This retrospective study collected a total of 685,829 cases from the SEER database, spanning from 2010 to 2019. The raw data downloaded from the SEER database spans a period of ten years, from 2010 to 2019. Due to the registration of data regarding whether patients have distant metastases (including those in organs and lymph nodes) beginning in 2016, the patients analyzed in this article are from the years 2016 to 2019. Due to the sensitive personal information of the patients involved, the SEER database does not provide specific dates, only monthly information. The diagnosis period is from January 1, 2016, to December 31, 2019, and the follow-up period ends on December 31, 2019. The latest data can be accessed by applying on the official SEER website (https://seer.cancer.gov/). After the removal of incomplete or non-compliant data, Table 1 shows a total of 119,760 cases of gastrointestinal cancers and subgroups included in this study, based on the data selection criteria outlined in Fig. 1. Patients were divided into the OP group and the MP group. The MP group was further subdivided into the FMP group and the NFMP group based on the sequence of occurrence of the patient’s cancer. The summary of the baseline comparison of patient characteristics in each group was presented in Fig. 2 (refer to Supplementary Table 1 for details).

Characteristics of patients with various primary gastrointestinal cancers in the United States from 2016 to 2019. 1 The bold characteristics correspond to the comparison between the OP and MP groups. 2 The non-bold characteristics correspond to the comparison between the OP, FMP, and NFMP groups. 3 Combined summary stage based on the SEER database, including localized, regional, and distant. (https://seer.cancer.gov/seerstat/variables/seer/lrd-stage/). *Variables highlighted in green are statistically significant

The primary outcome was the OS of the patients. The first type of OS comparison was between the OP and MP groups for each histological type of gastrointestinal cancer. The further subgroup analysis of OS was conducted between the OP, FMP, and NFMP groups, with the latter two groups being separated from the MP group (Fig. 3).

Overall survival of patients with various primary gastrointestinal cancers in the United States from 2016 to 2019

This study included the first and second common primary liver cancers, HCC and ICC, respectively (Table 2). Patients in the OP group were generally younger than those in the MP group, while early-stage patients in the MP group were more than those in the OP group. The treatment strategies in the OP, FMP, and NFMP groups differed, but the overall systemic therapy ratio was not statistically significant. There were statistical differences in cancer metastasis and months from diagnosis to treatment (MFDTT) between the OP, FMP, and NFMP groups (Fig. 2, Supplementary Table 1.1). The OS comparison between the OP group and the MP group was statistically significant in ICC but not in HCC. The MP group was divided into the FMP and the NFMP groups for further subgroup analysis of OS. Patients with HCC in the FMP group had better OS than those in the OP group, and patients with ICC either in the FMP group or the NFMP group had better OS (Fig. 3). After conducting univariate and multivariate analyses, we found that patients in the FMP group could serve as an independent lower risk factor for OS in patients with HCC or ICC (Figs. 4 and 5, Supplementary Table 2.1).

Univariate analysis of variables affecting overall survival in patients with various primary gastrointestinal cancers in the United States from 2016 to 2019

Multivariate analysis of variables affecting overall survival in patients with various primary gastrointestinal cancers in the United States from 2016 to 2019

GBAC was the most common subtype of gallbladder cancer, accounting for approximately 80% of gallbladder cancer cases eligible for this study (Table 2). Patients with GBAC in the MP group, including the FMP and NFMP group, were receiving more passive treatments, such as fewer surgical procedures of other regional/distant sites (Surg Oth Reg/Dis), chemotherapy, and systemic treatments (Fig. 2, Supplementary Table 1.2). This therapy strategy might be related to poor OS in the GBAC patients, with no statistically significant difference between the OP and MP groups (Fig. 3). The univariate and multivariate analyses conducted with the Cox regression model demonstrated that age, p-Grade (pathological-Grade), stage, and positive metastases were independent risk factors for OS (Figs. 4 and 5, Supplementary Table 2.2).

The main histologic types of pancreatic cancers were PAC, PIDC, and PCT, with approximately 43%, 27%, and 20% of the selected cases (Table 2). Patients with PAC in the MP group had better tumor related characteristics, such as a lower proportion of advanced stage tumors, a higher proportion of regional lymph node surgery (RLN-Sur) with lower positive RLN, receiving a higher proportion of systemic therapy, and fewer metastases. Thus, the patients with PAC in the MP group, particularly in the FMP group, had a better OS than those in the OP group (Fig. 3).

