A Randomized Double Blind, Multicenter Trial to Assess Time-interval Between Cytoreductive Surgery and Adjuvant Chemotherapy After Administration of Local Anesthetic Intraperitoneally/Perioperatively in Advanced Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the common term for cancer that originate from the surface of the ovary, lining of the fallopian tube and the peritoneum. There are different histopathological subtypes with high grade serous adenocarcinomas being the most prevalent (70%) followed by endometrioid (10%), clear cell (10%), low-grade serous (5%) and mucinous adenocarcinomas (3%).The pattern of dissemination is foremost through early exfoliation or seeding of tumour-cells in the peritoneum (carcinomatosis) and the majority of women have advanced stage disease at presentation, why ovarian cancer is the gynecologic malignancy with highest mortality.

Ovarian cancer affects 295 000 women every year globally and causes 185 000 cancer-related deaths annually . The highest incidence is seen in Northern Europe and North America and the lowest in South East Asia and parts of Africa. In the Nordic countries 2300 women are diagnosed annually and the corresponding number in Sweden is 700. Ovarian cancer constitutes 3% of all female cancers in Sweden and the risk of developing disease before the age of 75 is 1.1%. A decline in incidence is evident since the 1970s most probably due to increase in use of contraceptive pills but also change in criteria for diagnosis (an adnexal biopsy is mandatory for diagnosis today). The median age at diagnosis is 63 years.

Risk-factors include genetic mutations, family history, hormone replacement therapy and endometriosis. Pregnancy, lactation, contraceptive pills, sterilization, salpingectomy, hysterectomy and salpingoophorectomy are all factors associated with decreased risk of developing EOC.

Staging of ovarian cancer is surgical and according to the International Federation of Gynecology and Obstetrics (FIGO), latest revised in 2014 (7). In stage III and IV, advanced ovarian cancer, extra-pelvic dissemination is evident. Stage of disease is a strong prognostic factor for survival. The total 5-year relative survival in Sweden is 50% but ranges from 90% for stage I to 20% for stage IV. However, treatment is also an important prognostic factor and may increase survival even in advanced stage.

Surgical treatment of advanced EOC is often accompanied by a severe inflammatory and immuno-compromised perioperative course associated with early morbidity, delayed rehabilitation and, sometimes, delayed start of chemotherapy. Early start of chemotherapy has been repeatedly associated with improved survival. For this reason, perioperative factors such as choice of anaesthesia and analgesia and fluid replacement may be important.