Angiogenic Burst After Parp Inhibitor Maintenance Therapy in Relapsed Ovarian Cancer: A Case Report

In the post-PARP inhibitor era, potential changes in tumor biology after maintenance therapy have not been well investigated in recurrent ovarian cancer. We reported a case with alterations in the clinical and histological features of multiple relapsed disease associated with PARP inhibitor maintenance therapy. The patient with high-grade serous carcinoma exhibited BRCA wildtype and homologous recombination proficiency status, and suffered from three recurrences and surgeries accordingly. Olaparib maintenance had been used during the second-line therapy. We compared the differences in clinics and pathology among three recurrences and relapsed lesions. Disease-free survivals were dramatically decreased after the exposure to olaparib. At exploration of quaternary cytoreduction, the relapsed tumor was characterized by a carcinomatosis-like metastasis pattern and an easy tendency of bleeding. Tumor cytopathological changes and alterations were observed in both the tumoral and non-tumoral stroma, among relapsed tumor tissues derived from secondary, tertiary and quaternary cytoreduction. Histopathology indicated hemorrhage, necrosis, atypical tumor cells, massive angiogenesis, and decreased CD8+ tumor-infiltrating lymphocytes, particularly in the third relapsed disease. To our knowledge, this is the first report to show a unique metastatic pattern of angiogenic burst after PARP inhibitor maintenance therapy in ovarian cancer, which seemed to trigger invasive tumor growth and immune suppression. Further prospective studies and translational research focusing cytoreductive surgery after PARP inhibitor could progressively lead to an understanding of the biological behavior and metastatic patterns.