Littérature scientifique sur le sujet « Advanced Ovarian Cancer, Optimal Cytoreduction, Upper Abdominal Disease, Tumor Residual »

The standard frontline treatment for advanced-stage ovarian cancer (ASOC) consists of maximal cytoreduction surgery associated with platinum/paclitaxel-based chemotherapy. Several studies have proven that patients with no gross residual disease (RD) have better survival rates than those with optimal but visible RD (RD ≤1 cm). In order to achieve this, more radical cytoreductive procedures such as radical pelvic resection and extensive upper abdominal procedures are performed. However, some investigators have suggested that, although effective, radical surgery cannot fully compensate tumor biology, which is a major determinant in survival and in turn influences the likelihood of surgical cytoreduction. The aim of this review was to present the procedures defining ultra-radical (extensive) surgery and to evaluate its feasibility and morbidity in the management of ASOC.

Purpose: Several studies have shown the benefit of cytoreductive surgery in advanced disease, that is why the residual tumor has prognostic value. Our primary objective was to determine the frequency of involvement of the upper abdomen, defined as the extension of the disease above the transverse colon (diaphragm, spleen, gallbladder, stomach, hepatic parenchyma, hepatic capsule, minor omentum, hepatic ilium, pancreas). Our secondary objective was to analyze the possibilities of complete cytoreduction in these patients, their complications and results. Materials and methods: We retrospectively include patients undergoing primary and secondary cytoreduction due to ovarian carcinoma between January 2008 and December 2012, in the gynecology department of the German Hospital. Results: One hundred and thirty nine patients with ovarian carcinoma were analyzed. An average age of 60 years (28-90). 91 of them with attempted primary cytoreduction and 48 secondary cytoreduction. In the group of primary cytoreductions we excluded 17 patients that were stages I and II, 20 (22%) of the 74 stages III-IV had upper abdomen involvement, 17 stages III and 3 stages IV. Those stage IV patients were only limited to hepatic intraparenchymal involvement. Of the 48 secondary cytoreductions, 21 (43%) presented upper abdominal involvement. Including both groups we have 30% of upper abdomen compromise. Complete or optimal cytoreduction was achieved in 56% of them. Conclusion: The exploration of the superior abdomen in ovarian cancer surgery is key, and the approach of this patients by a team of properly trained gynecologists is mandatory if we want to obtain better complete cytoreduction rates.

e15568 Background: The efficacy of PDS for advanced ovarian cancer has recently been challenged by data suggesting equivalent clinical outcomes for neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). The strongest known predictor of prolonged survival in either group is the ability to achieve complete resection (CR) to no residual disease. PDS that results in a CR is associated with the longest overall survival of any sequence of treatment. The aim of this study was to determine what type of surgical approach is required to successfully perform PDS. Methods: All women with newly diagnosed stage IIIC epithelial ovarian carcinoma treated at our institution from 2000 to 2010 were identified. Pathology was prospectively reviewed by a faculty gynecologic pathologist. Treatment planning was discussed and documented at our weekly multidisciplinary tumor board conference. Data was retrospectively extracted from computerized medical records. Results: 344 (86%) of 401 women underwent PDS. Optimal debulking was achieved in 278 patients (81%): 35% had CR while 46% had 0.1-1.0 cm residual disease. 56 stage IIIC pts (19%) had a suboptimal surgical outcome with ≥ 1.0 cm. Compared to those having a CR, patients with 0.1-1.0 cm residual were more likely to require splenectomy (17 v 5%; P = 0.002) and transverse colectomy (19 v 10%; P = 0.042), with comparable rates of rectosigmoid resection (41 v 39%; P = 0.712) and en bloc pelvic resection including total peritonectomy (26 v 30%; P = 0.050). Patients undergoing CR were more likely to have diaphragmatic surgery (31 v 20; P = 0.068) and lymphadenectomy (67 v 33%; P < 0.001). Conclusions: PDS is the preferred treatment of stage IIIC epithelial ovarian cancer at high-volume centers demonstrating >75% rates of optimal cytoreduction. Tumor biology may lead to the need for more aggressive upper abdominal procedures in patients with 0.1-1.0 residual. Diaphragm resection, stripping or ablation is more often required in order to achieve CR. Since subclinical macroscopic nodal metastases are often present, lymphadenectomy is also frequently performed to ensure that all possible disease has been resected.

