face time constraints and integration challenges; regulators struggle with rapidly evolving technologies and genomics-specific complexities including variant classification and data governance. We propose that dedicated translational medicine centres are essential to bridge this divide. These centres require multidisciplinary teams spanning clinician-scientists, regulatory affairs specialists, health economists, biostatisticians and bioinformaticians, providing end-to-end support from feasibility assessment through to regulatory approval. Success requires government investment, explicit health equity assessments and measuring achievement through clinical uptake rather than traditional academic metrics.
Objective To examine the extent to which epididymo-orchitis or urinary tract infections (UTI) may precede testicular cancer (TC) in Sweden. Methods and analysis We conducted a nationwide, open-cohort study including 8 382 433 men between 1964 and 2018. Standardised incidence ratios (SIR) with 95% CIs were calculated to compare TC incidence rates in men diagnosed with epididymo-orchitis or UTI—either in the same calendar year as TC or in preceding calendar years (mean follow-up: 6.85 years, ±8.31 SD)—with those in men without these infections. Analyses were controlled for potential confounders and a sensitivity analysis on cystitis was also conducted. Results A total of 11 903 men were diagnosed with TC during the study period; of these, 400 (3.36%) had been diagnosed with epididymo-orchitis and 122 (1.02%) with UTI. The TC incidence rate per 100 000 person-years was 5.09 (95% CI 4.99 to 5.18) for the entire study period and increased from 2.84 (2.68 to 3.02) in 1964–1973 to 8.37 (7.99 to 8.77) in 2014–2018. Among men with epididymo-orchitis (n=89 596), TC was diagnosed in 0.45%, with an overall SIR of 6.34 (95% CI 5.73 to 7.00) in the full model. For TC diagnosed in the same calendar year as epididymo-orchitis (289 cases), the SIR was 85.97 (76.33 to 96.50). For TC diagnosed in subsequent calendar years (111 cases) the SIR was 1.86 (1.53 to 2.24), with most cases diagnosed within 1–4 calendar years of follow-up (65 cases). Among men with UTI (n=294 201), TC was diagnosed in only 0.04%, with an overall SIR of 1.74 (1.44 to 2.08). The associations were not significant for TC diagnosed 1–4 years after UTI, nor between cystitis and subsequent TC. Conclusion The association between epididymo-orchitis and TC was strong and persisted for several years after the infection. The findings support clinicians maintaining a heightened awareness of TC in patients with epididymo-orchitis, particularly when in diagnostic doubt or if symptoms persist, and could be a foundation for more detailed clinical studies on epididymo-orchitis as a potential TC risk factor. Although a potential link between UTI and TC was identified, the absolute risk was almost negligible.
Objective:Unlike survival measures, life expectancy readily illustrates the burden of cancer on society and the average impact on individuals diagnosed with cancer. Cancer stage at diagnosis is a key prognostic factor and hence it is important to obtain stage-specific life expectancy estimates. However, completeness of recording for cancer stage at diagnosis is often historically poor in cancer registries. Therefore, it can be challenging to obtain the long-term stage-specific survival estimates required for estimating stage-specific life expectancy. We provide the first stage-specific life expectancy estimates using whole population data in England. Methods and analysis:Multiple imputation was used to impute values of cancer stage at diagnosis for patients with missing stage at diagnosis information. The simultaneous application of period analysis to obtain up-to-date estimates restricts the contribution of patients with historical diagnoses and hence improves the overall completeness of stage at diagnosis information. For each of the 10 cancer sites in this study, we fit a flexible parametric excess hazard model for each cancer stage on the cumulative excess hazard scale and estimated stage-specific life expectancy using the relative survival framework. Results:The differences in stage-specific and sex-specific life expectancy were evaluated from 40 to 90 years of age. Colorectal cancer, prostate cancer and bladder cancer yield much lower estimates of life expectancy for patients diagnosed with stage IV cancer compared with stages I-III. For example, female patients diagnosed with stage IV colorectal cancer at 70 years of age have a life expectancy of 72.3 years, while those with stages I-III can expect to live beyond 82.0 years. The remaining cancer sites yield approximately equal reductions in life expectancy with each increase in stage at diagnosis from I to IV. Conclusion:We offer the first stage-specific life expectancy estimates for a range of cancer sites in England using data from the National Cancer Registration and Analysis Service, with follow-up until February 2020. Estimates of stage-specific life expectancy provide a real-world, intuitive metric to evaluate the impact of cancer stage at diagnosis on prognosis up to a lifetime horizon. Stage-specific life expectancy estimates also provide key information regarding the potential benefits of early diagnosis initiatives in terms of gains in life years.
