Do age at diagnosis, tumour thickness and tumour site explain sex differences in melanoma survival? A causal mediation analysis using cancer registry data.

Women diagnosed with melanoma have better survival than men, but little is known about potential intervention targets to reduce this survival gap by sex. We conducted a population-based study using Victorian Cancer Registry data including 5833 women and 6780 men aged 15 to 70 years when diagnosed with first primary melanoma between 2007 and 2015. Deaths to the end of 2020 were identified through linkage to the Victorian and national death registries. We estimated the effect of age at diagnosis, tumour thickness and tumour site on reducing the melanoma-specific survival gap by sex (ie, interventional indirect effects [IIEs]) on risk difference (RD) scale. Compared to women, there were 211 (95% CI: 145-278) additional deaths per 10 000 in men within 5 years following diagnosis. We estimated that 44% of this gap would be reduced by a hypothetical intervention shifting the distribution of melanoma thickness in men to be the same as that observed for women (IIEthickness RD 93 [95% CI: 75-118] per 10 000) and 20% by an intervention on tumour site (head and neck/trunk vs upper limb/lower limb; IIEsite RD 42 [95% CI: 15-72] per 10 000), while an intervention on age at diagnosis would have a negligible effect. Tumour thickness, tumour site and age at diagnosis mediated 65% of the effect of sex on 5-year melanoma survival in Victoria. Of these factors, tumour thickness had the most considerable mediating effect, suggesting that effective promotion of earlier detection of melanoma in men could potentially nearly halve the gap in melanoma-specific survival by sex.

Disparities in quality of life, social distress and employment outcomes in Australian cancer survivors.

PURPOSE: To examine how socio-demographic, comorbidities and information needs influence quality of life (QoL) outcomes of survivors of breast, colorectal, or prostate cancer, non-Hodgkin lymphoma or melanoma. METHODS: Cross-sectional postal survey with eligible participants identified through a population-based cancer registry. QoL outcomes were assessed by EQ-5D-5L, social difficulties index (SDI) and, for those employed at diagnosis, current employment. Regression analyses explored associations between outcome variables and cancer type, age, time since diagnosis, residential location, socio-economic disadvantage, comorbidities and unmet information needs. Mediation analyses examined whether comorbidities and information needs explained relationships between outcome variables and socio-economic disadvantage. RESULTS: 2115 survivors participated. Mean EQ-5D-5L scores (mean = 0.84) were similar to population averages and SDI scores were low for the entire sample (mean = 3.80). In multivariate analyses, being aged over 80, greater socio-economic disadvantage, comorbidities and unmet information needs decreased EQ-5D-5L scores. Higher SDI scores were associated with socio-economic disadvantage, comorbidities and unmet information needs. Not being employed was associated with being aged over 50, more comorbidities and socio-economic disadvantage. Comorbidities but not information needs partially mediated the impact of socio-economic disadvantage on EQ-5D-5L and SDI accounting for 17% and 14% of the total effect of socio-economic disadvantage respectively. Neither comorbidities nor information needs mediated the association between socio-economic disadvantage and employment outcomes. CONCLUSIONS: To improve quality of life, survivorship care should be better tailored to address the needs of individuals given their overall health and impact of comorbidities, their age and type of cancer and not simply time since diagnosis.

Factors Explaining Socio-Economic Inequalities in Cancer Survival: A Systematic Review.

BACKGROUND: There is strong and well-documented evidence that socio-economic inequality in cancer survival exists within and between countries, but the underlying causes of these differences are not well understood. METHODS: We systematically searched the Ovid Medline, EMBASE, and CINAHL databases up to 31 May 2020. Observational studies exploring pathways by which socio-economic position (SEP) might causally influence cancer survival were included. RESULTS: We found 74 eligible articles published between 2005 and 2020. Cancer stage, other tumor characteristics, health-related lifestyle behaviors, co-morbidities and treatment were reported as key contributing factors, although the potential mediating effect of these factors varied across cancer sites. For common cancers such as breast and prostate cancer, stage of disease was generally cited as the primary explanatory factor, while co-morbid conditions and treatment were also reported to contribute to lower survival for more disadvantaged cases. In contrast, for colorectal cancer, most studies found that stage did not explain the observed differences in survival by SEP. For lung cancer, inequalities in survival appear to be partly explained by receipt of treatment and co-morbidities. CONCLUSIONS: Most studies compared regression models with and without adjusting for potential mediators; this method has several limitations in the presence of multiple mediators that could result in biased estimates of mediating effects and invalid conclusions. It is therefore essential that future studies apply modern methods of causal mediation analysis to accurately estimate the contribution of potential explanatory factors for these inequalities, which may translate into effective interventions to improve survival for disadvantaged cancer patients.

