Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

Role of Adjuvant Radiotherapy in Patients with Cervical Cancer Undergoing Radical Hysterectomy.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine adjuvant RT's impact on survival in accordance with Sedlis criteria. Patients with early-stage cervical cancer undergoing radical hysterectomy between 2005 and 2022 at a single tertiary care institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analysed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. 121 patients were included in this retrospective study, of whom 48 (39.7%) received adjuvant RT due to the presence of unfavourable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p = 0.584) or disease-free survival (DFS) (p = 0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate risk factors.

Impact of the Covid-19 pandemic on the management of gynecologic cancer: a Spanish survey. Observational, multicenter study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) pandemic changed the distribution of healthcare resources, leading in many cases to the suspension of all non-essential treatments and procedures and representing a challenge for medical professionals. The objective of this study was to evaluate whether clinical protocols in gynecologic oncology care were modified as a result of the pandemic and to assess surgeons' perceptions regarding the management of gynecologic cancers". METHODS: Data were collected through an anonymous and voluntary survey sent via email to healthcare professionals in the field of gynecologic oncology in Spain. RESULTS: A total of 75 gynecologic oncologists completed the online survey. Of these, 93.2% (69) reported working in public hospitals and 62.5% (45) in tertiary care hospitals. 97.3% (71) were affiliated with hospitals treating patients infected with SARS-CoV-2. 85.1% (63) of the respondents expressed concern about the SARS-CoV-2 pandemic and 52.1% (38) indicated that the pandemic impacted the diagnostic and therapeutic quality of care for oncology patients. SARS-CoV-2 nasopharyngeal swab PCR (Polymerase Chain Reaction) testing was always performed before surgical interventions by 97.3% (71), being considered a best practice in triage by 94.4% (68). 87.5% (63) reported no change in the type of surgical approach during the pandemic. 62.5% (45) experienced limitations in accessing special personal protective equipment for SARS-CoV-2. An impact on the follow-up of patients with gynecologic cancers due to the pandemic was reported by 70.4% (50). CONCLUSIONS: Most of the Spanish gynecologic oncologists who responded to our survey reported that the SARS-CoV-2 pandemic had affected their clinical practice. The primary measures implemented were an increase in telemedicine, restricting outpatient visits to high-risk or symptomatic patients and the use of SARS-CoV-2 screening prior to surgery. No major changes in the surgical approach or management of the treatment of ovarian, endometrial or cervical cancer during the pandemic were reported.

Personalized Sentinel Node Mapping in Endometrial Cancer by the Indocyanine Green Implementation as Single Tracer: A Case Control Study.

The main objective was to analyze the rate of bilateral sentinel lymph node (SLN) detection in endometrial cancer using indocyanine green (ICG) as a unique tracer compared to Technetium99 + ICG. As secondary objectives, we analyzed the drainage pattern and factors that might affect the oncological outcomes. A case-control ambispective study was carried out on consecutive patients at our center. Data on the SLN biopsy with ICG collected prospectively were compared to retrospective data on the use of a double-tracer technique including Technetium99 + ICG. In total, 194 patients were enrolled and assigned to both groups, in which the group with both tracers (controls) included 107 (54.9%) patients and the ICG-alone group (cases) included 87 (45.1%) patients. The rate of bilateral drainage was significantly higher in the ICG group (98.9% vs. 89.7%; p = 0.013). The median number of nodes retrieved was higher in the control group (three vs. two nodes; p < 0.01). We did not find survival differences associated with the tracer used (p = 0.85). We showed significant differences in terms of disease-free survival regarding the SLN location (p < 0.01), and obturator fossa retrieved nodes showed better prognosis compared to external iliac. The use of ICG as a single tracer for SLN detection in endometrial cancer patients seemed to obtain higher rates of bilateral detection with similar oncological outcomes.

Clustering Molecular Subtypes in Breast Cancer, Immunohistochemical Parameters and Risk of Axillary Nodal Involvement.

