Is minimally invasive surgical approach a reasonable option in apparent early stage epithelial ovarian cancer restaging? Results from a multicentric retrospective study.

INTRODUCTION: To perform surgical staging of early stage ovarian cancer (EOC), conventional laparoscopy (LS) and robot-assisted laparoscopy (RLS) appear to be reliable procedures compared to open surgery. But oncologicals results with long-term follow up are limited in the literature. The objective of this study is to evaluate the surgical and long-term survival for patients managed by minimally invasive surgery (MIS). MATERIALS AND METHODS: We conducted a multicentric retrospective study in 6 institutions. All patients referred for epithelial EOC (apparent stage I-IIa) managed with LS and RLS were involved. RESULTS: From December 2008 to December 2017, 140 patients were included (109 in LS group and 31 in RLS group). A total of 27 (19.2 %) patients were upstaged to an advanced ovarian cancer (FIGO stage > IIA), and 73 % of patients received chemotherapy. Mean operative time was 265,8 ± 88,4 min and significantly longer in RLS group (LS = 254,5 ± 86,8; RLS = 305,6 ± 85,5; p = 0,008). Rate of severe post-operative complications (grade 3) was 5,7 %. Thirteen conversion to laparotomy occurred, including one per-operative hemorrhaege. After a mean follow-up of 60,7 months, 29 (20.7 %) patients recurred, with a time to recurrence was >24 months in 51,7 % of cases. Overall survival (OS) was 88.6 % and disease-free survival (DFS) was 79.3 %. Oncologic outcomes were similar between LS and RLS group (OS: p = 0,504 and DFS: p = 0,213). CONCLUSION: Surgical staging of EOC by LS or RLS approach has long-term equivalent surgical and oncological approach. These results seem to be equivalent to open surgery according to literature review.

Clinical impact of CA-125 ELIMination rate constant K (KELIM) on surgical strategy in advanced serous ovarian cancer patients.

OBJECTIVES: The modeled CA-125 elimination constant K (KELIM) is a pragmatic early marker of tumor chemosensitivity in ovarian cancer patients treated with neoadjuvant chemotherapy before interval surgery. The primary objective of this study was to assess the prognostic value of KELIM regarding the feasibility of complete surgery, and secondary objectives were to assess the prognostic value of KELIM for the risk of a platinum resistant relapse, progression free survival, and overall survival. METHODS: The study was based on a retrospective cohort of 284 patients treated for an advanced serous high grade ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV, with neoadjuvant chemotherapy, followed by interval surgery, in a comprehensive cancer center. CA-125 concentrations at baseline and during neoadjuvant chemotherapy were collected. The KELIM predictive value regarding the tumor radiological response rate, likelihood of complete surgery, risk of subsequent platinum resistant relapse, progression free survival, and overall survival were assessed with univariate and multivariate tests. RESULTS: In 232 patients, KELIM was an independent and major predictor of the probability of complete surgery and survival. The final logistic regression model, including KELIM (odds ratio (OR) 0.36, 95% confidence interval (CI)0.16 to 0.73, p=0.006) and complete surgery (no vs yes, OR 0.29, 95% CI 0.15 to 0.53, p<0.001), highlighted the complementary impact of chemosensitivity and surgical outcome relative to the complete surgery. In the multivariate analysis, KELIM and complete surgery were significantly associated with a lower risk of early relapse. In the case of an unfavorable KELIM, when surgical efforts allowed complete cytoreduction, median overall survival was similar to that reported in the case of a favorable KELIM (46.3 months (range 34.6-60.3) vs 46.5 months (range 40.6-68.7), respectively). CONCLUSION: Primary tumor chemosensitivity, assessed by the modeled CA-125 KELIM, calculated during neoadjuvant chemotherapy, is a major parameter to consider for decision making regarding interval surgery. Complementary to the RECIST score and laparoscopy, this non-invasive tool, available online, helps tailor the interval surgery strategy according to patient tumor chemosensitivity.

[State of results of HIPEC for epithelial ovarian cancer in the primary treatment or for relapse]. / État des lieux des résultats en termes de survie de la CHIP en primo-traitement et en récidive dans le cancer épithélial de l'ovaire.

