Article: Ovarian Cancers[Show abstract] [Hide abstract] ABSTRACT: Absent residual tumor after primary debulking surgery is one of the main prognostic factors in advanced ovarian cancer. However, complete resection is very difficult to obtain, due to the wide spread diffusion of the disease both within the abdominal cavity on peritoneal surfaces, and to the liver/spleen, or far to the lung, brain and lymphnodes. Predicting successful surgical outcome depends on many variables including patients’ characteristics, serum markers, and disease extension. Here we describe more advanced techniques to assess pre-operative tumor burden, ongoing clinical trials and integrated clinical models to individualize therapeutic decision.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To further investigate the role of MIS comparing patients submitted to MI-IDS with a balanced population treated by standard 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 submitted 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 randomized clinical trial is now under evaluation in our Institution.
- [Show abstract] [Hide abstract] ABSTRACT: Background: Brain metastases (BM) from epithelial ovarian cancer (EOC) are considered a rare and unfavourable event. There is no consensus regarding the best management of these patients. Methods: A multicenter retrospective analysis of patients with BM from EOC treated between 1997 and 2014 in 18 institutions of the MITO (Multicenter Italian Trials in Ovarian cancer) group was conducted. Univariate and multivariate analysis were performed. Results: A total of 174 women were identified as having BM from EOC. The median time interval between primary diagnosis of EOC and occurrence of BM was 26months (range 2-129months). The median overall survival from primary EOC diagnosis was 48months (95% CI 39.5-56.4months) and from diagnosis of BM was 12months (95% CI 9.6-14.3months). The majority of enrolled women (81.7%) were classified as sensitive to platinum-based chemotherapy. Four variables were significantly associated with poor overall survival in multivariate analysis: multiple BM [HR: 1.86 (95% CI: 1.22-2.84)], presence of extracranial disease [HR: 1.77 (95% CI: 1.11-2.83)] age [HR: 1.74 (95% CI: 1.17-2.59)], and monotherapy [HR: 2.57 (95% CI: 1.64-3.86)]. On the contrary, residual tumor at primary surgery, FIGO stage at primary diagnosis and platinum sensitivity were found to have no significant impact on survival from diagnosis of brain lesions. Conclusions: Our results suggest that BM is a rare and late manifestation of EOC, with a 12-month life-span expectation. Multiple approach is a positive independent prognostic factor and should be proposed to carefully selected patients.
- [Show abstract] [Hide abstract] ABSTRACT: Study objective: To assess the feasibility of total robotic radical surgery (TRRS) in patients with locally advanced cervical cancer (LACC) who receive chemoradiation therapy (CT/RT). Design: Prospective (pre-planned) study: Non-randomized controlled trial (Canadian Task Force classification level 2). Setting: Catholic University of the Sacred Hearth, Rome, Italy. Patients: Between September 2013 and January 2016, a total of 40 patients with LACC (FIGO stage IB2-III) were enrolled into the study. Interventions: Robotic radical hysterectomy (RRH) plus pelvic and/or aortic lymphadenectomy was attempted within 6 weeks after CT/RT. The feasibility of TRRS, as well as the rate, pattern, and severity of early and late postoperative complications, were analyzed. Measurements and results: After CT/RT, 29 patients (72.5%) underwent type B2 RRH, 11 (27.5%) underwent type C1 RRH. Pelvic lymphadenectomy was performed in all cases. TRRS was successful in 39/40 cases (feasibility rate= 97.5%). In patients successfully completing TRRS, median operating time was 185 min (range 100-330), and median blood loss was 100 ml (range: 50-300). Median time of hospitalization, counted from the first postoperative day, was 2 days (range= 1-4). No intra-operative complications were recorded. During the observation period (median 18 months, range: 4-28), 9 of 40 (22.5%) experienced postoperative complications, for a total number of 12 complications. As of April 2016, recurrence of disease was documented in 5 cases (12.5%). Conclusions: TRRS is feasible in LACC patients administered pre-operative CT/RT, providing peri-operative outcomes comparable to those registered in early stage disease, and LACC patients receiving neoadjuvant chemotherapy.