(1) Background: To establish similarities in the risk of axillary lymph node metastasis between different groups of women with breast cancer according to immunohistochemical (IHC) parameters. (2) Methods: Data was collected retrospectively, from 2000 to 2013, of 1058 node-positive breast tumours. All patients were divided according to the St Gallen 2013 criteria and IHC features. The proportion of axillary involvement (pN > pN0; pN > pN1mi; pN > pN1) was calculated for each group. Similarities in axillary nodal dissemination were explored by cluster analysis and association between IHC and risk of axillary disease was studied with multivariate analysis. (3) Results: Among clinico-pathological surrogates of intrinsic subtypes, axillary involvement was more frequent in Luminal-B like HER2 negative (45.8%) and less frequent in Luminal-B HER2 positive (33.8%; p = 0.044). Axillary macroscopic involvement was more frequent in Luminal-B like HER2 negative (37.9%) and HER2 positive (37.8%) and less frequent in Luminal-B HER2 positive (25.5%) and Luminal-A like (25.6%; p = 0.002). Axillary involvement ≥pN2 was significantly less frequent in Luminal-A like (7.4%; p < 0.001). Luminal-A with Luminal-B HER2 positive, and triple-negative with Erb-B2 overexpressing tumours were clustered together regarding any axillary involvement, macroscopic disease or ≥pN2. Among the defined subgroups, axillary metastases were more frequent when Ki67 was higher. In a multivariate analysis, Ki67>14% were associated with a risk of axillary metastases (HR: 1.31; 95% CI, 1.51−6.80; p < 0.037). (4) Conclusions: there are two lymphatic drainage pathways of the breast according to the expression of hormone receptor-related genes. Positive-ER tumors are associated with lower axillary involvement and negative-ER tumors and Ki67 > 14% with higher nodal involvement.

One-Step Nucleic Acid Amplification (OSNA) of Sentinel Lymph Node in Early-Stage Endometrial Cancer: Spanish Multicenter Study (ENDO-OSNA).

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study, and 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1 mm portion of each lymph node was subjected to semi-serial sectioning at 200 µm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analyzed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/µL), the sensitivity of the OSNA assay was 92%, specificity was 82%, diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

Robot-assisted Extraperitoneal Para-aortic Lymphadenectomy Is Associated with Fewer Surgical Complications: A Post Hoc Analysis of the STELLA-2 Randomized Trial.

STUDY OBJECTIVE: To evaluate if extraperitoneal para-aortic lymphadenectomy (PALND) using a robot-assisted approach was associated with fewer complications than all other approaches (conventional laparoscopic transperitoneal or extraperitoneal and robot-assisted transperitoneal) without compromising lymph node yield, operative time, or length of stay. DESIGN: Post hoc analysis of the prospective randomized open-label multicenter trial (STELLA-2). SETTING: Three academic referral hospitals. PATIENTS: Two hundred and three eligible patients from the STELLA-2 trial were included. INTERVENTIONS: The patients were randomized to extraperitoneal or transperitoneal PALND using a minimally invasive approach (either laparoscopic or robot-assisted) for surgical staging of endometrial or ovarian cancer. The minimally invasive approaches were not subjected to randomization. MEASUREMENTS AND MAIN RESULTS: The primary end point was evaluated through a composite variable that included at least 1 of the following events: blood loss ≥500 mL during PALND, any intraoperative complication related to PALND, severe postoperative complication (Clavien-Dindo ≥grade IIIA), impossibility of completing the procedure, or conversion to laparotomy. Of the 203 patients analyzed, 68 were assigned to the extraperitoneal laparoscopic group (X-L), 62 to the transperitoneal laparoscopic group (T-L), 35 to the extraperitoneal robotic group (X-R), and 38 to the transperitoneal robotic group (T-R). A reduced trend in complications was observed in the extraperitoneal robot-assisted arm when considering the primary end point (X-L: 25.0%, T-L: 24.2%, X-R: 5.7%, T-R: 28.9%; p = .073). In a multivariable analysis, age (odds ratio [OR] 1.05; 95% confidence interval [CI], 1.00-1.09), body mass index (OR 1.09; 95% CI, 1.03-1.16), and waist-to-hip ratio (OR 1.66; 95% CI, 1.12-2.47) were found to independently increase the risk of PALND complications, whereas the extraperitoneal robotic approach (OR 0.13; 95% CI, 0.02-0.64) was an independent protective factor for complication occurrence. CONCLUSION: Robot-assisted extraperitoneal PALND is associated with fewer surgical complications, without compromising lymph node retrieval, operative time, or length of stay. Robot-enhanced 3D visualization, surgeon ergonomics, or hemostatic precision could explain our results.