Peritoneal carcinomatosis is an unavoidable development of ovarian cancer, from the first treatment to relapses, and is the main cause of patients death. Hyperthermic intraperitoneal chemotherapy (HIPEC), is a hope for cure for patients with ovarian cancer. HIPEC is based on direct application of chemotherapy on the perioneum with high concentration of chemotherapy enhanced with specific effects of hyperthermia. Theoretically, HIPEC could be proposed at different steps of ovarian cancer development. But the hypothesis of efficiency of a new treatment must be assessed before being routinely applied. Numerous clinical series are already published about HIPEC used in primary treatment of ovarian cancer or for relapses. These series are mostly retrospectives and based on heterogeneous parameters as inclusion criteria of patients, intra peritoneal chemotherapy, concentration, temperature, duration of HIPEC. Taking into account this heterogeneity it is not possible to draw strong scientific conclusions about HIPEC efficiency to treat ovarian cancer patients. We proposed a review allowing a better understanding of current recommendations of the use of HIPEC in ovarian cancer patients.

Delaying Surgery After Neoadjuvant Chemotherapy Affects Survival in Patients with Colorectal Peritoneal Metastases: A BIG-RENAPE Network Multicentric Study.

BACKGROUND: Multimodal treatment for patients with peritoneal metastases (PM) from colorectal cancer (CRC), including perioperative chemotherapy (CT) plus complete resection, is associated with prolonged survival. The oncologic impact of therapeutic delays is unknown. OBJECTIVE: The aim of this study was to assess the survival impact of delaying surgery and CT. METHODS: Medical records from the national BIG RENAPE network database of patients with complete cytoreductive (CC0-1) surgery of synchronous PM from CRC who received at least one neoadjuvant CT cycle plus one adjuvant CT cycle were retrospectively reviewed. The optimal interval between the end of neoadjuvant CT to surgery, surgery to adjuvant CT, and total interval without systemic CT were estimated using Contal and O'Quigley's method plus restricted cubic spline methods. RESULTS: From 2007 to 2019, 227 patients were identified. After a median follow-up of 45.7 months, the median overall survival (OS) and progression-free survival (PFS) was 47.6 and 10.9 months, respectively. The best cut-off period was 42 days in the preoperative interval, no cut-off period was optimal in the postoperative interval, and the best cut-off period in the total interval without CT was 102 days. In multivariate analysis, age, biologic agent use, high peritoneal cancer index, primary T4 or N2 staging, and delay to surgery of more than 42 days (median OS 63 vs. 32.9 months; p = 0.032) were significantly associated with worse OS. Preoperative delay of surgery was also significantly associated with PFS, but only in univariate analysis. CONCLUSION: In selected patients undergoing complete resection plus perioperative CT, a period of more than 6 weeks from completion of neoadjuvant CT to cytoreductive surgery was independently associated with worse OS.

Impact of consolidation chemotherapy after delayed complete surgery in advanced epithelial ovarian cancer: a propensity score analysis.

OBJECTIVES: This retrospective study aimed to assess the efficiency of consolidation chemotherapy after 6 cycles of neoadjuvant chemotherapy and delayed complete surgery on overall survival and progression-free survival among patients with advanced epithelial ovarian cancer. METHODS: This was a retrospective consecutive study with a propensity score to ensure balance for the baseline characteristics between the study groups. All patients treated for advanced ovarian cancer with 6 cycles of neoadjuvant chemotherapy followed by delayed complete surgery, without post-operative chemotherapy (group 1), or with post-operative chemotherapy (group 2), were included. We evaluated survival and the quality of cytoreductive surgery using the propensity score. RESULTS: From 2000 to 2017, 42 patients were included in group 1, and 59 in group 2. The median follow-up was 78 months (confidence interval (CI) 95% (60.1; not computable)). Neither progression-free survival nor overall survival were different between the two groups. The median progression-free survival was 10.2 months (CI 95% (8.8-17.0)) for group 1 and 10.4 months (CI 95% (7.9-12.8)) for group 2 (p=0.57). Five-year overall survival was 21.0% (CI 95% (10.4-42.3)) for group 1 and 26.1% (CI 95% (16.0-42.5)) for group 2 (p=0.73). CONCLUSIONS: Adding cycles of consolidation chemotherapy after delayed surgery following 6 cycles of neoadjuvant chemotherapy did not demonstrate any survival improvement in patients treated for advanced ovarian cancer not amenable to primary or interval surgery.

