Cytoreductive Surgery in Ovarian Cancer: Should the New Optimal Threshold Be 2.5 mm?

<b>Background/Objectives</b>: In patients with peritoneal metastases from ovarian cancer, current clinical guidelines recommend "optimal cytoreductive surgery (CRS)", defined as leaving no residual tumor nodules greater than 1 cm in diameter. Of note, the 1 cm threshold is somewhat arbitrary, as even a minimal residual tumor burden may adversely impact the patient's outcomes. The aim of the current study is to identify the independent risk factors associated with overall survival (OS) and progression-free survival (PFS) after "optimal" CRS, with a special focus on the impact of completeness of cytoreduction (defined according to Sugarbaker's scoring system). <b>Methods</b>: This retrospective cohort study included all the patients with peritoneal metastasis from ovarian cancer who underwent "optimal CRS" (residual nodules less than 1 cm), performed by a single team. Regarding the completeness of cytoreduction (CC), the patients were divided into two groups (without residual disease or with residual nodules less than 2.5 mm (CC0/CC1), and those with residual nodules larger than 2.5 mm and less than 1 cm ("optimal" CC2)). Risk factors associated with OS and PFS were identified by univariate and multivariate analysis. <b>Results</b>: Between September 2010 and February 2025, 52 patients with a median age of 62 [53.25-66.5] years underwent "optimal" CRS. For the entire group, the median OS was 70.83 months, and the median PFS was 25.8 months. In univariate analysis, the factors associated with significantly better OS were a peritoneal cancer index (PCI) lower or equal to 10 (vs. PCI > 10; <i>p</i> = 0.025) and CC0/CC1 status (vs. "optimal" CC2; <i>p</i> = 0.004), while in multivariate analysis, the only independent factor associated with higher OS was CC0/CC1 (HR = 0.253; 95% CI: 0.092-0.696, <i>p</i> = 0.008). Regarding PFS, the only factors independently associated with higher PFS were CC0/CC1 (HR = 0.155; 95% CI: 0.046-0.527, <i>p</i> = 0.003) and no preoperative chemotherapy (HR = 0.387; 95%CI: 0.155-0.963, <i>p</i> = 0.041). <b>Conclusions</b>: To the best of our knowledge, this is the first study to reveal that in patients with peritoneal metastases from ovarian carcinoma who underwent "optimal" CRS, the only independent factor associated with both better OS and PFS was the achievement of CC0/CC1 (no residual macroscopic nodules or residual nodules less than 2.5 mm). This observation supports the notion of redefining the threshold of "optimal" cytoreduction and potentially of implementing the Sugarbaker classification of cytoreduction even in ovarian cancer.