Survival from ovarian cancer depends on the resection status after primary surgery. We performed genome-wide association analyses for resection status of 7705 ovarian cancer patients, including 4954 with high-grade serous carcinoma (HGSOC), to identify variants associated with residual disease. The most significant association with resection status was observed for rs72845444, upstream of MGMT, in HGSOC (p = 3.9 × 10-8). In gene-based analyses, PPP2R5C was the most strongly associated gene in HGSOC after stage adjustment. In an independent set of 378 ovarian tumours from the AGO-OVAR 11 study, variants near MGMT and PPP2R5C correlated with methylation and transcript levels, and PPP2R5C mRNA levels predicted progression-free survival in patients with residual disease. MGMT encodes a DNA repair enzyme, and PPP2R5C encodes the B56γ subunit of the PP2A tumour suppressor. Our results link heritable variation at these two loci with resection status in HGSOC.

Chemotherapy induces histopathological tumor necrosis and fibrosis which results in macroscopic tissue changes, making surgeons' intraoperative visual evaluation of the disease distribution more difficult to interpret. The aim of the study was to assess the sensitivity, specificity, and accuracy of intraoperative laparoscopic visual evaluation of the diaphragmatic peritoneum and compare it with histopathological examination.

Patients receiving diaphragmatic peritonectomy at time of IDS were retrospectively included. The population was grouped based on the surgeon's assessment of the diaphragmatic peritoneum during diagnostic laparoscopy. Group 1 included patients with a "visually pathologic" diaphragmatic peritoneum, and group 2 included patients with a "visually dubious" diaphragmatic peritoneum. Sensitivity, specificity, predictive values, and accuracy were calculated considering the final formalin-fixed pathology as the reference standard.

155 patients were included (92 in group 1 and 63 in group 2). The accuracy rate of visual examination was 67.1%, the negative predictive value was 19%, specificity was 100%, and sensitivity was 64.3%.

NACT strongly affects the ability of the surgeon to discern between peritoneal scars and truly pathologic peritoneum. The diaphragmatic laparoscopic visual examination showed a low overall accuracy. We propose an algorithm that can guide the surgeon towards a more tailored approach to diaphragmatic peritonectomy during IDS.

Ovarian cancer is the seventh most common cancer among women and the leading cause of death in women with gynaecological malignancies. Opinions differ regarding the role of ultra-radical (extensive) cytoreductive surgery in ovarian cancer treatment.

To evaluate the effectiveness and morbidity associated with ultra-radical/extensive surgery in the management of advanced-stage epithelial ovarian cancer.

We searched CENTRAL (2021, Issue 11), MEDLINE Ovid and Embase Ovid up to November 2021. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.

Randomised controlled trials (RCTs) or non-randomised studies (NRS), analysed using multivariate methods, that compared ultra-radical/extensive and standard surgery in women with advanced primary epithelial ovarian cancer.

Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed the risk of bias. We identified three NRS and conducted meta-analyses where possible.

