1 INTRODUCTION

Globally, the cancer burden is estimated to be 18.1 million new cases and 9.6 million deaths in 2018.¹ Approximately 70% of cancer deaths occur in developing countries.² By 2030, there will be 23.6 million new cancer cases worldwide per year.³ This growing trend of cancer incidence has spurred more work on cancer prevention and treatments.⁴

Colorectal, gastric, esophageal, and liver cancers are the most frequently diagnosed gastrointestinal cancers globally.⁵ Moreover, gastrointestinal cancers account for 26% of the global cancer incidence and 35% of all cancer deaths.⁶

Although the incidence of some gastrointestinal cancer types has diminished, they continue to pose substantial challenges to public health.⁶ Gastric cancer incidence has decreased dramatically in the past 50 years because of a decrease in Helicobacter pylori infection, smoking habits, and the use of processed meat.⁷ Complete eradication of the organism after treatment reduced the risk.⁸ Although the treatment outcomes of advanced gastric cancer have improved with the advancement of chemotherapy and surgery, there are still areas for improvement in achieving substantial beneficial effects to increase patient survival.⁹ Gastric cancer is an age-related disease and is commonly diagnosed in the older population. Therefore, achieving the desired outcomes of treatment is difficult due to age-related reduced organ function.¹⁰

In contrast, in developed countries, despite the incidence of gastric cancers steadily falling in the past 50 years, treatment outcomes remain poor, mainly due to the diagnosis of the disease at an advanced stage. Besides, the prognosis for advanced stages of gastrointestinal cancer remains very poor, despite extensive attempts to improve treatment, including the development of new medicines. Therefore, there is an immediate need for effective disease management to ensure that patients are given the most suitable care.¹¹ The treatment outcome of cancer patients is poor in sub-Saharan Africa compared to other regions due to the lack of adequate treatment and diagnostic facilities.¹²

There are many inconclusive pieces of evidence of survival outcomes of gastric cancer patients globally. Besides, the studies available in East Africa are few and non-comprehensively covered. Thus, this study aimed to assess survival outcomes among gastric cancer patients at Kenyatta National Hospital (KNH).

2 METHODS

3 RESULTS

3.3 Survival outcomes of the study participants

Among the 247 patients, 33.3% (64) had evidence of new distant metastasis in the follow-up period. Of those cases, metastasis to the liver and lung were the most common sites of spread. Nonetheless, metastasis to the ovary, bone, and multiorgan metastases were the least common sites of spread during the last follow-up period.

The present study showed that 42.1% (104) of the patients had disease progression during the follow-up period. Besides, the mortality rate was 33.6% (83), even though 1.6% had unknown outcomes. Furthermore, 14.6% and 7.7% of patients had complete responses and partial responses, respectively (Figure 1). The five-year survival of gastric cancer patients was 32.7%, with a mean cancer-specific survival of 27.6 ± 3.1 months.

The study showed no statistically significant mean differences in survival estimates between age groups, gender, and histological type of cancer compared to their respective counterparts. However, the mean survival estimates of gastric cancer patients with co-morbidity (44.4 months), advanced stage of disease (40.7 months), and distant metastasis (13.3 months) were significantly shorter than their counterparts. In contrast, patients treated with surgery (49.1 months) and chemotherapy (56.9 months) had a longer duration of mean survival estimates than their counterparts. On the other hand, radiotherapy-treated patients did not significantly differ in mean survival estimates compared to patients without radiotherapy. Comparatively, chemotherapy-treated gastric cancer patients had the longest duration of mean survival estimates than other treatment modalities (Table 3 and Figure 2).

