Is perioperative visual estimation of intra-abdominal tumor spread reliable in ovarian cancer surgery after neoadjuvant chemotherapy? Influence of Intraperitoneal Dissemination Assessed by Laparoscopy on Prognosis of Advanced Ovarian Cancer: An Exploratory Analysis of a Single-Institution Experience Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial Neoadjuvant chemotherapy in advanced ovarian cancer: On what do we agree and disagree? Differences in Regional Diagnostic Strategies and in Intended Versus Actual First-Line Treatment of Patients With Advanced Ovarian Cancer in Denmark Evaluation of single-port laparoscopy for peritoneal carcinomatosis assessment in advanced ovarian cancer. Neoadjuvant chemotherapy or primary debulking surgery in advanced ovarian carcinoma: a retrospective analysis of 285 patients. A multicentric trial (Olympia-MITO 13) on the accuracy of laparoscopy to assess peritoneal spread in ovarian cancer. Role of laparoscopy to assess the chance of optimal cytoreductive surgery in advanced ovarian cancer: a pilot study. Accuracy and Reproducibility of the Peritoneal Cancer Index in Advanced Ovarian Cancer During Laparoscopy and Laparotomy Secondary surgical cytoreduction for advanced ovarian carcinoma. Diagnostic accuracy of hand-assisted laparoscopy in predicting resectability of peritoneal carcinomatosis from gynecological malignancies. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial ovarian cancer: a prospective study. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. Laparoscopy to predict the result of primary cytoreductive surgery in advanced ovarian cancer patients (LapOvCa-trial): a multicentre randomized controlled study
OBJECTIVE Most cases of epithelial ovarian cancer ( EOC ) are diagnosed in an advanced stage . When the disease has spread intra-abdominally , complete surgical tumor debulking is the single most important prognostic factor . Neoadjuvant chemotherapy ( NACT ) before surgery can cause fibrosis and adhesions in the peritoneal cavity and may interfere with the perioperative evaluation of tumor spread . In this prospect i ve study , we evaluated whether perioperative visual assessment of tumor dissemination is similar in patients undergoing primary and interval surgery for EOC . METHODS Systematic visual evaluation of tumor spread was performed at the start of primary surgery/diagnostic laparoscopy  ( n=39 ) or interval surgery ( n=16 ) . Peritoneal cavity was divided into 22 anatomical regions . The carefully documented results of the visual assessment were compared with the histopathological analysis of 220 biopsies from primary and 92 biopsies from interval surgery . RESULTS In primary surgery , perioperative visual estimation of tumor spread showed 98 % sensitivity , 76 % specificity and 95 % accuracy compared to histopathology . The corresponding figures after NACT were 86 % , 76 % and 84 % , respectively . The difference in sensitivity and accuracy in primary and interval operations was statistically significant ( p<0.001 ) . CONCLUSIONS In advanced EOC , microscopically carcinomatous areas have a benign visual appearance more often after NACT than at primary surgery . NACT may interfere with the perioperative visual evaluation of tumor spread and thus lead to incomplete resection of tumor in potentially resectable areas Purpose The aim of this study was to investigate whether preoperative laparoscopic evaluation of the dissemination of disease may have an independent impact on survival in advanced epithelial ovarian cancer ( AEOC ) . Methods All AEOC women were su bmi tted to staging laparoscopy before receiving primary debulking surgery ( PDS ) or neoadjuvant chemotherapy ( NACT ) . All study women received a laparoscopic score ( predictive index value [ PIV ] ) and were stratified into three groups based on volume of disease : high tumor load ( HTL ) for PIV ≥8 , intermediate tumor load ( ITL ) for PIV equal to 6 and 4 , and low tumor load ( LTL ) for PIV < 4 . Surgical and survival outcome were evaluated by univariate and multivariate analysis . Results Among 348 consecutive patients , almost half ( 48.0 % ) had an HTL . Among 165 cases receiving PDS , residual tumor ( RT ) was as follows : no gross residual in 102 patients ( 61.8 % ) ; RT ≤1 cm in 48 patients ( 29.1 % ) and RT > 1 cm in 15 cases ( 9.1 % ) . When stratifying the whole population according to laparoscopic tumor load , the median progression-free survival ( PFS ) was 33 months for LTL , 18 months for ITL , and 14 months for HTL ( p = 0.0001 ) . The median overall survival ( OS ) with respect to laparoscopic PIV was not reached for LTL , whereas it was 47 months for ITL and 33 months for HTL , respectively ( p = 0.0001 ) . At multivariate analysis , tumor load stratified