Sunday, December 3, 2023

Delay in diagnosis to treatment and impact on survival of gastric adenocarcinoma in a low income setting without screening facility – Scientific Reports

This Sri Lankan study explored into components of delay in the diagnosis and treatment of GCA. It showed that delayed patient presentation to hospital and delays in initiating definitive treatment were potentially adversely associated with the survival. The study additionally revealed that patients with advanced clinical presentation had delays in getting the definitive treatment initiated. GCA patients presenting with advanced symptoms, had more chance of developing incurable disease requiring palliative chemotherapy, than getting a curative surgical resection. It also identified that advanced tumour stages (Stage III/IV) were associated with higher median delays in seeking medical advice and these patients had significant pathology delay (due to longer specimen transfer and report dispatch times) and delay in initiating treatment as well.

This information is invaluable and has to be addressed in future, with a view to improve the outcomes of GCA in Sri Lanka and in similar settings. The waiting time is considered an important quality indicator for cancer care8,15. This study showed that a longer waiting time is associated with significant chances of being allocated for palliative chemotherapy due to advanced stage of disease, and with worse survival outcomes. The longer waiting times are known to negatively influence patients’ quality of life, resulting in psychological distress, and poor oncological outcomes in various cancers8,15,16. In the diagnostic pathway of patients with GCA, the patient delay is the longest delayed component in this cohort. Overall delays in endoscopy and pathology were relatively shorter.

An Iranian study17 involving 63 patients, revealed that median patient, endoscopy, pathology, surgeon delays were 1.1, 8.1, 1.7 and 1 weeks respectively. In a study by Tata et al.18 median patient delay was 15.23 and endoscopy delay was 3.37 weeks. Both these studies17,18 had included a mixture of GCA and GOJ tumours. In a study19 on both oesophageal and GCA in Netherlands found that delays involving primary care interval to be, 12 days (interquartile interval 1–43), secondary care interval: 13 days (interquartile interval 6–29) and diagnostic interval: 31 days (11–74). In contrast, in the present study had higher median duration of delays for patient, endoscopy, pathology, definitive treatment and were 18 (IQR 14–27), 2 (IQR 2–3), 4 (IQR 4–5) and 6 (IQR 4–8) weeks respectively.

Sinister symptoms like weight loss20,21,22, palpable abdominal mass21,23,24 have been identified as independently-related adverse factors that result in fatal outcome in GCA. The majority of our patients presented with advanced stage with sinister symptoms precluding curative resection. Hence, they were referred for palliative chemotherapy. Therefore; GCA patients presenting with advanced symptoms, had more chance of developing incurable disease requiring palliative chemotherapy, compared to those who received curative surgical resection.

Prognosis of GCA is highly dependent on disease stage at diagnosis25. Surgery, is the mainstay of treatment that could only cure some patients with early-stage disease26. To date, the survival rates of GCA, as well as the differences in survival rates observed between Eastern and Western GCA, have been mainly attributed to the TNM stage25. Therefore, an efficient diagnostic pathway is the key to timely diagnosis. In the diagnostic pathway of patients with GCA, the patient delay is the longest, followed by delay in initiating definitive treatment either surgery or chemotherapy. In contrast, delays in performing endoscopy and pathology delays are shorter. Findings of the present study indicate that patients may not be fully aware of alarm symptoms, since durations of the patient delays were long. Raising the awareness of GCA alarm symptoms in susceptible population may be the most efficient way to improve prompt presentation to health services and shorten the time from the development of symptoms to diagnosis. On the other hand, exploring more into the reasons for postponing healthcare consultation would enable designing a targeted approach to the problem.

Thus interventions can be integrated into the well-developed public health infrastructure in Sri Lanka, under which each household is allocated into a geographical public health unit called as Medical Officer of Health (MOH) area. The MOH staff deliver public health services in clinic-based settings as well as visiting the houses as domiciliary-services. Hence if a set of health education advices can be developed targeting the GCS alarm symptoms, those messages could be delivered to the community through these staff members who arrange the public health services according to the life-cycle approach.