TABLE 3. Mean survival time estimates among the study participants

Variables	Mean survival estimate (months) ± standard error (95% CI)	Log-rank test (p-value)
Age (years)		0.532
< 60 years	46.4 ± 3.5 (39.5–53.2)
≥ 60 years	46.1 ± 2.6 (40.9–51.3)
Gender		0.918
Male	46.4 ± 3.4 (39.7–53.2)
Female	47.9 ± 2.9 (42.2–53.6)
Co-morbidity		0.007*
Present	44.4 ± 3.1 (38.3–50.6)
Absent	53.9 ± 1.9 (50.2–57.6)
Stage of cancer		0.031*
Early-stage (I &II)	53.1 ± 3.2 (46.7–59.4)
Advanced stage (III & IV)	40.7 ± 2.9 (34.9–46.5)
Histological type of cancer		0.838
Adenocarcinoma	49.1 ± 2.4 (44.4–53.7)
Squamous cell carcinoma	17.3 ± 2.2 (13.1–21.6)
Distant metastasis at diagnosis		< 0.001*
Yes	13.3 ± 1.6 (10.1–16.4)
No	54.6 ± 2.2 (50.4–58.8)
Distant metastasis in the follow-up period		0.118
Yes	43.9 ± 2.7 (38.6–49.2)
No	53.5 ± 3.7 (46.3–60.8)
Treatment regimen
Chemotherapy		< 0.001*
No	18.7 ± 2.0 (14.7–22.6)
Yes	56.9 ± 2.0 (52.9–62.9)
Gastrectomy		0.041*
No	45.3 ± 3.5 (38.5–52.1)
Yes	49.1 ± 2.9 (43.4–54.9)
Radiotherapy		0.500
No	45.2 ± 2.5 (40.2–49.9)
Yes	52.1 ± 5.3 (41.7–62.5)
Symptomatic therapy		< 0.001*
No	55.1 ± 2.1 (51.0–59.1)
Yes	6.7 ± 0.9 (4.9–8.5)

• * Statistically significant p-value ≤0.05.

Patients with co-existing co-morbidities had a 3.3 times more risk of dying than those without co-morbidities (AHR: 3.3, 95% CI: 1.3–8.7, p = 0.014). Patients with advanced-stage diseases and distant metastasis at diagnosis had 2.4 (AHR: 2.4, 95% CI: 1.1–5.2, p = 0.03) and 7.7 (AHR: 7.7, 95% CI: 3.1–19.1, p < 0.001) times more risk of dying than their counterparts, respectively. Gastric cancer patients who did not receive chemotherapy (AHR: 5.2, 95% CI: 1.5–17.8, p = 0.008) and gastrectomy (AHR: 1.7, 95% CI: 1.1–2.6, p = 0.016) had a statistically significant higher risk of dying compared to patients who received the respective treatment modalities. In contrast, radiotherapy did not show a statistically significant difference in mortality risk among gastric cancer patients. Nonetheless, patients treated with symptomatic management had a higher risk of dying than patients without symptomatic management. Age, gender, histological type of cancer, and distant metastasis in the follow-up period were not statistically significant determinants of survival outcomes among gastric cancer patients (Table 4).