by PIV retained an independent prognostic value on PFS and OS , together with RT and performance status . Conclusions RT remains an important prognostic factor in patients with AEOC , but tumor dissemination can play a role in determining prognosis in these women OBJECTIVE The purpose of this study was to vali date the performance of a laparoscopy-based model to predict optimal cytoreduction in advanced ovarian cancer patients . STUDY DESIGN In a consecutive prospect i ve series of 113 advanced ovarian cancer patients , the presence of omental cake , peritoneal and diaphragmatic extensive carcinosis , mesenteric retraction , bowel and stomach infiltration , spleen and /or liver superficial metastasis were investigated by laparoscopy . By summing the scores relative to all parameters , a laparoscopic assessment for each patient ( total predictive index value = PIV ) has been calculated . Sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and accuracy have been calculated for each PIV . RESULTS The overall accuracy rate of the laparoscopic procedure ranged between 77.3 and 100 % . At a PIV > /= 8 the probability of optimally resecting the disease at laparotomy is equal to 0 , and the rate of unnecessary exploratory laparotomy is 40.5 % . CONCLUSION The proposed laparoscopic model appears a reliable and flexible tool to predict optimal cytoreduction in advanced ovarian cancer BACKGROUND The international st and ard of care for women with suspected advanced ovarian cancer is surgical debulking followed by platinum-based chemotherapy . We aim ed to establish whether use of platinum-based primary chemotherapy followed by delayed surgery was an effective and safe alternative treatment regimen . METHODS In this phase 3 , non-inferiority , r and omised , controlled trial ( CHORUS ) undertaken in 87 hospitals in the UK and New Zeal and , we enrolled women with suspected stage III or IV ovarian cancer . We r and omly assigned women ( 1:1 ) either to undergo primary surgery followed by six cycles of chemotherapy , or to three cycles of primary chemotherapy , then surgery , followed by three more cycles of completion chemotherapy . Each 3-week cycle consisted of carboplatin AUC5 or AUC6 plus paclitaxel 175 mg/m(2 ) , or an alternative carboplatin combination regimen , or carboplatin monotherapy . We did the r and om assignment by use of a minimisation method with a r and om element , and stratified participants according to the r and omising centre , largest radiological tumour size , clinical stage , and prespecified chemotherapy regimen . Patients and investigators were not masked to group assignment . The primary outcome measure was overall survival . Primary analyses were done in the intention-to-treat population . To establish non-inferiority , the upper bound of a one-sided 90 % CI for the hazard ratio ( HR ) had to be less than 1.18 . This trial is registered , number IS RCT N74802813 , and is closed to new participants . FINDINGS Between March 1 , 2004 , and Aug 30 , 2010 , we r and omly assigned 552 women to treatment . Of the 550 women who were eligible , 276 were assigned to primary surgery and 274 to primary chemotherapy . All were included in the intention-to-treat analysis ; 251 assigned to primary surgery and 253 to primary chemotherapy were included in the per- protocol analysis . As of May 31 , 2014 , 451 deaths had occurred : 231 in the primary -surgery group versus 220 in the primary -chemotherapy group . Median overall survival was 22.6 months in the primary -surgery group versus 24.1 months in primary chemotherapy . The HR for death was 0.87 in favour of primary chemotherapy , with the upper bound of the one-sided 90 % CI 0.98 ( 95 % CI 0.72 - 1.05 ) . Grade 3 or 4 postoperative adverse events and deaths within 28 days after surgery were more common in the primary -surgery group than in the primary -chemotherapy group ( 60 [ 24 % ] of 252 women vs 30 [ 14 % ] of 209 , p=0.0007 , and 14 women [ 6 % ] vs 1 woman [ < 1 % ] , p=0.001 ) . The most common grade 3 or 4 postoperative adverse event was haemorrhage in both groups ( 8 women [ 3 % ] in the primary -surgery group vs 14 [ 6 % ] in the primary -chemotherapy group ) . 