Surgery of resectable local recurrence following colorectal cancer: Compartmental surgery improves local control.

BACKGROUND: This study aims to identify prognostic factors and define the best extent of surgery for optimizing treatment of local recurrence (LR) following colorectal cancer (CRC). METHODS: An institutional database of consecutive patients who underwent radical resection (R0/R1) of LR following CRC was analyzed prospectively from 2010 to 2021 at one tertiary cancer center. RESULTS: In this study, 75 patients were included with LR following CRC and analyzed. Patients were categorized as compartmental resections (CompRe) (n = 47) if all adjacent organs were systematically removed, with or without tumor involvement, or noncompartmental resections (NoCompRe) (n = 28) if only contiguously involved organs were resected. NoCompRe were mainly related to contact between major vessels or bone and the tumor, with only 8/19 (42.1%) resections. Five-year overall survival and locoregional-free survival were 37.5% and 38.8% respectively. Local control was better in the CompRe than the NocompRe group (61.4% vs. 11%; p < 0.01). CompRe (hazard ratio: 2.34 [1.16-4.68]; p = 0.017) and absence of peritoneal metastasis (3.05 [1.03-9.02]; p = 0.044) were the two factors associated with decreased abdominal recurrences in multivariate analysis. CONCLUSION: Complete compartmental surgery is safe and improves local control. Optimal LR resection needs to remove all contiguous organs, with or without tumor involvement.

Survival after cytoreductive surgery for peritoneal metastases in colorectal cancer patients: Does a history of resected liver metastases worsen the prognosis?

BACKGROUND: Nowadays, resection of two (liver and peritoneum) concomitant colorectal cancer metastatic sites is no longer contraindicated. However, the oncologic outcomes of resecting peritoneal metastases (PM) occurring more than six months after resection of liver metastases (LM) are unknown. AIM: The aim of this study was to compare patients with complete cytoreductive surgery (CRS) with or without a history of previous liver resection (LR). METHODS: Analysis from a prospective database of 74 patients with metachronous PM treated with CRS between 2010 and 2020. RESULTS: All patients had PM metachronous to primary, 64 patients underwent CRS alone (CRSa) and 10 CRS more than six months after LR (LR-CRS). There was no statistical difference between the groups for clinical or therapeutic characteristics. There were more signet ring cell/mucinous adenocarcinomas in the CRSa group than in the LR-CRS group (19% vs. 0%, p = 0.049). The median peritoneal cancer index (PCI) was 4 and 6 (p = 0.749) in the LR-CRS and CRSa groups, respectively. Median overall survival (OS) and disease-free survival (DFS) were not statistically different between the two groups with 43.6 and 13 months for the CRSa group and 31.1 months and 9.4 months for LR-CRS. Advanced age was an independent negative prognostic factor for OS and high PCI was limit significant. No prognostic factor for DFS was found. CONCLUSIONS: LR before CRS has no major prognostic impact. Resection of iterative liver and peritoneum metastases can achieve long-term survival.

ACOSOG Z-0011 criteria impact on axillary surgery for early breast cancer in clinical practice: Evaluation in a retrospective cohort of 1900 patients.