Differences in cancer survival by remoteness of residence: an analysis of data from a population-based cancer registry.

PURPOSE: Cancer survival is generally lower for rural compared with urban residents, but findings have been inconsistent. We aimed to assess inequalities in cancer survival by remoteness of residence in Victoria, Australia. METHODS: Incident cancer cases diagnosed in 2001-2015 with 30 cancer types (n = 331,302) were identified through the Victorian Cancer Registry and followed to the end of 2015 through death registries. Five-year net survival was estimated using the Pohar-Perme method and differences assessed by excess mortality rate ratios (EMRRs) using Poisson regression, adjusting for sex, age and year of diagnosis. EMRRs adjusted for socio-economic disadvantage were also estimated. RESULTS: People living outside major cities had lower survival for 11 cancers: esophagus, stomach, colorectum, liver, gallbladder/biliary tract, pancreas, lung, connective/soft tissue, ovary, prostate, kidney. No differences in survival were found for cancers of uterus, small intestine and mesothelioma. After adjusting for socio-economic disadvantage, the observed differences in survival decreased for most cancers and disappeared for colorectal cancer, but they remained largely unchanged for cancers of esophagus, stomach, liver, pancreas, lung, connective/soft tissue, ovary and kidney. CONCLUSION: People with cancer residing outside major cities had lower survival from some cancers, which is partly due to the greater socio-economic disadvantage of rural residents.

Rural-urban residence and cancer survival in high-income countries: A systematic review.

There is some evidence that place of residence is associated with cancer survival, but the findings are inconsistent, and the underlying mechanisms by which residential location might affect survival are not well understood. We conducted a systematic review of observational studies investigating the association of rural versus urban residence with cancer survival in high-income countries. We searched the Ovid Medline, EMBASE, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases up to May 31, 2016. Forty-five studies published between 1984 and 2016 were included. We extracted unadjusted and adjusted relative risk estimates with the corresponding 95% confidence intervals. Most studies reported worse survival for cancer patients living in rural areas than those in urban regions. The most consistent evidence, observed across several studies, was for colorectal, lung, and prostate cancer. Of the included studies, 18 did not account for socio-economic position. Lower survival for more disadvantaged patients is well documented; therefore, it could be beneficial for future research to take socio-economic factors into consideration when assessing rural/urban differences in cancer survival. Some studies cited differential stage at diagnosis and treatment modalities as major contributing factors to regional inequalities in cancer survival. Further research is needed to disentangle the mediating effects of these factors, which may help to establish effective interventions to improve survival for patients living outside major cities.

Correction to: Differences in cancer survival by sex: a population-based study using cancer registry data.

In the original publication of the article, the concluding paragraph of the Discussion section was inadvertently missed and is provided below.

Differences in cancer survival by sex: a population-based study using cancer registry data.

PURPOSE: Few large-scale studies have investigated sex differences in cancer survival and little is known about their temporal and age-related patterns. METHODS: We used cancer registry data for first primary cancers diagnosed between 1982 and 2015 in Victoria, Australia. Cases were followed until the end of 2015 through linkage to death registries. Differences in survival were assessed for 25 cancers using the Pohar-Perme estimator of net survival and the excess mortality rate ratio (EMRR) adjusting for age and year of diagnosis. RESULTS: Five-year net survival for all cancers combined was lower for men (47.1%; 95% CI 46.9-47.4) than women (52.0%; 95% CI 51.7-52.3); EMRR 1.13 (95% CI 1.12-1.14; p < 0.001). A survival disadvantage for men was observed for 11 cancers: head and neck, esophagus, colorectum, pancreas, lung, bone, melanoma, mesothelioma, kidney, thyroid, and non-Hodgkin lymphoma. In contrast, women had lower survival from cancers of the bladder, renal pelvis, and ureter. For the majority of cancers with survival differences, the EMRR decreased with increasing age at diagnosis; for colorectal, esophageal, and kidney cancer, the EMRR increased with time since diagnosis. CONCLUSION: Identifying the underlying reasons behind sex differences in cancer survival is necessary to address inequalities, which may improve outcomes for men and women.

Cancer inequalities experienced by people with disability: a systematic review protocol.

