AA is a rare malignancy, accounting for only 1% of gastrointestinal neoplasms and the understanding of AA remained limited. In our study, we applied a PSM to analyze the demographic and clinical differences between AA and ASCC. Elder population (> 70 years old), better differentiation, and metastasis were more common in patients with AA. Before-PSM, AA has worser CSS and OS compared to ASCC. Conversely, after PSM, patients with AA had a longer OS than those with ASCC, especially in subpopulation who had age range from 50 to 70 years old, were absence of organ metastasis, underwent surgery or chemotherapy. The age, sex, grade, M stage, and surgery were independent prognostic factor of CSS in patients with AA and were included in establishing nomogram, which showed excellent accuracy and efficiency in prediction of CSS in AA patients.
It is controversial of the prognosis for adenocarcinoma (AC) and SCC. The current studies revealed diverse conclusions in survival advantages between AC and SCC in different locations[13–15]. As regarding to anal canal, previous studies indicated that AA has a worser prognosis compared with ASCC[3, 4, 16, 17]. Robert A Franklin et.al., revealed that the lack of a standard approach to the treatment of AA might be associated with the poor prognosis. Another retrospective study suggested that AA patients were more likely to occur in older age, advanced stage, which may result in the poor prognosis of AA. In our study, AA was associated with a worser survival before PSM. Compared with ASCC, AA was inclined to occur in advanced T stage, older age, and have a higher proportion of metastases. Besides, a lower proportion of patients with AA suffered from the chemotherapy and radiation. It appears that these aggressive factors may contribute to its worse survival. In order to make the above uneven variables well-balanced and comparable, a PSM was established to analyze the prognostic distinguish between AA and ASCC. And survival analysis was also performed after PSM. The results indicated that AA has a similar CSS to ASCC and was associated with a significantly prolonged OS compared to ASCC, which shows that AA has a better prognosis under the same baseline variables. It remained unclear about the concreate mechanism of well prognosis of AA. It was difficult to identify whether prognosis was associated with pathologic difference. Patients with AA was related to worse survival compared with those with rectal adenocarcinoma , indicating that histology alone cannot explain the survival difference between AA and ASCC. Further large-scale studies are needed to explore the potential molecular mechanism.
Due to the rarity of AA, no standard treatment guidelines exist currently. Therapeutic regimens of AA were derived from the rectal adenocarcinoma treatment, with frequent use of neoadjuvant chemoradiation followed by transabdominal resection[17–19]. A retrospective study based on National Cancer Database reported that surgery in the initial management could improve survival compared to chemoradiation alone and should be considered as internal part of the management of AA. Other studies also concluded the crucial role of surgery in treatment of AA[20, 21]. While another study explored that chemoradiation prolonged survival compared to the radiotherapy plus surgery therapy as well as surgery alone, and it recommended surgery as salvage treatment. But this study only reported 6 of 88 patients who were treated with surgery alone, which made the comparison lacking of rationality. In the largest series of AA to date, chemoradiation followed by surgical resection was associated with a significant improved survival compared with chemoradiation alone after PSM. In our study, surgery and chemotherapy were independent prognostic factors of survival of AA. In a word, surgical resection combined with chemotherapy or radiation may offer the best chance of survival in patients with AA.
In our study, a novel nomogram was established and suggested that age, sex, grade, surgery, and M stage were independent factors of prognosis of AA, and the conclusion was further verified by C-index, DCA, and calibration curves. There are also studies investigating the prognostic factors in patients with AA. Gary D Lewis et al. conducted a retrospective study of 1183 patients from the National Cancer Data Base (NCDB) to evaluate the prognostic risk factors of AA. They found the following factors like older age, male gender, T stage of 3 or higher, more comorbidity, and lower income were associated with worse survival. In the study conducted by QH Wang, the number of positive lymph nodes was an independent prognostic factor of AA. Other variables, including T and N stage, histologic grade, and treatment modality also have impact on the survival of AA. However, those studies did not establish a predictable model to identify prognostic factors of AA. For the first time, we performed a novel nomogram of AA and the nomogram was validated in different ways, which is more precise to predict the prognosis of patients with AA.
Though we successfully constructed and validated a nomogram to predict individual survival probability for patients with AA, our study did have several limitations. First, some important factors may be overlooked due to unavailable data in the SEER database, such as chemotherapy regimen, targeted therapy. Second, single-center data were used for external validation. Although the model still worked well, multi‐institutional external validation would provide more convincing evidence. To avoid these limitations, some large prospective randomized controlled trials are wanted in the future.