BACKGROUND: There is a trend towards de-escalation in early breast cancer axillary surgery. In the American College of Surgeons Oncology Group (ACOSOG) Z-0011 trial, observation was shown to be non-inferior in terms of overall survival to complementary axillary lymph node dissection (cALND) in patients with up to two sentinel lymph node (SLN) metastases. The study included patients with T1-T2 invasive breast cancer, clinically node negative, undergoing breast-conserving surgery with SLN biopsy, followed by systemic therapy and radiotherapy. The aim of our study was to evaluate the impact of applying these ACOSOG Z-0011 inclusion criteria in routine practice. PATIENTS AND METHODS: This retrospective observational study was conducted in a French comprehensive cancer center where patients treated for breast cancer with primary surgery were prospectively included between 2010 and 2016. Patients meeting ACOSOG Z-0011 inclusion criteria were analyzed. RESULTS: Among the 1900 included patients, 1497 (79 %) met the ACOSOG Z-0011 criteria before surgery. Of these, 390 (20 %) had one or two metastatic SLN and could have avoided cALND. Out of these patients, 319 (81 %) presented cT1 tumors. During the study period, cALND was performed in 320 (82 %) patients and was free of metastases in 80 % of cases, having an impact on eligibility for adjuvant chemotherapy in only 3 (0.8 %) patients. CONCLUSIONS: In situations of primary breast cancer surgery, use of ACOSOG Z-0011 criteria could reduce the rate of cALND by 20 %. Further studies are needed to help select patients for whom abstention from any axillary surgery would be reasonable.

Individual learning curve of cytoreductive surgery for peritoneal metastasis from colorectal cancer: A process with an impact on survival.

BACKGROUND: This study aimed to assess the learning curve (LC) of cytoredutive surgery (CRS) of peritoneal metastasis (PM) from colorectal cancer (CRC). Information about learning curves is important for developing teaching tools and well-structured training programs for the implementation of this complex procedure in new healthcare centers. The aim of this study was to estimate how many procedures an inexperienced surgeon must perform (the length of the learning period) in order to demonstrate an acceptably low rate of locoregional recurrence. METHODS: All consecutive 74 patients with CRS for CRC performed by a novice surgeon between 2012 and 2017 in a tertiary cancer center were included. The learning curve was calculated by a cumulative sum control chart (CUSUM) graph. Two groups were formed based on the length of the learning period and were compared on overall and disease free survival. RESULTS: The risk of locoregional recurrence decreased after surgeons had performed 19 cases, suggesting a learning period of this length. Overall survival and postoperative morbidity were not significantly different between learning and proficiency periods. Multiple linear regression analysis showed that the learning period and peritoneal cancer index are the only factors affecting disease free survival. A second learning period was observed in cases where patient care became more complex. CONCLUSIONS: This study confirms that learning period has negative impacts on disease-free survival. An initial experience supervised in specialized centers allow to have a short learning curve for CRS for peritoneal metastases for CRC.

Quality of advanced ovarian cancer surgery: A French assessment of ESGO quality indicators.

OBJECTIVES: In 2016, the European Society of Gynecology Oncology (ESGO) published indicators defining the quality of surgical management of advanced ovarian cancer. The objective of the study was to assess the quality of ovarian cancer patient management in regional centers authorized for gynecological cancer, based on the ESGO list of quality indicators. METHODS: A multicenter retrospective observational cohort study was conducted from January 1 to June 30, 2016. The following quality indicators 1 "rate of complete surgical resection", 4 "center participating in clinical trials in gynecologic oncology", 5 "treatment planned and reviewed at a multidisciplinary team meeting", 6 "required preoperative workup", 8 "minimum required elements in operative reports" and 9 "minimum required elements in pathology reports" were selected. RESULTS: 91 patients were evaluated in 16 centers. The required preoperative workup was incomplete in 25% of cases. Treatment was not planned at a multidisciplinary team meeting for 24%. An evaluation score of peritoneal involvement was included in 40% of the operative reports and the quality of surgical resection was reported in 72%. Primary surgery was most often performed in a peripheral hospital (48%), interval surgery in a private center (37%), and closure surgery in a regional cancer center (43%). No institution respected the six quality indicators evaluated. One regional cancer center respected five items and two private centers did not respect any. CONCLUSION: Whilst the ESGO quality indicators provide objective, validated and evaluable support which centers can use to improve quality of care, we observed heterogeneous practices amongst the centers evaluated.

