Residual Microscopic Peritoneal Metastases after Macroscopic Complete Cytoreductive Surgery for Advanced High-Grade Serous Ovarian Carcinoma: A Target for Folate Receptor Targeted Photodynamic Therapy?

Abstract

Despite conventional treatment combining complete macroscopic cytoreductive surgery (CRS) and systemic chemotherapy, residual microscopic peritoneal metastases (mPM) may persist as the cause of peritoneal recurrence in 60% of patients. Therefore, there is a real need to specifically target these mPM to definitively eradicate any traces of the disease and improve patient survival. Therapeutic targeting method, such as photodynamic therapy, would be a promising method for such a purpose. Folate receptor alpha (FRα), as it is specifically overexpressed by cancer cells from various origins, including ovarian cancer cells, is a good target to address photosensitizing molecules. The aim of this study was to determine FRα expression by residual mPM after complete macroscopic CRS in patients with advanced high-grade serous ovarian cancer (HGSOC). A prospective study conducted between 1 June 2018 and 10 July 2019 in a single referent center accredited by the European Society of Gynecological Oncology for advanced EOC surgical management. Consecutive patients presenting with advanced HGSOC and eligible for complete macroscopic CRS were included. Up to 13 peritoneal biopsies were taken from macroscopically healthy peritoneum at the end of CRS and examined for the presence of mPM. In case of detection of mPM, a systematic search for RFα expression by immunohistochemistry was performed. Twenty-six patients were included and 26.9% presented mPM. In the subgroup of patients with mPM, FRα expression was positive on diagnostic biopsy before neoadjuvant chemotherapy for 67% of patients, on macroscopic peritoneal metastases for 86% of patients, and on mPM for 75% of patients. In the subgroup of patients with no mPM, FRα expression was found on diagnostic biopsy before neoadjuvant chemotherapy in 29% of patients and on macroscopic peritoneal metastases in 78% of patients. FRα is well expressed by patients with or without mPM after complete macroscopic CRS in patients with advanced HGSOC. In addition to conventional cytoreductive surgery, the use of a therapeutic targeting method, such as photodynamic therapy, by addressing photosensitizing molecules that specifically target FRα may be studied.

Fluorescence-guided photoimmunotherapy using targeted nanotechnology and ML7710 to manage peritoneal carcinomatosis

“…Microscopic peritoneal metastasis is regularly present after complete cytoreductive surgery in advanced ovarian cancer patients ( 4 ). Recent reports suggested that complete cytoreductive surgery followed by locoregional therapies such as hyperthermic intraperitoneal chemotherapy (HIPEC) ( 42 , 43 ) or molecular PDT ( 44 ) could improve survival outcomes for patients with peritoneal metastasis. Additionally, our previous study has already shown that combination of PDT and EGFR-targeted therapy can enhance survival in human ovarian carcinomatosis mouse models ( 45 ).…”

Folate Receptor Targeted Photodynamic Therapy: A Novel Way to Stimulate Anti-Tumor Immune Response in Intraperitoneal Ovarian Cancer

“…Several reports have described that 80% of epithelial ovarian cancers overexpress FRα, while this expression is low in the normal epithelial ovarian tissues [28]. Furthermore, a recent study showed that FRα was well expressed by 75% of patients with microscopic peritoneal metastases (which are the cause of peritoneal recurrence) after complete macroscopic cytoreductive surgery [29]. Moreover, levels of FRα seems to correlate with the grade of ovarian cancer and, therefore, with the overall survival rate [30].…”