5530 Background: In January 2001, we initiated a programatic change in our primary surgical approach to advanced ovarian carcinoma utilizing extensive upper abdominal procedures as needed to achieve maximal cytoreduction. The objective of this study was to determine the impact of incorporating these procedures on overall survival in advanced ovarian, fallopian tube, and primary peritoneal carcinomas. Methods: Two groups of patients (pts) with stage IIIC and IV ovarian, tubal, and primary peritoneal carcinoma were identified for comparison. Group 1, the control group, consisted of all 168 pts who underwent primary cytoreduction between 1/96 and 12/99. Group 2, the study group, was composed of all 209 pts who underwent primary surgery between 1/01 and 12/04, during which time a more comprehensive debulking of upper abdominal disease was used, including diaphragm peritonectomy/resection, splenectomy, distal pancreatectomy, liver resection, resection of porta hepatis tumor, and cholecystectomy. Results: Comparison between the 2 groups revealed no significant difference in age, BMI, performance status, stage, tumor grade, proportion with primary ovarian cancer, preoperative CA-125 levels, preoperative platelet counts, percentage with ascites, or type of postoperative primary chemotherapy. The only 2 variables that differed significantly between the 2 groups were percentage of pts who had extensive upper abdominal surgery and percentage of pts cytoreduced to ≤1 cm residual disease (RD). Patients in Group 2 were more likely to have undergone extensive upper abdominal procedure(s) (37% vs. 1%; P <0.001). Cytoreduction to RD ≤1 cm was achieved in 50% of Group 1 pts compared to 80% of Group 2 pts (P <0.01). Overall median survival was significantly improved in Group 2 versus Group 1 pts (58 vs. 43 mos, [P=0.042], respectively). Conclusions: The recent incorporation of extensive upper abdominal surgical procedures to increase the rate of primary cytoreduction to residual disease ≤1 cm resulted in significantly improved overall survival. A paradigm shift toward more complete primary cytoreduction can improve survival for pts with advanced ovarian, fallopian tube, and primary peritoneal carcinomas. No significant financial relationships to disclose.

Background. Diaphragmatic peritoneal metastasis by advanced epi­thelial ovarian cancer is a very common holdback precluding optimal cytoreduction. The aim of this study was to determine the rate of dia­phragmatic peritonectomy during optimal cytoreductive surgery and its role in postoperative morbidity and survival in patients with advanced ovarian cancer. Materials and methods. 100 consecutive patients with advanced epithelial ovarian cancer underwent cytoreductive surgery and were followed up prospectively (January 2009 – March 2014). Characteristics of surgery, rate of diaphragmatic peritonectomy and post operative complications were assessed. The Kaplan-Meier method was used for survival analysis. Results. The median age of the entire cohort at the time of primary cytoreduction was 58.5 years (23–83). Optimal cytoreduction was achieved in 73 cases out of 100 patients. From 73 patients in 30 cases (41.1%) upper abdominal procedures, specifically diaphragmatic peritonectomy, was performed to achieve the main goal of cytoreduction – no visible or palbable disease at the end of cytoreduction. Non-optimal cytoreduction was achieved in 27 cases. According to the Clavien-Dindo complication grading system grade I and grade II complications occurred more often in patients that underwent diaphragmatic surgery. The median overall survival from the time of diagnosis to the last follow-up or death was 28 months (range 0–63 months). The factors associated with the longest survival after primary cytoreductive surgery were the disease free interval from the primary cytoreduction of more than 19 months (n = 51) versus less than 19 months (n = 49) (95% confidence interval, 51.7–59.5; P = 0.013) and no visible or palpable residual disease at the end of cytoreduction (n = 73) versus visible or palpable residual di­sease (n = 27) (95% confidence interval, 52.7–61.2; P = 0.03). Conclusions. Based on our prospective analysis of advanced ovarian cancer patients, diaphragmatic peritonectomy is feasible and safe, ensures better rates of optimal cytoreduction and should not be an obstacle towards better survival.

