Establishment of prognostic nomogram for elderly colorectal cancer patients: a SEER database analysis

Colorectal cancer has been ranked as the second most common malignancy in women and third in men across the world. Annual global incidence is approximately 1.4 million with nearly 700,000 deaths [1, 2]. There are more than 50,000 death reports and over 130,000 newly occurred cases in the United States [2]. In European Union, 215,000 cases have been reported with colorectal cancer being listed as the second common cause of death [3]. In China, colorectal cancer is listed as one of the five most commonly malignancies both in men and women [4].

Genomic characterization of colorectal cancer has been well elucidated and the role of immunology is increasingly valued [5‐7]. Therapeutically, surgical intervention and chemotherapy-based strategies have been widely accepted for colorectal cancer [8, 9]. Noteworthy, the impact of colorectal cancer surgery on the elder group, regarding long term survival, is similar to that of younger group [10].

Generally, elderly colorectal cancer patients (ECRC), defined by age surpass 70 years old, may naturally associate with increased mortality as age increased. However, no study did fully cover nor depict the quantified association of age and risks for prognosis of ECRC [11, 12]. Previously, tumor-node-metastasis (TNM) stage system of American Joint Committee on Cancer (AJCC) is widely used in the therapeutic and prognostic administration of colorectal cancer. Given increasing values of multiple variables, including tumor size and marital status, have been noticed [13, 14], a more comprehensive prognostic predictor is necessary for ECRC.

Of note, knowledge regarding the clinical prediction of ECRC is limited, with very few studies focusing on the nomogram implementation. In this study, a ECRC-targeting nomogram was established for prognostic prediction based on large sample size retrieved from the Surveillance, Epidemiology, and End Results (SEER) database in hopes of elucidating further prognostic insights [15].

Up to now, numerous studies had investigated the role of prognostic nomograms for colorectal cancer patients using SEER database for variable objects [19, 20]. In fact, increasing studies tended to focus more on the therapeutics or modified classification, with very rare highlighted the role of age in the prognostic assessment of colorectal cancer. Our previous study reported that a nomogram for early-onset colorectal cancer patients could display comparably higher C-index value and better performance than conventional variables [21]. ECRC, on the other hand, had been explored with limited studies. Li et al. reported that, with 18,937 included cases, adjuvant chemotherapy did not offer additional survival benefits to elderly patients with stage II or III [22]. Nonetheless, a general prognostic nomogram of ECRC is yet to be fully characterized. In this study, the nomograms displayed higher C-index and convinced calibration plots for OS and CSS prediction using SEER database. Moreover, they achieved higher values regarding both AUC and DCA assessment systems compared to AJCC TNM and SEER stages.

Of note, in OS, 12 variables (sex, age, marital status, grade, AJCC TNM, bone metastasis, brain metastasis, liver metastasis and lung metastasis and tumor size) out of 15 variables were determined for the construction of nomogram. Similar feature had also been noticed in CSS nomogram. It was highly possible that the prognosis of ECRC could be associated with more variables than common colorectal cancer cases. Moreover, four types of distant metastasis, for the first time, had been incorporated for nomogram of ECRC in SEER analysis.

In addition, X-tile tool was introduced for the best cutoff values of age and tumor size in this study. X-tile tool was established as a powerful graphic method to illustrate potential subsets (cutoff) with construction of a two dimensional projection [18]. It had been widely used in numerous investigations, including esophageal squamous cell carcinoma, bladder cancer and chondrosarcoma [23‐25]. In this study, for the first time, subsets of consecutive variables, age and tumor size, were determined by X-tile tool. In fact, the role of tumor size had been intensively studied [26]. However, the cutoff points of tumor size in colorectal cancer remain largely arbitrary. Therefore, introduction of X-tile for the classification of tumor size could be both reliable and replicated.

Generally, elderly patients may naturally associate with increased mortality as age increased. However, no study did fully cover nor depict the quantified association of age and risks for prognosis, particularly when elderly patients had surpassed 70 years old. In our study, age itself was identified as a higher risk factor in OS compared to CSS nomogram, with age ≥ 87 representing nearly 90 points in OS but less than 60 points in CSS. Interestingly, female was identified as a protective factor in OS nomogram, instead of CSS nomogram. Moreover, marriage is also identified as a protective factor in both OS and CSS nomogram. By comparing OS and CSS nomograms, insightful clues had been noticed for further external clinical investigation.

This study established nomograms of elderly colorectal cancer patients with distinct clinical values compared to AJCC TNM and SEER stages regarding both OS and CSS.