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In some countries, breast cancer age-standardised mortality rates have decreased by 2–4% per year since the 1990s, but others have yet to achieve this outcome. In this study, we aimed to characterise the associations between national health system characteristics and breast cancer age-standardised mortality rate, and the degree of breast cancer downstaging correlating with national age-standardised mortality rate reductions. In this population-based study, national age-standardised mortality rate estimates for women aged 69 years or younger obtained from GLOBOCAN 2020 were correlated with a broad panel of standardised national health system data as reported in the WHO Cancer Country Profiles 2020. These health system characteristics include health expenditure, the Universal Health Coverage Service Coverage Index (UHC Index), dedicated funding for early detection programmes, breast cancer early detection guidelines, referral systems, cancer plans, number of dedicated public and private cancer centres per 10 000 patients with cancer, and pathology services. We tested for differences between continuous variables using the non-parametric Kruskal-Wallis test, and for categorical variables using the Pearson χ2 test. Simple and multiple linear regression analyses were fitted to identify associations between health system characteristics and age-standardised breast cancer mortality rates. Data on TNM stage at diagnosis were obtained from national or subnational cancer registries, supplemented by a literature review of PubMed from 2010 to 2020. Mortality trends from 1950 to 2016 were assessed using the WHO Cancer Mortality Database. The threshold for significance was set at a p value of 0·05 or less. 148 countries had complete health system data. The following variables were significantly higher in high-income countries than in low-income countries in unadjusted analyses: health expenditure (p=0·0002), UHC Index (p<0·0001), dedicated funding for early detection programmes (p=0·0020), breast cancer early detection guidelines (p<0·0001), breast cancer referral systems (p=0·0030), national cancer plans (p=0·014), cervical cancer early detection programmes (p=0·0010), number of dedicated public (p<0·0001) and private (p=0·027) cancer centres per 10 000 patients with cancer, and pathology services (p<0·0001). In adjusted multivariable regression analyses in 141 countries, two health system characteristics were significantly associated with lower age-standardised mortality rates: higher UHC Index levels (β=–0·12, 95% CI −0·16 to −0·08) and increasing numbers of public cancer centres (β=–0·23, −0·36 to −0·10). These findings indicate that each unit increase in the UHC Index was associated with a 0·12-unit decline in age-standardised mortality rates, and each additional public cancer centre per 10 000 patients with cancer was associated with a 0·23-unit decline in age-standardised mortality rate. Among 35 countries with available breast cancer TNM staging data, all 20 that achieved sustained mean reductions in age-standardised mortality rate of 2% or more per year for at least 3 consecutive years since 1990 had at least 60% of patients with invasive breast cancer presenting as stage I or II disease. Some countries achieved this reduction without most women having access to population-based mammographic screening. Countries with low breast cancer mortality rates are characterised by increased levels of coverage of essential health services and higher numbers of public cancer centres. Among countries achieving sustained mortality reductions, the majority of breast cancers are diagnosed at an early stage, reinforcing the value of clinical early diagnosis programmes for improving breast cancer outcomes. None.

Antibody–drug conjugates (ADCs) have emerged as a transformative approach in cancer therapy by enhancing tumor targeting and minimizing systemic toxicity compared to traditional chemotherapy. Initially developed with chemotherapy agents as payloads, ADCs have now incorporated alternative payloads, such as immune-stimulating agents, natural toxins, and radionuclides, to improve therapeutic efficacy and specificity. A significant advancement in ADC technology is the integration of Proteolysis Targeting Chimeras (PROTACs), which enable the precise degradation of cellular targets involved in tumorigenesis. This strategy enhances the specificity and precision of cancer therapies, addressing key mechanisms in cancer cell survival. Moreover, incorporating radioactive isotopes into ADCs is an emerging strategy aimed at further improving therapeutic outcomes. By delivering localized radiation, this approach offers the potential to enhance the efficacy of treatment and expand the therapeutic arsenal. Despite these innovations, challenges remain, including dysregulated immune activation, severe adverse effects, and intrinsic immunogenicity of some agents. These emerging issues highlight the ongoing need for optimization in ADC therapy. This review summarizes the latest developments in ADC technology, focusing on novel payloads, PROTAC integration, and the potential for combining ADCs with other therapeutic modalities to refine cancer treatment and improve patient outcomes. Plain language summary New treatments for cancer: using antibody–drug conjugates to deliver more than just chemotherapy Antibody-drug conjugates (ADCs) are a new type of cancer treatment that can target cancer cells more precisely, reducing side effects compared to traditional chemotherapy. ADCs were first combined with chemotherapy drugs, but now they also use other treatments like immune-boosting agents, natural toxins, and even radioactive substances to make the treatment more effective. These advances allow ADCs to deliver treatment directly to cancer cells, improving the chances of success. While there are still some challenges to overcome, such as managing side effects, researchers are working on making these therapies safer and more effective. ADCs offer a more targeted approach to cancer treatment, with the potential to improve outcomes and reduce harm to healthy cells.