110 ( 49 % ) of 225 women receiving primary surgery and 102 ( 40 % ) of 253 receiving primary chemotherapy had a grade 3 or 4 chemotherapy related toxic effect ( p=0.0654 ) , mostly uncomplicated neutropenia ( 20 % and 16 % , respectively ) . One fatal toxic effect , neutropenic sepsis , occurred in the primary -chemotherapy group . INTERPRETATION In women with stage III or IV ovarian cancer , survival with primary chemotherapy is non-inferior to primary surgery . In this study population , giving primary chemotherapy before surgery is an acceptable st and ard of care for women with advanced ovarian cancer . FUNDING Cancer Research UK and the Royal College of Obstetricians and Gynaecologists Following the recent publication of the r and omized study in stages IIIC and IV ovarian cancer of the European Organisation for Treatment and Research —Gynaecological Cancer Group ( EORTC-GCG ) and the National Cancer Institute of Canada ( NCIC ) Clinical Trials Group [ 1 ] , a lot of controversy on the role of neoadjuvant chemotherapy and primary debulking in advanced ovarian cancer emerged [ 2–5 ] . At the recent Gynecologic Cancer InterGroup ( GCIG ) consensus conference a majority of 21 out of 23 member groups supported the statement : “ Delayed primary surgery after neoadjuvant chemotherapy is an option for selected patients with stage IIIC or IV ovarian cancer as included in the EORTC55971 ” [ 6 ] . However , two member groups ( the Arbeitsgemeinschaft Gynaekologische Onkologie [ AGO ] Study Group Germany and the AGO-Austria ) voted for the minority statement “ Neoadjuvant chemotherapy can not be regarded as adequate routine therapy of advanced ovarian cancer and should be limited to selected patients with very advanced International Federation ofGynecology and Obstetrics stage IIIC or IV disease and contraindications against upfront debulking surgery or tumor dissemination , implying no chance for complete resection . ” The latter was also the official statement of the German Society of Gynecologic Oncology [ 7 ] . The authors discussed the role of neoadjuvant chemotherapy in advanced ovarian cancer on many conferences . However , the authors believe it is important to summarize in this paper in which groups of patients we agree that primary debulking should be the preferred treatment strategy and in which patients will probably not benefit from upfront surgery and alternative strategies as neoadjuvant chemotherapy followed by interval debulking should be preferred . Furthermore , we summarize in which groups of patients with advanced ovarian cancer we disagree on the preferred treatment policy . The opinions expressed in this paper are solely the opinion of the authors and not of the Cooperative groups or Societies the authors are member of Background Triage of patients with ovarian cancer to primary debulking surgery ( PDS ) or neoadjuvant chemotherapy ( NACT )  is challenging . In Denmark , the use of NACT has increased , but substantial differences in the use of NACT or PDS exist among centers . We aim ed to characterize the differences between intended and actual first-line treatments in addition to the differences in the triage process among the centers and to evaluate the different diagnostic modalities and the clinical aspects ’ influence in the triage process . Material s and Methods From 4 centers , forms containing data about the diagnostic process and intended treatment were prospect ively collected and merged with data from the Danish Gynecological Cancer Data base and medical records . Results Of the 671 completed forms , 540 patients had stage IIIC or IV epithelial ovarian cancer . Of the 238 ( 44 % ) referred to PDS  , 91 % received PDS and 4 % never had debulking surgery . Of the 288 patients ( 53 % ) referred to NACT  , 44 % were never debulked . Fourteen patients ( 3 % ) were referred to palliative treatment . The use of different imaging modalities , diagnostic laparoscopy , and laparotomy varied significantly among the centers . Diagnostic surgical procedures were considered to be most influential in the triage process . Regardless of the intended first-line treatment or center , the tumor size and dissemination was the most influential clinical aspect . Conclusions In Denmark , substantial differences exist between intended and actual first-line treatments as well as in the diagnostic process and use of NACT , calling for further discussion on diagnostic strategy and therapeutically approach for patients with advanced ovarian cancer OBJECTIVES Ovarian cancers are usually diagnosed at an advanced stage . The extent of the disease before surgery partly determines the ability to perform a complete cytoreduction . The peritoneal cancer index ( PCI ) is used to evaluate peritoneal carcinomatosis and has been vali date d in ovarian cancer and correlated with resectability . The aim of our study was to assess the feasibility of single-port laparoscopy ( SPL ) for suspicion of advanced ovarian cancer and to describe the ability to calculate the PCI score at the time of laparoscopy . STUDY DESIGN Between February 2011 and January 2013 , 33 patients underwent SPL for suspected advanced ovarian cancer . Individual records for all patients were prospect ively review ed and analyzed . For each patient , we determined the PCI score . RESULTS 33 patients underwent initial