Gallbladder cancer (GBC) is a highly fatal disease with a poor prognosis. It is the most common malignancy of the biliary system and the fifth most common malignancy of the digestive system (1). There are significant ethnic and geographic differences in the incidence of gallbladder cancer, which is higher in Chile and some Asian countries, and has a high mortality rate (2). Radical surgery is the only treatment modality that may completely cure gallbladder cancer, but because of the lack of specific clinical symptoms, many patients are already at an advanced stage at diagnosis, thus losing the opportunity for surgical treatment. The prognosis of patients with gallbladder cancer remains poor, although several new diagnostic and prognostic biomarkers have been identified in recent years (3, 4). The overall average survival rate for patients with GBC is 6 months and the 5-year survival rate is 5% (5).

Mucinous adenocarcinomas (MAs) are a rare pathological subtype of adenocarcinoma in which more than 50% of the total tumor volume is extracellular mucinous component (6). In general, the abundance of mucin disrupts intercellular interactions and promotes cell growth independent of apposition, thus creating the necessary conditions for metastasis and invasion (7). However, the prognostic value of MAs compared to non-MAs is controversial. Several studies have shown that mucinous adenocarcinoma of the colorectum has a poor prognosis (8, 9), but in the breast mucinous adenocarcinoma has a better prognosis than invasive ductal carcinoma (10), and some studies have shown no significant difference in prognosis between patients with mucinous and non-mucinous cancers (11, 12). Gallbladder mucinous adenocarcinoma (GBMAC) is one of the rarest subtypes of gallbladder cancer, accounting for less than 5% of case reports (13). There are very few studies on the clinical features and prognosis of GBMAC, which are limited to some case reports and small retrospective studies (14–16). Because of its rarity, its clinicopathological features and prognosis have not been well explored so far.

Nomograms are digital graphical tools that integrate a number of important characteristics and are increasingly frequently used for event prediction, particularly for cancer prognostic prediction. Several nomograms have been developed for the prognosis and treatment of patients with gallbladder cancer (17–19). However, due to the rarity of GBMAC, no nomograms that predict overall survival (OS) or cancer-specific survival (CSS) have been created so far.

SEER database is a comprehensive and authoritative online source that collects and integrates cancer data of about 34.6% of the United States population (20). Therefore, in this present study, based on data from the SEER database, we aimed to identify clinicopathologic characteristics of GBMAC, then constructed and validated OS and CSS nomograms for GBMAC patients.

Based on a large population from the SEER database, we were able to successfully design two nomograms to predict OS and CSS at 1, 3, and 5 years for patients with GBMAC. The prediction accuracy and capabilities of our nomograms were validated further in both the training cohort and validation cohort. A number of important prognostic indicators were identified and included in our nomograms. OS and CSS prediction factors include grade, SEER stage, radiation, and surgery. The GBMAC prediction model that we built contributes to the understanding of the features of GBMAC patients and clinical decision-making.

Nomograms are utilized as a visual numerical graphical tool to forecast the probability of occurrence of a particular event based on data with known factors. In recent years, nomograms have been widely used to predict the prognosis of various cancers, such as esophageal, pancreatic, breast and prostate cancers (21–24). For gallbladder cancer, several nomograms with different predictive functions have also been developed (18, 25, 26). However, because the GBMAC is so rare, most of the current research on it comes from case reports and small cohort studies. Limited evidence suggests that it is more advanced at the time of diagnosis and exhibits a more aggressive and poorer survival outcome compared to common adenocarcinoma (14, 16). As a result, it is necessary to develop a reliable prognostic model in order to make accurate predictions regarding the outcome of GBMAC.

Our research revealed that the incidence was higher in older and female patients, that the vast majority of patients had local or distant metastases at the time of diagnosis, that the majority of patients underwent surgery, and that the proportion of patients receiving chemotherapy and radiotherapy was relatively low. Grade, SEER stage, surgery, and radiation were found to be important risk factors affecting patients’ OS and CSS. The only effective curative treatment for those with gallbladder cancer is surgical resection. The majority of patients were treated with surgery, which was also a predictor of a good prognosis, according to our study. Regarding its use as an adjuvant therapy for people with gallbladder cancer, radiotherapy is still debatable. Radiotherapy is not the primary treatment for patients with gallbladder cancer, it can be an effective adjuvant treatment for certain specific patient groups, especially those at high risk of recurrence such as R1 resection or lymph node positivity. However, the general condition of the patient needs to be evaluated before radiotherapy. A previous study showed that in patients with gallbladder cancer who underwent radical resection, radiation provided a short-term survival benefit (27). An earlier study showed that adjuvant radiotherapy improved survival in patients with gallbladder cancer with regional lymph node metastasis (28). Our study also showed that radiotherapy was a protective factor for patient prognosis. Poorly differentiated pathological types imply a more aggressive nature, while local metastases or distant metastases imply a loss of access to surgical treatment and a higher risk of recurrence, often implying a poorer prognosis. Grade and SEER stage have been identified as risk factors in several previously established models for predicting the prognosis of patients with gallbladder cancer (29, 30). The same results were obtained in our current study that grade and SEER stage were the important risk factors. Based on the scores obtained from the nomograms of OS and CSS, we classified the patients into high-risk and low-risk groups, respectively. The K-M curves revealed additional evidence of a statistically significant difference in the amount of time spent alive between these two groups. Consequently, if the nomogram recognizes a patient whose OS score or CSS score is in the high-risk group, the clinician can be on the lookout for this patient and make timely adjustments to the follow-up treatment methods, such as implementing combined modality therapy as soon as possible, to help the patient achieve a better curative effect. This will serve as a reference for clinicians, allowing them to make decisions on their work more effectively.

However, this research has some limitations. First, all of our data came from the SEER database, which includes patients from the United States. Validation is required to determine whether it can be used for prognostic analysis of all patients, and it may require external multicenter validation. Second, the accuracy of the prediction model may be impacted by incomplete data on several variables in the SEER database, such as chemotherapy regimen and radiation dose. Finally, due to the large time gap between the earliest and most recent patients included in this study, changes in detection tests and treatment modalities may have had an impact on patient survival rates.

We constructed new nomograms to predict OS and CSS at 1-, 3-, and 5-year for patients with GBMAC. The nomograms were evaluated with robust predictive accuracy and capability whereby to contribute to clinical management and risk decisions.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

The data of this study is obtained from the SEER database. The patients’ data is public and anonymous, so this study does not require ethical approval and informed consent.

XX and JW designed the study. XX collected and analyzed the data. XX drafted the initial manuscript. JW reviewed and edited the article. All authors approved the final manuscript. All authors contributed to the article and approved the submitted version.