We identified three retrospective observational studies for inclusion in the review. Two studies included women exclusively undergoing upfront primary debulking surgery (PDS) and the other study including both PDS and interval debulking surgical (IDS) procedures. All studies were at critical risk of bias due to retrospective and non-randomised study designs. Meta-analysis of two studies, assessing 397 participants, found that women who underwent radical procedures, as part of PDS, may have a lower risk of mortality compared to women who underwent standard surgery (adjusted HR 0.60, 95% CI 0.43 to 0.82; I2 = 0%; very low-certainty evidence), but the evidence is very uncertain. The results were robust to a sensitivity analysis including women with more-extensive disease (carcinomatosis) (adjusted HR 0.61, 95% CI 0.44 to 0.85; I2 = 0%; n = 283, very low-certainty evidence), but the evidence is very uncertain. One study reported a comparison of radical versus standard surgical procedures associated with both PDS and IDS procedures, but a multivariate analysis was only undertaken for disease-free survival (DFS) and therefore the certainty of the evidence was not assessable for overall survival (OS) and remains very low. The lack of reporting of OS meant the study was at high risk of bias for selective reporting of outcomes. One study, 203 participants, found that women who underwent radical procedures as part of PDS may have a lower risk of disease progression or death compared to women who underwent standard surgery (adjusted HR 0.62, 95% CI 0.42 to 0.92; very low-certainty evidence), but the evidence is very uncertain. The results were robust to a sensitivity analysis in one study including women with carcinomatosis (adjusted HR 0.52, 95% CI 0.33 to 0.82; n = 139; very low-certainty evidence), but the evidence is very uncertain. A combined analysis in one study found that women who underwent radical procedures (using both PDS and IDS) may have an increased chance of disease progression or death than those who received standard surgery (adjusted HR 1.60, 95% CI 1.11 to 2.31; I2 = 0%; n = 527; very low-certainty evidence), but the evidence is very uncertain. In absolute and unadjusted terms, the DFS was 19.3 months in the standard surgery group, 15.8 in the PDS group and 15.9 months in the IDS group. All studies were at critical risk of bias and we only identified very low-certainty evidence for all outcomes reported in the review. Perioperative mortality, adverse events and quality of life (QoL) outcomes were either not reported or inadequately reported in the included studies. Two studies reported perioperative mortality (death within 30 days of surgery), but they did not use any statistical adjustment. In total, there were only four deaths within 30 days of surgery in both studies. All were observed in the standard surgery group, but we did not report a risk ratio (RR) to avoid potentially misleading results with so few deaths and very low-certainty evidence. Similarly, one study reported postoperative morbidity, but the authors did not use any statistical adjustment. Postoperative morbidity occurred more commonly in women who received ultra-radical surgery compared to standard surgery, but the certainty of the evidence was very low.

We found only very low-certainty evidence comparing ultra-radical surgery and standard surgery in women with advanced ovarian cancer. The evidence was limited to retrospective, NRSs and so is at critical risk of bias. The results may suggest that ultra-radical surgery could result in improved OS, but results are based on very few women who were chosen to undergo each intervention, rather than a randomised study and intention-to-treat analysis, and so the evidence is very uncertain. Results for progression/DFS were inconsistent and evidence was sparse. QoL and morbidity was incompletely or not reported in the three included studies. A separate prognostic review assessing residual disease as a prognostic factor in this area has been addressed elsewhere, which demonstrates the prognostic effect of macroscopic debulking to no macroscopic residual disease. In order to aid existing guidelines, the role of ultra-radical surgery in the management of advanced-stage ovarian cancer could be addressed through the conduct of a sufficiently powered, RCT comparing ultra-radical and standard surgery, or well-designed NRSs, if this is not possible.

Predictive models based on radiomics features are novel, highly promising approaches for gynaecological oncology. Here, we wish to assess the prognostic value of the newly discovered Radiomic Prognostic Vector (RPV) in an independent cohort of high-grade serous ovarian cancer (HGSOC) patients, treated within a Centre of Excellence, thus avoiding any bias in treatment quality.

RPV was calculated using standardised algorithms following segmentation of routine preoperative imaging of patients (n = 323) who underwent upfront debulking surgery (01/2011-07/2018). RPV was correlated with operability, survival and adjusted for well-established prognostic factors (age, postoperative residual disease, stage), and compared to previous validation models.

The distribution of low, medium and high RPV scores was 54.2% (n = 175), 33.4% (n = 108) and 12.4% (n = 40) across the cohort, respectively. High RPV scores independently associated with significantly worse progression-free survival (PFS) (HR = 1.69; 95% CI:1.06-2.71; P = 0.038), even after adjusting for stage, age, performance status and residual disease. Moreover, lower RPV was significantly associated with total macroscopic tumour clearance (OR = 2.02; 95% CI:1.56-2.62; P = 0.00647).

RPV was validated to independently identify those HGSOC patients who will not be operated tumour-free in an optimal setting, and those who will relapse early despite complete tumour clearance upfront. Further prospective, multicentre trials with a translational aspect are warranted for the incorporation of this radiomics approach into clinical routine.