TABLE 4. Determinants of mortality among the study participants

Variable	Bivariate analysis		Multivariate analysis
	CHR (95% CI)	p-value	AHR (95% CI)	p-value
Age (years)
< 60 years	1		1
≥ 60 years	0.8 (0.4–1.6)	0.537	0.9 (0.4–1.9)	0.741
Gender
Male	1		1
Female	0.9 (0.5–1.9)	0.919	2.1 (0.9–4.8)	0.067
Co-morbidity
Absent	1		1
Present	3.4 (1.3–8.8)	0.012*	3.3 (1.3–8.7)	0.014*
Types of co-morbidity
Hydronephrosis
No	1		1
Yes	12.6 (1.6–3.6)	0.014*	31.4 (3.9–10.2)	0.001*
Hypovolemic shock
No	1		1
Yes	8.3 (1.1–3.3)	0.039*	20.7 (2.6–12.5)	0.004*
Anemia
No	1		1
Yes	2.9 (1.5–5.8)	0.002*	3.8 (1.8–7.8)	<0.001*
Acute kidney injury
No	1		1
Yes	2.5 (1.0–6.1)	0.043*	4.2 (1.6–10.7)	0.003*
Ascites
No	1		1
Yes	3.7 (1.5–9.1)	0.005*	5.1 (1.9–13.1)	0.001*
Stage of cancer
Early-stage (I &II)	1		1
Advanced stage (III & IV)	2.3 (1.1–5.2)	0.038*	2.4 (1.1–5.2)	0.03*
Histological type of cancer
Adenocarcinoma	1		1
Squamous cell carcinoma	1.2 (0.2–9.1)	0.840	0.2 (0.1–1.5)	0.103
Distant metastasis at diagnosis
No	1		1
Yes	6.4 (3.2–12.8)	<0.001*	7.7 (3.1–19.1)	<0.001*
Distant metastasis in the follow-up period
No	1		1
Yes	0.5 (0.2–1.2)	0.130	0.6 (0.2–1.8)	0.326
Treatment regimen
Chemotherapy
Yes	1		1
No	7.5 (3.2–17.3)	<0.001*	5.2 (1.5–17.8)	0.008*
Gastrectomy
Yes	1		1
No	2.1 (1.1–4.5)	0.04*	1.7 (1.1–2.6)	0.016*
Radiotherapy
Yes	1		1
No	1.5 (0.5–4.9)	0.507	0.8 (0.2–3.2)	0.754
Symptomatic therapy
Yes	1		1
No	0.08 (0.1–0.2)	<0.001*	0.3 (0.1–0.9)	0.034*

• Abbreviations: AHR, Adjusted hazard ratio; CHR, Crude hazard ratio.
• * Statistically significant p-value ≤0.05.

In the subgroup analyses, in males, adults (<60 years), and older patients (>60 years), chemotherapy and gastrectomy treatment modalities were statistically significant predictors of mortality. However, chemotherapy (p = 0.001) was the only significant predictor of mortality in female gastric cancer patients (Table 5). In the advanced stage of gastric cancer (stage III &IV), chemotherapy (p ≤ 0.002), gastrectomy (p = 0.002), radiotherapy (p = 0.01) and co-morbidity (p = 0.04) were the significant predictors of mortality. Nonetheless, gastrectomy (p = 0.02) treatment was the only significant predictor in the early stage (I &II) gastric cancer patients (Table 6).

TABLE 5. Subgroup analysis of the determinants of mortality based on age and gender among the study participants

