Di Carlo, V; (2024) What explains global variation in population-based survival from malignant melanoma of the skin? PhD thesis, London School of Hygiene & Tropical Medicine. DOI: https://doi.org/10.17037/PUBS.04673559
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Abstract
This thesis provides a comprehensive examination of the reasons for world-wide differences in survival from cutaneous melanoma. It comprises five chapters, of which three are research papers. Population-based cancer survival estimates are key to assess the overall effectiveness of a health system in managing cancer. The third cycle of the CONCORD programme for the global surveillance of cancer survival (CONCORD-3) included data for more than 37.5 million cancer patients diagnosed during 2000-2014 with one of 18 cancers, including melanoma. It highlighted substantial world-wide disparities in survival for most solid tumours. Age-standardised five-year net survival for adults (15-99 years) diagnosed with melanoma of the skin during 2010-2014 was 90% or higher in the USA, Australia, New Zealand and most Nordic countries, but 60% or lower in Ecuador, China, Korea, Singapore and Taiwan. This PhD thesis examines the impact of some of the main established prognostic factors on survival disparities world-wide, as well as some of the more controversial prognostic factors. Following an introduction to the background, aims and methods of the research in Chapter 1, the second chapter (Research paper 1) is focused on stage at diagnosis and trends in one-year net survival for patients diagnosed with distant-stage disease in the US during 2001-2013. Research paper 1 is the largest population-based study to date to show an improvement in one-year survival for distant-stage melanoma in the US, particularly among younger patients, from 2010. This improvement is likely to be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. Persistent survival inequalities between Blacks and Whites were also shown, suggesting differential access to treatment. Chapter 3 (Research Paper 2) is focused on the most controversial prognostic factor for melanoma: morphology. This chapter provides, for the first time, world-wide comparisons of population-based survival after five years since diagnosis for the main morphological subtypes of melanoma, for over 1.5 million adults diagnosed during 2000–2014. Chapter 3 highlights the less favourable distribution of morphological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas. The results from the multivariable analysis on data provided by four registries with complete information on stage and treatment shows that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma than for superficial spreading melanoma. I hope that Chapter 3 may serve as the basis to persuade clinicians, dermatologists, pathologists and other experts of the importance of morphology as a relevant prognostic factor for melanoma of the skin, and that national and international clinical guidelines may in due course be updated to include morphology as a core item in the pathology report. In Chapter 4 (Research Paper 3) I have aimed to explain the reasons for the generally higher survival in women than in men with cutaneous melanoma. These differences were particularly pronounced in Brazil, Bulgaria, Ecuador, Lithuania, Poland, Romania, Russia and Türkiye. Men with melanoma were generally older than women. Men were also more frequently diagnosed with melanomas with a poor prognosis, especially melanomas located on the scalp and neck, or with metastatic disease. These reasons may help to explain the survival disadvantage for men with melanoma. To our knowledge, this is the largest international study of population-based survival trends from cutaneous melanoma. Its world-wide coverage, the robust and rigorous methodology deployed for centralised data collection, data quality assessment and statistical analysis analyses, and the relevance of the research findings on the role of each prognostic factor, will provide a baseline against which countries can monitor the progress of their efforts to improve the control of melanoma, and will set a benchmark for future global comparisons.
Item Type | Thesis |
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Thesis Type | Doctoral |
Thesis Name | PhD |
Contributors | Allemani, C |
Faculty and Department | Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology |
Research Centre | Cancer Survival Group |
Copyright Holders | Veronica Di Carlo |
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Filename: 2024_EPH_PhD_Di Carlo_V.pdf
Licence: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
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