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Background Despite being widely used, to date (June 2021), the regimen of bevacizumab 10 mg/kg every 2 weeks (Q2W) combined with chemotherapy is not approved in Japan for patients with platinum-resistant recurrent ovarian cancer. In this retrospective analysis, we evaluated the usage patterns of bevacizumab administered for platinum-resistant recurrent ovarian cancer. Methods We obtained clinical data from 155 Japanese medical facilities between November 2013 and December 2018 via a survey. Items included the number of cases of platinum-resistant recurrent ovarian cancer treated with bevacizumab according to dosage. For regimens including bevacizumab 10 mg/kg Q2W, additional information was requested relating to concomitantly administered agents, and the efficacy and safety of the regimen. Results Of 1739 bevacizumab-containing regimens reported in 1633 patients with recurrent ovarian cancer, 264 used 10 mg/kg Q2W. The overall response rate (ORR) with this regimen was 26.1%. Response rates varied according to regimen and were particularly favorable when bevacizumab 10 mg/kg Q2W was administered with paclitaxel (ORR, 53.0%) versus liposomal doxorubicin (15.0%; P P Conclusions Bevacizumab 10 mg/kg Q2W appears efficacious for patients with recurrent ovarian cancer, with a manageable toxicity profile. Approval of this regimen is clinically desirable for Japanese patients with ovarian cancer.

Background Epithelial ovarian cancer has a clear predilection for the omentum as the site of metastasis; however, its contribution to clinical outcomes remains unresolved. This study aimed to evaluate the prognostic significance and efficacy of chemotherapy in the presence of omental metastasis. Methods A retrospective cohort study was performed in 56 patients with stage III–IV ovarian cancer who underwent primary debulking surgery between 2004 and 2018 at Kumamoto University Hospital. Results Thirty-six (64.3%) patients were categorized into the omental metastasis-positive group, whereas 20 (35.7%) patients were in the omental metastasis-negative group. The 5-year overall survival rates were 43.4% in the omental metastasis-positive group and 93.8% in the omental metastasis-negative group. Statistically significant differences were observed in overall survival (p = 0.002) and progression-free survival (p = 0.036) between the omental metastasis-positive and metastasis-negative groups. Notably, multivariate analysis demonstrated that the existence of omental metastasis is an independent risk factor for overall survival in patients with stage III–IV ovarian cancer (hazard ratio 8.90, 95% confidence interval 1.16–69.77; p = 0.038). Furthermore, the omental metastasis-positive group had significantly lower overall response rates to chemotherapy for recurrent disease, compared to the omental metastasis-negative group (31.6% vs. 85.7%, p = 0.026). Conclusion Our present data demonstrated that omental metastasis is closely associated with an unfavorable prognosis due to increased chemoresistance in patients with stage III–IV ovarian cancer. Elucidating the biological mechanism of omental metastasis will shed light on novel therapeutic approaches for the management of advanced ovarian cancer patients.

Endometrial carcinoma (EC) is rapidly increasing worldwide. In the twentieth century, it was believed that endocrine and metabolic disturbances might determine the biological features and clinical course of EC. The dualistic pathogenetic classification suggested in 1983 provided an understanding of a complex and heterogeneous disease, and thereafter, the immunohistochemical status of hormonal receptors provided a clue for discriminating EC based on two representative histological types, namely, endometrioid carcinoma and serous carcinoma. Molecular advancements in the 1990s revealed genomic alterations in the dualistic types of EC: the endometrioid type is primarily characterized by KRAS mutation, microsatellite instability, and PTEN mutation, and the serous type is characterized by TP53 mutation. In 2013, integrated genomic transcriptomic and proteomic analyses classified EC into four categories: POLE, microsatellite instability, copy-number low, and copy-number high. The reclassification further contributed to a more comprehensive understanding of the molecular alterations and signaling pathways in EC and thus provides potential targeted approaches for the personalized treatment of EC.

