Cancer presents a significant public health challenge and plays a pivotal role in the global burden of diseases (1–3). According to the latest data from the Global Cancer Observatory (GLOBOCAN) 2020 database, the impact of cancer on human health is staggering. Approximately 10 million deaths occur worldwide each year due to cancer, which equates to one death every six seconds (4). The incidence of EC ranks eighth globally, while it stands as the sixth leading cause of cancer-related mortality worldwide (5). According to a recent study, the leading causes of cancer deaths in China in 2022 were lung cancer (733,300 deaths), followed by liver cancer (316,500 deaths), stomach cancer (260,400 deaths), colorectal cancer (240,000 deaths), and esophageal cancer (187,500 deaths). These five types of cancers accounted for 67.50% of total cancer deaths in China (6). In 2021, there were approximately 24,318 new cases of esophageal cancer and 18,226 deaths reported in Hebei Province (7).

For cancers that can be screened, efforts have been directed towards the early identification of cancer cases, leading to a higher percentage of patients being diagnosed at an early stage when surgical intervention offers a potential cure. The increasing number of patients diagnosed with malignant cancer will consequently be provided with greater access to medical interventions (8, 9). Unfortunately, the growing complexity of multimodality cancer care led to a significant time gap of several weeks between diagnosis and treatment (10–15). Continuous evidence from systematic reviews and meta-analyses indicate that variations in the effects of extended waiting periods between diagnosis and treatment on clinical outcomes were detected among individuals diagnosed with different forms of cancer (16–18). Several studies demonstrated that the relationship of treatment delays with an increased overall risk of mortality in patients diagnosed with various types of cancers, including but not limited to lung cancer (10, 11), colorectal cancer (12), endometrial cancer (13), liver cancer (14) and female-specific malignancies (15). The available evidence suggested an increase in wait times for EC treatment over the past decade, as well as disparities among different racial populations in the United States (19, 20). Nevertheless, the impact of treatment waiting time on survival outcomes in Chinese patients with EC remains uncertain.

The objective of this study is to investigate whether the duration from diagnosis to surgical treatment has an impact on the OS and CSS among Chinese patients with EC in Hebei, a region identified as one of the high-risk areas for EC. Furthermore, we aimed to assess the association between the time from diagnosis to treatment and the risk of all-cause and cancer-specific mortality.

This study investigated the impact of delayed EC treatment on OS and CSS, while controlling for individual and clinical characteristics among Chinese EC surgical patients from 2000 to 2020. The 3-, 5-, and 10-year OS rates for patients who experienced a long delay in EC treatment (≥3 months) were found to be 49.8%, 39.8%, and 21.4% respectively, while the CSS rates were determined as 55.1%, 47.8%, and 37.9%. A prolonged delay in EC treatment was independently associated with significantly higher all-cause and cancer-cause mortality among patients. The investigation into the impact of treatment delays on the long-term survival of patients with the most prevalent EC could assist physicians in developing more evidence-based interventions for this specific population.

The accumulation of substantial evidence indicates that a delay in the initiation of cancer treatment can lead to unfavorable outcomes (16–18). A comprehensive meta-analysis revealed that even a mere four-week delay in cancer treatment is associated with an elevated risk of mortality across various types of cancer, including surgical, systemic treatment, and radiotherapy indications. The findings consistently indicate a mortality risk ranging from 1.06 to 1.08 for every four-week delay in surgeries. Estimates for systemic treatment varied between hazard ratios of 1.01 and as high as 1.28, while the estimates for radiotherapy were reported as follows: radical radiotherapy for head and neck cancer (HR=1.09; 95%CI=1.05-1.14), adjuvant radiotherapy after breast conserving surgery (HR=0.98; 95%CI=0.88-1.09), and cervix cancer adjuvant radiotherapy (HR=1.23; 95%CI=1.00-1.50) (16). Similarity, a large cohort study indicated that there is a consistent association between delayed initiation of treatment and increased 5-year and 10-year predicted mortality rates across various cancers, including nonmetastatic breast, prostate, non-small cell lung, and colon cancers. This study also provided evidence suggesting that shorter time-to-treatment initiation is linked to reduced mortality rates for all examined cancer types, implying an indirect relationship between treatment deferral and mortality (21). The findings of another extensive cohort study suggested a significant prolongation in the time to treatment initiation, which is associated with an absolute increase in mortality risk ranging from 1.2% to 3.2% per week in curative settings such as early-stage breast, lung, renal, and pancreatic cancers (22). Recently conducted multi-cancer analyses revealed that, upon adjusting for confounding factors, a prolonged duration from diagnosis to treatment initiation (<6 months) was associated with adverse effects on the survival outcomes of patients diagnosed with early-stage female cancers, including non-small cell lung cancer, breast cancer, thyroid cancer, colorectal cancer, and cervical cancer (15). The relationship between the delay in EC treatment and survival outcomes has been seldom investigated. However, the impact of delayed EC treatment on survival outcomes remains understudied despite its high incidence, mortality rate, and overall poor prognosis (6).

