In the current research, we constructed a prognostic nomogram for predicting the overall survival of CRC patients with distant metastasis, and validated the model in both training and validation cohorts. In all, 12 demographic and clinicopathological parameters were identified as independent risk factors to OS. Further C-index calculation in both training and validation groups indicated accepted coherence degree of the nomogram. Calibration curves in both groups confirmed the model’s predicting capacity on 2- and 3-year OS in CRC patients with distant metastasis. Risk stratification on patients according to weighted risk scores given by the nomogram can effectively distinguish differed OS outcomes of patients, suggesting potential application for clinical practice.
In views of epidemiology, age has been widely accepted as a major risk factor for sporadic CRC (14). This is consistent with our findings in the study. Previous epidemic researches suggested that CRC incidence, especially large bowel caner, begins to increase in the ages of 40, and age-specific incidence rates keep increasing in the succeeding decades (15, 16). In this research, we further elaborated that not only incidence but also survival outcomes would be independently influenced by age. CRC patients older than 55 years ended with less life expectancy, and those older than 75 years may be even worse. Different outcomes according to race appear to be attributable to different life behaviors and genetic backgrounds. We were surprised to notice that marital status also contributed to patients’ survival outcomes. There have been studies indicating the correlation between marital status and survival outcomes of cancer patients (17, 18). Some of them owed this connection to socioeconomic status and family care and support. We believe more investigations should be required for providing more guidance for social support.
Though liver is the dominant metastatic site for patients with CRC, brain metastasis turned out to be related to the worst prognosis, followed by bone, liver and lung metastasis. The AJCC guidelines for CRC management have pointed out that regional treatment like surgery for CRC with isolated liver metastasis may be recommended to be combined with systemic chemotherapy (19). Our findings supported the propose that for CRC with isolated metastasis in liver and lung, relatively aggressive treatment for optimal survival may be considered. The idea that malignancies from solid organs may manifest organ-specific metastasis tendency influencing survival outcomes differently has long been raised. We previously reported the metastatic preference of extrahepatic cholangiocarcinoma ultimately determined variant prognosis (20). Depicting characteristic metastasis patterns of malignancies can be of vital significance guiding treatment and prognosis prediction.
We also found that differed primary sites resulted in differed survival outcomes, with rectus the best, right colon the worst. Classification of CRC based on primary site has been long been a hot-discussed issue (21, 22). In this research, we defined the site classification as the canonical pattern put, that right colon includes colon starting from cecum to proximal splenic flexure, while left colon refers to segments from distal splenic flexure to sigmoid colons. In the view of embryology, right colon mainly originates from midgut and left colon formation initiates from hindgut. Differed histological derivation determines different malignant degrees for carcinogenesis. Owing to the characters of thin walls and mucus secretion, malignancy originating from right colon can be symptom-latent at the early phase (23, 24). Delayed onset of symptoms leads to ignorant detection during the early phase of the cancer.
Both adjuvant and neoadjuvant chemotherapy as an essential part of systemic treatment for metastatic CRC patients have been explored in last decades. Profound promotion in patients’ long-term survival has been achieved by newly emerged chemo-regimens like FOLFOX and FOLFIRI (25). With the assistance of systematic chemotherapy, indications for surgery on CRC with distant metastatic sites have also been widen. Previously distant metastasis used to be absolute contradictions to surgical resections. Now surgical options on CRC with distant metastasis have been more radical than ever (26). Yet, not all evidence supports that surgical treatment promotes prognosis of advanced CRC patients in all. In this research, we found that for CRC patients of high risk could not benefit from surgeries, suggesting that accurate screening on risk factors be necessary for CRC patients with distant metastasis to consider surgical interventions. Moreover, roles of locoregional radiotherapy in treatment for metastatic CRC patients have been controversial (27). Several RCT and meta-analysis have been debating on the question that whether and to what fraction should radiotherapy be added to treatments of advanced CRC (28, 29). We once reported that for advanced HCC patients, internal radiation therapy may achieve better therapeutic effect than external ways (30). However, in this retrospective research we identified radiotherapy as a non-beneficial treatment to CRC patients of high-risk, even though it can moderately promote prognosis for patients of low and intermediate risk. Conclusively, for CRC patients of high-risk, locoregional treatment options including surgery and radiation therapy may not achieve survival benefit as systematic chemotherapy does. Caution should be put on evaluating CRC patients’ risk stratification before making medical decisions.
As far as we are concerned, this study is among the pioneering work to construct a visualized prognostic model in metastatic CRC patients. Still, as a retrospective study, there exist several limitations. Also, information on treatment provided by SEER database is general and relatively superficial. Detailed information on doses and regimens of chemotherapy and radiation remains unknown. Moreover, external validation in the nomogram was still performed based on cases from the SEER database, requiring independent external cohorts investigating its performance.
To conclude, in this study, an innovative prognostic nomogram was built based on data abstracted from the SEER database, to predict survival outcomes of patients with metastatic CRC. We anticipate this prognostic model can be further confirmed by well-designed clinical trials and be of great significance for guiding medical practice and decision making.