- [Show abstract] [Hide abstract] ABSTRACT: This review of the literature aims at assessing the safety and effectiveness of robotic versus laparoscopic surgery in benign and malignant gynecological diseases. Robotic-assisted laparoscopy is already widely used in the United States and Europe for the main gynecological procedure - hysterectomy - and has proved feasible and comfortable for other benign and malignant gynecological procedures. However, the clinical effectiveness and safety of robotic surgery compared with standard laparoscopy have not been undoubtedly established. We reviewed the literature by searching in the Ovid/MEDLINE, PubMed, Cochrane Library, and Google Scholar databases for all the articles published from January 1995 to September 2015. More rigorous experimental studies are needed, that compare robotic-assisted surgery and laparoscopic surgery for gynecological diseases. However, current data seem to encourage the use of minimally-invasive surgery to treat benign and malignant gynecological diseases.
- [Show abstract] [Hide abstract] ABSTRACT: Nowadays cervical cancer is frequently diagnosed at early stage. For these patients lymph node metastasis (LNM) is considered the most important prognostic factor. During the last decade many efforts have been made to reduce rate of complications associated with lymphadenectomy (LND). A great interest has arisen in sentinel lymph node (SLN) biopsy as a technique able to decrease number of LND performed and, at the same time, to assess lymph nodal status. High diagnostic performances have been reached thanks to SLN surgical algorithm. However, despite the efforts, about 25% of these patients undergo at least unilateral LND to meet NCCN recommendations. Data of women with International Federation of Gynecology and Obstetrics stage IA1-IB1/IIA1 cervical carcinoma were retrospectively collected by six Italian institutions. All patients underwent complete preoperative staging workup and were primarily treated by radical hysterectomy and pelvic bilateral LND. A total of 368 patients with early-stage cervical cancer were identified. Among them 333 (90.5%) showed no suspicious enlarged nodes at the preoperative magnetic resonance imaging (MRI). In this subset, tumor diameter ≥20 mm was the only independent predictor of LN status (P = 0.003). None of the 106 patients with negative MRI nodal assessment, with squamous and adenosquamous histotype and a tumor diameter less than 2 cm had LNM. Based on these results we propose a new modified SLN surgical algorithm that could safely reduce LND performed in patients with very low-risk early-stage cervical cancer.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: to evaluate the timing and pattern of relapse, and duration of response to second line chemotherapy in advanced ovarian cancer (AOC) patients treated with first line carboplatin-paclitaxel chemotherapy with or without bevacizumab. Patients and methods: this is a case-control study including 222 AOC patients. Seventy-four women treated with first line carboplatin-paclitaxel-bevacizumab chemotherapy (Cases) were matched based on laparoscopic predictive index value, and residual tumor at first surgery with 148 AOC patients treated with carboplatin-paclitaxel. Distribution of pattern of relapse, and response to second line chemotherapy was compared between the two groups. Time to Progression (TTP) for second line chemotherapy was also analyzed for study purpose. Results: median platinum-free interval (PFI) was 16months (range 2-65) in Cases, compared with 9months (1-83) in Controls (p-value=0.001). Twenty patients (51.3%) among Cases showed recurrence in multiple anatomic sites, compared with 31 (31.9%) in the Control group (p-value=0.035). Peritoneal recurrence occurred as diffuse in 