Cytoreductive surgery is feasible in patients with limited regional platinum-resistant recurrent ovarian cancer.

INTRODUCTION: To evaluate the efficacy of cytoreductive surgery versus chemotherapy for the treatment of limited regional, platinum-resistant ovarian cancer (PROC). MATERIALS AND METHODS: The clinical records of all patients with PROC treated in our center between March 2015 and March 2022 were retrospectively reviewed. We compared the oncology outcomes of patients who received cytoreduction or chemotherapy alone at relapse and presented information about postoperative adjuvant chemotherapy. RESULTS: Among 52 patients with limited regional recurrence, 40.4% (21/52) underwent cytoreduction because of platinum resistance, and 59.6% (31/52) received chemotherapy alone. No residual disease (R0) was achieved in 20 patients (95.2%). The severe morbidity rate within 30 days after the surgery was 15%. The median follow-up was 70.6 months. Compared with the chemotherapy alone group, the surgery group with R0 had better progression-free survival (PFS) (10.6 vs. 5.1 months; hazard ratio (HR) = 0.421; P = 0.0035) and post-relapse survival (PRS) (32.6 vs. 16.3 months; HR = 0.478; P = 0.047), but there was no difference in overall survival (OS) between the two groups. Laparoscopy is associated with lesser intraoperative blood loss with no differences in survival and postoperative complications compared to the open approach (P = 0.0042). Subgroup survival analysis showed that compared with chemotherapy alone, surgery prolonged PFS in patients regardless of tumor size (greater than or equal to 4 cm or less). Surgery group patients who achieved R0 had an objective response rate (ORR) of 36.8% (7/19), among whom 40% (4/10) received platinum rechallenge chemotherapy and 33.3% (3/9) were administered non-platinum chemotherapy. CONCLUSION: When well-selected PROC patients with limited regional recurrence achieved R0, their outcomes were superior to those of patients who received only chemotherapy with an acceptable morbidity rate. Laparoscope technology could be a reliable alternative surgical approach. The reintroduction of platinum agents may be considered following surgery. Further analyses in a larger population are warranted to elucidate the risks and benefits of this surgery and adjuvant chemotherapy strategy.

A durable response to programmed cell death 1 blockade in a multidrug-resistant recurrent ovarian cancer patient with HLA-B44 supertype: A case report.

Relapsed/refractory ovarian cancer, especially platinum resistance recurrence, remains a major therapeutic challenge. Here, we present the case of a patient with recurrent ovarian clear cell carcinoma (OCCC) who failed to respond to multiline chemotherapy and target therapy but achieved an immune complete response (iCR) with programmed cell death 1 (PD-1) inhibitor treatment. The overall survival (OS) was 59 months, and the recurrence-free survival (RFS) was 34 months after immunotherapy, which was counting. Meantime, molecular testing results revealed that traditional biomarkers for immunotherapy, including PD-L1 expression, microsatellite instability (MSI), and tumor mutational burden (TMB), were negative. HLA-B44 (B*18:01) supertype was confirmed by sequence-based HLA typing. This case raises the possibility that ovarian cancer patients with multidrug resistance may still benefit from PD-1 inhibitor therapy, even if PD-L1 pathology is negative.

Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer.

Background: Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME). These cells play a supportive role throughout cancer progression. Their ability to modulate the immune system has also been noted. However, there has been limited investigation of CAFs in the TME of epithelial ovarian cancer (EOC). Methods: We comprehensively evaluated the CAF landscape and its association with gene alterations, clinical features, prognostic value, and immune cell infiltration at the pan-cancer level using multi-omic data from The Cancer Genome Atlas (TCGA). The CAF contents were characterized by CAF scores based on the expression levels of seven CAF markers using the R package "GSVA." Next, we identified the molecular subtypes defined by CAF markers and constructed a CAF riskscore system using principal component analysis in the EOC cohort. The correlation between CAF riskscore and TME cell infiltration was investigated. The ability of the CAF riskscore to predict prognosis and immunotherapy response was also examined. Results: CAF components were involved in multiple immune-related processes, including transforming growth factor (TGF)-ß signaling, IL2-STAT signaling, inflammatory responses, and Interleukin (IL) 2-signal transducer and activator of transcription (STAT) signaling. Considering the positive correlation between CAF scores and macrophages, neutrophils, and mast cells, CAFs may exert immunosuppressive effects in both pan-cancer and ovarian cancer cohorts, which may explain accelerated tumor progression and poor outcomes. Notably, two distinct CAF molecular subtypes were defined in the EOC cohort. Low CAF riskscores were characterized by favorable overall survival (OS) and higher efficacy of immunotherapy. Furthermore, 24 key genes were identified in CAF subtypes. These genes were significantly upregulated in EOC and showed a strong correlation with CAF markers. Conclusions: Identifying CAF subtypes provides insights into EOC heterogeneity. The CAF riskscore system can predict prognosis and select patients who may benefit from immunotherapy. The mechanism of interactions between key genes, CAF markers, and associated cancer-promoting effects needs to be further elucidated.