Criticisms have emerged that cancer medicines offer modest benefits at increasingly high prices. Reimbursement decisions made by health technology assessment (HTA) agencies have become a complex endeavour for cancer medicines. Most high-income countries (HICs) use HTA criteria to identify high-value medicines for reimbursement under public drug coverage plans. We compared HTA criteria specific for cancer medicines in economically similar HICs, to understand how these criteria contribute to reimbursement decisions. We did an international, cross-sectional analysis in collaboration with author investigators across eight HICs, from the Group of Seven (known as G7; Canada, England, France, Germany, Italy, and Japan) and Oceania (Australia and New Zealand). Publicly available data from HTA agency reports and official documentation were extracted and analysed between Aug 15, 2021, and July 31, 2022. We collected data pertaining to the decision-making criteria used by the national HTA agency; HTA reimbursement status for 34 medicine–indication pairs corresponding to 15 unique US top-selling cancer medicines; and HTA reimbursement status for 18 cancer medicine–indication pairs (13 unique medicines) with minimal clinical benefit (score of 1 on the European Society of Medical Oncology Magnitude of Clinical Benefit Scale). Descriptive statistics were used to compare HTA decision criteria and drug reimbursement recommendations (or for Germany and Japan, final reimbursement status) across the eight countries. Therapeutic impact related to clinical outcomes of the new medicine was a uniform criterion across the eight countries, whereas quality of evidence (under the remit of therapeutic impact assessment) and equity were infrequently cited criteria. Only the German HTA agency mandated that surrogate endpoints be validated in therapeutic impact assessment. All countries except Germany included formal cost-effectiveness analyses within HTA reports. England and Japan were the only countries that specified a cost-effectiveness threshold. Of the 34 medicine–indication pairs corresponding to US top-selling cancer medicines, Germany reimbursed the maximum (34 [100%]), followed by Italy (32 [94%] recommended for reimbursement), Japan (28 [82%] reimbursed), Australia, Canada, England, and France (27 [79%] recommended for reimbursement), and New Zealand (12 [35%] recommended for reimbursement). Of the 18 cancer medicine–indication pairs with marginal clinical benefit, Germany reimbursed 15 (83%) and Japan reimbursed 12 (67%). France recommended nine (50%) for reimbursement, followed by Italy (seven [39%]), Canada (five [28%]), and Australia and England (three [17%] each). New Zealand did not recommend any medicine–indications with marginal clinical benefit for reimbursement. Considering the overall cumulative proportion across the eight countries, 58 (21%) of 272 indications for the US top-selling medicines and 90 (63%) of 144 marginally beneficial medicine–indications were not recommended for reimbursement or reimbursed. Our findings indicate discordance in public reimbursement decisions across economically similar countries, despite overlapping HTA decision criteria. This suggests a need for improved transparency around the nuances of the criteria to ensure improved access to high-value cancer medicines, and deprioritisation of low-value cancer medicines. Health systems have opportunities to improve their HTA decision-making processes by learning from the systems in other countries. None.

