The patient, diagnostic, and treatment intervals in adult patients with cancer from high- and lower-income countries: A systematic review and meta-analysis

Abstract

Background Longer time intervals to diagnosis and treatment are associated with worse survival for various types of cancer. The patient, diagnostic, and treatment intervals are considered core indicators for early diagnosis and treatment. This review estimated the median duration of these intervals for various types of cancer and compared it across high- and lower-income countries. Methods and findings We conducted a systematic review with meta-analysis (prospectively registered protocol CRD42020200752). Three databases (MEDLINE, Embase, and Web of Science) and information sources including grey literature (Google Scholar, OpenGrey, EThOS, ProQuest Dissertations & Theses) were searched. Eligible articles were published during 2009 to 2022 and reported the duration of the following intervals in adult patients diagnosed with primary symptomatic cancer: patient interval (from the onset of symptoms to first presentation to a healthcare professional), diagnostic interval (from first presentation to diagnosis), and treatment interval (from diagnosis to treatment start). Interval duration was recorded in days and study medians were combined in a pooled estimate with 95% confidence intervals (CIs). The methodological quality of studies was assessed using the Aarhus checklist. A total of 410 articles representing 68 countries and reporting on 5,537,594 patients were included. The majority of articles reported data from high-income countries (n = 294, 72%), with 116 (28%) reporting data from lower-income countries. Pooled meta-analytic estimates were possible for 38 types of cancer. The majority of studies were conducted on patients with breast, lung, colorectal, and head and neck cancer. In studies from high-income countries, pooled median patient intervals generally did not exceed a month for most cancers. However, in studies from lower-income countries, patient intervals were consistently 1.5 to 4 times longer for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries. Across both high- and lower-income countries, the longest diagnostic intervals were observed for hematological (71 days [95% CI 52 to 85], e.g., myelomas (83 days [47 to 145])), genitourinary (58 days [50 to 77], e.g., prostate (85 days [57 to 112])), and digestive/gastrointestinal (57 days [45 to 67], e.g., colorectal (63 days [48 to 78])) cancers. Similarly, the longest treatment intervals were observed for genitourinary (57 days [45 to 66], e.g., prostate (75 days [61 to 87])) and gynecological (46 days [38 to 54], e.g., cervical (69 days [45 to 108]) cancers. In studies from high-income countries, the implementation of cancer-directed policies was associated with shorter patient and diagnostic intervals for several cancers. This review included a large number of studies conducted worldwide but is limited by survivor bias and the inherent complexity and many possible biases in the measurement of time points and intervals in the cancer treatment pathway. In addition, the subintervals that compose the diagnostic interval (e.g., primary care interval, referral to diagnosis interval) were not considered. Conclusions These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal the extent of global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries. Estimates for the diagnostic and treatment intervals came mostly from high-income countries that have powerful health information systems in place to record such information. Dafina Petrova and colleagues review the median duration of patient, diagnostic, and treatment intervals in adult patients with various types of cancer across high and lower-income countries. Author summary Why was this study done? Cancer is a leading cause of death globally and timely diagnosis and treatment are considered essential for improving cancer outcomes. Three main intervals describe the time patients spend in the pathway to treatment of cancer: the patient interval (from symptom start to first presentation to a healthcare professional), the diagnostic interval (from first presentation to diagnosis), and the treatment interval (from diagnosis to the start of treatment). The duration of these intervals could vary greatly depending on the type of cancer and the socioeconomic level of the country. What did the researchers do and find? We conducted a systematic review with meta-analysis of the duration of the patient, diagnostic, and treatment intervals in adult patients with diverse types of cancer. We included 410 articles representing 68 countries and reporting on 5,537,594 patients; the majority of articles reported data from high-income countries (72%), with only 28% reporting data from lower-income countries. Patient intervals in studies from lower-income countries were consistently 1.5 to 4 times longer that patient intervals from studies from high-income countries for almost all cancer sites. The majority of data on the diagnostic and treatment intervals came from high-income countries, and there was large variation according to the type of cancer. What do these findings mean? These results identify the cancers where diagnosis and treatment initiation may take the longest and reveal important global disparities in early diagnosis and treatment. Efforts should be made to reduce help-seeking times for cancer symptoms in lower-income countries and conduct more research in lower-income contexts, especially on the intervals to diagnosis and treatment. This review summarized a large number of studies conducted worldwide but is limited by biases that could arise due to patient selection (e.g., only patients who survived a certain amount of time) and the difficulty of accurately measuring time intervals for past events.