5572 Background: We previously reported that preoperative CA-125 may predict primary cytoreductive outcome in patients (pts) with stage III ovarian carcinoma. We performed a contemporary analysis of the ability of preop CA-125 to predict cytoreductive outcome in advanced ovarian, tubal and peritoneal carcinoma. Methods: In 1/01, we initiated a programmatic change in our primary surgical approach to advanced gynecologic malignancies using extensive upper abdominal procedures to achieve maximal cytoreduction. We reviewed the records of all pts with advanced ovarian, tubal or peritoneal carcinoma who underwent primary cytoreduction at our institution between 1/01 and 4/05. Results: The study cohort included 277 pts. Primary disease site was: ovary; 232 (84%); tubal, 9 (3%); and peritoneum, 36 (13%). Stage was: IIIA, 6 (2%); IIIB, 12 (4%); IIIC, 215 (78%); and IV, 44 (16%). Tumor grade was: I, 6 (2%); II, 30 (11%), III, 235 (85%), and unknown, 6 (2%). Cytoreductive outcome was: no gross residual disease (RD), 68 (25%); ≤ 1 cm RD, 153 (55%); and > 1 cm RD, 56 (20%). There was no threshold CA-125 level that accurately predicted cytoreductive outcome. With CA-125 values > 500 U/mL, 50% (57/113) of pts required extensive upper abdominal surgery to achieve RD ≤ 1 cm, compared to 27% (25/93) for those with CA-125 < 500 U/mL (P = 0.03). The table demonstrates the number of pts cytoreduced to = 1 cm RD in relation to preoperative serum CA-125 and the proportion of pts who needed extensive upper abdominal surgery to achieve this degree of cytoreduction. Conclusions: After the incorporation of extensive upper abdominal procedures, preop CA-125 did not predict the primary cytoreductive outcome of pts with advanced ovarian, tubal or peritoneal carcinoma. With preoperative CA-125 > 500 U/mL, extensive upper abdominal procedures were necessary in 50% of pts to achieve residual disease ≤ 1 cm. These data may be useful as part of preoperative surgical counseling and planning. [Table: see text] No significant financial relationships to disclose.

Surgery plays a critical role in the optimal management of all stages of ovarian carcinoma. In apparent early-stage ovarian cancer, a comprehensive surgical evaluation allows stratification of patients into low- and high-risk categories. Low-risk patients may be candidates for fertility-sparing surgery and can safely avoid chemotherapy and be observed. Treatment of patients with high-risk early- or advanced-stage ovarian cancer usually requires a combined modality approach. Although it is well known that epithelial ovarian cancer is moderately chemosensitive, what distinguishes it most from other metastatic solid tumors is that surgical cytoreduction of tumor volume is highly correlated with prolongation of patient survival. Procedures such as radical pelvic surgery, bowel resection, and aggressive upper abdominal surgery are commonly required to achieve optimal cytoreduction. Women who develop recurrent disease may be eligible for a secondary cytoreductive surgery or may require a surgical intervention to palliate disease-related symptoms. For women at high risk of ovarian cancer, prophylactic bilateral salpingo-oophorectomy significantly reduces the incidence of this disease. The purpose of this article is to provide a comprehensive review of the surgical management of ovarian carcinoma. The roles of primary, interval, and secondary cytoreductive surgeries; second-look procedures; and palliative surgery are reviewed. The indications for fertility-sparing and minimally invasive surgery as well as the current guidelines for prophylactic surgery in high-risk mutation carriers are also discussed.