Ultra-radical (UR) procedures, including splenectomy, are utilized to increase complete cytoreduction rates during Cytoreductive Surgery (CRS) performed with the aim of complete macroscopic clearance of disease. The purpose of this study was to investigate if splenectomy negatively impacts survival when undertaken during CRS for advanced ovarian cancer (AOC) and compare published splenectomy and cytoreduction rates.

A retrospective review of all consecutive patients who underwent cytoreductive surgery for AOC between 16/05/2013-28/01/2019. Survival, baseline patient characteristics, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed to reduce bias.

154 patients identified over 71 months. 97 underwent standard, 57 underwent UR surgery, 27 patients received splenectomy (17.5%) No difference was seen in overall survival (OS) between all patients (median OS 34 months (95%CI 25.9-41.1) and patients who underwent splenectomy (median OS not yet reached) (p = >0.05). After PSM for various baseline covariates, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56%) (P > 0.05). Three splenectomy specific complications occurred; one each of pancreatic tail injury, left pleural effusion and streptococcal pharyngitis during chemotherapy. We found wide variation in utilization of splenectomy in published case series; from 9% to 35%.

Splenectomy performed as part of CRS is not detrimental to survival in AOC. There is a wide variation in utilization of splenectomy in published case series with little correlation with cytoreduction rates.

Advanced ovarian cancer surgery (AOCS) frequently results in serious postoperative complications. Because managing AOCS is difficult, some standards need to be established that allow surgeons to assess the quality of treatment provided and consider what aspects should improve. This study aimed to identify quality indicators (QIs) of clinical relevance and to establish their acceptable quality limits (i.e., standard) in AOCS.

We performed a systematic search on clinical practice guidelines, consensus conferences, and reviews on the outcome and quality of AOCS to identify which QIs have clinical relevance in AOCS. We then searched the literature (from January 2006 to December 2018) for each QI in combination with the keywords of advanced ovarian cancer, surgery, outcome, and oncology. Standards for each QI were determined by statistical process control techniques. The acceptable quality limits for each QI were defined as being within the limits of the 99.8% interval, which indicated a favorable outcome.

A total of 38 studies were included. The QIs selected for AOCS were complete removal of the tumor upon visual inspection (complete cytoreductive surgery), a residual tumor of < 1 cm (optimal cytoreductive surgery), a residual tumor of > 1 cm (suboptimal cytoreductive surgery), major morbidity, and 5-year survival. The rates of complete cytoreductive surgery, optimal cytoreductive surgery, suboptimal cytoreductive surgery, morbidity, and 5-year survival had quality limits of < 27%, < 23%, > 39%, > 33%, and < 27%, respectively.

Our results provide a general view of clinical indicators for AOCS. Acceptable quality limits that can be considered as standards were established.

Debulking surgery is the key step of advanced stage ovarian cancer treatment with chemotherapy. The quality of surgical resection is the main prognosis factor, thus a complete resection must be achieved (grade A) in an expert center (grade B). Surgery for stage IV is possible and has a benefit in case of complete peritoneal resection (LoE3). Pelvic and aortic lymphadenectomies are recommended in case of clinical or radiological suspicious lymph nodes (grade B). In absence of clinical or radiological suspicious lymph nodes and in case of complete peritoneal resection during initial debulking surgery, lymphadenectomy can be omitted because it won't change nor medical treatment nor overall survival (grade B). Neoadjuvant chemotherapy can be proposed in case of: impossibility to perform initial complete surgical resection (grade B) ; alteration of general state or co-morbidities or elderly patient (in order to decrease morbidity and increase quality of life) (grade B); stage IV with multiple intra-hepatic or pulmonary metastasis or important ascites with miliary (grade B). In case of stage III or IV ovarian cancer diagnosed on a biopsy during prior laparotomy, a neoadjuvant chemotherapy and interval debulking surgery should be preferred (gradeC). In case of palliative surgery or peroperative impossibility to perform a complete resection, no data regarding the type of surgery to perform influencing survival or quality of life is available. Peritoneal carcinosis description before resection and residual disease at the end of the surgery should be reported (size, location and reason of non-extirpability) (grade B). A score of peritoneal carcinosis such as Peritoneal Carcinosis Index (PCI) should be used in order to objectively evaluate the tumoral burden (gradeC). A standardized operative report is recommended (gradeC).

