The main histological type of cervical cancer is SCC [25]. However, the incidences of AC and ASC of the uterine cervix have increased over the past 40 years, especially among younger women [26-29]. In this retrospective cohort study, we examined the records of Chinese patients with FIGO stage IB-IIA AC or ASC to evaluate potential prognostic factors among these patients. All patients underwent surgery as the primary treatment. Multivariate analyses showed that FIGO stage and LNM were independent prognostic factors for OS.
Previous studies showed that FIGO stage, tumour size, and LNM were independent prognostic factors for survival [13, 30, 31]. Shu et al. [2] reported that in patients with AC/ASC, differentiation was an independent predictor of OS, and LVSI was an independent predictor of DFS. We investigated whether histology (AC vs. ASC) is a prognostic factor in patients with cervical cancer. There were no differences, in terms of clinical impact on OS, between the two histological groups in early-stage cervical cancer, although a greater proportion of patients with ASC had LVSI and SCC-Ag >5 ng/ml; moreover, patients with ASC were much older than those with AC. Multivariate Cox regression analysis revealed that CEA > 5 ng/ml and SCC-Ag > 5 ng/ml were independent risk factors for RFS and OS in patients with AC, but not in patients with ASC. This suggests that pre-treatment levels of CEA > 5 ng/ml and SCC-Ag > 5 ng/ml can be regarded as risk factors for AC, providing additional information for patient-tailored therapy, and should be analysed in prospective studies. Previous studies reported that elevated pre-treatment serum SCC-Ag levels were associated with poor prognosis [32, 33], but the histologic type of most patients was cervical squamous cell carcinoma a few patients had AC. Nakamura et al. [34] showed that AC, DOI, tumour size, and LVSI were significantly associated with disease recurrence.
The respective 5-year survival rates for patients with stages IB and IIA were 72.7% and 56% for the AC group and 81.0% and 62% for the ASC group. Saigo et al. [35] reported that 5-year survival rates for patients with stages I and II (IIA, IIB) AC were 79% and 37%, respectively. Presumably because the latter group also included patients with IIB cancer, the 5-year survival rate for patients with stage II cancer was lower than the rate observed in our study. These results suggest that as FIGO stage increases, the survival time is reduced accordingly. Our results demonstrated that FIGO stage (IB vs. IIA) was significantly associated with survival time (P<0.05). Similarly, Noh et al. [30] reported that ASC histology was associated with more favourable survival outcomes, compared to AC histology, although the differences were not statistically significant. Lai et al. [12] found no differences between the ASC and AC subtypes in RFS or cancer-specific survival (CSS).
Wang et al. [36] demonstrated that higher tumour grade and more vascular invasion were present in patients with ASC, compared to patients with AC. Reis et al. [11] found that Grade III histology and LVSI were more common in patients with ASC than in patients with AC. In addition, they demonstrated that although the time to recurrence was shorter for patients with ASC (7.9 months vs. 15 months; P=0.01), differences in OS or recurrence rates between patients with AC and patients with ASC were not statistically significant. Baek et al. [18] reported greater mean tumour size and more frequent LVSI in patients with ASC, but found that histologic type did not influence RFS or OS in multivariate analyses, following adjustment for significant prognostic factors. In contrast, several studies reported poor survival for patients with ASC. A meta-analysis by Lee et al. [16] demonstrated that ASC patients may have poorer outcomes than those with AC of the cervix. Farley et al. [20] observed an increased risk of death among patients with ASC histology compared to those with AC histology. Twu et al. [37] found that survival for ASC was slightly worse than that for AC in a univariate analysis, but the RFS and CSS of the two subtypes were not significantly different in multivariate analyses.
Our study demonstrated a tendency for better RFS and OS in patients with ASC than in those with AC, in both the low-risk and intermediate/high-risk groups, although the difference was not statistically significant. The prognosis for the ASC subtype appears to be intermediate (i.e. between those of the SCC and AC subtypes) [31]. Previous studies showed no statistically significant differences between patients with AC and those with ASC in low-, intermediate-, or high-risk groups (P>0.05) [9,18]. However, Lea et al. reported that ASC histology was associated with reduced disease-free survival relative to AC histology, among patients with low-risk stage IB1 cancer [38].
We also examined the effect of treatment on OS in intermediate-risk ASC and AC patients. Univariate analysis indicated that in patients with ASC, CCRT was associated with significantly better RFS and OS. RT alone was related to RFS but not OS. This indicated that RT alone may be effective for local control, while CCRT is advantageous for control of distant metastasis. In addition, RT and CCRT did not confer any survival benefit in patients with AC. This may have been because there is greater radio resistance and more aggressive behaviour of tumours in patients with AC relative to those with ASC. A retrospective study suggested that RT and CCRT after radical hysterectomy were not beneficial in intermediate-risk patients. In particular, RT and CCRT appeared to increase the incidence of lymphedema, and even led to RT-related morbidities such as small-bowel obstruction and leg oedema [34, 39]. Twu et al. confirmed that adjuvant therapy (radiotherapy with or without chemotherapy) following RH-PLND, for early stage AC/ASC patients with a low prognostic score, may not improve survival. Therefore, omitting adjuvant therapy could decrease morbidity [37]. We suspected that systemic CT alone could confer a survival benefit for patients with AC. Takekuma et al. [40] reported that chemotherapy alone after surgery for high-risk patients had similar efficacy to CCRT, but with less toxicity. Further prospective randomized studies including larger patient populations are needed to confirm our findings.
Our study was limited by its retrospective design. Furthermore, since most patients in the high-risk group received CCRT, while most patients in the low-risk group underwent observation only, the statistical power may not have been sufficient to detect a statistical difference in the impact of adjuvant therapies on survival. Finally, systemic CT alone, i.e., without RT, might confer a survival benefit. However, we did not investigate the effects of chemotherapy because no patient received systemic CT alone. Despite these limitations, to our knowledge this study included the largest number of FIGO stage IB–IIA cervical AC/ASC patients undergoing radical hysterectomy. It also provided sufficient data on prognosis and adjuvant treatment efficacy, given the long follow-up period.