Cancer is a leading cause of mortality worldwide. By 2040, over 30 million new cancers are predicted, with the greatest cancer burden in low-income countries. In 2015, the UN passed the Sustainable Development Goal 3.4 (SDG 3.4) to tackle the rising burden of non-communicable diseases, which calls for a reduction by a third in premature mortality from non-communicable diseases, including cancer, by 2030. However, there is a paucity of data on premature mortality rates by cancer type. In this study, we examine annual rates of change for cancer-specific premature mortality and classify whether countries are on track to reach SDG 3.4 targets. This is a retrospective, cross-sectional, population-based study investigating premature mortality trends from 2000–19 using the WHO Global Health Estimates data. All cancers combined and thirteen individual cancers in 183 countries were examined by WHO region, World Bank income level, and sex. The risk of premature mortality was calculated for ages 30–69 years, independent of other competing causes of death, using standard life table methods. The primary objective was to compute average annual rate of change in premature mortality from 2000 to 2019. Secondary objectives assessed whether this annual rate of change would be sufficient to reach SDG 3.4. targets for premature mortality by 2030. This study was conducted using data retrieved for the years 2000–19. Premature mortality rates decreased in 138 (75%) of 183 countries across all World Bank income levels and WHO regions, however only eight (4%) countries are likely to meet the SDG 3.4 targets for all cancers combined. Cancers where early detection strategies exist, such as breast and colorectal cancer, have higher declining premature mortality rates in high-income countries (breast cancer 48 [89%] of 54 and colorectal cancer 45 [83%]) than in low-income countries (seven [24%] of 29 and four [14%]). Cancers with primary prevention programmes, such as cervical cancer, have more countries with declining premature mortality rates (high-income countries 50 [93%] of 54 and low-income countries 26 [90%] of 29). Sex-related disparities in premature mortality rates vary across WHO regions, World Bank income groups, and by cancer type. There is a greater reduction in premature mortality for all cancers combined and for individual cancer types in high-income countries compared with lower-middle-income and low-income countries. However, most countries will not reach the SDG 3.4 target. Cancers with early detection strategies in place, such as breast and colorectal cancers, are performing poorly in premature mortality compared with cancers with primary prevention measures, such as cervical cancer. Investments toward prevention, early detection, and treatment can potentially accelerate declines in premature mortality. WHO.

The WHO Essential Medicines List (EML) identifies priority medicines that are most important to public health. Over time, the EML has included an increasing number of cancer medicines. We aimed to investigate whether the cancer medicines in the EML are aligned with the priority medicines of frontline oncologists worldwide, and the extent to which these medicines are accessible in routine clinical practice. This international, cross-sectional survey was developed by investigators from a range of clinical practice settings across low-income to high-income countries, including members of the WHO Essential Medicines Cancer Working Group. A 28-question electronic survey was developed and disseminated to a global network of oncologists in 89 countries and regions by use of a hierarchical snowball method; each primary contact distributed the survey through their national and regional oncology associations or personal networks. The survey was open from Oct 15 to Dec 7, 2020. Fully qualified physicians who prescribe systemic anticancer therapy to adults were eligible to participate in the survey. The primary question asked respondents to select the ten cancer medicines that would provide the greatest public health benefit to their country; subsequent questions explored availability and cost of cancer medicines. Descriptive statistics were used to compare access to medicines between low-income and lower-middle-income countries, upper-middle-income countries, and high-income countries. 87 country-level contacts and two regional networks were invited to participate in the survey; 46 (52%) accepted the invitation and distributed the survey. 1697 respondents opened the survey link; 423 were excluded as they did not answer the primary study question and 326 were excluded because of ineligibility. 948 eligible oncologists from 82 countries completed the survey (165 [17%] in low-income and lower-middle-income countries, 165 [17%] in upper-middle-income countries, and 618 [65%] in high-income countries). The most commonly selected medicines were doxorubicin (by 499 [53%] of 948 respondents), cisplatin (by 470 [50%]), paclitaxel (by 423 [45%]), pembrolizumab (by 414 [44%]), trastuzumab (by 402 [42%]), carboplatin (by 390 [41%]), and 5-fluorouracil (by 386 [41%]). Of the 20 most frequently selected high-priority cancer medicines, 19 (95%) are currently on the WHO EML; 12 (60%) were cytotoxic agents and 13 (65%) were granted US Food and Drug Administration regulatory approval before 2000. The proportion of respondents indicating universal availability of each top 20 medication was 9–54% in low-income and lower-middle-income countries, 13–90% in upper-middle-income countries, and 68–94% in high-income countries. The risk of catastrophic expenditure (spending >40% of total consumption net of spending on food) was more common in low-income and lower-middle-income countries, with 13–68% of respondents indicating a substantial risk of catastrophic expenditures for each of the top 20 medications in lower-middle-income countries versus 2–41% of respondents in upper-middle-income countries and 0–9% in high-income countries. These data demonstrate major barriers in access to core cancer medicines worldwide. These findings challenge the feasibility of adding additional expensive cancer medicines to the EML. There is an urgent need for global and country-level policy action to ensure patients with cancer globally have access to high priority medicines. None.

