Despite significant advancements in imaging technologies, surgical techniques, chemotherapeutic regimens, and treatment strategies in recent years, ovarian cancer continues to remain the most deadly gynecological malignancy. Approximately 90% of ovarian cancers originate from the coelomic epithelium or modified mesothelial cells and are classified as epithelial ovarian cancers. The majority of patients with epithelial ovarian cancer (70-80%) present in advanced stages. The primary treatment for advanced-stage (stage 3-4) disease consists of primary cytoreductive surgery followed by adjuvant chemotherapy. Cytoreductive surgery aims to remove all visible tumor implants regardless of the extent of the disease and achieve no visible residual tumor (complete cytoreduction, R0) at the end of the surgery. In cases where R0 cannot be achieved (due to poor general condition and/or extensive tumor that cannot be completely excised surgically), the option of neoadjuvant chemotherapy followed by interval cytoreductive surgery is considered. Primary cytoreductive surgery is still the preferred option and is considered a quality indicator for centers performing advanced-stage ovarian cancer surgeries. Despite advancements in surgery, the decision for interval surgery following primary surgery or neoadjuvant chemotherapy is often based on the surgeon's experience, imaging results, and clinic preferences. Various methods and scores have been published and applied to predict which patients are suitable for primary surgery.

The Cukurova score developed in our clinic conceptualizes prioritizing surgical procedures using radiological imaging and diagnostic exploratory laparoscopy to achieve complete cytoreduction in harmony with the patient's clinical and performance status, rather than focusing solely on tumor burden. The score showed high success rates for complete cytoreduction and also was useful in terms of predicting the morbidity and mortality. However, the Cukurova score study was conducted in single center. Validation of scores in centers with different capacities is expected to facilitate their widespread use and acceptance. Therefore, in this study, the investigators plan to conduct a validation study of the score in a total of 20 centers in Turkey, including our center. This study aims to evaluate the validity of the Cukurova score in predicting outcomes of primary cytoreduction in advanced ovarian cancer patients and thus determining the decision for primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery.

Aim: The majority of patients with epithelial ovarian cancer (70-80%) present in advanced stages. The primary treatment for advanced-stage (stage 3-4) disease consists of primary cytoreductive surgery followed by adjuvant chemotherapy. Cytoreductive surgery aims to remove all visible tumor implants regardless of the extent of the disease and achieve no visible residual tumor (complete cytoreduction, R0) at the end of the surgery. In cases where R0 cannot be achieved (due to poor general condition and/or extensive tumor that cannot be completely excised surgically), the option of neoadjuvant chemotherapy followed by interval cytoreductive surgery is considered. Primary cytoreductive surgery is still the preferred option and is considered a quality indicator for centers performing advanced-stage ovarian cancer surgeries. Despite advancements in surgery, the decision for interval surgery following primary surgery or neoadjuvant chemotherapy is often based on the surgeon's experience, imaging results, and clinic preferences. Various methods and scores have been published and applied to predict which patients are suitable for primary surgery.

The Cukurova score developed in our clinic conceptualizes prioritizing surgical procedures using radiological imaging and diagnostic exploratory laparoscopy to achieve complete cytoreduction in harmony with the patient's clinical and performance status, rather than focusing solely on tumor burden. The score showed high success rates for complete cytoreduction and also was useful in terms of predicting the morbidity and mortality. However, the Cukurova score study was conducted in single center. Validation of scores in centers with different capacities is expected to facilitate their widespread use and acceptance. Therefore, in this study, the investigators plan to conduct a validation study of the score in a total of 20 centers in Turkey, including our center. This study aims to evaluate the validity of the Cukurova score in predicting outcomes of primary cytoreduction in advanced ovarian cancer patients and thus determining the decision for primary cytoreductive surgery or neoadjuvant chemotherapy followed by interval cytoreductive surgery.

Method: Informed consent forms will be obtained from all participants. Patients over the age of 18 suspected of having primary stage III-IV epithelial ovarian cancer will be included in this study. Cases with suspected peritoneal carcinomatosis findings on imaging studies or histologically confirmed at any time will be considered for the study. The followings are the exclusion criteria of the study; 1- refusing to participate in the study, 2- benign ovarian cases, 3- borderline ovarian tumors, 4- metastatic ovarian malignancies, 5- non-epithelial ovarian malignancies, 6- stage I-II epithelial ovarian cancers, and 7- being under 18 years old. Contrast-enhanced magnetic resonance imaging (MRI) will be preferred for abdominal imaging, and contrast-free computed tomography (CT) will be preferred for thoracic imaging. Imaging performed less than 3 weeks before surgery will be considered. Patients unable to undergo MRI will be evaluated with contrasted abdominopelvic CT scans. Imaging findings will be recorded, and necessary surgical procedures to achieve R0 will be discussed based on these findings, with a score assigned for each anticipated surgical procedure. These findings and anticipated surgical procedures are discussed through a multidiciplinary tumor board including at least two gynecological oncologists. Patients' age, body mass index, and performance scores will be recorded and scored, also. Scoring will be made according to the following parameters;

