rSCC was first discovered in 1933.(19) rSCC is a rare pathological type. The occurrence of rSCC may be related to several reasons. The pluripotent stem cells of mucosal endodermal origin have the ability to differentiate in multiple directions, which may lead to the development of squamous epithelium and malignant transformation.(20) Damage to the mucosa may result in the proliferation of basal cells into squamous cells.(21) Human papillomavirus (HPV) can induce rSCC by disrupting local cell proliferation.(22) rSCC is different from AC in terms of treatment and prognosis.(3, 23) rSCC tend to occur in the elderly, women.(24)
In clinical guidelines, there is a lack of consensus on the treatment of patients with rSCC. The principles of treatment for different stages are discussed in this study. For patients with TNM Stage 1, the difference between surgery and RT was not statistically significant. Adding CT or RT based on surgery has no survival benefit. Adding CT to RT does not benefit patients. Compared with monotherapy, combination therapy is more likely to reduce tolerance and increase adverse reactions in patients. In TNM Stage 2, the curative effect of CRT is superior to surgery. It is important to note that surgery combined CRT did not increase survival benefits. In TNM Stage 3, CT or RT alone did not increase survival benefits compared with no treatment. The curative effect of CRT is superior to that of surgery combined with CRT. In TNM Stage 4, The efficacy of CRT is superior to CT alone. Schizas D and D. C. Steinemann et al. suggest that surgery is the standard treatment regimens.(19, 25) In our study, surgery was significant, but only for stage 1 patients. In stage 2 and 3 patients, the survival benefit from surgery was not as good as that from CRT. Additional surgery on top of chemoradiotherapy did not increase survival benefits, consistent with previous studies.(26) The survival benefit of surgery in stage 4 patients was not analyzed due to the limited sample size. Considering the poor quality of life of surgery patients, surgery is not recommended as a standard treatment. We recommend RT-based multimodality treatment as paradigm for patients with rSCC, which is consistent with the view of previous studies.(17, 18, 27, 28) surgery can be used as salvage treatment after the failure of CRT.(16) But salvage surgery does not seem to increase survival benefits.(26) Immunotherapy has achieved remarkable efficacy in rAC and aSCC patients with MSI-H/MSS.(29–31) Neoadjuvant immunotherapy has achieved delightful results in rSCC. (32)Patients may experience prolonged remission. And can achieve surgical exemption, significantly improve the quality of life of patients. In the future, multi-center phase 3 clinical trials are worth looking forward to.
In this study, univariate and multivariate COX regression analysis were performed, and results showed that age, marital status, N, M, PIN, size, RT, CT, and surgery were independent prognostic factors for CSS. This is similar to the independent risk factor for OS.(33) The 1 -, 3 -, and 5-year AUC values of the model were 0.869, 0.777, 0.759, respectively, which indicated that the model had excellent discrimination. The calibration curve showed that the model had successful calibration. DCA showed that the model had outstanding clinical utility. The model constructed by the independent prognostic factors can successfully predict the 1-, 3- and 5-year CSS of patients with rSCC. In our study, age ≥ 70 years was an independent risk factor, which is consistent with previous studies.(34, 35) This may be because patients are more likely to not receive the full recommended treatment as they age.(36) Wang et al suggested that RC patients with partners have better survival prognosis(37).This is consistent with our study. Distant metastasis is an important factor affecting patients' CSS. In our study, the median CSS of stage 4 patients was only 16 months, far less than that of non-stage 4 patients.This study found that like aSCC, tumor size was an independent prognostic factor in patients with rSCC. Our results agree with the study by P. Goffredo et al., which may be explained by the fact that the larger the tumor, the more advanced the patient stage.(28) However, there is no consensus on the cut-off value of tumor size.
The study has several strengths. Firstly, the data were obtained from the SEER database and are therefore highly reproducible. Secondly, the treatment options of patients with different TNM stages were explored for the first time using a large sample size, which provided great guiding value for clinical treatment. Thirdly, the established prediction model has strong predictive performance and can accurately predict the survival mode of patients. Predictors are common clinical variables, which makes the model more broadly applicable.
There are also certain limitations in that study. Firstly, this study was based on retrospective information from the SEER database, which may have led to an inherent selection bias. Secondly, the clinicopathological variables included in the study were limited, such as the inability to analyze the effect of specific treatment regimens on patient cancer-specific survival, and there was also a lack of information on immunotherapy. At the time of prognostic analysis, common prognostic factors such as gene expression, microsatellite status, vascular invasion, and tumor deposition are lacking, which makes the prognostic model less comprehensive. Thirdly, this study only included information from online databases and lacked prospective data to verify the findings. It should be noted that due to the rarity of rectal squamous cell carcinoma, later analyses are more likely to be based on retrospective public databases. At the same time, the joint research of multiple countries and medical centers is very important for rSCC.