To determine which descriptors of cytoreductive surgical extent in advanced ovarian cancer (AOC) best predict postoperative morbidity.

Retrospective notes review.

A gynaecological cancer centre in the UK.

Six hundred and eight women operated on for AOC over a period of 114 months at a tertiary cancer centre, between 16 August 2007 and 16 February 2017.

Outcome data were analysed by six approaches to classify the extent of surgery: standard/ultra-radical surgery; standard/radical/supra-radical surgery; presence/absence of gastrointestinal resections; low/intermediate/high surgical complexity score (SCS); presence of bowel anastomoses and/or diaphragmatic surgery; and the presence/absence of multiple bowel resections.

Major (grades 3-5) postoperative morbidity and mortality.

Forty-three (7.1%) patients experienced major complications. Grade-5 complications occurred in six patients (1.0%). Patients who underwent multiple bowel resections had a relative risk (RR) of 7.73 (95% confidence interval, 95% CI 3.92-15.26), patients with a high SCS had an RR of 6.12 (95% CI 3.25-11.52), patients with diaphragmatic surgery and gastrointestinal anastomosis had an RR of 5.57 (95% CI 2.65-11.72), patients with 'any gastrointestinal resection' had an RR of 4.69 (95% CI 2.66-8.24), patients with ultra-radical surgery had an RR of 4.65 (95% CI 2.26-8.79), and patients with supra-radical surgery had an RR of 4.20 (95% CI 2.35-7.51) of grades 3-5 morbidity, compared with patients undergoing standard surgery as defined by the National Institute for Health and Care Excellence (NICE) in the UK. No significant difference was seen in the rate of major morbidity between standard (6/59, 10.2%) and ultra-radical (9/81, 11.1%) surgery within the cohort who had intermediate complex surgery (P > 0.05).

The numbers of procedures performed significantly correlate with major morbidity. The number of procedures performed better predicted major postoperative morbidity than the performance of certain 'high risk' procedures. We recommend using SCS to define a higher risk operation. NICE should re-evaluate the use of the term 'ultra-radical' surgery.

Multiple bowel resection is the best predictor of morbidity and is more predictive than 'ultra-radical surgery'.

To examine prospectively the accuracy of ultrasound in predicting rectosigmoid tumor infiltration in patients with epithelial ovarian cancer.

Patients referred for a suspicious pelvic mass between 2012 and 2014 were examined by ultrasound following the standard protocol for assessment of tumor infiltration. Of the 245 patients examined, 191 had proven ovarian cancer and underwent primary surgery and were included in the analysis. Patients with apparently benign or inoperable disease were excluded. Rectosigmoid infiltration was evaluated by histopathology or according to perioperative findings. Clinical, pathological and laboratory parameters were analyzed as factors potentially affecting the sensitivity and specificity of sonography.

The sensitivity of ultrasound in detecting rectosigmoid infiltration in patients with ovarian cancer was 86.3%, with specificity of 95.8%, positive predictive value of 92.6%, negative predictive value of 91.9% and overall accuracy of 92.1%.

Ultrasound is a highly accurate method for detecting rectosigmoid tumor infiltration in ovarian cancer patients, and thus, can be used for planning adequate management, including patient consultation, surgical team planning, suitable operating time and postoperative care. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The aim of this study was to document the need of including the perigastric area when performing omentectomy in patients with stage III to IV serous epithelial ovarian tumors.

Patients undergoing omentectomy in the setting of surgery for advanced epithelial serous ovarian cancer between February and September 2015 were included. Patients with macroscopic involvement of the perigastric area, nonepithelial serous tumors, and recurrences of ovarian cancer were excluded. The perigastric area was isolated and comprehensively processed for pathological examination.