Purpose To compare surgeons' operative assessments of residual disease (RD) to those identified on postoperative computed tomography (CT) scans in patients with advanced ovarian carcinoma reported to have undergone optimal primary cytoreduction. Patients and Methods All patients at one of two institutions, who were scheduled to have primary surgery for presumed advanced ovarian cancer, were asked to consent to a postoperative CT scan if cytoreduction to ≤ 1 cm RD was reported. CT scan findings were graded using a qualitative analysis scale from 1 (normal) to 5 (definitely malignant). Results From January 2001 to September 2006, 285 patients were enrolled. A total of 78 patients met eligibility criteria and had postoperative CT scans. In 41 cases (52%), postoperative scan findings correlated with the surgical report of no RD more than 1 cm, and in seven cases (9%), the CT findings were indeterminate. In 10 cases (13%), more than 1 cm RD was noted by the radiologist as probably malignant, and in 20 cases (26%), definitely malignant. In these 30 cases, the radiologically reported median largest residual mass was 1.9 cm (range, 1.1 to 5.1), with RD more than 1 cm reported most commonly in the right upper quadrant (15 patients [50%]) and central abdomen (nine patients [30%]). Conclusion There was only a 52% correlation between surgeons' assessments and postoperative CT scan evaluations of RD in patients reported to have undergone optimal cytoreduction. Further study is required to determine whether this lack of correlation is due to rapid interval tumor regrowth, RD underestimated by the surgeons, and/or overestimated by the radiologists; and to determine the clinical implications of these discrepancies.

Ovarian cancer is one of the leading causes of death in the world, in 80% of cases the diagnosis is made at a late stage. In 50% of cases, a relapse occurs even after the optimal treatment has been performed. The initial treatment of ovarian cancer, regardless of the stage of the tumor process, begins with surgical treatment, and at the second stage, combined chemotherapy is performed. Since the tumor process in ovarian cancer, as a rule, local, limited in the abdominal cavity, in order to reduce the toxicity of chemotherapy drugs on the body as a whole, the alternative options for the administration of chemotherapy drugs is intra-abdominal, which allows increasing the concentration of the drug directly in the tumor locus. Purpose of research. In our study, we want to describe the laparoscopic method of placement of intra-abdominal port systems, assess the disadvantages and advantages, as well as the risks of complications in the case of port installation at the first stage of treatment (intraoperative port installation during laparotomy) and at stage 2 (laparoscopic). Materials and methods. Technically, the implantation of the intraperitoneal port system in order to carry out subsequent chemotherapy courses was carried out in two ways: 1) intraoperative; 2) laparoscopic approaches. In the first case, the installation is carried out directly after the implementation and evaluation of the surgical intervention. In the second, the intraperitoneal catheter is implanted with laparoscopic access after revision and assessment of the quality of cytoreductive surgery. The study included 77 patients with ovarian cancer stage Ic-IV, who underwent optimal cytoreduction at the first stage of treatment (residual tumor up to 1 cm in diameter). At the second stage of treatment, patients were planned to undergo intra-abdominal chemotherapy with palixaxel drugs in combination with intravenous cisplatin. Port systems in 56 cases (72.7%) were installed intraoperatively and in 21 cases (27.3%) laparoscopically. Results. In total, port systems were installed in 77 patients, of which - in 56 cases intraoperatively and in 21 cases laparoscopically. However, a total of 30 (38.9%) laparoscopic interventions were performed: in 21 (27.2%) cases a port system was installed, in 6 (7.8%) cases during laparoscopy contraindications were detected for port implantation, in 3 (3.9%) cases required a reinstallation of the port system due to complications arising after intraoperative implantation. As described above, 6 patients had contraindications for installing port systems, of which in 4 (5.2%) cases, it turned out to be a marked adhesive disease after primary cytoreduction, in two patients (2.6%) non-optimal amount of cytoreductive interventions in the first stage. Multiple metastases in the peritoneum of up to 3 cm in diameter were visualized in one patient, which did not correspond to the protocol of the operation, the patient subsequently received standard treatment; in the second case, there was a large omentum with metastatic lesions. The patient was re-operated in the optimal volume and intraperitoneal intraperitoneal port system was installed intraoperatively. Thus, in 7.8% of cases, the protocol data of the operation did not match the laparoscopic data. Conclusion. The method of laparoscopic implantation of intra-abdominal port systems is safe and effective, which in comparison with the intraoperative installation method provides several advantages: additional revision of the abdominal cavity to assess the optimality of cytoreductive surgery performed at the first stage, assessment of the degree of adhesions in the abdominal cavity, which in turn affects the uniform distribution of the drug.