Variables	Categories	Bivariate analysis		Multivariate analysis
		CHR (95% CI)	p-value	AHR (95% CI)	p-value
< 60 years	Comorbidity
	Absent	1		1
	Present	3.5 (1–11.9)	0.051	1.3 (0.3–5.2)	0.678
	Early-stage (I &II)	1		1
	Advanced stage (III & IV)	0.3 (0.1–1.0)	0.06	0.7 (0.2–2.2)	0.519
	Chemotherapy
	Yes	1		1
	No	4.5 (1.5–15.9)	0.007*	11.7 (3.1–12.0)	<0.001*
	Gastrectomy
	Yes	1		1
	No	2.5 (0.9–6.5)	0.066	3.7 (1.3–10.4)	0.012*
	Radiotherapy
	Yes	1		1
	No	0.9 (0.2–2.5)	0.386	1.1 (0.2–3.3)	0.744
≥ 60 years	Co-morbidity
	Absent	1		1
	Present	3.2 (0.7–14.5)	0.123	1.5 (0.3–7.5)	0.624
	Early-stage (I &II)	1		1
	Advanced stage (III & IV)	0.6 (0.2–1.8)	0.371	0.5 (0.1–1.5)	0.200
	Chemotherapy
	Yes	1		1
	No	10.5 (3.0–20.2)	<0.001*	10.1 (2.6–20.2)	0.001*
	Gastrectomy
	Yes	1		1
	No	1.8 (0.6–5.9)	0.305	4.1(1.2–14.2)	0.028*
	Radiotherapy
	Yes	1		1
	No	0.8 (0.2–2.7)	0.664	1.2 (0.4–4.5)	0.788
Male	Co-morbidity
	Absent	1		1
	Present	2.1 (0.7–6.3)	0.178	0.6 (0.2–2.2)	0.446
	Early-stage (I &II)	1		1
	Advanced stage (III & IV)	0.4 (0.1–1.1)		0.4 (0.2–1.2)	0.113
	Chemotherapy
	Yes	1		1
	No	7.2 (2.4–21.5)	<0.001*	13.6 (3.8–30.2)	<0.001*
	Gastrectomy
	Yes	1		1
	No	2.7 (1.2–7.5)	0.05*	5.4 (1.9-15.5)	0.001*
	Radiotherapy
	Yes	1		1
	No	1.3 (0.6–2.8)	0.441	1.5 (0.7–3.2)
Female	Comorbidity
	Absent	1		1
	Present	8.3 (1.1–10.2)	0.042*	2.3 (0.6-3.4)	0.127
	Early-stage (I &II)	1		1
	Advanced stage (III & IV)	0.5 (0.1–1.9)		1.0 (0.2–4.5)	0.963
	Chemotherapy
	Yes	1		1
	No	8.4 (2.3–23.3)	0.001*	10.3 (2.5–10.0)	0.001*
	Gastrectomy
	Yes	1		1
	No	1.4 (0.4–4.4)	0.569	2.9 (0.8–10.3)	0.105
	Radiotherapy
	Yes	1		1
	No	1.0 (0.4–2.9)	0.939	1.3 (0.4–4.5)	0.665

• Abbreviations: AHR, Adjusted hazard ratio; CHR, Crude hazard ratio.
• * Statistically significant p-value ≤0.05.

TABLE 6. Subgroup analysis of the determinants of mortality based on the stages of the disease among gastric cancer patients

Variables	Categories	Bivariate analysis		Multivariate analysis
		CHR (95% CI)	p-value	AHR (95% CI)	p-value
Early stage (I&II)
	Chemotherapy
	Yes	1		1
	No	2.5 (0.6–10.3)	0.200	3.4 (0.7–15.4)	0.114
	Gastrectomy
	Yes	1		1
	No	1.9 (0.5–8.3)	0.352	2.5 (0.5–13.2)	0.02*
	Radiotherapy
	Yes	1		1
	No	0.4 (0.1–2.1)	0.296	0.6 (0.1–3.4)	0.535
	Co-morbidity
	Absent	1		1
	Present	1.1 (0.3–4.6)	0.912	0.7 (0.1–3.3)	0.640
Advanced stage (III&IV)
	Chemotherapy
	Yes	1		1
	No	13.8 (4.1–20.2)	<0.001*	16.6 (4.5–20.2)	<0.002*
	Gastrectomy
	Yes	1		1
	No	1.9 (0.8–4.6)	0.140	4.2 (1.7–10.4)	0.002*
	Radiotherapy
	Yes	1		1
	No	3.5 (0.5–26.6)	0.002*	3.2 (0.4–24.2)	0.01*
	Co-morbidity
	Absent	1		1
	Present	6.2 (1.5–20.2)	0.013*	2.7 (1.3–7.9)	0.04*

• Abbreviations: AHR, Adjusted hazard ratio; CHR, Crude hazard ratio.
• * Statistically significant p-value ≤0.05.

4 DISCUSSION

Although early detection of gastric cancer can lead to long-term survival,¹⁵ there is much inconclusive evidence about the survival outcome of gastrointestinal cancer patients globally. In addition, some countries have an increased incidence of gastric cancer in the younger population.²³ However, the studies available in the East African setting are minimal in assessing survival outcomes after treatment in gastric cancer patients. Therefore, this study highlights the determinants of survival outcomes among gastric cancer patients.