SPL  , 85 % had increased carcinological markers and 67 % a radiological suspicion of peritoneal carcinomatosis . The median operative time was 90min . During SPL , 76 % of patients underwent ascites evacuation ; all patients had peritoneal cytology and peritoneal biopsies . Only 3 patients experienced perioperative complications . Two open conversions were recorded . Quotation of the PCI score was possible for all patients . Eighteen patients ( 55 % ) had a PCI score below 10 ; one had a maximal PCI score of 39 . The PCI score was null for 9 patients . Non-browsing areas marked 8 procedures . CONCLUSIONS SPL appeared to be feasible , with satisfying immediate results and postoperative outcome , compared to conventional laparoscopy . It allowed a satisfying exploration of the abdomino-pelvic cavity and a good description of peritoneal carcinomatosis with only a few non-browsing PCI areas OBJECTIVE This study was aim ed at comparison of neoadjuvant chemotherapy with primary debulking surgery in advanced ovarian carcinoma . METHODS Retrospective analysis of 285 patients with advanced ovarian carcinoma treated between 1980 and 1997 was performed . RESULTS In the period 1980 - 1988 all patients underwent primary debulking surgery and 82 % were cytoreduced to less than 0.5 cm largest residual tumor mass ( n = 112 ) . Analysis of this group of patients showed that some subgroups of patients ( e.g. , Stage IV disease or a total metastatic tumor load of more than 1000 g prior to debulking surgery ) had a poor survival despite cytoreduction to no or less than 1 g of total residual tumor load . The complication rate was high especially in the group with unfavorable prognosis ( postoperative mortality , 6 % ) . In the period 1989 - 1997 ( n = 173 ) the patients were surgically evaluated to receive primary chemotherapy ( 43 % ) or primary debulking surgery ( 57 % ) . Prognostic variables were similar for both treatment periods . The actuarial crude survival was higher in the second time period ( 3-year crude survival of 26 % + /- 4 . 3 and 42 % + /- 4.6 for the first and second time periods , respectively ; P = 0.0001 ) . The postoperative mortality was 0 % during the second time period . From 1993 on , the decision to give neoadjuvant chemotherapy or to perform primary debulking surgery in patients with clinical ly obvious metastatic disease was made with the help of an open laparoscopy ( n = 77 ) . Median duration of the laparoscopy , blood loss , and hospital stay due to this procedure were 25 min , 10 ml , and 2 days . Primary and interval debulking surgery was performed in 36 and 63 % of this subgroup of patients , respectively . CONCLUSION In this retrospective analysis over two different time periods , crude survival was higher when treating about half of the patients with advanced ovarian carcinoma with primary chemotherapy instead of primary debulking surgery . The role of neoadjuvant chemotherapy should be evaluated in a prospect i ve r and omized study OBJECTIVE The objective of the study was to prospect ively evaluate the accuracy of laparoscopy performed in satellite centers ( SCs ) to describe intraabdominal diffusion of advanced ovarian cancer ( AOC ) . STUDY DESIGN Patients with a clinical /radiological suspicion of AOC were included in the protocol . SCs were selected among those surgeons , spending a short intensive training period at the coordinator center ( CC ) to learn the application of staging laparoscopy ( S-LPS ) in AOC . All women underwent  S-LPS at the SCs , and the surgical procedure was recorded and blindly review ed at the CC . Calculating specificity , positive and negative predictive values , and the accuracy for each parameter with respect to the CC assessed the diagnostic performance of S-LPS . The Cohen 's kappa was used to test the interobserver agreement of each parameter . RESULTS One hundred sixty-eight cases were considered eligible for the study . A per- protocol analysis was performed on 120 cases . The worst laparoscopic assessable feature was mesenteric retraction , whereas the remaining variables ranged from 99.2 % ( peritoneal carcinomatosis ) to 90 % ( bowel infiltration ) . All but 1 SC ( SC number 4 ) reached an accuracy rate of 80 % or greater for both single parameters and overall score . The Cohen 's kappa and the P value for overall predicitive index value were 0.685 and .01 , respectively , but improved to 0.773 and .388 after removing the SC number 4 from the analysis . CONCLUSION S-LPS allows an accurate and reliable assessment of intraperitoneal diffusion of disease in AOC patients in trained gynecological oncology centers OBJECTIVE To investigate whether laparoscopy can be considered as adequate and reliable as st and ard laparotomy in predicting optimal