30 Cases (96.8%), and 60 Controls (82.2%; p-value=0.046). Secondary cytoreductive surgery (SCS) was successfully completed in 53.5% of Controls compared to 10.0% of Cases (p-value=0.016). In women with fully platinum-sensitive relapse, response rate to second line chemotherapy was 85.2% in Controls, compared to 38.4% in Cases (p-value=0.002). Finally, Cases showed a shorter TTP, compared to Controls (5months vs 8months; p-value=0.041). Conclusions: incorporation of bevacizumab into upfront regimens prolongs PFI in AOC patients, but is associated with wider presentation of relapse, lower rate of complete SCS, and shorter TTP to second line chemotherapy in women with platinum-sensitive disease.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To establishing whether neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is superior primary debulking surgery (PDS) in terms of clinical outcome as well as peri-operative morbidity in advanced epithelial ovarian cancer (AEOC) endowed with high tumour load (HTL). Material and methods: This is a single-Institution, superiority, randomised phase III trial enrolling supposed AEOC women. Patients considered pre-operatively eligible were triaged to staging laparoscopy to assess the predictive index (PI) of tumour load. All AEOC women with PI≥8 or≤12 (considered as HTL) were included. They were randomly assigned (1:1 ratio) to undergo either PDS followed by systemic adjuvant chemotherapy (arm A, standard), or NACT followed by IDS (NACT/IDS) (arm B, experimental). Co-primary outcome measures were postoperative complications (graded according to the Memorial Sloan Kettering Cancer Center surgical secondary events grading system) and progression free survival (PFS); secondary outcomes were overall survival, and quality of life (QoL). QoL was assessed using the EORTC QoL questionnaires. A sample size of 110 patients was required for the analysis of the first co-primary end-point (major peri-operative morbidity) whereas recruitment is still on-going to achieve the statistical power on PFS. Results: Between October 2011 and November 2014, we registered 280 AEOC. Of the 110 eligible women, 55 were assigned to arm A and 55 to arm B. Despite different extension of surgery, rates of complete residual disease (residual tumour=0 cm) were superimposable between the groups (45.5% versus 57.7%; p=0.206). Twenty-nine patients (52.7%) in arm A experienced early grade III-IV complications versus three patients (5.7%) in IDS (p=0.0001). The most common complication was grade III and consisted of symptomatic pleural effusion requiring thoracic drainage (17/55 women (30.9%) in arm A versus 1/52 (1.9%) in arm B, p=0.0001). Three grade IV (5.4%) (i.e., two re-operations for postoperative haemorrhage and one septic multi-organ failure), and two grade V (3.6%) (two deaths for acute cardiopulmonary failure) early complications were observed in arm A only. Mean QoL scores of several scales/items were shown to ameliorate over time in both arms. Emotional functioning, cognitive functioning, nausea/vomiting, dyspnoea, insomnia and hair loss were statistically and clinically better in NACT/IDS compared to PDS arm. Conclusions: Perioperative moderate/severe morbidity as well as QoL scores were shown to be more favourable in NACT/IDS arm than PDS in AEOC patients with very HTL. Completion of patient enrolment and analysis of survival data will clarify whether PDS with such a high rate of severe complications is an acceptable treatment in AEOC women with HTL.
- [Show abstract] [Hide abstract] ABSTRACT: To compare patterns and rates of early and late complications, and survival outcome in FIGO stage III cervical cancer patients submitted underwent to completion radical hysterectomy after chemo-radiation vs. chemo-radiation alone.