Similar characteristics appeared in the PIDC patients with a lower proportion of advanced stage tumors, a higher proportion of RLN-Sur with lower positive RLN (Fig. 2, Supplementary Table 1.3). The OS of patients PIDC in the FMP group was better than those in the OP group. The PCT cases in this study showed that the OP group had more low-grade patients, but a higher proportion of patients with advanced stage and metastases than the MP group. However, the patients with PCT in the OP group presented higher OS than those in the MP group, and the NFMP group particularly (Fig. 3).

Combined with the results of the univariate and multivariate analyses, we found that age, p-Grade, stage, and positive metastases were high-risk factors for OS, whereas the FMP in patients with PAC or PIDC was a low-risk factor for OS but not with PTC (Figs. 4 and 5, Supplementary Table 2.3).

The two most prevalent histological types of esophageal cancer were EAC and ESCC, accounting for approximately 64% and 29% of the selected cases, respectively (Table 2). The patients EAC in the MP group exhibited a higher proportion of patients with early-stage and age (≥ 60), as well as lower rates of positive RLN and metastases, in comparison to the OP group. The subsequent subgroup analysis revealed that patients in the FMP group received a higher proportion of RLN-Sur, radiation therapy, and systemic therapy compared to the OP group (Fig. 2, Supplementary Table 1.4). Consequently, patients with EAC enrolled in the MP group had a superior OS compared to the OP group. The statistically significant difference was observed between the OP and FMP groups (Fig. 3).

In patients with ESCC, the proportion of female patients in the MP group was higher than that in the OP group. The MP group had a higher proportion of patients with early-stage tumors, fewer metastases, and received chemotherapy and radiation therapy (Fig. 2, Supplementary Table 1.4). In the OS analysis, we found that the OS in the MP group, whether in the FMP or NFMP group, was better than that in the OP group (Fig. 3).

There were similarities and differences in the risk factors for OS in EAC and ESCC. The age, p-Grade, stage, and positive metastases were high-risk factors, while the FMP was found to be a low-risk factor in EAC and ESCC. In patients with EAC, the NFMP was regarded as a high-risk factor in multivariate analysis but not in the univariate analysis. Gender female was considered to be an independent low-risk factor in patients with ESCC (Figs. 4 and 5, Supplementary Table 2.4).

The study examined three histologic types of gastric cancers, including GAC, GISS, and GCT, which accounted for approximately 59%, 12%, and 9% of cases, respectively (Table 2). Patients with GAC exhibited various differences in characteristics, except for gender, Surg Oth Reg/Dis, and radiation therapy between the OP and MP groups. Patients with GISS exhibited characteristic differences in age, gender, chemotherapy, and systemic therapy. Patients with GCT exhibited only a characteristic difference in age (Fig. 2, Supplementary Table 1.5).

Significant differences in OS were observed in the comparison between the OP and FMP groups in GAC, the OP and MP groups in GISS, the OP and NMP groups in GISS, and the OP and NFMP groups in GCT. All OP groups had better OS in the above comparison (Fig. 3).

Three types of gastric cancers possessed different independent risk factors for OS. For patients with GAC, the high-risk factors were p-Grade, stage, positive metastases, and NFMP, and the low-risk factors were female and FMP. For patients with GISS, the high-risk factors for OS were age (≥ 60), positive metastases, and the NFMP. Among patients with GCT, the high-risk factors were p-Grade, positive metastases, and the NFMP (Figs. 4 and 5, Supplementary Table 2.5).

The two most common histologic types of cancers in the small bowel were SBA and SBCT, with 1,137 cases (22%) and 3,337 cases (64%) included in this study (Table 2). Patients with SBA or SBCT in the MP group had a higher proportion of age (≥ 60), a higher proportion of advanced stage tumors, and a lower rate of positive RLN compare to the OP group (Fig. 2, Supplementary Table 1.6). In patients with SBA, the OS of the FMP groups was superior to that of the OP group. Regarding SBCT, the OP group demonstrated superior OS compared to the MP group (Fig. 3).