16035 Background: We evaluated clinical prognostic factors in ovarian carcinoma for their association with upfront treatment in advanced stage ovarian cancer patients with effusions. Methods: Our study consists of a retrospective analysis of 214 patients with stage IIIc and IV primary ovarian cancer, primary peritoneal carcinoma and tubal cancer, treated at the Norwegian Radium Hospital (NRH) in the period 1998–2003. One-hundred and thirty-eight patients underwent primary cytoreduction, 51 patients received neoadjuvant chemotherapy followed by delayed debulking and 25 patients received only chemotherapy. Results: Residual disease of less than 1 cm was achieved in 31.9 % of primary surgery patients and in 47.1 % of delayed surgery patients. Standard taxane/platinum treatment was given to 79.7 % and 67.1 % patients in the surgery and neoadjuvant treatment group, respectively. Hazard ratio for relapse was significantly higher for upfront treatment with neoadjuvant chemotherapy (1.69, CI 95 % 1.12–2.55) compared to primary surgery and for suboptimal debulking surgery and/or suboptimal chemotherapy (1.66, CI 95 % 1.14–2.41) compared to optimal treatment. The incidence of disease-related death was also significantly higher for the neoadjuvant chemotherapy group (1.83, CI 95 % 1.21–2.79) and for patients treated suboptimally (1.50, CI 95 % 1.03–2.19). Median cancer-specific survival was 31 months for the primary surgery group and 15 months for the neoadjuvant treatment group. Conclusions: In this retrospective analysis, the two most important prognostic factors for advanced ovarian, tubal and peritoneal cancer with malignant pleural and/or abdominal effusion were surgical treatment as first-line therapy and combination of optimal tumor debulking (<1cm) and taxane/platinum chemotherapy. The role of neoadjuvant chemotherapy is still controversial. No significant financial relationships to disclose.

Objective. The objective of the present study was to determinate the impact of maximal cytoreductive surgery on progression free survival, overall survival rates and morbidity, in patients with advanced epithelial ovarian or fallopian tube cancer (stage IIIC-IV) treated in a referral cancer center. Methods. After obtaining Institutional Review Board approval, we reviewed all medical records of patients with stage IIIC–IV epithelial ovarian cancer who were managed at our institution between January 2001 and December 2008. Individual records were reviewed and the following information collected: age at surgery, date of surgery, American Society of Anestesiology (ASA) class, primary site of disease, presence of peritoneal carcinomatosis, histologic type and tumor grade, pre-operative serum CA-125 level, location and size of the largest tumor mass, the initial ascites volume (if present), all surgical procedures performed, size of residual disease after surgery. The Kaplan–Meier method was used to estimate survival curves. Cox proportional hazards regression was performed to identify independent prognostic variables for overall survival by univariate and multivariate analysis. Results. A total of 269 patients with advanced epithelial ovarian cancer were referred to our institution between January 2001 and December 2008, and of them 240 consecutive patients met inclusion criteria for the study. The median age was 58 years (range 22 to 77 years). After a median follow up of 29.8 months, the overall median survival (OS) and progression free survival (PFS) were 61.1 and 20.4 months respectively. On univariate analysis, factors significantly associated with decreased survival included: age grater than median (>60 years), presence of ascites >1000 cc, diffuse peritoneal carcinomatosis, omentum as anatomical location of the largest tumor mass, positive lymph-nodes and diameter of residual disease. On multivariate analysis confirmed the independent association of age grater than 60 years and residual disease > 5 mm with worse survival. Conclusion. Our study seems to demonstrate that a more extensive surgical approach is associated with improved survival in patients with stages IIIC-IV epithelial ovarian cancer. Age grater than 60 years and residual tumor grater than 5 mm were independently associated with a worse prognosis.