INTRODUCTION: Cancer is a leading cause of death and has a significant impact on individuals, families and society. Emerging evidence shows that people with disability face challenges in accessing services which could assist in early cancer diagnosis and optimal treatment, like cancer screening. Consequently, cancer patients with disabilities may present with later-stage disease, have reduced treatment options and experience lower survival rates compared with people without disability.This systematic review aims to summarise and evaluate the existing evidence on (a) inequalities in cancer survival and mortality between people with and without disability, (b) the inequalities in cancer screening and (c) stage at diagnosis that may contribute to the survival/mortality gap. METHODS AND ANALYSIS: A literature search will be performed on MEDLINE, Embase, PsycInfo and Scopus up to May 2023. The review will include quantitative studies that reported inequalities in cancer survival and mortality, screening and stage at diagnosis between adults with and without disability. A summary of the characteristics and findings of the included studies will be provided. We will assess the quality of each study using the Risk Of Bias In Non-randomised Studies-of Exposure tool. Depending on the heterogeneity of studies, we will assess whether meta-analysis is appropriate. ETHICS AND DISSEMINATION: Ethics approval is not applicable for this study since no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023427288.

Factors beyond diagnosis and treatment that are associated with return to work in Australian cancer survivors-A systematic review.

Return to work (RTW) is a marker of functional recovery for working-age cancer survivors. Identifying factors that impact on RTW in cancer survivors is an essential step to guide further research and interventions to support RTW. This systematic review aimed to identify nontreatment, non-cancer-related variables impacting RTW in Australian cancer survivors. A systematic search was conducted in EMBASE, PsycINFO, CINAHL, PubMed, and Google Scholar. Studies were eligible if they included: (1) adults living post diagnosis of malignancy; (2) quantitative data for nontreatment, non-cancer-related variables impacting RTW; (3) only Australian participants. Included studies were critically appraised, and relevant data extracted and synthesized narratively. Six studies were included in the review, published between 2008 and 2020. Studies were of variable quality and mixed methodologies. One study included malignancies of any type with the remainder focusing on survivors of colorectal cancer (n = 3), oropharyngeal cancer (n = 1), and glioblastoma multiforme (n = 1). Multiple factors were related to RTW in individual studies, including older age, presence of three or more comorbidities, fewer work hours pre-morbidly, lower body mass index, longer than recommended sleep duration, and not having private health insurance; however, there was limited consistency in findings between studies. Other variables examined included: occupation type, household income, healthy lifestyle behaviors, flexibility, and duration of employment with workplace; however, no significant associations with RTW were reported. Further research is required to gather compelling evidence on factors that influence RTW in Australian cancer survivors.

Adherence to 2018 WCRF/AICR Cancer Prevention Recommendations and Risk of Cancer: The Melbourne Collaborative Cohort Study.

BACKGROUND: We examined associations between adherence to adaptations of the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and total, exposure-related and site-specific cancer risk. METHODS: A total of 20,001 participants ages 40 to 69 years at enrollment into the Melbourne Collaborative Cohort Study in 1990 to 1994, who had diet, body size, and lifestyle reassessed in 2003 to 2007 ("baseline"), were followed-up through June 2021. We constructed diet and standardized lifestyle scores based on core WCRF/AICR recommendations on diet, alcohol intake, body size and physical activity, and additional scores incorporating weight change, sedentary behavior, and smoking. Associations with cancer risk were estimated using Cox regression, adjusting for confounders. RESULTS: During follow-up (mean = 16 years), 4,710 incident cancers were diagnosed. For highest quintile ("most adherent") of the standardized lifestyle score, compared with lowest ("least adherent"), a HR of 0.82 [95% confidence interval (CI): 0.74-0.92] was observed for total cancer. This association was stronger with smoking included in the score (HR = 0.74; 95% CI: 0.67-0.81). A higher score was associated with lower breast and prostate cancer risk for the standardized score, and with lung, stomach, rectal, and pancreatic cancer risk when the score included smoking. Our analyses identified alcohol use, waist circumference and smoking as key drivers of associations with total cancer risk. CONCLUSIONS: Adherence to WCRF/AICR cancer prevention recommendations is associated with lower cancer risk. IMPACT: With <0.2% of our sample fully adherent to the recommendations, the study emphasizes the vast potential for preventing cancer through modulation of lifestyle habits.

Dietary Inflammatory Index, Alternative Healthy Eating Index-2010, Mediterranean Diet Score and the risk of pancreatic cancer.