Age (≥ 60) and p-Grade were independent high-risk factors for OS in both SBA and SBCT. The stage and positive metastases were independent high-risk factors for OS in SBA, while the FMP was a low-risk factor. In regard to SBCT, the NFMP was a high-risk factor for OS. The advanced stage was found to be an independent low-risk factor (Figs. 4 and 5, Supplementary Table 2.6).

Approximately 76%, 5%, and 5% of the selected cases of colon cancers were classified as COAD, COPA, and COCT, respectively (Table 2). Patients with COAD in the OP group exhibited statistically different characteristics compared to the MP group including a higher proportion of patients under the age of 60, a higher proportion of low-grade and early-stage patients, a shorter MFDTT, and receiving more positive treatments. Nevertheless, the positive rates of RLN and metastases in the OP group were higher than those in the MP group (Table 4). The characteristic differences between the OP group and the MP group in patients with COPA were age, gender, race, p-Grade, stage, chemotherapy, systemic therapy, and positive rates of RLN. In regard to COCT, there were several characteristic differences between the OP and MP groups, except for gender, race, Surg Oth Reg/Dis, and radiation therapy (Fig. 2, Supplementary Table 1.7).

The OS analysis of patients with these three types of colon cancers demonstrated that patients in the OP group obtained superior OS than those in the MP group, regardless of whether they were in the FMP or NFMP group (Fig. 3). Age (≥ 60), low p-Grade, advanced stage, and positive metastases were independent high-risk factors for OS in patients with COAD, COPA, or COCT. The FMP was an independent high-risk factor for OS in patients with COPA. Whereas the NFMP was an independent high-risk factor for OS in patients with COAD, COPA, or COCT (Tables 5 and 6; Figs. 4 and 5, Supplementary Table 2.7).

The three types of rectal cancers enrolled in the study were READ, REPA, RECT, with approximately 77%, 6%, and 8% of the selected cases (Table 2). Patients with READ had various statistically different characteristics between the OP and MP groups, except for gender, race, and p-Grade. Patients with READ in the OP group, in comparison to the MP group, had a lower proportion of patients over the age of 60 and several tumor-related characteristics including a higher proportion of low-grade patients, a higher proportion of positive RLN and metastases, and a higher proportion of patients receiving positive treatments with shorter MFDTT. Similar characteristic differences were observed in patients with RECT, excluding metastases, MFDTT, and radiation therapy. Patients with REPA in the OP group had a higher proportion of RLN-Sur with a lower positive rate of RLN compared to those in the MP group (Fig. 2, Supplementary Table 1.8).

According to OS analyses for patients with READ, REPA, or RECT, patients in the OP group exhibited superior OS than those in the MP group. Further subgroup analysis revealed statistical differences in OS between the OP group and the NFMP group in READ, REPA, and RECT (Fig. 3). The univariate and multivariate analyses demonstrated that age (≥ 60), non-white race, low p-Grade, advanced stage, positive metastases, and the NFMP were independent high-risk factors, while gender female was an independent low-risk factor for OS in patients with READ. In patients with REPA, we found that independent high-risk factors were age (≥ 60), advanced stage, positive metastases, and the NFMP, while independent low-risk factor was gender female. In regard to RECT, the independent high-risk factors for OS were low p-Grade, advanced stage, positive metastases, and the NFMP (Figs. 4 and 5, Supplementary Table 2.8).

The most common type of anal cancer that occurs in the anus is squamous cell carcinoma. The study comprised 2,999 cases of ASCC, which accounted for 85% of the total cases of anal cancer (Table 2). Patients in the OP group received a lower ratio of RLN-Sur, had a lower rate of positive RLN, and received positive treatment such as radiation therapy and chemotherapy compared to the MP group (Fig. 2, Supplementary Table 1.9). Hence, the OS of the OP group was significantly superior to that of the MP group. A subsequent subgroup analysis revealed a statistical difference in OS between the OP group and the NFMP group (Fig. 3). Gender was an independent risk factor for OS in ASCC, with females at low risk. Age (≥ 60), non-white race, advanced stage, positive metastases, and the NFMP were identified as high-risk factors for OS in patients with ASCC (Figs. 4 and 5, Supplementary Table 2.9).