Although a screening endoscopy program for upper gastrointestinal (GI) cancers is unavailable in Sri Lanka, the upper GI endoscopy facilities have much improved over the past decade. Despite ample access to upper GI endoscopy, delays in diagnosis still seem to be common and virtually affect the stage of GCA at diagnosis, as well as outcome of the patients. In fact, in a country like Sri Lanka, where a screening programme is not feasible due to the lower incidence of the disease, diagnosis of GCA inevitably relies on symptoms reported by patients. Furthermore, better collaboration between curative and preventive sector is the way forward to improve outcomes in GCA. Therefore, increased awareness of GCA symptoms by the susceptible population, as well as correct interpretation of the symptoms and prompt referral for endoscopic investigation, could reduce the diagnostic delay and, theoretically, improve survival. Once method of intervention in this regard could be the formulation of guidelines aiming to facilitate General Practitioners to promptly refer these patients for specialized care.

In the present study there were higher median delays in seeking medical advice in patients having advanced tumour stages (Stage III/IV). These belonged to the group of patients who had significant pathology delay confirming the diagnosis, and delay in initiating treatment. Pathology results are critical for the diagnosis and surgical decision making regarding GCA. In the palliative group of GCA, tissue diagnosis with pathology report is a key factor in initiation of chemotherapy. The present study showed that specimen transfer delay to lab and delay in receipt of the pathology report to the ward mainly contributed to overall pathology delay. Therefore, it is important to minimize these preventable delays and there should be time limits in producing the histopathology report. It is also important to establish online portals of hospital information system (HIS) and laboratory information system (LIS) for easy access of histology reports in future with in our hospital system. Furthermore, one method of intervention isto make sure that specimens are immediately transferred to the laboratory at the end of resection in theater or at the end of endoscopy list.

According to Cox regression analysis, age of the patient and the treatment modality, were significantly associated with the survival of the cohort. Patients who had palliative treatment (biopsies) had a higher hazard ratio compared to those who underwent surgical intervention which is plausible with their advanced disease profile. There was no significant association between histopathology, treatment delay with the hazard function. This could be due to other unrecognized contributing factors which need to be investigated with a larger sample.

Improving delay with the survival by timely detection of GCA among patients without alarm symptoms is challenging, given the high incidence of common upper GI symptoms and functional disorders at low risk of cancer. On the other hand, simply lowering the threshold for endoscopy is not the solution for reducing the time to referral as there is already a growing demand for diagnostic endoscopy services in secondary care. Lowering the threshold for endoscopy might result in increased risk of non-indicated endoscopies with normal results. Therefore, early referral of patients with alarm symptoms (i.e. anorexia, anaemia) without further delay is an important aspect in early diagnosis.

In Sri Lanka, despite the improvement of endoscopic facilities, delays in diagnosis still seem to be common. The patient delay and delay in initiating definitive treatment are the most important contributors to waiting time in GCA in this setting. This might affect the stage of GCA at diagnosis as well as outcome. Therefore, the increased awareness of symptoms, as well as correct interpretation of the symptoms and prompt referral for investigation, could reduce the diagnostic delay and, theoretically, improve survival.

This study is with several limitations. The factors which resulted in delayed presentation of patients to healthcare services as well as factors that resulted in delay in starting palliative chemotherapy such as patients’ wishes on alternative treatment strategies, beliefs, fears on initiating chemotherapy etc. were not investigated. Getting an insight in to these reasons for postponing medical consultation would be required for a targeted approach. Secondly, in patients who had delays in having primary resections, the exact reasons and possible causative factors such as postponement due to lack of adequate intensive care beds were not evaluated. The survival follow-up time was also not uniform and was in the range of 0–240 weeks. However as the exposures except for the “duration of chemotherapy” did not change in the follow up period, authors are confident that a major degree survival bias can be excluded. The “duration of chemotherapy” is usually decided based on case-by-case basis. The study only explored the patients visiting the government setting and did not explore those visiting the private sector.

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