Twenty-four patients were included. Six patients underwent primary debulking surgery, and 18 patients underwent an interval debulking surgery. The mean number of pathologic blocks in the perigastric area was 24 (range, 8-41). Microscopic involvement of the perigastric omentum area was found in 62.5% of the cases. One patient had a low-grade serous carcinoma, with microscopic involvement of the perigastric area. Among the 23 patients with a high-grade serous carcinoma, 10 (83%) of 12 patients with a gross involvement of the rest of the omentum had a microscopic involvement of the perigastric area. The presence of microscopic disease in the perigastric arcade was found in 4 (36.3%) of 11 patients with a macroscopically normal omentum.

In this study, evidence is given that total omentectomy including the perigastric area is a necessary component of complete cytoreductive surgery in advanced ovarian cancer, whatever the macroscopic appearance of the omentum.

To describe the technique and evaluate the feasibility, efficacy and morbidity of the Laparoscopic En-Bloc Resection of the Pelvis (L-EnBRP) during Visceral-Peritoneal Debulking (VPD) at time of interval surgery.

This report is part of a prospective non randomized study (service evaluation protocol) on the feasibility and safety of laparoscopy in patients with stage IIIC-IV ovarian cancer and gross residual disease following neoadjuvant chemotherapy. Primary endpoints of this part of the study were the feasibility (rate of patients in whom the surgery could be completed by laparoscopy), efficacy (rate of patients ended with a complete resection) and morbidity (number of patients that suffered complications specifically associated to the procedure) of L-EnBRP. The results were compared between patients in group 1 (L-EnBRP+L-VPD), group 2 (L-EnBRP+VPD) and group 3 (VPD).

Eighteen patients were in group 1, 8 in group 2 and 32 in group 3. Feasibility of L-EnBRP was 45% (26 patients out of 58), efficacy was 100% of the pelvic disease (94.4% overall disease) and morbidity was 5.5%. Main cause for conversion to laparotomy was high tumor load on diaphragm and/or mesentery. All but one patient had a complete resection (CR) of the disease. Group 1 patients had significantly earlier hospital discharge, lower blood loss and reduced overall morbidity than group 2 and 3.

L-EnBRP was feasible in almost half of the patients. In these patients a CR was achieved with a low morbidity rate. The latter was significantly decreased when compared to the patients who had a laparotomy.

Describing the pattern of and reasons for post-operative tumor residuals in patients with advanced epithelial ovarian cancer (AOC) operated in a specialized gynecologic cancer center following a strategy of maximum upfront debulking followed by systemic chemotherapy.

All consecutive AOC-patients treated between 2005 and 2015 due to stages FIGO IIIB/IV were included in this single-center analysis.

739 patients were included in this analysis. In 81 (11.0%) patients, chemotherapy had already started before referral. Of the remaining 658 patients, upfront debulking was indicated in 578 patients (87.8%), while 80 patients (12.8%) were classified ineligible for upfront debulking; mostly due to comorbidities. A complete tumor resection was achieved in 66.1% of the 578 patients with upfront surgery, 25.4% had residuals 1-10mm and 8.5% had residuals exceeding 10mm, and 12.5% of patients had multifocal residual disease. Most common localization was small bowel mesentery and serosa (79.8%), porta hepatis/hepatoduodenal ligament (10.1%), liver parenchyma (4.3%), pancreas (8.0%), gastric serosa (3.2%), and tumor surrounding/infiltrating the truncus coeliacus (2.7%); 14.9% of the patients had non-resectable supra diaphragmatic lesions. Size of residual tumor was significantly associated with progression-free and overall survival.

Upfront debulking for AOC followed by systemic chemotherapy was our main treatment strategy in almost 90% of all patients. The majority experienced a benefit by this approach; while 11.7% of patients probably did not. Understanding sites and reason for residual disease may help to develop adequate surgical training programs but also to identify patients that would better benefit from alternative treatment strategies.