There is increasing global recognition that national cancer plans are crucial to effectively address the cancer burden and to prioritise and coordinate programmes. We did a global analysis of available national cancer-related health plans using a standardised assessment questionnaire to assess their inclusion of elements that characterise an effective cancer plan and, thereby, improve understanding of the strengths and limitations of existing plans. The results show progress in the development of cancer plans, as well as in the inclusion of stakeholders in plan development, but little evidence of their implementation. Areas of continued unmet need include setting of realistic priorities, specification of programmes for cancer management, allocation of appropriate budgets, monitoring and evaluation of plan implementation, promotion of research, and strengthening of information systems. We found that countries with a non-communicable disease (NCD) plan but no national cancer control plan (NCCP) were less likely than countries with an NCCP and NCP plan or an NCCP only to have comprehensive, coherent, or consistent plans. As countries move towards universal health coverage, greater emphasis is needed on developing NCCPs that are evidence based, financed, and implemented to ensure translation into action.

Immunotherapy has revolutionized cancer treatment. Immune-checkpoint inhibitors, on balance, showed a favorable efficacy/toxicity profile with durable response in different cancer types. No predictive biomarker has been validated thus far to select patients who would benefit from therapy. Among the candidate predictive biomarkers, mismatch repair status of the tumor is currently one of the most promising. Indeed, tumors displaying mismatch repair deficiency or microsatellite instability showed remarkable response to immunotherapy in clinical trials. This correlation has been first reported in colorectal cancers, but similar results have been observed also in other cancer types. The possible mechanism behind this correlation may be the higher mutational load observed in mismatch repair deficient tumors, leading to neoantigens formation, recruitment of immune cells, and release of proinflammatory factors in the microenvironment. These results support an approach to treatment based on assessment of the genomic stability of the tumor besides its biologic characteristics and may change our therapeutic decision making process. However, due to the small percentage of patients with tumors displaying mismatch repair deficiency, data from clinical trials should not be considered definitive and need further confirmation.

The definition of a therapeutic indication formulated by regulatory agencies is a decisive element for the marketing authorisation of medicinal products and for patient access. Trotta and colleagues found that oncological indications granted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) in the period between 1999 and 2008 were clinically different in about 10% of cases. In this Policy Review, we compared the 162 therapeutic indications of 80 medicinal products for solid tumours and blood cancers authorised by the EMA between January, 2015, and September, 2022, with the corresponding labels approved by the FDA. Clinically relevant discrepancies in the EMA summary of product characteristics and FDA labels were identified for 51·9% of the evaluated indications. Differences arise in the place in therapy, in the need for patients to be refractory to previous therapies, in biomarker requirement for eligibility, in concomitant treatments, or in patient characteristics. These differences lead to a different population for which drugs can be prescribed on label, with the FDA granting broader indications more often than the EMA. Therapeutic indications are a legal basis that define the eligible population to specific treatments. The fact that about half of the indications are different between the USA and Europe affect patient access to medications and should stimulate a debate on the weight that uncertainty plays in regulatory decisions.

