Figure 11 Subgroup analysis for CSS and OS between before PSM cohort and after PSM cohort. (A) Forest map for CSS of before PSM cohort. (B) Forest map for OS of before PSM cohort. (C) Forest map for CSS of after PSM cohort. (D) Forest map for OS of after PSM cohort.
  1. DiscussionPatient survival varies significantly in cases of rectal cancer, irrespective of whether all patients undergo surgical resection and receive chemotherapy [22]. High-risk patients with rectal cancer may experience improved overall survival if they receive personalized treatment following surgical resection. Currently, the TNM staging system is commonly used to predict individual survival in patients with rectal cancer, but it has limitations in its accuracy. In recent years, several prognostic models have been developed to address this issue [23-25], however, there is currently no ideal survival prediction model specifically designed for older patients with rectal cancer. This is concerning as elderly patients make up a significant portion of rectal cancer patients and have distinct biological and clinical characteristics compared to younger patients. The physical condition of elderly patients naturally deteriorates with age, and they often have multiple chronic illnesses and a reduced tolerance for treatment. Furthermore, the efficacy of therapy in elderly patients is still debated due to the limited number of studies conducted on this specific population. As a result, treatment decisions are often based on the subjective opinions of clinicians rather than concrete evidence. Therefore, the development of an individualized risk assessment model for this demographic is of great importance. Through the use of univariate and multivariate COX regression analyses, as well as implementing the LASSO regression algorithm, it was determined that variables such as marital status, grade, T stage, N stage, CEA, tumor size, surgery, and chemotherapy are independent risk factors affecting the prognosis of CSS. Additionally, variables like grade, chemotherapy, and the time period between diagnosis and treatment are independent risk factors influencing the prognosis of OS. To present the findings of the regression analysis, a nomogram was developed, which not only provides a visual representation of the results but also allows for the prediction of the survival probability in elderly patients with rectal cancer. Traditionally, CEA has served as one of the tumor biomarkers employed to anticipate recurrence, prognosis, and treatment outcomes in these patients [26-27]. An elevated CEA level generally signifies the potential presence of larger tumors, increased lymph node metastases, and lower quality of differentiation [28]. In our research, the CEA level showed significance in both univariate and multivariate regression analyses, and was ultimately included in the development of the nomogram model. Similar to our study, Shang et al. discovered that combining surgery with chemotherapy leads to higher survival rates for patients [29]. However, Liu et al. found that patients over the age of 75 with stage II-III colorectal cancer who receive adjuvant chemotherapy or not face similar risks of postoperative recurrence. It should be noted that the number of participants in the study was relatively small and the chemotherapy regimens used were varied [30]. Hence, it is crucial to factor in various treatment methods during the formulation of a treatment strategy, encompassing surgical procedures as well as radiotherapy/chemotherapy, in order to enhance patient survival rates and overall well-being. Patients who cannot undergo surgery have been found to benefit from radiotherapy and chemotherapy in terms of survival. The methods of treating locally advanced rectal cancer have changed over time, giving patients various standard treatment options. These options include different radiation schedules, sequencing of different treatment modalities, and in some cases, the possibility of not needing surgery. A neoadjuvant therapy approach called TNT has proven successful in certain patients, enabling them to achieve a complete response to chemotherapy and radiation, potentially eliminating the need for surgery [31]. In our study, the receipt of radiation therapy did not significantly impact the prognosis of survival and was not considered in the risk assessment model. One possible reason for this was that patients experienced severe acute and long-term toxic effects, making it difficult for them to tolerate the therapy. The RAPIDO study found no notable differences in the frequency or severity of side effects between short and long course radiation. Additionally, the use of radio-sensitizing chemotherapy alongside radiation therapy could increase the occurrence of toxicities. The decision to undergo surgery also influenced gastrointestinal toxicities and the time required for recovery. Late toxicities resulting from radiation therapy typically emerge months after the completion of treatment and can persist or appear throughout a person’s