Comparison of treatment invasiveness between upfront debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. Correlation between Surgeon's assessment and radiographic evaluation of residual disease in women with advanced stage ovarian cancer reported to have undergone optimal surgical cytoreduction: An NRG Oncology/Gynecologic Oncology Group study. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial Open versus robot-assisted sphincter-saving operations in rectal cancer patients: techniques and comparison of outcomes between groups of 100 matched patients. Minimally invasive versus standard laparotomic interval debulking surgery in ovarian neoplasm: A single-institution retrospective case-control study. Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy Delivering successful randomized controlled trials in surgery: Methods to optimize collaboration and study design Minimally invasive interval debulking surgery in ovarian neoplasm (MISSION trial-NCT02324595): a feasibility study. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. Interval Laparoscopic En-Bloc Resection of the Pelvis (L-EnBRP) in patients with stage IIIC-IV ovarian cancer: Description of the technique and surgical outcomes.
BACKGROUND We conducted a phase III , non-inferiority trial comparing upfront primary debulking surgery ( PDS ) and interval debulking surgery ( IDS ) following neoadjuvant chemotherapy ( NAC ) for stage III/IV ovarian , tubal , and peritoneal cancers ( JCOG0602 ) . Two earlier studies , EORTC55971 and CHORUS , demonstrated non-inferior survival of patients treated with NAC .  However , they could not evaluate true treatment invasiveness because of adding diagnostic laparotomy or laparoscopy before treatment in over 30 % of both arms of EORTC55971 and in 16 % of NAC arm of CHORUS . METHODS Patients were r and omised into the st and ard arm ( PDS  followed by eight cycles of paclitaxel and carboplatin [ TC ] ) and NAC arm ( four cycles of TC , IDS , and four cycles of TC ) . In the st and ard arm , IDS was optional for patients who had undergone suboptimal or incomplete PDS . Treatment invasiveness was compared between arms ( UMIN000000523 ) . RESULTS Between November 2006 and October 2011 , 301 patients were r and omised . In the st and ard arm , 147/149 underwent PDS and 49 underwent IDS . In the NAC arm , 130/152 underwent IDS . The NAC arm required fewer surgeries ( mean 0.86 versus 1.32 , p < 0.001 ) and shorter total operation time ( median 273 min versus 341 min , p < 0.001 ) than the st and ard arm and required a lower frequency of abdominal organ resection ( 23.7 % versus 37.6 % , p = 0.012 ) or distant metastases resection ( 3.9 % versus 10.7 % , p = 0.027 ) . In the NAC arm IDS , blood/ascites loss was smaller ( median 787 ml versus 3235 ml , p < 0.001 ) and albumin transfusion and G3/4 adverse events after surgery in total were less frequent ( 26.2 % versus 58.5 % , p < 0.001 ; 4.6 % versus 15.0 % , p = 0.005 , respectively ) . CONCLUSION Our findings demonstrated that NAC treatment is less invasive than st and ard treatment . NAC treatment may become the new st and ard treatment for advanced ovarian cancer when non-inferior survival is confirmed in the planned primary analysis in 2017 PURPOSE We sought to determine the level of concordance among surgeons ' assessment of residual disease ( RD ) and pre-treatment computed tomography ( CT ) findings among women who underwent optimal surgical cytoreduction for advanced stage ovarian cancer . METHODS This is a post-trial ad hoc analysis of a phase 3 r and omized clinical trial evaluating the impact of bevacizumab in primary and maintenance therapy for patients with advanced stage ovarian cancer following surgical cytoreduction . All subjects underwent imaging of the chest/abdomen/pelvis to establish a post-surgical baseline prior to the initiation of chemotherapy . Information collected on trial was utilized to compare surgeon 's operative assessment of RD , to pre-treatment imaging . RESULTS Of 1873 enrolled patients , surgical outcome was described as optimal ( RD≤1 cm ) in 639 subjects . Twelve patients were excluded as they did not have a baseline , pretreatment imaging , leaving 627 participants for analysis .  The average interval from surgery to baseline scan was 26days ( range : 1 - 109 ) . In 251 cases ( 40 % ) , the post-operative scan was discordant with surgeon assessment , demonstrating RD>1 cm in size . RD>1 cm was most commonly identified in the right upper quadrant ( 28.4 % ) , retroperitoneal para-aortic lymph nodes ( RD>1.5 cm ; 28.2 % ) and the left upper quadrant ( 10.7 % ) . Patients with RD>1 cm on pre-treatment CT ( discordant ) exhibited a significantly greater risk of disease progression ( HR 1.30 ; 95 % CI 1.08 - 1.56 ; p=0.0059 ) . CONCLUSIONS Among patients reported to have undergone optimal cytoreduction , 40 % were found to have lesions > 1 cm on postoperative , pretreatment imaging . Although inflammatory changes and /or rapid tumor regrowth could account for the discordance , the impact on PFS and distribution of RD may suggest underestimation by the operating surgeon 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 BACKGROUND Although open resection using a sphincter-saving operation ( SSO ) remains the st and ard of care for rectal cancer , few studies have compared open and robot-assisted ( RA ) SSOs . This study aim ed to compare the operative features , functional outcomes , and oncological validity of open and RA SSO for rectal cancer . METHODS A total of 200 rectal cancer patients undergoing curative SSO were enrolled prospect ively . The open and RA groups ( n = 100 , respectively ) were matched for clinical stage and operation type . RESULTS The mean operation time was significantly longer in the RA group than in the open group ( 188 vs. 103 min , P < 0.001 ) , but it was significantly reduced in the latter half of the RA patients compared with that in the first half ( 164 vs. 214 min , P < 0.001 ) . The mean distal resection margin was significantly longer in the RA than in the open group ( 2.7 vs. 1.9 cm ; P = 0.001 ) , but only one patient in either group had positive circumferential resection margin . Bowel peristalsis returned one day earlier in the RA than in the open group ( P < 0.001 ) . Postoperative complication rates and anorectal functional outcomes were comparable between the two groups . The operator 's physical discomfort , assessed on a visual analog scale , was significantly lower in the RA than in the open group ( P < 0.001 ) . CONCLUSIONS According to this short-term study , the RA SSO showed equivalent oncological safety , functional outcome , and morbidities to open SSO . Although the operation takes longer , the robotic system enables a technically versatile SSO with fine dissection in a limited surgical field OBJECTIVE To further investigate the role of MIS comparing patients su bmi tted to MI-IDS  with a balanced population treated by st and ard laparotomy . METHODS The investigational arm ( Cases ) includes 30 AEOC patients treated with MI-IDS . The Control arm included a consecutive series of 65 AEOC patients su bmi tted to laparotomic IDS . Inclusion criteria were : age>18years , histologically proven EOC , clinical complete/partial response after NACT , and ECOG PS < 2 . Preoperative clinical data , perioperative and oncological outcomes were analyzed . General Well-Being Schedule ( GWBS ) was administered to evaluate quality of life before and after surgery . RESULTS Both groups were well-balanced . A higher percentage of women among Cases received bevacizumab-containing NACT compared with Controls . No statistical differences were registered in terms of surgical procedures and residual tumor . A significantly longer median OT in Cases was counterbalanced by more favorable EBL and median length of stay and TTC . No statistically significant differences were registered in terms of postoperative complications . Cases showed a 6months longer PFS compared to Controls . However , in multivariate analysis only the administration of Bevacizumab and a shorter TTC were independently associated with a longer PFS . Regarding QoL , no statistically significant differences were registered in Cases between pre- and postoperative GWBS score . Differently from Controls where this difference was statistically significant and a more intense distress were recorded . CONCLUSIONS Minimally invasive approach could represent an advantageous alternative surgical way to perform interval debulking surgery in this specific subset of patients , with no impact on PFS . Based on these findings a r and omized clinical trial is now under evaluation in our Institution Background : Presently , the use of laparoscopy in advanced ovarian cancer ( AOC ) is extremely controversial . In the era of neoadjuvant chemotherapy ( NACT ) , endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease . Objectives : To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC su bmi tted to NACT . Methods : This is a pilot observational study on initially unresectable , high- grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy ( group 1 ) or laparotomy ( group 2 ) . The inclusion criteria were clinical complete response , CA-125 normalization , imaging without disease in critical areas , and optimal cytoreduction . Results : From January 2011 to March 2014 , 21 patients were included . Ten women underwent laparoscopy and 11 laparotomy . No epidemiological or oncologic differences were observed between the groups . No surgery-related casualties , intraoperative complications , conversion to laparotomy , or excessive blood loss or transfusion was detected in the laparoscopic procedures . The mean time of operation was 292 min . The length of hospital stay averaged 3.6 days . Two women in group 1 developed relevant complications . After a mean follow-up of 20 months , the recurrence rates were similar , i.e. 80 % in group 1 versus 88 % in group 2 . Although statistical significance was not reached , the mortality related to cancer was considerably higher ( 20 vs. 0 % ; p = 0.086 ) and the mean chemotherapy-free interval was markedly shorter in group 1 ( 13.3 vs. 20.5 months ; p = 0.288 ) . Conclusion : Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients . Nevertheless , laparoscopy was substantially associated with inferior oncologic results . Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospect i ve trials confirm the observed results R and omized controlled trials in surgery are notoriously difficult to design and conduct due to numerous method ological and cultural challenges . Over the last 5 years , several UK-based surgical trial-related initiatives have been funded to address these issues . These include the development of Surgical Trials Centers and Surgical Specialty Leads ( individual surgeons responsible for championing r and omized controlled trials in their specialist fields ) , both funded by the Royal College of Surgeons of Engl and ; networks of research -active surgeons in training ; and investment in method ological research relating to surgical r and omized controlled trials ( to address issues such as recruitment , blinding , and the selection and st and ardization of interventions ) . This article discusses these initiatives more in detail and provides exemplar cases to illustrate how the method ological challenges have been tackled . The initiatives have surpassed expectations , result ing in a renaissance in surgical research throughout the United Kingdom , such that the number of patients  entering surgical r and omized controlled trials has doubled BACKGROUND Laparoscopy has acquired an increasing role in the management of ovarian cancer . Laparoscopic cytoreduction could represent a new frontier for selected patients after neoadjuvant chemotherapy ( NACT ) .  OBJECTIVE We sought to assess feasibility and early complication rate of minimally invasive ( MI ) interval debulking surgery ( IDS ) in stage III-IV epithelial ovarian cancer ( EOC ) patients after NACT .  STUDY DESIGN This is a phase II multicentric study in advanced EOC cases with clinical complete response after NACT , according to Gynecologic Cancer Intergroup and Response Evaluation Criteria In Solid Tumors criteria . Institutional review board approval was obtained and all patients signed written informed consent to be included in the protocol . The study was registered in clinical trials.gov ( NCT02324595 ) and was named " MISSION " trial . For patients meeting inclusion criteria , surgical procedures started with diagnostic laparoscopy to confirm preoperative findings and assess surgical complexity . MI-IDS included hysterectomy , bilateral salpingo-oophorectomy , appendectomy , omentectomy , peritonectomy , and bowel resection . Pelvic and /or aortic lymphadenectomy was not considered as st and ard procedure in these cases . Intraoperative and postoperative outcomes , time to restart chemotherapy , survival rate , and quality of life data were registered . RESULTS From December 2013 through February 2015 , of 184 advanced EOC patients considered eligible for IDS , 52 ( 28.2 % ) met inclusion criteria and were enrolled in the study . For 22 ( 12 % ) of them , st and ard laparotomic approach was preferred because of intraoperative surgeon evaluation . Thirty ( 16.3 % ) patients received the planned treatment of MI-IDS . Median age was 61 ( range 39 - 81 ) years and median body mass index was 24 ( range 20 - 31 ) kg/m(2 ) .  Median numbers of NACT cycles was 4 ( range 3 - 7 ) . Median operative time was 285 ( range 124 - 418 ) minutes and median estimated blood loss was 100 ( range 50 - 200 ) mL. Surgical procedures included 28 ( 93.3 % ) hysterectomy and bilateral salpingo-oophorectomy , 29 ( 96.6 % ) omentectomy , 2 ( 6.6 % ) appendectomy , 11 ( 36.6 % ) regional peritonectomy , and 1 ( 3.4 % ) bowel resection . A residual tumor of 0 cm was reached in 29 ( 96.6 % ) patients and 0.5 cm in only 1 ( 3.4 % ) case . The vast majority of patients were discharged on postoperative day 2 ( range 2 - 3 ) . No early postoperative complications were registered . Median time to restart chemotherapy was 20 ( 10 - 30 ) days and all patients successfully completed the cycles . Histological findings showed 3 ( 10 % ) complete response , 9 ( 30 % ) microscopic residual disease , and 18 ( 60 % ) evidence of macroscopic residual disease . With a median follow-up of 10.5 month , 5 peritoneal and 2 lymph nodal recurrences were observed . Psychometric test revealed moderate discomfort in the vast majority of patients ( 66.7 % ) . All patients are still alive . CONCLUSION Invasive-IDS in patients with clinical ly complete response to NACT seems to be feasible and safe in terms of perioperative outcomes , psycho-oncological impact , and survival rate . The equivalence between MI surgery and laparotomy needs to be confirmed with a longer follow-up and a larger number of patients 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 . OBJECTIVE 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 . METHODS This report is part of a prospect i ve non r and omized 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 ) . RESULTS 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 . CONCLUSION 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
The introduction of minimally invasive surgery in other gynecologic cancers has shown benefits with similar oncologic outcomes .
However , the biology and complexity of surgery for ovarian cancer may preclude this approach for ovarian cancer patients .
Our objective is to assess feasibility to achieve complete cytoreductive surgery after neoadjuvant chemotherapy for stage IIIC – IV ovarian cancer patients via  minimally invasive surgery .