Advanced ovarian cancer

Abstract

Ovarian cancer spreads early in the disease into the abdomen. An en bloc resection of the tumor, according to surgical principle, is not possible in patients with high-stage ovarian cancer. At surgery, large pelvic tumor lesions are found together with multiple tumor lesions involving the omentum, bowel, and mesentery together with a diffuse peritoneal carcinomatosis and diaphragmatic involvement. A multimodality approach with cytoreductive surgery and taxol platinum-based chemotherapy is therefore the mainstay of treatment of advanced ovarian cancer. The size of residual disease after surgery is one of the most important prognostic factors for survival. Patients with an optimal tumor cytoreduction (residual lesions smaller than 1 cm) have a significant longer survival (almost two times the median survival) than patients with larger residual lesions. This holds true even for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IV disease. Patients in whom all macroscopic tumor is resected do have the longest survival. The 2-year survival of patients with a radical resection of all macroscopic tumors is 80%, in contrast to less than 22% for the patients with lesions larger than 2 cm. An optimal primary cytoreductive surgery can generally be performed in 30% to 50% of patients. Only in more experienced gynecologic oncology centers is the percentage as high as 85%, but sometimes at the cost of an increased morbidity and even mortality. The worse prognosis of the patients with a suboptimal primary cytoreductive surgery can be improved by an interval cytoreductive surgery after platinum-containing induction chemotherapy. The median survival and progression-free survivals are significantly lengthened by cytoreductive surgery. After more than 5-years follow-up there is still a significant survival benefit: the 5-year survival of the surgery patients was 24% versus 13% for the no-surgery patients (P = 0.0032). All patients, including those with unfavorable prognostic factors (stage IV disease, peritonitis carcinomatosis, or ascites at primary surgery), and even patients with stable disease after induction chemotherapy, seem to benefit from interval cytoreductive surgery. The increase in progression-free survival and overall survival does outweigh the morbidity associated with interval debulking surgery, which is not different from those associated with primary surgery.

Role of Neoadjuvant Chemotherapy (NACT) Followed by Surgical Cytoreduction in Advanced Epithelial Ovarian Cancer

“…Most people today accept optimal cytoreduction as residual tumor volume of \1 cm or even \0.5 cm. However, due to bulky disease in advanced ovarian cancer, optimal cytoreduction is possible in only 40-50% of the patients [7]. These data suggest that patients with advanced stage ovarian cancer could only benefit from an optimal surgical debulking, which usually does not exceed 40% even in experienced surgical centers in case of primary debulking procedure.…”

“…Studies have shown that by primary cytoreductive surgery about 30-70% of patients with advanced disease are not optimally debulked [7]. Patients with poor performance status and those with lesion involving diaphragm, base of small bowel, mesentery, liver parenchyma, retroperitoneal nodes and upper abdominal structures, stomach and splenic hilum are often unresectable, otherwise even if resectable it requires major surgical intervention in the form of bowel resection anastomoses, colostomy, ileostomy etc.…”

Methylation status of TUSC3 is a prognostic factor in ovarian cancer

“…31,32 By using publicly available gene-expression profiling data, we have systematically screened the region on 8p22 for differentially regulated genes and identified TUSC3 as a candidate tumor suppressor gene in ovarian cancer. 14 In our current work, we validate our previous observations in a larger, completely independent patient population and demonstrate that the expression of TUSC3 in ovarian cancer may be regulated by promoter methylation.…”

SOX2 Expression Associates with Stem Cell State in Human Ovarian Carcinoma

“…Ovarian carcinoma has the seventh highest morbidity rate of cancer in women (22). Because of the lack of early specific symptoms, ovarian carcinoma is mostly diagnosed at advanced metastatic stages that cannot be cured by surgical resection alone.…”

“…Because of the lack of early specific symptoms, ovarian carcinoma is mostly diagnosed at advanced metastatic stages that cannot be cured by surgical resection alone. Despite initially good response rates to Platinbased chemotherapies, relapse is a common event during the clinical course of the disease (22). An explanation for ovarian carcinoma relapse is provided by the tumor stem cells hypothesis, proposing that conventional chemotherapeutic approaches target the fast proliferating bulk of the ovarian cancer cells, while sparing the tumor-initiating CSCs (23).…”