Objectives Patient-reported outcomes (PROs) are essential for understanding how cancer treatments affect individuals’ symptoms, daily functioning and quality of life. This study examined how PRO data from pivotal clinical trials in breast cancer (BC), gastrointestinal (GI) cancers and non-small cell lung cancer (NSCLC) are reflected in regulatory drug labels and public-facing communications such as American Society of Clinical Oncology daily news. The goal was to identify gaps in the communication of these data, particularly in formats accessible to non-technical audiences and to highlight opportunities for improvement.Methods and analysis We conducted a targeted review of oncology drugs approved between 2014 and 2024 by the US Food and Drug Administration and the European Medicines Agency. For each product, we assessed pivotal trials for PRO endpoints and reviewed regulatory labels for PRO claims. Public-facing materials—including sponsor websites, medical society platforms and patient advocacy content—were evaluated for the presence, clarity and visibility of PRO messaging. Messaging strength was internally rated as low, medium or high.Results Among 128 pivotal trials (28 BC, 34 GI, 66 NSCLC), 105 (82%) included PROs—84 as secondary and 40 as exploratory endpoints. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) was used in 83 trials (79.0%), and EuroQol Group in 72 (68.6%). Only 10 products included PRO content in their regulatory labelling. Of 16 BC drugs, all had PRO data, but only 4 had regulatory PRO claims. Most sponsor websites lacked PRO content; only seven products across all indications included healthcare professional-facing PRO narratives and only two on patient-facing websites. No product achieved a high messaging strength rating; 53 of 64 rated products were categorised as low (limited or no PRO communication).Conclusions Despite widespread PRO data collection, integration into labelling and public communication remains limited. While label inclusion supports compliant dissemination, some PRO findings appear in public materials without formal claims. Advancing both methodological rigour and clear regulatory guidance is essential to promote balanced, patient-relevant communication in oncology.
Objective Anaemia is common in healthcare and may indicate undiagnosed cancer. Despite this, evidence regarding risk estimates informing clinical decision-making remains limited, particularly regarding haemoglobin dynamics and the role of mean corpuscular volume (MCV). We aimed to quantify the 18-month risks of incident cancer (IC) and all-cause mortality (ACM) following incident anaemia (IA), and to examine how MCV modifies these risks.Methods and analysis Population-based, age- and sex-matched cohort study. The study used the Stockholm Early Detection of Cancer Study (STEADY-CAN), covering almost all adults residing in Stockholm County, Sweden, during 2011–2021. STEADY-CAN links laboratory tests with national registers, capturing healthcare use, diagnoses, cancer outcomes and prescribed medications.We included 190 057 adults with IA and 190 057 age- and sex-matched non-anaemic controls from the STEADY-CAN cohort. Eligible individuals were ≥18 years old, cancer-free, had ≥2 Hb measurements during 2011–2020 and a concurrent MCV value at the IA date. IA was defined as the first Hb value from 2012 onwards below 130 g/L in men or 120 g/L in women after prior normal values.Sex-stratified adjusted piecewise competing-risks multi-state Cox regression models were used, with separate HRs for IA during 0–3, 3–6, 6–12 and 12–18 months of follow-up. The main outcome measures were IC and ACM during the 18-month follow-up.Results IC occurred in 6.2% of male and 2.8% of female IA cases, compared with 2.4% and 1.1% of controls. Corresponding ACM rates were 7.4% and 4.0% in IA cases versus 2.5% and 1.7% in controls. IA implied a 9.17-fold higher IC risk and 8.50-fold higher ACM risk among men during 0–3 months of follow-up, with 8.25- and 6.14-fold higher risks among women (all p<0.001). These risks decreased over time but were still significant for both sexes at 6–12 months of follow-up for IC and 12–18 months of follow-up for ACM. Microcytosis was linked to the highest IC risk, particularly for digestive and haematological cancers, whereas macrocytosis was more strongly associated with ACM.Conclusions IA is a strong marker of both IC and ACM in routine care. Microcytic anaemia should prompt timely gastrointestinal evaluation, while macrocytic anaemia warrants broader assessments for comorbid conditions and systemic disease. Persistently elevated risks underscore the need for structured safety-netting and continued follow-up after IA, even without a cancer identification. Our findings highlight the value of using anaemia patterns and MCV in early risk stratification.