While there is an ongoing debate regarding the timing of the maximal surgical effort in epithelial ovarian cancer, it is well established that patients with suboptimal tumor debulking derive no benefit from the surgical procedure. The amount of residual disease after cytoreductive surgery has been repeatedly identified as a strong predictor of survival, and accordingly, the surgical effort to achieve the goal of complete gross tumor resection has been constantly evolving. Centers that have adopted the concept of radical surgery in patients with advanced ovarian cancer have reported improvements in their patients' survival. In addition to the expected improvements in the pharmacologic treatment of this disease, some of the next challenges in the surgical management of ovarian cancer include the preoperative prediction of suboptimal debulking, improving the drug delivery to the tumor, and increasing access to centers of excellence in ovarian cancer regardless of geographical, financial, or other social barriers. This review will discuss an update on the role of surgery in the treatment of primary epithelial ovarian cancer as it has evolved since the emergence of the concept of surgical cytoreduction.

Although the standard of care after recurrence of epithelial ovarian cancer (EOC) is chemotherapy, increasing data suggest that combining cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising option for patients with recurrent EOC. Our aim was to determine the prognostic value of the addition of HIPEC to secondary cytoreductive surgery (SCR) in recurrent EOC.

We analyzed a series of 79 patients with platinum-sensitive recurrent EOC who were treated from May 2000 to January 2014. Fifty patients who underwent SCR were compared to 29 who had SCR in combination with HIPEC.

The SCR group had a higher median age (58.4 years) compared to the SCR + HIPEC group (51.6 years) (p = 0.006). The median hospital stay length was longer for SCR + HIPEC versus SCR patients (11 and 8 days, respectively; p = 0.009). More subjects experienced National Cancer Institute grade III-IV morbidity in the SCR + HIPEC group (34.5 %) compared to the SCR group (10.6 %) (p = 0.015). Conversely, there were no deaths in the SCR + HIPEC group and 2 (4.0 %) deaths the SCR group. The median disease-free survival did not differ between SCR and SCR + HIPEC patients (18.6 and 15.8 months, respectively; p = 0.82); nor did median overall survival (59.3 and 58.3 months, respectively; p = 0.95). The presence of carcinomatosis was the only variable that remained linked to a higher risk of recurrence and death in the multivariate analysis.

Our data suggest that the addition of HIPEC to cytoreduction in patients with recurrent platinum-sensitive EOC does not improve survival.

Our objective was to review the published experiences of the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced and recurrent ovarian cancer with a focus on survival outcomes.

A search of the PubMed database (2008-2014) for articles specifically addressing the topic "HIPEC and ovarian cancer" was performed. We found a total of 22 publications that included 1450 patients. A final group of eleven studies (248 patients with advanced ovarian cancer) and eight publications (499 patients with recurrent sensitive ovarian cancer) that included information about survival were reviewed.

Among patients with primary ovarian cancer who were treated with primary debulking and HIPEC, the weighted median overall survival was 37.3 months (range 27-78), the median disease-free survival was 14.4 months (range 12-30), and the 5-yr-survival rate was 40% (range 28-72). In the recurrent cohort, the overall survival after HIPEC was 36.5 months (range 23-62), and the median disease-free survival was 20.2 months (range 11-29). The rates of severe morbidity were 25 and 19% in the primary and recurrent groups, respectively.

Although randomized trials are ongoing, the recently published retrospective data regarding the use of HIPEC for primary advanced and for recurrent ovarian cancer do not indicate any apparent advantage of this treatment in terms of the survival outcomes in these patients. Therefore, HIPEC cannot be considered a standard treatment and should not be offered outside of clinical trials.

To quantify the impact of complete cytoreduction to no gross residual disease on overall survival among patients with advanced-stage ovarian cancer treated during the platinum-taxane era.

PubMed and Cochrane Library databases were searched for all articles on primary cytoreductive surgery for advanced-stage ovarian cancer published from 1/1996 to 7/2011. A total of 18 relevant studies (13,257 patients) were identified for analysis. Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median survival time of clinical and treatment-related factors.

The mean weighted median overall survival time for all cohorts was 44.4 months (range, 27.6-66.9 months). Simple linear regression analysis revealed that residual disease, stage IV disease, and use of intraperitoneal chemotherapy were significantly associated with median survival time. After controlling for other factors on multiple linear regression analysis, each 10% increase in the proportion of patients undergoing complete cytoreduction to no gross residual disease was associated with a significant and independent 2.3-month increase (95%CI = 0.6-4.0, p = 0.011) in cohort median survival compared to a 1.8-month increase (95%CI = 0.6-3.0, p = 0.004) in cohort median survival for optimal cytoreduction (residual disease≤1cm). Each 10% increase in the proportion of patients receiving intraperitoneal chemotherapy was associated with a significant and independent 3.9-month increase (95%CI = 1.1-6.8, p=0.008) in median cohort survival time.