- [Show abstract] [Hide abstract] ABSTRACT: Study objective: to report our experience to perform robotic TMMR (R-TMMR) comparing peri-operative results with a series of Laparoscopic TMMR (L-TMMR). Design: Multicentric retrospective case-control study (Canadian Task Force II-2). Setting: Catholic University of the Sacred Heart of Rome (Italy) and Campobasso (Italy). Patients: From July 2013 to August 2015 all cervical cancer patients with pre-operative FIGO stage IA2- IB1 were assessed at pre-operative MRI scan and clinically confirmed by investigation under anesthesia, adhering strictly to the FIGO criteria. The surgical and post-surgical data of the TMMR procedures were collected. Interventions: R-TMMR and L-TMMR for early cervical cancer were performed. Measurements and main results: 21 women underwent R-TMMR (Cases) and 42 patients were submitted to L-TMMR (Controls) for early cervical cancer. The median estimated blood loss was 150 ml in the Cases and 200 ml in the Controls (p=.992). The median operative time, calculated from the beginning of intraperitoneal procedures to the skin closure, was 246 minutes in the Cases and 260 minutes in the Controls (p=.913). The median time to discharge from the hospital was postoperative day 4 (2-5) and 6 (4-15) for R-TMMR and L-TMMR, respectively (p=.001). Conclusion: The few differences we registered do not seem clinically relevant, thus making the two procedures comparable. Further prospective trials are needed to confirm our results.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To develop and validate a simple adjusted laparoscopic score to predict major postoperative complications after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (AEOC). Methods: From January 2006 to June 2015, preoperative, intraoperative, and post-operative outcome data from patients undergoing staging laparoscopy (S-LPS) before receiving PDS (n=555) were prospectively collected in an electronic database and retrospectively analyzed. Major complications were defined as levels 3 to 5 of MSKCC classification. On the basis of a multivariate regression model, the score was developed using a random two-thirds of the population (n=370) and was validated on the remaining one-third patients (n=185). Results: Major complication rate was 18.3% (102/555). Significant predictors included in the scoring system were: poor performance status, presence of ascites (> 500cm(3)), CA125 serum level (> 1000U/ml), and high laparoscopic tumor load (predictive index value, PIV≥8). The mean risk of developing major postoperative complications was 3.7% in patients with score 0 to 2, 13.2% in patients with score 3 to 5, 37.1% in patients with score 6 to 8. In the validation population, the predicted risk of major complications was 17.8% (33/185) versus a 16.7% (31/185) observed risk (C-statistic index =0.790). Conclusion: This new score may accurately predict a patient's postoperative outcome. Early identification of high-risk patients could help the surgeon to adopt tailored strategies on individual basis.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: As a result of relevant achievements in the field of translational research, several active drugs and multiple biological targets are available in ovarian cancer (OC). In this complex scenario, there is an urgent need to effectively summarize the available data in order to update conclusions, and outline perspectives. Methods: The results in terms of target identification and drug development have been summarized using the well-known hallmarks of cancer firstly described, and recently modified by Hanahan and Weinberg [1-2]. Published data from clinical trials have been retrieved from PubMed, Embase, CINAHL and Cochrane database. Ongoing clinical trials were searched using clinicaltrials.gov web platform, and identified using NCT number. Results: Genomic instability and angiogenesis are the most actively investigated hallmarks in high-grade serous OC, and the inhibition of tumor immune evasion appears as the emerging strategy for molecularly-driven therapy. Targeting sustained proliferative signaling through MEK and mTOR inhibitors seems the most promising approach in clear cell, and low-grade serous OC. Conclusions: This substantial amount of data suggests that targeted therapies are already part of the clinical and therapeutic management of OC patients. The expectations of getting from translational research a better knowledge of tumor biology and therefore personalized drugs are high and worthy of maximum effort from referral centers.