BACKGROUND: Previous studies of dietary patterns and pancreatic cancer risk have been inconclusive; we aimed to investigate the association of Mediterranean Diet Score (MDS), Alternative Healthy Eating Index-2010 (AHEI-2010), and Dietary Inflammatory Index (DII®) with risk of pancreatic cancer. METHODS: We used data from the Melbourne Collaborative Cohort Study including 33,690 men and women aged 40-69 years at recruitment in 1990-1994. A total of 258 incident cases of pancreatic cancer was identified over an average of 23.7 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, with age as the underlying time metric, adjusting for potential confounders including sex, height, country of birth, education, socio-economic position, physical activity, energy intake, smoking status, pack-years smoking, years since quitting smoking, and alcohol intake. RESULTS: A healthier diet as assessed by the AHEI-2010 was associated with a lower risk of pancreatic cancer [HRQuartile4 vs Quartile1 = 0.58; 95%CI 0.40 - 0.85; p for trend 0.003]. Weaker but consistent evidence was observed for the other indexes [DII® HRQuartile4 vs Quartile1 = 1.30; 95%CI 0.82 - 2.06; p for trend 0.1], [MDS HRCategory3 vs Category1 = 0.79; 95%CI 0.49 - 1.26; p for trend 0.06]. CONCLUSION: Adherence to a healthier diet, as assessed by the AHEI-2010, may reduce the risk of pancreatic cancer.

Factors Explaining Socio-Economic Inequalities in Survival from Colon Cancer: A Causal Mediation Analysis.

BACKGROUND: Socio-economic inequalities in colon cancer survival exist in high-income countries, but the reasons are unclear. We assessed the mediating effects of stage at diagnosis, comorbidities, and treatment (surgery and intravenous chemotherapy) on survival from colon cancer. METHODS: We identified 2,203 people aged 15 to 79 years with first primary colon cancer diagnosed in Victoria, Australia, between 2008 and 2011. Colon cancer cases were identified through the Victorian Cancer Registry (VCR), and clinical information was obtained from hospital records. Deaths till December 31, 2016 (n = 807), were identified from Victorian and national death registries. Socio-economic disadvantage was based on residential address at diagnosis. For stage III disease, we decomposed its total effect into direct and indirect effects using interventional mediation analysis. RESULTS: Socio-economic inequalities in colon cancer survival were not explained by stage and were greater for men than women. For men with stage III disease, there were 161 [95% confidence interval (CI), 67-256] additional deaths per 1,000 cases in the 5 years following diagnosis for the most disadvantaged compared with the least disadvantaged. The indirect effects through comorbidities and intravenous chemotherapy explained 6 (95% CI, -10-21) and 15 (95% CI, -14-44) per 1,000 of these additional deaths, respectively. Surgery did not explain the observed gap in survival. CONCLUSIONS: Disadvantaged men have lower survival from stage III colon cancer that is only modestly explained by having comorbidities or not receiving chemotherapy after surgery. IMPACT: Future studies should investigate the potential mediating role of factors occurring beyond the first year following diagnosis, such as compliance with surveillance for recurrence and supportive care services.

Differences in cancer survival by area-level socio-economic disadvantage: A population-based study using cancer registry data.

Despite overall improvements in cancer survival due to earlier diagnosis and better treatment, socio-economically disadvantaged people have lower cancer survival than more advantaged people. We aimed to examine differences in cancer survival by area-level socio-economic disadvantage in Victoria, Australia and assess whether these inequalities varied by year of diagnosis, age at diagnosis, time since diagnosis and sex. Cases diagnosed with a first primary cancer in 2001-2015 were identified using the Victorian Cancer Registry and followed to the end of 2016. Five-year net survival and the excess risk of death due to a cancer diagnosis were estimated. People living in more disadvantaged areas had lower five-year survival than residents of less disadvantaged regions for 21 of 29 cancer types: head and neck, oesophagus, stomach, colorectum, anus/anal canal, liver, gallbladder/biliary tract, pancreas, lung, melanoma, connective/soft tissue, female breast, ovary, prostate, kidney, bladder, brain and central nervous system, unknown primary, non-Hodgkin lymphoma, multiple myeloma and leukemia. The observed lower survival in more deprived regions persisted over time, except head and neck cancer, for which the gap in survival has widened. Socio-economic inequalities in survival decreased with increasing age at diagnosis for cancers of connective/soft tissue, bladder and unknown primary. For colorectal cancer, the observed survival disadvantage in lower socio-economic regions was greater for men than for women, while for brain and central nervous system tumours, it was larger for women. Cancer survival is generally lower for residents of more socio-economically disadvantaged areas. Identifying the underlying reasons for these inequalities is important and may help to identify effective interventions to increase survival for underprivileged cancer patients.