Survival Outcomes after Hyperthermic Intraperitoneal Chemotherapy for a First Ovarian Cancer Relapse: A Systematic Evidence-Based Review.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is routinely used in the treatment of a first ovarian cancer relapse. METHODS: This systematic review, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, aimed to assess the quality of scientific proof of the survival benefits of HIPEC, using Medline and Google Scholar. Qualitative analysis using the Oxford CEBM Levels of Evidence 2011 grading is reported. RESULTS: Of 469 articles identified, 23 were included; 15 based on series of patients treated with HIPEC without a control group, and 8 case control series of patients treated with or without HIPEC. The series without a control group showed median overall survival (OS) ranged from 23.5 to 63 months, highlighting a broad standard deviation. Considering the case control series, OS was significantly better in the HIPEC group in 5 studies, and similar in 1. The current review showed considerable heterogeneity and biases, with an Oxford Level of Evidence grading of 4 for 22 selected series and 2 for one. CONCLUSIONS: There is no strong evidence to suggest efficacy of HIPEC in improving survival of patients treated for a first relapse of ovarian cancer due to the low quality of the data.

Comparison of postoperative complications and quality of life between patients undergoing continent versus non-continent urinary diversion after pelvic exenteration for gynecologic malignancies.

BACKGROUND: Pelvic exenteration and its reconstructive techniques have been associated with high postoperative morbidity and a negative impact on patient quality of life. The aim of our study was to compare postoperative complications and quality of life in patients undergoing continent compared with non-continent urinary diversion after pelvic exenteration for gynecologic malignancies. METHODS: We designed a multicenter study of patients from 10 centers who underwent an anterior or total pelvic exenteration with urinary reconstruction for histologically confirmed persistent or recurrent gynecologic malignancy after previous treatment with radiotherapy. From January 2005 to September 2008, we included patients retrospectively, and from September 2008 to May 2009, patients were included prospectively which allowed collection of quality of life data. Demographic, surgical, and follow-up data were analyzed. Postoperative complications were classified according to the Clavien-Dindo classification. Quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC)-QLQ-C30 (V.3.0) and EORTC-QLQ-OV28 quality of life questionnaires. We compared patients who underwent a continent urinary diversion with those who underwent a non-continent reconstruction. RESULTS: We included 148 patients, 92 retrospectively and 56 prospectively. Among them, 77.4% had recurrent disease and 22.6% persistent disease after the primary treatment. In 70 patients, a urinary continent diversion was performed, and 78 patients underwent a non-continent diversion. Median age of the continent and incontinent groups was 53.5 (range 33-78) years and 57 (26-79) years, respectively. There were no significant differences between the continent and non-continent groups in median length of hospitalization (28.5 vs 26 days, P=0.19), postoperative grade III-IV complications (42.9% vs 42.3%, P=0.95), complications needing surgical (27.9% vs 34.6%, P=0.39) or radiological (14.7% vs 12.8%, P=0.74) intervention, and complication type (digestive (23.2% vs 16.7%, P=0.32) and urinary (15.9% vs 16.7%, P=0.91)). There were no significant differences between the groups in global health, global quality of life, and body image perception scores 1 year after surgery. CONCLUSION: Continent and incontinent urinary reconstructions are equivalent in terms of postoperative complications and quality of life scores.

Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study.

PURPOSE: GANEA2 study was designed to assess accuracy and safety of sentinel lymph node (SLN) after neo-adjuvant chemotherapy (NAC) in breast cancer patients. METHODS: Early breast cancer patients treated with NAC were included. Before NAC, patients with cytologically proven node involvement were allocated into the pN1 group, other patient were allocated into the cN0 group. After NAC, pN1 group patients underwent SLN and axillary lymph node dissection (ALND); cN0 group patients underwent SLN and ALND only in case of mapping failure or SLN involvement. The main endpoint was SLN false negative rate (FNR). Secondary endpoints were predictive factors for remaining positive ALND and survival of patients treated with SLN alone. RESULTS: From 2010 to 2014, 957 patients were included. Among the 419 patients from the cN0 group treated with SLN alone, one axillary relapse occurred during the follow-up. Among pN1 group patients, with successful mapping, 103 had a negative SLN. The FNR was 11.9% (95% CI 7.3-17.9%). Multivariate analysis showed that residual breast tumor size after NAC ≥ 5 mm and lympho-vascular invasion remained independent predictors for involved ALND. For patients with initially involved node, with negative SLN after NAC, no lympho-vascular invasion and a remaining breast tumor size 5 mm, the risk of a positive ALND is 3.7% regardless the number of SLN removed. CONCLUSION: In patients with no initial node involvement, negative SLN after NAC allows to safely avoid an ALND. Residual breast tumor and lympho-vascular invasion after NAC allow identifying patients with initially involved node with a low risk of ALND involvement.