- [Show abstract] [Hide abstract] ABSTRACT: Epithelial ovarian cancer (EOC) remains the most lethal among gynecological malignancies. Evidence strongly suggests that administration of platinum-based hyperthermic intraperitoneal chemotherapy after cytoreductive surgery may represent an effective strategy to adequately treat both visible and microscopic disease, thus improving locoregional control.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: This study aims at evaluating the oncological outcome of early-stage ovarian cancer (eOC) patients managed by laparoscopy or laparotomy in a single high-volume gynecological cancer center. Methods: Data of consecutive women with eOC undergoing comprehensive laparoscopic staging between 2007 and 2013 were matched with a cohort of patients undergoing open surgery between 2000 and 2011. Four-year survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 60 women undergoing staging via laparoscopy were compared with a cohort of 120 patients undergoing open surgery. Baseline characteristics were similar between groups. Seventy percent of patients underwent adjuvant platinum-based chemotherapy without differences between the two groups. Operative time (p-value= 0.01), estimated blood loss (p-value= 0.032), and median hospital stay (p-value= 0.001) were higher in patients submitted to laparotomic versus laparoscopic staging. As of October 2015, median duration of follow-up was 38 months (range 24-48), recurrent disease was documented in 16 (13.3 %) patients in the laparotomic group and in 5 (8.3%) women in the laparoscopic group (p-value= 0.651), without differences in the pattern of recurrence presentation. Four-year progression free survival (PFS) and overall survival (OS) rates were 89% and 92% in the laparoscopic group, respectively, and 81% and 91% in the laparotomic group, without any statistical significant difference between the groups (4-year PFS p-value= 0.651; 4-year OS p-value= 0.719). Conclusions: The findings of the present study suggests that in the surgical treatment of FIGO stage I ovarian cancer, laparoscopy is associated with equivalent oncologic outcome compared to conventional abdominal approach.
- [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: To investigate the feasibility and safety of laparoscopic cytoreduction in ovarian cancer patients with localized carcinomatosis or lymph node involvement. Methods: Retrospective, multi-institutional study involving 69 preoperatively presumed early stage ovarian cancer patients who accidentally revealed localized carcinomatosis or lymph node involvement at laparoscopic evaluation or at postoperative pathological examination, managed by laparoscopic approach in 6 referral Gynecologic Oncology Units. Results: Between June 2005 and December 2014, a total of 69 ovarian cancer patients with limited carcinomatosis and/or lymph node metastases underwent laparoscopic surgical management. Twenty-eight (40.6 %) patients were staged III C because they had lymph node metastases. Pelvic lymphadenectomy was performed in 75.4 % of cases, while aortic lymphadenectomy was performed in 79.7% of cases. Lymph node metastases were found in pelvic and aortic regions in 11 and 13 patients, respectively, while 4 patients had lymph node metastases in both regions. Twelve (17.4%) patients underwent complete pelvic peritonectomy owing to the presence of nodules localized in several pelvic region sites. As of May 2015, the median follow-up was 35 months, and median disease free survival was 29 months. The 2-year disease free survival rate was 77.1%, while the 2-year overall survival rate was 90.6%. Median time to recurrence was 26 months (range 6-55); fifteen (21.7%) patients developed recurrence. Conclusions: The present study demonstrates the technical and clinical feasibility of laparoscopic cytoreduction in ovarian cancer patients with limited carcinomatosis or lymph node involvement.
- [Show abstract] [Hide abstract] ABSTRACT: Objective: To investigate the feasibility of laparoscopic splenectomy in recurrent ovarian cancer (ROC) patients with isolated spleen metastasis. Methods: From February 2013 to May 2015, 8 women with an isolated platinum sensitive splenic relapse of ovarian cancer were submitted to laparoscopic splenectomy. Results: All patients underwent laparoscopic splenectomy without conversion to open approach. The median estimated blood loss (EBL) was 100 ml (50 - 200). The median operating room time was 200 minutes (80-275). No intraoperative complication occurred and no intraoperative blood transfusions were required. The median length of hospital stay was 3 days (2-5). For all patients a complete tumor resection was achieved. The median time from surgery to adjuvant chemotherapy was 16 days (14-24). After a median follow-up of 23 months (6-32), no secondary recurrence or death of disease has been observed. Conclusions: Our report shows that a laparoscopic approach to remove the spleen is feasible for selected patients with a splenic relapse of ovarian cancer when performed in tertiary referral centers by well-trained surgeons.
