In the present study, positive ascites cytology had a negative impact on the survival of patients with epithelial OvCa, but not on those with stage IV tumors or a mucinous histology. The results obtained indicated that post-operative chemotherapy reduced the increased risk of progression and death associated with the presence of tumor cells in ascites. Collectively, the present results suggest the importance of not only recognizing positive ascites cytology as an independent significant prognostic factor in epithelial OvCa, but also examining ascites cytology in all patients with ovarian neoplasms other than those with apparent distant metastasis. Additionally, the omission of post-operative chemotherapy markedly worsened the prognosis of patients regardless of the tumor stage.
Positive ascites cytology was identified as a negative prognostic factor not only in stage I, but also in stages II and III tumors. It also correlated with a poorer prognosis in the majority of stratified classifications, but did not affect the site of recurrence. Furthermore, positive ascites cytology did not appear to affect the prognosis of patients with stage IV tumors in whom obvious distant metastasis was detected. Regarding the histological type, positive ascites cytology was not of clinical significance in patients with mucinous OvCa. This may be attributed to its distinct pathological and molecular features from other epithelial OvCa . However, this is not a sufficient reason for not performing ascites cytology during surgery because an intraoperative pathological diagnosis is sometimes discordant with the final diagnosis . Therefore, ascites cytology needs to be conducted during initial surgery for clinical and pathological staging because the result becomes a significant prognostic factor in patients with OvCa under most conditions.
Based on the results of the subgroup analysis, a significant interaction effect was observed between positive ascites cytology and chemotherapy, which indicated that this treatment reduces the risk of progression associated with positive ascites cytology under all conditions. On the other hand, the present results showed no significant interaction effect between complete staging surgery and positive ascites cytology; therefore, the significance of complete staging surgery, including systematic para-aortic and pelvic lymphadenectomy, remains unclear. Since the efficacy of lymph node dissection decreases at more advanced stages , further studies are needed to identify appropriate candidates for complete staging surgery with retroperitoneal lymphadenectomy. Based on these findings, chemotherapy appears to be more beneficial for OvCa than other gynecological cancers, while radical surgery may be of relatively low significance. Thus, OvCa with positive ascites cytology clinically distinct from solid tumor such that lymph node dissection may be irrelevant particularly in advanced tumors.
OvCa cells released and floating in ascites have metastatic potential to the peritoneum . The amount of tumor cells in the peritoneum, which is dependent on the total tumor mass in the peritoneum, is associated with the positivity rate on cytology. However, since the prognosis of stages IC1 and 1C3 differs , released OvCa cells gradually gain metastatic potential via an unknown mechanism in the peritoneal environment. Although some findings still support the potential for hematogenous peritoneal metastasis , clinical results showing that ascites cytology is associated with the progression of OvCa suggest that peritoneal metastasis is mainly promoted via ascites. Moreover, a cluster of heterogenous cells, including fibroblasts and mesothelial cells, was shown to exist and increase the metastatic potential of tumors [14, 15]. Therefore, the significance of ascites cytology needs to be reconsidered and gynecologists must perform this examination on every OvCa patient, even those at an advanced stage.
The strength of the present study was that clinical information from multiple affiliated institutions under a central pathological review system was analyzed. Therefore, the surgical procedure and administration of chemotherapy were relatively consistent. Additionally, imbalances between the two groups were statistically adjusted with the PS-based method to minimize possible bias. In contrast, the limitations of the present study included potential confounding factors, such as the cycle of chemotherapy, for which it was not possible to extract data from our records. Due to the retrospective design of the present study, the results obtained need to be evaluated in future trials.
In conclusion, positive ascites cytology was associated with a poorer prognosis in patients with epithelial OvCa, but not in those with stage IV tumors or a mucinous histology. Therefore, ascites cytology needs to be performed during initial surgery for clinical and pathological staging even in patients with advanced disease because the result is a significant prognostic factor for patients with OvCa. Additionally, chemotherapy significantly reduced the risk of recurrence and death associated with positive ascites cytology, whereas complete staging surgery did not. The impact of positive ascites cytology needs to be reconsidered in all patients with OvCa and management with chemotherapy must be selected whenever possible.