Purpose To prospectively assess discontinuation of indwelling bladder catheterization (IBC) and relief of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) following prostate artery embolization (PAE) in poor surgical candidates. Methods Patients ineligible for surgical intervention were offered PAE after at least 1 month of IBC for management of urinary retention secondary to BPH; exclusion criteria for PAE included eligibility for surgery, active bladder cancer or known prostate cancer. Embolization technical and clinical success were defined as bilateral prostate embolization and removal of IBC, respectively. Patients were followed for at least 6 months and evaluated for International Prostate Symptom Score, quality of life, prostate size and uroflowmetric parameters. Results A total of 43 patients were enrolled; bilateral embolization was performed in 33 (76.7%), unilateral embolization was performed in 8 (18.6%), and two patients could not be embolized due to tortuous and atherosclerotic pelvic vasculature (4.7%). Among the patients who were embolized, mean prostate size decreased from 75.6 ± 33.2 to 63.0 ± 23.2 g (sign rank p  = 0.0001, mean reduction of 19.6 ± 17.3%), and IBC removal was achieved in 33 patients (80.5%). Clavien II complications were reported in nine patients (21.9%) and included urinary tract infection (three patients, 7.3%) and recurrent acute urinary retention (six patients, 14.6%). Nine patients (22.0%) experienced post-embolization syndrome. Conclusions PAE is a safe and feasible for the relief of LUTS and IBC in highly comorbid patients without surgical treatment options.

Advanced hepatocellular carcinoma (HCC) is a serious condition associated with significant morbidity and mortality. Over the past few decades, however, this has drastically changed, primarily attributed to the development of new treatments, including tyrosine-kinase inhibitors (TKIs), vascular endothelial growth factor (VEGF) inhibitors, and immune checkpoint inhibitors (ICIs). This study aims to highlight the financial toxicity (FT) of advanced HCC treatments, across diverse healthcare systems and particularly in low- and middle-income countries (LMICs). We also aim to explore potential solutions to improve access to life-saving therapies such as ICIs. We conducted an exploratory targeted review of the current literature focusing on therapeutic advancements, their accessibility, and innovative strategies to overcome FT. The review particularly addresses barriers faced in LMICs and examines initiatives that could optimize ICI availability. Findings suggest that FT significantly limits access to ICIs globally, with heightened impact in resource-limited settings and increasingly recognized in high-income countries as well. This challenge is particularly severe in LMICs, where the high incidence of HCC is compounded by the unaffordability of effective treatments, creating a significant barrier to care. Key strategies to mitigate this include cost-saving measures such as dose rounding, vial sharing, lower dosage regimens, extended dosing intervals, and shorter treatment durations. Evidence from emerging studies, predominantly in non-HCC malignancies, suggests these measures may be tolerated without unexpected safety signals. However, HCC-specific prospective data remain limited, and these approaches are entirely off-label requiring further research. Addressing financial barriers to ICI access is essential for improving outcomes in advanced HCC, globally and particularly in LMICs. Global adoption of cost-saving strategies could enhance equitable access to innovative treatments, warranting further research and collaboration among stakeholders from both high- and low-income nations. Plain Language Summary Advanced liver cancer, also known as hepatocellular carcinoma (HCC), remains a life-threatening condition. In recent years, the introduction of targeted therapies, angiogenesis inhibitors, and immune checkpoint inhibitors has significantly improved clinical outcomes for many patients. However, these advances come at a high cost. The resulting financial burden, often termed financial toxicity, is a major concern, particularly in low- and middle-income countries (LMICs), where access to such treatments is limited. This review examined recent evidence on novel systemic therapies for HCC, barriers to treatment access, and potential strategies to improve affordability. The findings highlight that treatment cost is the primary factor limiting the use of immunotherapy in LMICs. Several practical cost-containment approaches have shown promise, including: Dose rounding and vial sharing to minimize drug wastage, Optimized dosing schedules, such as lower doses or extended dosing intervals, and Shortened treatment durations when supported by efficacy and safety data. Early clinical and pharmacoeconomic studies suggest that these strategies can maintain therapeutic benefit while substantially reducing costs. Broader implementation of such approaches, coupled with coordinated efforts among governments, healthcare systems, and pharmaceutical companies, could help expand global access to life-saving therapies for HCC. Graphical Abstract