cytoreduction ( RT < or = 1 cm ) in patients with advanced ovarian cancer . METHODS From March to November 2003 , 95 patients with suspected advanced ovarian or peritoneal cancer have been evaluated . Thirty-one cases were excluded due to an anesthesiological class of risk ASA III-IV ( 51.6 % ) and for the presence of a large size mass reaching the xiphoid ( 48.4 % ) . Sixty-four patients completed the study . All patients were su bmi tted to preoperative clinico-radiological evaluation and then to both laparoscopy and st and ard longitudinal laparotomy , sequentially . Some specific preoperatively defined parameters were analyzed during each procedure in order to obtain the most accurate evaluation on the possibility to get an optimal cytoreduction . RESULTS The overall accuracy rate of laparoscopy in assessing optimal cytoreduction was 90 % . The negative predictive value ( NPV ) of the clinical -radiologic evaluation corresponded to 73 % , whereas in no case was the judgment of unresectable disease obtained by laparoscopy changed by the laparotomic approach ( NPV 100 % ) . On the contrary , an optimal debulking was achievable in 34 of 39 cases ( 87 % ) selected as completely resectable by explorative laparoscopy . CONCLUSIONS Laparoscopy can be considered super imposable to st and ard longitudinal laparotomy in identifying not optimally resectable advanced ovarian cancer patients Background The aim of this prospect i ve study was to evaluate the accuracy of the peritoneal cancer index ( PCI ) between laparoscopy and laparotomy and to evaluate the reproducibility of this index between 2 surgeons ( junior vs senior ) in advanced-stage ovarian cancer ( ASOC ) . In ASOC , the quality of cytoreductive surgery , which is the main prognostic factor , is correlated with the extent of the disease and thus with the PCI . The reliability of this scoring index between different surgeons during laparoscopy and laparotomy has not been investigated in this disease . Methods Between April 2010 and October 2011 , for each of the 29 patients undergoing complete cytoreductive surgery , 1 senior surgeon and 1 junior surgeon quantified the  PCI score  at 3 time points on the same day : during laparoscopy and during laparotomy , at the beginning and at the end . A concordance analysis was conducted with Bl and and Altman ’s method and estimated by intraclass correlation coefficients . Results There was high concordance of the PCI score between the junior and senior surgeons during the laparoscopic and laparotomic procedures : the mean differences were not significantly different from 0 ( P < 0.05 ) and 95 % limits of agreement were ±3.5 and ±3.0 , respectively . Laparoscopy underestimated the PCI score by approximately 2 points compared to the beginning of the laparotomy : the mean biases were −2.0 ( 95 % confidence interval , −2.8 to −1.2 ) for the senior surgeon and −2.2 ( 95 % confidence interval , −3.1 to 1.3 ) for the junior surgeon . Conclusions The PCI is reproducible and reliable for evaluating peritoneal spread in ASOC BACKGROUND We evaluated the effect of adding secondary cytoreductive surgery to postoperative chemotherapy on progression-free survival and overall survival among patients who had advanced ovarian cancer and residual tumor exceeding 1 cm in diameter after primary surgery . METHODS Women were enrolled within six weeks after primary surgery . If , after three cycles of postoperative paclitaxel plus cisplatin , a patient had no evidence of progressive disease , she was r and omly assigned to undergo secondary cytoreductive surgery followed by three more cycles of chemotherapy or three more cycles of chemotherapy alone . RESULTS We enrolled 550 women . After completing three cycles of postoperative chemotherapy , 216 eligible patients were r and omly assigned to receive secondary surgical cytoreduction followed by chemotherapy and 208 to receive chemotherapy alone . Surgery was declined by or medically contraindicated in 15 patients who were assigned to secondary surgery ( 7 percent ) . As of March 2003 , 296 patients had died and 82 had progressive disease . The likelihood of progression-free survival in the group assigned to secondary surgery plus chemotherapy , as compared with the chemotherapy-alone group , was 1.07 ( 95 percent confidence interval , 0.87 to 1.31 ; P=0.54 ) , and the relative risk of death was 0.99 ( 95 percent confidence interval , 0.79 to 1.24 ; P=0.92 ) . CONCLUSIONS For patients with advanced ovarian carcinoma in whom primary cytoreductive surgery was considered to be maximal , the addition of secondary cytoreductive surgery to postoperative chemotherapy with paclitaxel plus cisplatin does not improve progression-free survival or overall survival OBJECTIVES Residual disease after