- [Show abstract] [Hide abstract] ABSTRACT: Minimally invasive surgery (MIS) currently is performed to stage and treat ovarian cancer at different stages of disease; however, the higher level of evidence from existing studies is IIB. Despite the absence of randomized controlled trials, MIS represents a safe and adequate procedure for treating and staging early ovarian cancer, and its use has increased significantly in clinical practice. Major concerns are related to minimizing tumor disruption or dissemination, removing the adnexal mass intact, adequate retroperitoneal staging, and fertility-sparing surgery for young patients. The main goal for patients with advanced ovarian cancer is to determine the best therapeutic strategy by evaluating the risks and benefits of primary debulking surgery versus neoadjuvant chemotherapy followed by interval debulking surgery. The use of staging laparoscopy in patients with advanced epithelial ovarian cancer appears to be the most researched and accepted approach. Regarding other types and stages of ovarian cancer, although the evidence is very promising, clinical trials performed by expert gynecologic oncology surgeons in referral centers are still needed to prove the efficacy of such an approach in these patients. In particular, MIS has provided an opportunity to remove localized recurrences, with both retroperitoneal and intraperitoneal diffusion.
- [Show abstract] [Hide abstract] ABSTRACT: Background: To analyze the 5- and 7-year survival outcomes for women with platinum-sensitive recurrent epithelial ovarian cancer (REOC) who underwent secondary cytoreductive surgery (SCS) plus platinum-based hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: From the electronic databases of the Department of Obstetrics and Gynecology at the Catholic University of the Sacred Heart of Rome and of the S. Orsola Hospital, University of Bologna, a consecutive series of REOC patients were selected using the following inclusion criteria: primary platinum-free interval (PFI-1) of 6 months or longer, completeness of secondary cytoreduction score (CC) of 1 or lower, minimum follow-up period of 48 months, Eastern Cooperative Group (ECOG) performance status at recurrence of 1 or less, and platinum-based HIPEC. Progression-free survival (PFS) and post-relapse survival (PRS) were calculated as the time between SCS + HIPEC and secondary recurrence or death, respectively. Results: The final study population included 70 women with platinum-sensitive REOC. The median follow-up time was 73 months (range 48-128 months), and the median PFI-1 was 19 months (range 6-100 months). At the time of recurrence, the median peritoneal cancer index was 7 (range 1-21), and a CC score of 0 was achieved for 62 patients (88.6 %). As the HIPEC drug, we used oxaliplatin in 17 cases (38.6 %) and cisplatin in 43 cases (61.4 %). No postoperative deaths were observed, and the complication rate for grades 3 and 4 disease was 8.6 %. The median PFS duration was 27 months (range 5-104 months), and the 5- and 7-year PRS rates were respectively 52.8 and 44.7 %, (median PRS 63 months). Conclusions: The current study demonstrated favorable 5- and 7-year PRS rates for platinum-sensitive REOC patients undergoing SCS + HIPEC, which encourages the inclusion of patients in randomized clinical trials for definitive conclusions to be drawn.
- [Show abstract] [Hide abstract] ABSTRACT: This is a review of literature to assess the safety and effectiveness of robotic versus laparoscopic surgery in benign and malignant gynecological diseases. Robotic assisted laparoscopy is already widely used in the United States and Europe for the main gynecological procedure: hysterectomy and has been shown to be feasible and comfortable for other benign and malignant gynecological procedures. However, the clinical effectiveness and safety of robotic surgery compared with standard laparoscopy have not been undoubtedly established. We reviewed the literature by searching in the Ovid/MEDLINE, PubMed, Cochrane Library, and Google Scholar databases for all the articles published from January 1995 to September 2015. It is necessary more rigorous experimental studies that compare the RAS and laparoscopic surgery for gynecological diseases. Currently, data are encouraging to continue in minimally invasive surgery to treat benign and malignant gynecological diseases.
Catholic University of the Sacred Heart
Milano, Lombardy, Italy
- • School of Obstetrics and Gynecology
- • School of Oncology
Università degli Studi di Perugia
Perugia, Umbria, Italy
- Department of Cellular and Environmental Biology
Sacred Heart UniversityФеърфилд, Connecticut, United States
The Catholic University of AmericaWashington, Washington, D.C., United States