Each of 12 points:

• ECOG score ≥3
• ASA score ≥3
• Absolute stoma or blood transfusion refuse

Each of 2 points:

• Body mass index ≥40 or <18
• Age ≥75 years

Each of 12 points:

• Non-resectable extra-abdominal metastases
• Non-resectable multiple parenchymal liver metastases
• Non-resectable liver hilus involvement or non-repairable vessel-involved hepatoduodenal or celiac nodes
• Diffuse involvement of small bowel root represented in cocoon syndrome, non-movable or firmly retracted small bowel
• Confluent or extensive small bowel or meso involvement requiring resection which could lead to short bowel syndrome (<150cm)

Each of 6 points:

• Total gastrectomy
• Mesh necessitating diaphragmatic resection
• Ampullar region involvement requiring Whipple modifications
• Liver lobectomy
• Nephrectomy
• Total cystectomy
• Proctectomy

Each of 2 points:

• Liver segmentectomy (two points for each segment)

• Various surgical liver procedures (>2 procedures, covering >2 cm for each one, including metastasectomies, wedge resections, Glissonian excisions)

• Suprarenal lymphadenectomy(1)

• Splenectomy with or without distal pancreatectomy

• Bowel resections and anastomoses, 2 points for each anastomosis including small bowel anastomosis (eg, low anterior resection=2, total colectomy=2)

• Partial gastrectomy or full thickness gastric excisions

• Diaphragm stripping or primary sutured partial resections

• Ureteral anastomosis, 2 points for each one, including unilateral neocystostomy and significant partial cystectomy

• Video-assisted thoracic surgery (VATS)(2)

  1. Including direct suprarenal, hepatoduodenal, celiac, cardiophrenic, mediastinal, scalene, or cervical lymph nodes.
  2. Only in cases where surgical procedure is performed; diagnostic procedures with or without effusion drainage are not scored.

ASA, American Society of Anesthesiologists; ECOG, Eastern Cooperative Oncology Group.;

To calculate the clinic-Cukurova score; existing parameters' points are summed and multiplied by the ECOG score. In case of ECOG 0, only the summing process is done. Then diagnostic explorative laparoscopy ± VATS is performed and the required surgical procedures to achieve R0 are modified according to both radiological and laparoscopic evaluations. Again, the abovementioned parameters are scored and now the Cukurova score is calculated in similar manner (existing parameters' points are summed and multiplied by the ECOG score). Subsequently, in cases where the Cukurova score is equal or less than 12, primary debulking surgery will be performed. Neoadjuvant chemotherapy will be the choice in cases with Cukurova score more than 12. Laparoscopic evaluations will be approved by two gynecologic oncologists, and the decision regarding primary debulking surgery or neoadjuvant chemotherapy will be made with their agreement. If laparoscopic evaluation is inadequate due to extensive tumor adhesions and/or a large mass, Cukurova score will be calculated with a diagnostic explorative laparotomy. VATS will be performed in patients with pleural effusion and/or suspicious radiological findings in the thorax. Clinical, surgical, and postoperative follow-up information of the patients will be collected. Data collected from all centers will be statistically analyzed.

Sample size: According to the figures obtained from the Cukurova Score study, it has been observed that the R0 resection rate after primary debulking is 89%. Under the assumption that the AUC value for the Cukurova score in this group is 0.810, it has been calculated that at least 91 patients need to undergo primary debulking surgery with a 5% error rate and 90% power. Furthermore, considering that the percentage of patients undergoing primary debulking in this study is 70%, it has been planned to include at least 130 patients in total (including interval debulking patients).

Inclusion Criteria:

• 18 years old and over
• Suspected advanced ovarian/fallopian tube/ primary peritoneal carcinomatosis on imaging
• Pathologically confirmed Stage III-IV epithelial ovarian cancer/fallopian tube/ primary peritoneal carcinomatosis
• Consent to participate in the study

Exclusion Criteria:

• Stage I-II epithelial ovarian/fallopian tube/peritoneal cancer
• Nonepithelial Ovarian Cancer
• Benign Ovarian tumors
• Borderline Ovarian Tumors
• Metastatic Ovarian Tumors
• Rejecting to Participate in the Study
• <18 years old

Women who have advanced epithelial ovarian cancer