excision surgery is the main prognostic factor in advanced ovarian cancer . Open surgery can delay neoadjuvant chemotherapy initiation . Therefore , a minimally invasive method for evaluating resectability would be of great interest . Aim of our study is to evaluate a new technique for assessing the extent of peritoneal carcinomatosis , combining manual palpation and st and ard laparoscopy . METHODS Prospect i ve single-center study from October 2008 to January 2010 . Patients with peritoneal carcinomatosis from gynecological malignancies were investigated by st and ard laparoscopy followed by laparoscopy plus manual palpation using Lapdisc ( ® ) ( Ethicon Inc. ) , at 43 abdominopelvic sites . When both techniques indicated resectability , st and ard cytoreduction surgery was performed via a midline laparotomy . The Fagotti , modified Fagotti , and Sugarbaker scores were computed . The diagnostic performance of each evaluation criterion was assessed by computing sensitivity , specificity , positive predictive value ( PPV ) , negative predictive value ( NPV ) , and area under the receiver-operating characteristic curves ( ROC-AUCs ) . RESULTS Of the 29 included patients , 18 ( 62.1 % ) were considered to have resectable disease . Fourteen ( 14/18 , 77.8 % ) had macroscopically complete cytoreduction . With Lapdisc ( ® ) , sensitivity was 100 % , specificity 73.3 % , PPV 77.8 % , NPV 100 % , and ROC-AUC 0.87 . Corresponding values were as follows : laparoscopy , 100 % , 40 % , 60.9 % , 100 % , and 0.70 ; Fagotti and modified Fagotti scores , 100 % , 46.7 % , 63.6 % , 100 % , and 0.73 ; Sugarbaker score , 64.3 % , 93.3 % , 90 % , 73.7 % , and 0.79 . The ROC-AUCs showed significantly better performance of Lapdisc ( ® ) than of st and ard laparoscopy ( P = 0.008 ) . CONCLUSION H and -assisted laparoscopy may perform better than laparoscopy alone for predicting the resectability of peritoneal carcinomatosis by increasing the number of sites evaluated Primary surgery followed by platinum‐taxane based chemotherapy has been the st and ard therapy in advanced ovarian cancer . However , the prognostic role of complete and so‐called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined OBJECTIVE Despite correlation between the completeness of surgical cytoreduction and survival for patients with advanced ovarian cancer , relatively few undergo complete cytoreduction . This study was initiated to prospect ively determine the ability to surgically eliminate all visible disease in patients with stage IIIC and IV epithelial ovarian cancer and the associated impact on survival . METHODS Between 1990 and 1996 , 163 consecutive patients underwent primary cytoreduction .  The goal was the excision or ablation of all visible disease prior to initiation of systemic platinum-based combination chemotherapy . A multivariate analysis determined which clinical and pathologic variables influenced the probability of achieving complete cytoreduction ( logistic regression ) and survival ( Cox proportional hazards model ) . RESULTS One hundred thirty-nine patients ( 85.3 % ) underwent removal of all visible tumor , 22 ( 13.5 % ) had cytoreduction to < /=1 cm residual disease , and 2 ( 1.2 % ) had unresected bulky disease . The median and estimated 5-year survival for the entire cohort was 54 months and 48 % , respectively . The probability of achieving complete cytoreduction was influenced independently by the preoperative Gynecologic Oncology Group performance status ( 0 - 1 vs 2 - 3 , P = 0.04 ) , the number of mesenteric and intestinal serosal implants ( < /=75 vs > 75 implants , P = 0.005 ) , and stage ( IIIC vs IV , P = 0.006 ) . The probability of survival was independently influenced by age ( < /=61 vs > 61 years , P = 0.003 ) , volume of ascites ( < /=1 vs > 1 liter , P = 0.01 ) , stage ( IIIC vs IV , P = 0.04 ) , histology ( clear cell and mucinous vs all other , P = 0.03 ) , and the completeness of cytoreductive operation ( complete vs incomplete cytoreduction , P = 0.02 ) . CONCLUSIONS Complete cytoreduction is possible for the majority of patients and improves survival , even compared to operations with minimal ( < /=1 cm ) residual disease . Unless their medical condition prohibits anesthesia and surgery , patients with advanced epithelial ovarian cancer should undergo primary cytoreductive surgery with the intention of complete tumor removal BACKGROUND Primary debulking surgery before initiation of chemotherapy has been the st and ard of care for patients with advanced ovarian cancer . METHODS We r and omly assigned patients with stage IIIC or IV epithelial ovarian carcinoma , fallopian-tube carcinoma , or primary peritoneal carcinoma to primary debulking surgery followed by platinum-based chemotherapy or to neoadjuvant