For advanced-stage ovarian cancer treated during the platinum-taxane era, the proportions of patients left with no gross residual disease and receiving intraperitoneal chemotherapy are independently significant factors associated with the most favorable cohort survival time.

Whilst cytoreductive surgery is the mainstay treatment for primary ovarian cancer, its role in relapse is still unclear. Surgery in platinum-sensitive recurrent ovarian cancer might be beneficial if it results in complete resection of the disease. Clinical scores could help to identify suitable patients. Level I evidence is still missing; however, two randomized trials (DESKTOP III and GOG 213) are ongoing.

To analyze the impact of radical cytoreductive surgery-as part of primary tumor debulking-on the amount of residual tumor and survival in patients with advanced ovarian cancer and to evaluate the prognostic significance of no gross residual disease (RD) after surgery.

Medical records of 203 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIC-IV ovarian cancer were reviewed. All patients underwent primary cytoreductive surgery followed by taxane- and platinum-based chemotherapy. Various clinicopathologic characteristics were collected.

Of 203 patients, 119 patients underwent simple surgery, while radical surgery was performed in 84 patients. Advanced age (hazard ratio [HR] 1.04, 95 % confidence interval [CI] 1.02-1.06, P < 0.01), FIGO stage IV disease (HR 3.61, 95 % CI 1.48-8.83, P < 0.01), and grossly visible RD (HR 3.24, 95 % CI 1.90-5.53, P < 0.01) were identified as significant factors associated with poor prognosis in the entire cohort of 203 patients. Radical surgery (HR 0.56, 95 % CI 0.37-0.87, P = 0.01) was associated with improved survival. In the subgroup of patients with stage IIIC disease with peritoneal carcinomatosis, independent prognostic factors were advanced age (HR 1.04, 95 % CI 1.01-1.06, P = 0.01), radical surgery (HR 0.58, 95 % CI 0.35-0.96, P = 0.03), and grossly visible RD (HR 2.86, 95 % CI 1.55-5.30, P < 0.01). Patients with no gross RD had the longest overall survival (86 months) compared with RD 0.1-1 cm (46 months) and RD >1.0 cm (37 months) (P < 0.01).

No gross RD is associated with improved overall survival, and radical surgery was effective for achieving no gross RD.

Over the past 40 years, the survival of patients with advanced ovarian cancer has greatly improved due to the introduction of combination chemotherapy with platinum and paclitaxel as standard front-line treatment and the progressive incorporation of increasing degrees of maximal cytoreductive surgery. The designation of "optimal" surgical cytoreduction has evolved from residual disease ≤ 1 cm to no gross residual disease. There is a growing body of evidence that patients with no gross residual disease have better survival than those with optimal but visible residual disease. In order to achieve this, more radical cytoreductive procedures such as radical pelvic resection and extensive upper abdominal procedures are increasingly performed. However, some investigators still suggest that tumor biology is a major determinant in survival and that optimal surgery cannot fully compensate for tumor biology. The aim of this review is to outline the theoretical rationale and historical evolution of primary cytoreductive surgery, to re-evaluate the preferred surgical objective and procedures commonly required to achieve optimal cytoreduction in the platinum/taxane era based on contemporary evidence, and to redefine the concept of "optimal" residual disease within the context of future surgical developments and analysis of treatment outcomes.

Risk of malignancy index (RMI), based on a serum cancer antigen 125 level, ultrasound findings and menopausal status, is used to discriminate ovarian cancer from benign pelvic mass. In Denmark, patients with pelvic mass and RMI ≥200 are referred to tertiary gynecologic oncology centers according to the national guidelines for ovarian cancer treatment. The guidelines include recalculation of RMI at the tertiary center and, if indicated, positron emission tomography/computed tomography and fast-track surgery by specialists in cancer surgery. The aim of this study was to validate the use of RMI ≥200 as a tool for preoperative identification of ovarian cancer at a tertiary center.