The findings of a study conducted on 315 cases of EC in the Netherlands revealed that there were no significant differences in disease-free survival (p = 0.884) or OS (p = 0.374) between patients with waiting times of less than 8 weeks and those with waiting times of 8 weeks or more, regardless of whether they received neoadjuvant therapy followed by surgery or primary surgery with curative intent (23). Another study conducted in the Netherlands, involving 3839 cases of EC, also indicated that an extended waiting period from diagnosis to treatment for patients undergoing curative intent does not adversely impact OS (24). The former studies yielded similar findings (25, 26). In fact, a similar finding was observed in our study. We discovered that there was no significant association between surgery delay and mortality risk when the duration of surgical treatment delay was less than two months. These results may provide valuable insights for clinical practice regarding EC surgery treatment. Further analysis by Grotenhuis et al. found that a prolonged hospital delay (between endoscopic diagnosis and surgery) was associated with poorer short-term patient outcomes, characterized by higher overall morbidity and mortality rates. However, this delay did not have a detrimental effect on long-term outcomes, specifically OS (27). Our findings suggest that a delay of ≥3 months in starting EC treatment is independently associated with significantly higher rates of all-cause and cancer-specific mortality among patients. Notably, our study population was divided into four subgroups based on delay in treatment [no delay (0 month), brief delay (1 month), moderate delay (2 months), and long delay (≥3 months)], and longer delays were associated with worse OS and CSS. Specifically, 9,977 patients with EC who experienced wait-time intervals exceeding 90 days had significantly lower OS and CSS rates compared to those who received treatment within 30 days. Therefore, the use of different cutoffs for wait-time intervals may have contributed to the observed differences in OS and CSS rates. The findings of this study thus indicated that timely treatment within a clinically relevant waiting period may enhance survival outcomes, highlighting the importance of early intervention for patients.

Significantly, accumulating evidence suggested that the presence of a multi-level social network has an impact on the survival outcomes of cancer patients. The proportion of male EC patients accounted for the highest among all patients in our study, and male EC patients consistently exhibited poorer OS and CSS. This trend is not only observed in Hebei province but also globally (28). Some potential factors that might contribute to the higher incidence of EC among men could include differences in lifestyle habits, such as smoking and alcohol consumption, as well as differences in genetic susceptibility (29). The ethnic composition of the participants also demonstrated variations in previous studies. Recent studies have confirmed inconsistent survival patterns among patients with cancer from diverse ethnic and racial backgrounds (30, 31). Specifically, the survival rate of Black patients has been reported to be comparatively lower than that of Asian/Pacific Islanders. While the underlying mechanisms of survival are still under investigation, factors such as lifestyle and socioeconomic status are believed to play a pivotal role in determining survival outcomes (32, 33). To date, numerous scholars posit that the correlation between marital status and cancer survival is indicative of social support. Spouses play a pivotal role in motivating patients to seek regular medical care, thereby facilitating early diagnosis and treatment of diseases. Patients with cancer receive unwavering encouragement from their spouses to adhere to their treatment regimen and actively engage with other cancer survivors (34–36). A lot of studies have extensively explored the link between marital status and both breast cancer risk and survival (37–41). Consistent with the findings of our study, individuals from low-income backgrounds and residing in nonmetropolitan counties who experienced a prolonged delay in receiving cancer treatment demonstrated significantly improved survival outcomes compared to those who did not receive any treatment within a specific timeframe. Further investigation is required to explore the underlying factors contributing to the relationship between socioeconomic status and cancer outcomes, as well as its impact on clinical aspects. The current study revealed that patients in the long delay treatment group with poor differentiation and stage IV had significantly worse OS and CSS outcomes. These findings suggest that a prolonged time from diagnosis to treatment may negatively impact the prognosis of EC patients with poor differentiated and stage IV EC, highlighting the importance of minimizing wait-time intervals between diagnosis and treatment as a crucial prognostic factor. Notably, over an extended period marked by numerous advances in treatment paradigms and other related factors, we observed that EC patients who experienced prolonged delays in surgical intervention had poorer survival outcomes compared to those without such delays during the years 2000-2010, as opposed to the period from 2011-2020. This finding suggests that advancements in treatment paradigms may mitigate the adverse effects of surgical treatment delays to a certain extent.