platinum-based chemotherapy followed by debulking surgery ( so-called interval debulking surgery ) . RESULTS Of the 670 patients r and omly assigned to a study treatment , 632 ( 94.3 % ) were eligible and started the treatment . The majority of these patients had extensive stage IIIC or IV disease at primary debulking surgery ( metastatic lesions that were larger than 5 cm in diameter in 74.5 % of patients and larger than 10 cm in 61.6 % ) . The largest residual tumor was 1 cm or less in diameter in 41.6 % of patients after primary debulking and in 80.6 % of patients after interval debulking . Postoperative rates of adverse effects and mortality tended to be higher after primary debulking than after interval debulking . The hazard ratio for death ( intention-to-treat analysis ) in the group assigned to neoadjuvant chemotherapy followed by interval debulking , as compared with the group assigned to primary debulking surgery followed by chemotherapy , was 0.98 ( 90 % confidence interval [ CI ] , 0.84 to 1.13 ; P=0.01 for noninferiority ) , and the hazard ratio for progressive disease was 1.01 ( 90 % CI , 0.89 to 1.15 ) . Complete resection of all macroscopic disease ( at primary or interval surgery ) was the strongest independent variable in predicting overall survival . CONCLUSIONS Neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary debulking surgery followed by chemotherapy as a treatment option for patients with bulky stage IIIC or IV ovarian carcinoma in this study . Complete resection of all macroscopic disease , whether performed as primary treatment or after neoadjuvant chemotherapy , remains the objective whenever cytoreductive surgery is performed . ( Funded by the National Cancer Institute ; Clinical Trials.gov number , NCT00003636 . Background St and ard treatment of advanced ovarian cancer is surgery and chemotherapy . The goal of surgery is to remove all macroscopic tumour , as the amount of residual tumour is the most important prognostic factor for survival . When removal off all tumour is considered not feasible , neoadjuvant chemotherapy ( NACT ) in combination with interval debulking surgery ( IDS ) is performed . Current methods of staging are not always accurate in predicting surgical outcome , since approximately 40 % of patients will have more than 1 cm residual tumour after primary debulking surgery ( PDS ) . In this study we aim to assess whether adding laparoscopy to the diagnostic work-up of patients suspected of advanced ovarian carcinoma may prevent unsuccessful primary debulking surgery for ovarian cancer . Methods Multicentre r and omized controlled trial , including all gynaecologic oncologic centres in the Netherl and s and their affiliated hospitals . Patients are eligible when they are planned for PDS after conventional staging . Participants are r and omized between direct PDS or additional diagnostic laparoscopy . Depending on the result of laparoscopy patients are treated by PDS within three weeks , followed by six courses of platinum based chemotherapy or with NACT and IDS 3 - 4 weeks after three courses of chemotherapy , followed by another three courses of chemotherapy . Primary outcome measure is the proportion of PDS 's leaving more than one centimetre tumour residual in each arm . In total 200 patients will be r and omized . Data will be analysed according to intention to treat . Discussion Patients who have disease considered to be resectable to less than one centimetre should undergo PDS to improve prognosis . However , there is a need for better diagnostic procedures because the current number of debulking surgeries leaving more than one centimetre residual tumour is still high . Laparoscopy before starting treatment for ovarian cancer can be an additional diagnostic tool to predict the outcome of PDS . Despite the absence of strong evidence and despite the possible complications , laparoscopy is already implemented in many countries . We propose a r and omized multicentre trial to provide evidence on the effectiveness of laparoscopy before primary surgery for advanced stage ovarian cancer patients .Trial registration Netherl and s Trial Register number
BACKGROUND The presence of residual tumour after primary debulking surgery is the most important prognostic factor in patients with advanced ovarian cancer .
In up to 60 % of cases , residual tumour of more than 1 cm is left behind , stressing the necessity of accurately selecting those patients who should be treated with primary debulking surgery and those who should receive neoadjuvant chemotherapy instead .
OBJECTIVES To determine if performing an open laparoscopy after the diagnostic work-up of patients suspected of advanced ovarian cancer is accurate in predicting the resectability of disease .