lifetime. These toxicities may not be reversible, and they are challenging to assess due to the lack of patient follow-up visits and potential loss to follow-up [32-33]. In our analysis of subgroups, we compared patients who underwent surgery alone to those who underwent surgery in addition to radiation therapy or chemotherapy. By adjusting for variables that could affect CSS and OS using PSM, we discovered that there was no significant difference in CSS or OS between the surgery-only group and the combined treatment group. These findings may contrast with certain studies that found neoadjuvant SCRT and sequential chemotherapy followed by delayed surgery to be safe and effective for older patients with locally advanced rectal cancer compared to younger patients [34]. While a combined therapy approach can reduce the extent of locally advanced rectal cancer and slightly decrease the likelihood of distant recurrence, older patients are exposed to the potential toxicity of doublet or triplet oxaliplatin-based therapy when receiving adjuvant chemotherapy after surgery, with questionable benefits in the adjuvant and metastatic stages [35]. Bowel and rectal inflammation caused by radiation is responsible for the majority of the toxic side effects, including diarrhea, cramping, and urgency. When surgery and radiation are combined, these symptoms can worsen. In patients undergoing doublet chemotherapy, neurotoxicity is the most frequently observed long-term toxicity [33]. In the context of longer life spans, it is important to tailor the treatment of older patients in order to find a balance between the advantages of therapy and the potential decrease in quality of life caused by the side effects of additional treatments. Age should not be viewed as a hindrance to receiving chemotherapy and proper care [36-37]. While the TNM staging system is an essential tool for prognosis prediction, it fails to include certain significant prognostic factors like age, resulting in inadequate accuracy in its predictive outcomes. Our nomogram, on the other hand, not only incorporates the parameters of the AJCC staging system but also takes into account individual demographic and pathological characteristics, enabling doctors to distinguish the group that will benefit from chemotherapy. As a result, it offers a more comprehensive and convenient approach. Furthermore, elderly individuals with rectal cancer often succumb to chronic diseases such as heart disease, lung disease, and cerebrovascular disease, rather than the rectal cancer itself [38]. Survival analysis methods commonly used, such as Kaplan-Meier analysis and Cox proportional hazards regression analysis, have a tendency to overestimate cancer mortality by considering deaths from other causes as censored events [39]. Therefore, CSS was selected as the endpoint of this research, thereby eliminating the influence of mortality caused by other illnesses and enhancing the precision of the findings. Despite successfully creating and confirming a nomogram for predicting the survival probability of older patients with Rectal cancer, our study also had some limitations. Firstly, we had a limited amount of data available, and we utilized the SEER database for a retrospective study. This may have resulted in information bias, so we encourage further randomized controlled trials to validate our models. Secondly, we did not have external validation from other institutions. Many popular nomograms currently in use incorporate clinical examination data from patients, most of whom are from the American population. Although our model performed well in our own cohort, which underwent strict validation, external validation from multiple institutions would offer more convincing evidence.
  2. ConclusionsOverall, our research developed and verified a novel predictive nomogram that can be used by doctors to accurately assess the individual survival of postoperative older patients with rectal cancer. This tool will also help identify high-risk patients who may require more intensive treatment approaches. Additionally, our results highlight the importance of carefully administering adjuvant therapy and follow-up plans to older patients following surgery.
  3. Author contributionsStudy conception and design: Wei-Ming Zhang. Data Acquisition and quality control: all authors. Statistical analysis: Si-Kai Nong and Qi-Yan Mo. Manuscript preparation: Si-Kai Nong and Huan Huang. Manuscript review: all authors.
  4. AcknowledgmentsThis work was supported by the Guangxi Medicine and Health Self-financing Program(Z20201311).
  5. Conflict of interestThe author reports no conflict of interest in this work.
  6. Data availability statementThe data that support the findings of this study are available in the Surveillance, Epidemiology, and End Results database (http://seer.cancer.gov/SEERstat).
  7. Ethics statementThis study was approved by the Ethics and Human Subject Committee of Wuming Hospital of Guangxi Medical University.References
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