Ovarian cancer is the leading cause of death from gynecological malignancy worldwide, as most patients are diagnosed at advanced stages due to a lack of sensitive screening tests and the lack of specific symptoms at early stages. The standard of treatment is surgery followed by platinum-based chemotherapy11, and optimal debulking is the goal, as residual tumors decrease progression-free survival and overall survival12. To achieve the goal of optimal debulking, multivisceral surgeries such as bowel section and splenectomy are performed13,14.
Invasive procedures are associated with high risks of morbidity and mortality; in addition, poor outcomes, such as hypoalbuminemia, are predictive of severe postoperative complications4, and complications delay the start of subsequent chemotherapy, which reduces progression-free survival6. Therefore, neoadjuvant chemotherapy offers an alternative treatment for patients with advanced ovarian cancer and makes surgery highly feasible15. In our study, we found that the level of albumin was elevated after the course of NACT (37.47 ± 5.42 vs 42.61 ± 3.46, P༜0.05). Cancer patients have low preoperative albumin levels, especially those with advanced-stage disease and patients with ascites16; the mechanisms for this low level involve a decrease in amino acid intake and albumin synthesis 17 as well as an increase in albumin leakage to the extravascular space in patients with ascites. There were 21 (80.77%) patients with massive ascites upon diagnosis, and the largest mean diameter of the ascites assessed by ultrasound was 104.05 ± 31.75 mm. After the course of NACT, ascites was not detected in 3 patients, and the largest mean diameter of the remaining cases of ascites was 65.00 ± 35.32 mm (t = 3.636, P = 0.001). Furthermore, decreases in CA12-5 and HE4 levels were found (P༜0.05) in the NACT group, and side effects of chemotherapy (lowered hemoglobin levels) also occurred. Previous studies have observed that patients who receive interval debulking surgery after NACT have better surgical outcomes than patients who receive PDS, including less severe surgical complexity, fewer upper abdominal procedures, a shorter surgical duration, a lower amount of perioperative blood loss, a shorter hospital stay5,8,18, and reduced surgical morbidity and mortality7,8. In our study, there was no difference in the surgical outcomes between the NACT and PDS groups, as NACT may induce fibrosis, which may influence surgical procedures.
The presence of residual disease after surgery largely impact the prognosis of EOC19; one study showed that the 7-year overall survival rate decreased from 73.6% in patients without residual tumors to 21% in patients with any type of residual disease20. Therefore, the goal of debulking surgery has been changed from the presence of a residual tumor less than 1 cm in diameter to the presence of no visible tumor21; however, advanced-stage disease is associated with a low rate of complete tumor resection22. A previous study demonstrated that patients who received IDS after NACT were likely to achieve optimal cytoreduction20,23 but that they did not have superior survival24, and there was a decreasing trend in median survival with an increase in the number of NACT cycles24,25. These studies suggest that NACT impacts the evaluation of tumor spread and leads to incomplete tumor resection in potentially resectable areas.
In addition, patients treated with NACT-IDS suffer from recurrence more often than patients treated with PDS26. In our study, during the follow-up period, 14 (56.00%) patients experienced recurrence in the NACT group, and 8 (36.36%) had recurrence in the PDS group; the difference was not significant (P༞0.05). However, recurrence-free survival was poorer in the NACT-IDS group than in the PDS group (HR 2.406, 95% CI[1.024, 5.657]). Rauh-Hain and colleagues found that 88.8% of cases of recurrence in the NACT-IDS group were platinum resistant compared to 55.3% of cases in the PDS group (P = 0.001)27. The same outcome was also found by Gao, who showed that 40.3% of patients in the NACT-IDS group and 23.1% in the PDS group experienced platinum-resistant recurrence and 28; similarly, NACT induced chemotherapy resistance in cancer stem cell colonies29. A limited number of studies have found that the TP53 gene mutation is the most common (70.3%) mutation after courses of NACT compared with before courses of NACT30; additionally, in platinum-resistant patients (relapsed within 6 months), the TP53 K351N mutation was significantly more severe in the NACT-IDS group than in the PDS group (57.14% vs 0%, P༜0.01). Even so, in our study, we found that there was no significant difference in the platinum-free interval (164.93 ± 94.65 vs. 288.75 ± 188.56, P = 0.1115) or in the < 6-month PFI (6/25 vs. 2/22, P = 0.333).
There were some limitations in this study. First, this was a retrospective analysis in a single institution with a small sample size; thus, much stronger evidence is needed to confirm the results. Additionally, due to limited information, we did not compare overall survival between the two groups.