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.
- 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.
- 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.
- 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.
- AcknowledgmentsThis work was supported by the Guangxi Medicine and Health
Self-financing Program(Z20201311).
- Conflict of interestThe author reports no conflict of interest in this work.
- 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).
- Ethics statementThis study was approved by the Ethics and Human Subject Committee of
Wuming Hospital of Guangxi Medical University.References
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