At the time of diagnosis, 22.3% of patients with gastric cancer exhibited distant metastasis, with the liver and lung being the most prevalent sites of metastasis. Besides, 33.3% of patients had evidence of new distant metastasis in the follow-up period, which can worsen survival. This could probably be linked to late diagnosis and delayed initiation of optimal treatment in our setting.

The mortality rate was significantly higher than Africa's estimated mortality rate (3.8%).²⁴ This high mortality rate could be due to the late diagnosis and lack of adequate facilities for treatment in the study setting. Despite this, 14.6% and 7.7% of patients had complete and partial responses, respectively, contrasting findings in the Cameroon study, which demonstrated a 70.8% mortality.¹⁶ Therefore, educational programs should be implemented nationally about the essence of early diagnosis and treatment of gastric cancer patients for improved survival outcomes.

Previous studies showed a mean five-year survival rate of 15.5% among gastric cancer patients with a reduction in the survival trends from the first to the fifth year.¹⁵ In addition, a Cameronian study also reveals a 4.6% five-year survival rate.¹⁶ A previous systematic review shows a relatively poor five-year survival rate in Africa compared to Korean and Japanese gastric cancer patients.²⁵ In contrast, the findings in our study reported a significantly higher five-year survival rate (32.7%) despite the survival rate being reduced from 1 year to the fifth year after the diagnosis of the disease. However, awareness creation education programs about early signs and symptoms of gastric cancer, optimal management and availability of anticancer drugs in all cancer treatment centers are essential to enhance overall survival in our setting.

The mean cancer-specific survival of gastric cancer patients (27.6 months) was slightly higher than the Cameronian study (5.91 months).¹⁶ On the other hand, a Turkish (51 months) and Nigerian (13.6 months) study reports a longer median overall survival.^{18, 19} This relatively lower mean survival time in our setting could probably be linked to delay in treatment initiation and late diagnosis as most (60%) of the patients had locally advanced and metastatic disease. Therefore, early gastric cancer screening should be regularly implemented in our setting to improve overall survival in these populations.

The study shows no statistically significant mean differences in survival estimates between age groups, gender, and histological type of cancer compared to their counterparts. Contrastingly, a previous study showed that female and younger patients had shorter and longer survivals, respectively.²⁶ However, the mean survival estimates of gastric cancer patients with co-morbidity (44.4 months), advanced stage of disease (40.7 months), and distant metastasis (13.3 months) were significantly shorter than their counterparts. Therefore, optimal management with frequent follow-up of these patients is essential to improve survival and health-related quality of life. Likewise, patients with metastatic gastric cancer had poor survival outcomes despite the efficacy of current chemotherapy in treating gastric cancer.²⁷

In contrast, patients treated with gastrectomy (49.1 months) and chemotherapy (56.9 months) had a longer duration of mean survival estimates than their counterparts. This finding is consistent with another study that shows gastric cancer patients treated with surgery and chemotherapy had the longest median overall survival (14.2 months).²⁰ These disparities among the studies in survival time could probably be due to the difference in the cancer stage, co-morbidity, and age of the study participants. On the other hand, radiotherapy-treated patients did not significantly differ in mean survival estimates from patients without radiotherapy.

In the sub-group analysis, chemotherapy (p ≤ 0.002), gastrectomy (p = 0.002), and radiotherapy (p = 0.01) treatment approaches were significant determinants of survival in the advanced stage of gastric cancer (stage III &IV) patients. Nonetheless, gastrectomy (p = 0.02) was the only significant determinant of survival in the early stage (stage I & II) gastric cancer patients. Therefore, gastrectomy, radiotherapy, and chemotherapy should be the preferred treatment approaches to improve the survival of advanced-stage gastric cancer patients (stage III &IV) in our setting. In contrast, gastrectomy should be considered in the early stages of the disease (stages I &II).