To date, the bulk of the evidence underpinning the correlation between the time to treatment initiation and survival rates has been derived from data meticulously compiled in cancer registries across developed nations. However, this wealth of information may not be representative of the global cancer patient population, as it predominantly originates from high-income countries. Consequently, there is an urgent need for future research to delve into the middle- or low-income countries, where the consequences of delayed treatment are likely to be more severe due to the increased vulnerability of cancer patients to disease progression. Such an investigation would require a meticulous examination and comprehensive evaluation of the time taken from diagnosis to the initiation of treatment within various healthcare institutions. This scrutiny, when coupled with an in-depth understanding of the factors contributing to treatment delays, could have far-reaching implications. It could pave the way for public health administrators to make well-informed, tailored decisions on treatment deferrals in resource-constrained regions. Moreover, this knowledge could also facilitate the progress of global health missions, enabling healthcare providers to allocate resources more effectively and ensure that patients in need receive prompt and appropriate care. It could also serve as a vital tool in identifying gaps in the healthcare system and informing strategies to optimize treatment initiation times, ultimately improving survival rates and overall patient outcomes.

Related mechanistic studies remain limited, and the conclusions drawn are still controversial. Some studies indicated that delays in the timing of surgery or diagnosis may adversely affect cancer stage and even impact survival outcomes (42–44). Further research suggested that prolonged delays in initiating definitive treatment for EC may result in progression to advanced tumor stages, potentially adversely affecting patients’ prognosis and survival rates (45, 46). Mathematical models indicated that it may take over a decade from the emergence of the first cancer cell to the point at which a tumor becomes clinically detectable through conventional diagnostic methods. However, median potential doubling times for EC ranged from 4 to 5 days, with some cases exhibiting rapid doubling within a span of 2 to 20 days-making them among the fastest-growing tumor types (47). Furthermore, tumor growth follows an exponential pattern; therefore, even if the duration before discovery is relatively short, a significantly rapid growth rate at that point can still have substantial implications. Therefore, prolonged delays are likely detrimental factors affecting patient prognosis and survival outcomes (48).

The current study has certain limitations that warrant attention. Firstly, it is an observational study conducted retrospectively with potential selection bias, uneven baseline characteristics, and other confounding factors. Secondly, our data lacks information on patient characteristics such as lifestyle choices, educational background, insurance status, Charlson-Deyo comorbidity index score, mental health status or medical knowledge which could have influenced their prognosis, as our patient data was sourced from hospitals that did not collect individual-related information (22). Additionally, the present data does not provide detailed records regarding reasons for treatment delays which are crucial information for further investigation into this important topic and reducing cancer progression due to delayed treatment.

Our findings suggest that a delay in treatment initiation for patients with EC who require surgery, lasting three months or longer, has a detrimental impact on their survival. In Hebei province, recognized as a high-risk area for EC, undergoing surgical intervention for EC within two months may yield more favorable outcomes regarding the patient’s long-term prognosis. Further investigation and validation are needed to determine if these results can serve as evidence supporting the implementation of a more comprehensive pretreatment evaluation.