[Clinical practice for morbidly obese endometrial cancer patients: A french multicentric study]. / Réalité de la prise en charge du cancer de l'endomètre chez les patientes en obésité morbide : étude française bicentrique.

INTRODUCTION: Morbid obesity may lead to difficulties for management of endometrial cancer. The aim of this study was the assessment of management of endometrial cancer for morbidly obese women and the implementation of recommendations. METHODS: this is retrospective study including women with BMI =40kg/m2 treated for endometrial cancer between November 2010 and April 2017 in the university hospital in Nantes and the Cancer Center René Gauducheau in Nantes. Patients' demographics, pre-operative intra operative, post-operative data and survival were analyzed. RESULTS: Twenty patients met the inclusion criteria with a median age of 65.5 (28-86) and a median BMI of 47kg/m2 (40-60). Type I histologic was identified in 90% and of a stage I FIGO I in 75% of the cases. All the patients have benefited from a biopsy of endometrium before surgery. 70% of the patients have benefited from a MRI before surgery (14/20). The surgery was realized by laparotomy in 40%, by mini invasive surgery in 50% and by vaginal procedure in 10% of. Mini invasive surgery was converted in laparotomy in 40% (4/10). A discrepancy of the ESMO's recommandation was observed in 40% of the cases (8/20). Two patients did not benefit from the adjuvant radiotherapy recommended because of delay of healing. DISCUSSION: Although good prognosis, the endometrial cancer of morbidly obese women seem to be under treat. These patients do not seem benefited an optimal pre-operative assessment. The surgery is mainly realized by laparotomy with a not complete surgical stadification for one more than a third of the patients.

Dual docking robotic surgical staging for high risk endometrial cancer.

OBJECTIVE: The standard of care for patients with high intermediate and high risk endometrial cancer is surgical staging including total hysterectomy with bilateral salpingo-oophorectomy, and pelvic and para-aortic lymphadenectomy. Over the past decade, laparoscopic or robot-assisted minimally invasive surgery has showed many benefits in the management of endometrial cancer. Few studies have specifically assessed the use of minimally invasive surgery for staging of high risk endometrial cancer. The objective of this study was to evaluate the feasibility, the morbidity and oncologic outcomes of dual docking robot-assisted surgical staging of high risk endometrial cancer. METHODS: We conducted a retrospective observational study from January 2014 to March 2016 in patients with high risk endometrial cancer who underwent dual docking robotic hysterectomy with pelvic and paraaortic lymphadenectomy (± omentectomy). Patients' demographics, operative time, conversion rate, intra and postoperative complications, pathologic results, length of stay and survival were analyzed. RESULTS: Twenty patients met the inclusion criteria. Staging surgical procedure was performed robotically with a dual docking in 18 patients. Two patients were converted to laparotomy (1 for bladder extension, 1 for exposure reasons) and no patient had a laparoconversion for complication (conversion rate 10%). One patient was post operatively re-operated within 30 days because of port hernia. In one case, paraaortic lymphadenectomy was not performed because of hemorrhage risk. When the procedure was performed with robot-assisted surgery, the median number of paraaortic nodes was 19.5 (3-45). The median operative time was 240 min (180-300). Eighty-five percent (17/20) of patients were discharged at day 4 or before. The median time to start adjuvant treatments, when indicated, was 5.5 weeks. With a median follow up of 8 months (1-18 months), no tumor recurrence was reported. CONCLUSION: Robotic surgical staging with dual docking in women with high risk endometrial cancer seems to be feasible with few complications. More studies are required to assess the safety of robotic surgery and its impact on survival.