Despite being widely used, to date (June 2021), the regimen of bevacizumab 10 mg/kg every 2 weeks (Q2W) combined with chemotherapy is not approved in Japan for patients with platinum-resistant recurrent ovarian cancer. In this retrospective analysis, we evaluated the usage patterns of bevacizumab administered for platinum-resistant recurrent ovarian cancer.We obtained clinical data from 155 Japanese medical facilities between November 2013 and December 2018 via a survey. Items included the number of cases of platinum-resistant recurrent ovarian cancer treated with bevacizumab according to dosage. For regimens including bevacizumab 10 mg/kg Q2W, additional information was requested relating to concomitantly administered agents, and the efficacy and safety of the regimen.Of 1739 bevacizumab-containing regimens reported in 1633 patients with recurrent ovarian cancer, 264 used 10 mg/kg Q2W. The overall response rate (ORR) with this regimen was 26.1%. Response rates varied according to regimen and were particularly favorable when bevacizumab 10 mg/kg Q2W was administered with paclitaxel (ORR, 53.0%) versus liposomal doxorubicin (15.0%; P 0.0001) and irinotecan (7.7%; P 0.028). The most frequent Grade ≥ 3 adverse events associated with bevacizumab 10 mg/kg Q2W were neutropenia (11.7%) and hypertension (11.7%). The most frequent bevacizumab-associated Grade ≥ 3 adverse events with bevacizumab plus paclitaxel versus bevacizumab plus liposomal doxorubicin were hypertension (9.0% versus 13.9%) and proteinuria (3.0% versus 8.4%).Bevacizumab 10 mg/kg Q2W appears efficacious for patients with recurrent ovarian cancer, with a manageable toxicity profile. Approval of this regimen is clinically desirable for Japanese patients with ovarian cancer.

Epithelial ovarian cancer (EOC) is associated with a variety of molecular and pathologic characteristics and has a spectrum of biological behavior. The current management of EOC is developing from traditional chemotherapy using cytotoxic agents to modern therapy using molecularly targeted agents, as the result of advances in translational research. This evolution has been based on our increased understanding of molecular pathology and numerous clinical trials in the field of gynecologic oncology. Current and future promising targeted therapy approaches for EOC can be classified into two types: (1) specific molecular targeting, using an apoptosis inducer associated with the unique molecular characteristics of the tumor, and (2) more generalized targeting strategies using angiogenesis and immune checkpoint inhibitors, which interact with the tumor microenvironment. Representative agents used in these two approaches include, respectively, (1) poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors, such as olaparib and niraparib, and (2) the angiogenesis inhibitor bevacizumab and the immune checkpoint inhibitor nivolumab. In this review, we discuss the present status of these promising agents in regard to the molecular targeting of EOC.

In recent history, cancer stem cells have been postulated as the driving force for carcinogenesis and the seeds of metastasis in several types of solid cancers. In addition, accumulating evidence suggests that the cell adhesion molecule CD44 and its variant isoforms are critical players in regulating the biology of cancer stem cells and cancer metastasis. However, the functional role of these molecules in ovarian cancer stem cells, particularly in the development of metastasis, remains completely unresolved in ovarian cancer patients.

All cancers arise as a result of dynamic changes in the cancer genome. Cancer cells show diverse biological capabilities that are conferred by numerous genetic and epigenetic changes. Over the past years, comprehensive genomic studies using next-generation sequencing technology have resulted in an increasing wealth of the understanding of molecular mechanisms with respect to the genomic features of gynecological malignancies, including ovarian, endometrial, and cervical cancers. These studies can be exploited to develop and improve cancer classification, new diagnostic methods, and novel therapeutic strategies.

Epithelial ovarian tumors (EOTs) are associated with a variety of distinct morphological characteristics that include serous, endometrioid, clear cell, and mucinous features and have a spectrum of biological behavior that ranges from benign to malignant. Traditionally, EOTs were believed to originate from the ovarian surface epithelium (OSE), but the latest research supports the concept that some subtypes of EOTs originate from extra-ovarian sites. Although a couple of paradigms in regard to the morphological and molecular pathogenesis of EOTs have dramatically changed in recent years, the delineation between old and new concepts remains confused. This chapter summarizes those concepts and the morphological and molecular alterations associated with each major subtype of EOT, to improve our understanding of the pathogenesis of EOTs.