Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.

Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas. In previous clinical studies, chemotherapy with cytotoxic anticancer drugs has failed to demonstrate better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers. The issues that need to be addressed include the most appropriate combination of therapies, identifying patients who may benefit from each therapy, and how results should be incorporated into the standard of care for ovarian clear cell and mucinous carcinomas. In this article, we have reviewed the most promising therapies for ovarian clear cell and mucinous carcinomas, which are regarded as intractable, with an emphasis on therapies currently being investigated in clinical studies.

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

Background/Objectives: Robot-assisted laparoscopic surgery (RALS) for endometrial cancer achieves outcomes comparable to those of conventional laparoscopy (Lap) but often requires a longer operative time, which may increase the early postoperative inflammatory response. We compared the postoperative day 1 (POD1) C-reactive protein (CRP) elevation between RALS and Lap and examined whether it was associated with the surgical platform or with patient- and procedure-related factors. Methods: This retrospective single-center study included 301 patients who underwent minimally invasive hysterectomy for endometrial cancer (Lap, n = 202; RALS, n = 99; 2018–2025). The primary outcome was CRP rise (POD1 minus the preoperative CRP level). Propensity score matching using preoperative covariates only (1:2, caliper 0.15 SD), multivariable regression, a formal mediation analysis with operative time as the mediator, and a test of the interaction between body mass index (BMI) category and surgical approach were performed. Results: RALS was associated with a greater CRP rise (2.88 vs. 2.13 mg/dL; p = 0.001) and a longer operative time (271.0 vs. 210.5 min; p < 0.001). In the matched cohort the median CRP rise was 2.91 mg/dL after RALS and 2.22 mg/dL after Lap, and the association persisted in a weighted model that accounted for the matched sets (β = 0.131; p = 0.023). On multivariable analysis, operative time (β = 0.0026 per minute; p < 0.001) and BMI (β = 0.0090 per kg/m²; p = 0.033) were associated with the CRP rise, whereas the surgical approach was not (β = −0.029; p = 0.623). Mediation analysis showed an indirect effect through operative time of +0.192 (95% CI, 0.120 to 0.278). The interaction between BMI category and surgical approach was not statistically significant (p = 0.750). Conclusions: The greater POD1 CRP rise after RALS was attenuated after accounting for operative time, and the mediation analysis was consistent with an indirect pathway through operative duration. This pathway cannot be established causally, because operative time could not be separated from surgeon experience, the learning curve and the era of each platform. A difference of this magnitude has no established clinical correlate, and no BMI-specific effect was demonstrated. Whether improving operative efficiency reduces the early postoperative inflammatory response should be evaluated prospectively.

Objective: Bevacizumab (BEV) and Olaparib (OLA) have demonstrated clinical efficacy as maintenance therapies for first platinum-sensitive recurrent ovarian cancer. However, direct comparisons between these agents independent of homologous recombination deficiency (HRD) and BRCA status, remain limited and the clinical validity of OLA dose reduction has not yet been confirmed. This study aimed to compare the efficacy and safety of BEV, standard-dose OLA, and dose-reduced OLA as maintenance therapy and to evaluate the clinical utility of OLA dose reduction. Methods: This retrospective multicenter study included 101 patients with first platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer who received maintenance therapy after achieving a response to chemotherapy. Patients were classified into three groups: BEV (n = 34), standard-dose OLA (n = 31), and dose-reduced OLA (n = 36). The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and adverse events. Survival outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results: Median PFS was 16 months in the BEV group, 16 months in the standard-dose OLA group, and 24 months in the dose-reduced OLA group, with significantly longer PFS in the dose-reduced OLA group (p < 0.001). In the multivariate Cox analysis, treatment remained an independent prognostic factor for PFS (HR 0.67, 95% CI 0.46–0.96, p = 0.030). Median OS was 44, 45, and 64 months, respectively, with no significant differences among groups; PFI ≥12 months was the only independent prognostic factor for OS. Grade ≥3 hematologic toxicities were more frequent in the OLA groups but were manageable. Conclusions: Dose-reduced OLA was associated with prolonged PFS while maintaining manageable toxicity, supporting its clinical validity as a maintenance option independent of HRD and BRCA status.