Adenocarcinoma is a small pathological subtype in cervical cancer. In recent years, while the incidence of cervical cancer has generally declined[22], the incidence of AC has increased[5]. According to NCCN guidelines, the standard treatment for locally advanced cervical cancer is radiotherapy and concomitant chemotherapy using cisplatin, a protocol that was developed in SCC patients. However, using the same treatment as for SCC may not be appropriate for AC patients[23]. As a result, there has been increasing interest in determining optimum treatments for AC. There are still considerable debates about the prognostic patterns between patients of AC and SCC as well as the proper treatment based on subgroup. A study based on the SEER database by Vijaya Galicet, et al. showed that the incidence of AC and ASC was increasing 1-2% every 6 years[9]. In other words, ASC and AC cancers together represented 21.3%, 22.9% and 24.1% of cases for the years 1988–1993, 1994–1999 and 2000–2005, respectively[10].
With this increasing pattern, researchers are increasingly interested in cervical AC. The literature shows that there is still a significant debate regarding the prognosis of patients with AC and SCC of the cervix. Some studies have shown that SCC of the cervix has a similar OS as that of AC[6]. Other studies have shown that AC is less sensitive to radiotherapy than SCC of the cervix, especially in patients with poor prognostic factors[8]. Therefore, in this study, we collected cervical cancer data from the SEER database to identify predictive factors associated with cervical cancer, and survival outcomes in patients with AC and SCC.
In 2011, a previous study by Katanyoo, et al. included a total of 423 patients with stages IIB–IVA and showed that the 5-year OS rates of AC and SCC were 59.9% and 61.7% (p=0.191), respectively. When all prognostic factors were adjusted, clinical staging was the only factor that influenced OS[6]. In 2014, Rose, et al. performed a retrospective analysis of 1,671 patients with cervical cancer and suggested that when treated with radiotherapy alone, the OS of AC was worse than that of SCC. When the treatment was radiotherapy and concomitant platinum-based chemotherapy, the OS of patients is similar[11]. In our study, we saw similar patterns. However, in 2018, Hu, et al. compared the treatment outcomes between SCC and AC of the cervix after definitive radiotherapy or concurrent chemoradiotherapy and showed that, when compared with SCC of the cervix, AC affected younger women, was more aggressive, and had more para-aortic metastatic lymph nodes. The 3-year disease-free survival, OS, local control rate, and distant control rate were worse for AC when compared to SCC[3]. In the same year, a propensity score matching study by Yin, et al. enrolled 181 locally advanced cervical cancer patients who were treated with intensity modulated radiotherapy/volumetric modulated arc therapy and concurrent chemotherapy. The results showed that after a 1:1 ratio PSM, the 5-year OS, DFS, locoregional failure-free survival, and distant metastasis-free survival in the locally advanced cervical cancer of AC were 46.0%, 43.3%, 70.0%, and 45.4%, respectively. These results were significantly lower than the corresponding rates of 90.0%, 75.8%, 96.6%, and 78.8% in the matched locally advanced cervical cancer patients of SCC, respectively (p < 0.05)[24]. These studies showed a lower OS of AC in cervical cancer.
However, in the present study, we found that histology is not is not an independent factor of OS. Before PSM, the 3.5-year OS rates in the AC group were 44% and 18%, and the rates were 39% and 16% in the SCC group, respectively (p=0.67).After PSM, the 3-year and 5-year OS of the AC group was 43% and 17%, compared to 40% and 16% in the SCC group (P=0.53). There was no significant difference in OS between AC group and SCC group, regardless of matching status, leading to different conclusions from the previous studies. When comparing these studies, we did not exclude the impact of different treatments on the prognosis of the two pathological types. To make the results stronger, we divided the treatments into four groups and analyzed the difference between the AC and SCC groups.
In the subgroup analysis, when treated with radiotherapy alone, we found that the OS of patients with SCC was worse than that of patients with AC (P=0.015), in contrast with other studies. The number of people in the analysis was small and the power to detect the difference between AC and SCC may have been too low. When we compared the treated with radiotherapy combined with chemotherapy or radiotherapy combined with chemotherapy plus surgery, the OS of patients with SCC and AC was similar (P=0.62, P=0.92). When treated with radiotherapy combined with surgery, the median survival time and the 3-year and 5-year OS of patients with AC was worse than patients with SCC. However there was no significant difference between two groups(P=0.71). In univariable and multivariable analysis, the factors which had the strongest association with survival outcomes was FIGO stage, chemotherapy and external radiation combined with brachytherapy. The difference of study period, number of patients, criteria of enrolled patients, statistical methods and treatment modalities may help us understand the difference of our results when compared to the literature.
This study has some certain limitations. First, we used retrospective studies and we may have unintentional selectivity bias. Second, because the SEER database only recorded the sequence of radiotherapy and surgery, it did not record the sequence of surgery and chemotherapy, and we could not judge whether neoadjuvant therapy or adjuvant therapy is used in the treatment of cervical cancer patients. There was no recorded objective response time and disease-free survival time after treatment; therefore, we could not compare the difference between SCC and AC. In the future, we may need prospective clinical studies to confirm our conclusions.