The mean survival estimate of squamous cell carcinoma (17.3 months) was shorter than adenocarcinoma (49.1 months), suggesting gastric squamous cell carcinoma had poorer survival outcomes than gastric adenocarcinoma. This could probably be linked to the aggressive nature of squamous cell carcinoma and its frequent diagnosis at the advanced stage.^{28, 29} Hence, early screening and aggressive treatment modalities are highly recommended to improve survival in these patient populations. This finding agrees with other studies in China.^30-32

Co-morbidities have a negative prognostic impact on overall survival.³³ Correspondingly, gastric cancer patients with co-existing co-morbidities had 3.3 times more risk of dying than patients without co-morbidities. Subgroup analysis revealed that surgery (AHR = 0.18, 95% CI:01–0.4, p < 0.001) and chemotherapy (AHR = 0.13, 95% CI:0.1–0.3, p < 0.001) treatment modalities can enhance survival outcomes among patients with co-morbidities. Patients with advanced-stage diseases and distant metastasis at diagnosis had 2.4 and 7.7 times more risk of dying than their counterparts, respectively. Likewise, Talebi et al study also reported a higher hazard of mortality in the metastatic stage of the disease.³⁴ Gastric cancer patients who did not receive chemotherapy and gastrectomy treatment had a statistically significant risk of dying compared to patients who received the respective treatment modalities. This could probably be linked to presentation in late stage and only treated with palliative care or supportive treatments. This is consistent with other studies where gastrectomy and chemotherapy were associated with decreased overall mortality in gastric cancer patients.^35-37 Age, gender, and histological type of cancer were not statistically significant determinants of survival outcomes among gastric cancer patients. In contrast, a Korean study showed an increased hazard of mortality among older gastric cancer patients (≥60 years).³⁸ Hence, individualized treatment modalities should be considered in co-morbid and metastatic gastric cancer patients to reduce mortality.

Although molecular biomarkers are important recent advances in the prognostic prediction of treatment response and monitoring of recurrence of gastric cancer,³⁹ they are not commonly used in the African setting due to lack of access to these facilities. Therefore, for better prediction of treatment responses in gastric cancer, cancer treatment centers should be equipped with those diagnostic facilities in African settings.

Currently, radiomics coupled with artificial intelligence are also extensively studied for survival outcomes prediction in gastric cancer^40-42 despite our study not addressing these novel technologies. Hence, these risk prediction technologies are highly recommended due to their better capability to handle massive data compared to traditional statistical methods.

5 CONCLUSIONS

A significant proportion of gastric cancer patients had distant metastasis and disease progression (42.1%) in the last follow-up period. Co-morbidity, advanced-stage diseases, distant metastasis at diagnosis, chemotherapy, and gastrectomy were statistically significant determinants of survival among gastric cancer patients in our setting. Therefore, a multi-center study is required to determine survival outcomes in gastric cancer patients reliably.

AUTHOR CONTRIBUTIONS

Amsalu Degu: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Peter N Karimi: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). Sylvia A Opanga: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal). David G Nyamu: Conceptualization (equal); data curation (equal); formal analysis (equal); funding acquisition (equal); investigation (equal); methodology (equal); project administration (equal); resources (equal); software (equal); supervision (equal); validation (equal); visualization (equal); writing – original draft (equal); writing – review and editing (equal).

FUNDING INFORMATION

There was no funding to conduct this study.

CONFLICT OF INTEREST

The authors declare that they have no conflicts of interest.

ETHICS STATEMENT

The study protocol was approved by the Kenyatta National Hospital/University of Nairobi Ethics and Research Committee (Approval No: P195/03/2021). After approval, permission to collect the data was obtained from the Health Information Department of KNH before the data collection from patients' medical records. The patients' names and addresses were not recorded during the data collection to ensure the patients' confidentiality.

PATIENT CONSENT STATEMENT

Because the study was retrospective, we obtained participants' informed consent waivers from the Ethics committee.