In both men and women, colon cancer is one of the most prevalent causes of cancer development. Despite recent advances in CC screening, diagnosis, and treatment, the long-term prognosis of CC patients remains poor (1). The prognosis of patients with metastatic and non-metastatic FCC was compared with patients with MCC. To our knowledge, this study is the first gender-focused metastasis model-based analysis of colon cancer data.
In this study, the metastasis rate was 18.0% versus 15.9% in male versus female colon cancer patients, respectively. The incidence of colon cancer increased significantly with age. According to past research, younger cc patients are more likely to develop metastases than older patients and have limited surgical and chemotherapeutic treatment (12). Similarly, younger CC patients in this study developed metastases significantly more than older CC patients, and when women were diagnosed with colon cancer, they were significantly older than men and presented with more severe disease. The 2015 National Health Interview Survey showed that colorectal cancer screening was slightly lower in women than in men (60.2% vs 62.4%)(13). This may be explained by the lower rate of screening colonoscopy in women over 65 years of age than men of the same age (14). A higher rate of incomplete colonoscopy in women has also been reported (15), contributing to more colon cancers in women of advanced age. The population was more than 3/4 white in the data we included, but we found that black CC patients were more likely to have distant metastases, consistent with previously reported results (16). Previous studies have demonstrated a lack of awareness of screening guidelines in general and in African American men in particular (17, 18).
Furthermore, black patients with metastatic colorectal cancer are less likely to get chemotherapy or have liver metastasectomy, and they are less likely to discuss or contemplate participating in studies (19, 20). During the multivariate analysis of this study, no racial differences in OS were observed. Previous studies have shown that no racial difference in survival was observed among patients aged 50 years or older; however, among younger patients, non-Hispanic Blacks experienced worse survival than non-Hispanic Blacks(21). The effect of racial differences on female patients remains to be studied. The primary location of the tumor is strongly associated with patient prognosis, as reported in different types of cancer (22–24).In the same vein, Ishihara et al. (25) found that proximal indolent cell carcinoma is considered a distinct subgroup with a good tumor prognosis in colon cancer. Our analysis from a gender perspective showed that the primary tumor location of FCC was more often located in the right colon than MCC, which is consistent with previous reports (4). However, both were more likely to metastasize in the left colon than the right colon. In patients with colon cancer, researchers developed a nomogram that predicted risk variables for liver and lung metastasis, with tumor site being an independent risk factor for metastasis (26). As we mentioned earlier, women have a higher rate of incomplete colonoscopy (12). In addition, some women tend to have a more extended colon cross-section and smaller bowel diameter, making standard colonoscopy equipment usually unsuitable for this group of women (27). Therefore, we recommend that women need to choose a thinner colonoscopy device for a complete colonoscopy when undergoing colon cancer screening to reduce the number of missed right colon cancer due to the device and physiological configuration.
The preference for chemotherapy and radiation therapy over surgery in advanced cancers may also explain why patients with metastatic FCC rarely undergo surgery. However, we found that the risk ratio of primary site resection and primary site resection combined with metastasectomy was much smaller than that of non-surgical patients. Therefore, it is necessary to actively accept surgical treatment for colon cancer patients. Treatment of stage IV colon cancer remains challenging, and despite recent advances in chemotherapy and other palliative treatment modalities, the best treatment options for colon cancer with unresectable metastases remain to be elucidated. Interestingly, the number of patients treated with radiation is more than 5% for male and female patients. Adjuvant external beam radiation is usually not recommended due to the difficulty of targeting and the proximity of critical surrounding structures (e.g., small intestine), as these factors can limit the dose that can kill the tumor. Recent findings show that adjuvant radiotherapy can significantly prolong OS in patients with advanced local disease (pT4) and positive cut margins (28,29); therefore, adjuvant therapy for CC patients should not be abandoned due to the limitations of RT. Hypodifferentiated versus undifferentiated colon cancer is more likely to develop distant metastases, and there is no difference between men and women.
Although modern research has been able to elucidate the pathogenesis of CC and provide effective screening strategies, the prevalence of CC is still increasing. A better understanding of the occurrence, progression, and metastasis of CC can help develop molecular markers for early detection and risk stratification methods to improve clinical care for CC patients. We compared distant metastasis patterns in patients with MCC and FCC in depth using the SEER database to understand the survival differences between patients with different metastasis patterns. Single-site metastases occurred in more than three-quarters of the total number of patients. Overall, the liver and brain were the most common and least common sites of solitary metastases in patients with CC, respectively, consistent with prior reports (29). Due to the blood-brain barrier, fewer patients had brain metastases alone (0.3% vs. 0.5%), but when combined with metastases from other sites, brain metastases exceeded 1% in both sexes.
Similarly, when lung metastases were combined with liver metastases, the number of patients was much higher than that of patients with lung metastases alone. We believe that once a tumor develops distant metastasis in one organ, it may accelerate metastasis in other sites, although brain metastasis alone is uncommon when it has metastasis in other sites. Interestingly, FCC was more likely to have a single lung metastasis than MCC, yet we found no significant difference in their OS.
The clinicopathological characteristics and metastatic patterns of metastatic MCC and FCC were different in the present study. Multivariate Cox regression showed that in patients with FCC, advanced age, primary site in the right colon, higher pathological grade, tumor size > 2cm, positive CEA level, and distant organ metastasis were independent risk factors affecting the prognosis of patients with FCC (Table 3). The most common site of distant metastasis in patients with CC is the liver, but we found differences in prognosis by gender, and the survival of patients with single liver metastasis in FCC was significantly lower than that of MCC in the same group (P = 0.012), especially in the first 36 months. Once the tumor metastasized, patient survival decreased, and the OS decreased more with increasing metastatic sites, and the same results have been reported in other tumors (30, 31). Liver and lung are the two most common sites of solitary metastases in FCC (32), but there are differences in OS in patients with these two metastases. The OS of patients with solitary lung metastasis was significantly higher than that of patients with solitary liver metastasis. Reasons for the difference still need further exploration. However, there are some limitations which worth further research in this study; firstly, the data source used in this study was the SEER database. We were only able to study this with the available information on four organ metastases, namely liver, lung, bone, and brain, due to the inability to obtain data on other metastasis sites, we can not conduct a more comprehensive study. Secondly, there are differences in metastatic patterns between males and females, but we could not determine which factors are associated with them. That said, further research to clarify the rationale underlying these differences is necessary. Finally, our conclusions may apply only to patients from the United States.