Prospective observational study.

A tertiary center in Copenhagen, Denmark.

One thousand one hundred and fifty-nine women with pelvic mass.

The RMI was calculated after ultrasound examination and blood sampling for serum cancer antigen 125 analysis within two weeks before surgery.

Sensitivity, specificity, positive and negative predictive values were calculated to evaluate the ability of RMI to distinguish between ovarian cancer and benign pelvic mass.

There were 778 women diagnosed with benign pelvic mass, while 251 had ovarian cancer and 74 had borderline ovarian tumor. Fifty-six women were diagnosed with other forms of cancer. Sensitivity and specificity for ovarian cancer vs. benign pelvic mass for RMI ≥200 were 92 and 82%, respectively. Corresponding positive and negative predictive values were 62 and 97%.

Risk of malignancy index ≥200 is a reliable tool for identifying patients with ovarian cancer pelvic masses at a tertiary centre to select patients for further preoperative examinations.

To assess the survival impact of initial disease distribution on patients with stage III epithelial ovarian cancer (EOC) cytoreduced to microscopic residual.

We reviewed data from 417 stage III EOC patients cytoreduced to microscopic disease and given adjuvant intravenous platinum/paclitaxel on one of three randomized Gynecologic Oncology Group (GOG) trials. We subdivided patients into three groups based on preoperative disease burden: (1) minimal disease (MD) defined by pelvic tumor and retroperitoneal metastasis (2) abdominal peritoneal disease (APD) with disease limited to the pelvis, retroperitoneum, lower abdomen and omentum; and (3) upper abdominal disease (UAD) with disease affecting the diaphragm, spleen, liver or pancreas. We assessed the survival impact of potential prognostic factors, focusing on initial disease distribution using a proportional hazards model and estimated Kaplan-Meier survival curves.

The study groups had similar clinicopathologic characteristics. Median overall survival (OS) was not reached in MD patients compared to 80 and 56 months in the APD and UAD groups (P<0.05). The five-year survival percentages for MD, APD, and UAD were 67%, 63%, and 45%. In multivariate analysis, the UAD group had a significantly worse prognosis than MD and APD both individually and combined (Progression Free Survival (PFS) Hazards Ratio (HR) 1.44; P=0.008 and OS HR 1.77; P=0.0004 compared to MD+APD).

Stage III EOC patients with initial disease in the upper abdomen have a worse prognosis despite cytoreductive surgery to microscopic residual implying that factors beyond cytoreductive effort are important in predicting survival.

Ovarian cancer is the sixth most common cancer among women and the leading cause of death in women with gynaecological malignancies. Opinions differ regarding the role of ultra-radical (extensive) cytoreductive surgery in ovarian cancer treatment. 

To evaluate the effectiveness and morbidity associated with ultra-radical/extensive surgery in the management of advanced stage ovarian cancer.

We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE and EMBASE (up to November 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.

Randomised controlled trials (RCTs) or non-randomised studies, analysed using multivariate methods, that compared ultra-radical/extensive and standard surgery in adult women with advanced primary epithelial ovarian cancer.

Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed the risk of bias. One non-randomised study was identified so no meta-analyses were performed.

One non-randomised study met our inclusion criteria. It analysed retrospective data for 194 women with stage IIIC advanced epithelial ovarian cancer who underwent either ultra-radical (extensive) or standard surgery and reported disease specific overall survival and perioperative mortality. Multivariate analysis, adjusted for prognostic factors, identified better disease specific survival among women receiving ultra-radical surgery, although this was not statistically significant (Hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.40 to 1.04). In a subset of 144 women with carcinomatosis, those who underwent ultra-radical surgery had significantly better disease specific survival than women who underwent standard surgery (adjusted HR = 0.64, 95% CI 0.41 to 0.98). Progression-free survival and quality of life (QoL) were not reported and adverse events were incompletely documented. The study was at high risk of bias.

We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival.  It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery.In order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required.