Avoiding Full Lymphadenectomies in Intermediate- and High-Risk Endometrial Cancer by Sentinel Lymph Node Biopsy Implementation.

OBJECTIVE: To evaluate the role of sentinel lymph node biopsy (SLNB) to avoid staging lymphadenectomies by detecting nodal metastasis in intermediate- and high-risk endometrial cancer (EC). METHODS: A single institutional retrospective study was performed including all patients with intermediate- and high-risk EC who underwent surgical nodal staging between January 2012 and December 2019. Patients with disseminated disease detected on imaging techniques or at the time of surgery were excluded. Patients were evaluable if they underwent nodal staging with SLNB and pelvic (PLD) and paraaortic (PALD) lymph node dissection. We analyzed the accuracy of the sentinel lymph node technique. Only patients with at least one sentinel lymph node (SLN) detected were included in the sensitivity and negative predictive value (NPV) analyses. The tracers used were technetium 99m, blue dye, and indocyanine green. RESULTS: Eighty-eight patients presented intermediate- and high-risk EC (51 patients and 37 patients respectively) and underwent SLNB with consecutive PLD and PALD. The median (range) number of sentinel nodes retrieved was 2.9 (0-11). The global detection rate of SLN was 96.6% with a bilateral detection of 80.7% when considering all tracers used. However, when combination of indocyanine green and technetium was used the bilateral detection rate was 90.3%. Nodal metastases were detected in 17 (19.3%) cases, 8 (47%) of them corresponded to low volume metastasis (LVM), 7 (87.5%) of them diagnosed at ultrastaging pathologic exam. Finally, we obtained a sensitivity of 90%, a NPV of 97.5%, and a false negative rate (FNR) of 10% in the intermediate-risk EC compared to sensitivity of 85.7%, NPV of 96.6%, and FNR of 14.3% in the high-risk EC group. The only patient with isolated paraaortic nodal metastasis was found at the high-risk group, 1.1%. CONCLUSIONS: According to our results, full lymphadenectomy could be avoided by performing SLNB in patients with intermediate-risk EC because the only false negative case detected was at the beginning of ICG learning curve. For high-risk EC patients we did not find enough evidence to support the systematic avoidance of staging full lymph node dissection. Nevertheless, SLNB should be performed in all cases of EC as it improves LVM diagnosis substantially.

M-TRAP: Safety and performance of metastatic tumor cell trap device in advanced ovarian cancer patients.

OBJECTIVE: Despite radical surgery and chemotherapy, most patients with ovarian cancer die due to disease progression. M-Trap is an implantable medical device designed to capture peritoneal disseminated tumor cells with the aim to focalize the disease. This trial analyzed the safety and performance of the device. METHODS: This first-in-human prospective, multi-center, non-blinded, single-arm study enrolled 23 women with high-grade serous advanced ovarian cancer. After primary or interval debulking surgery, 3 M-Trap devices were placed in the peritoneum of the abdominal cavity. 18-months post-implantation or at disease progression, devices were initially removed by laparoscopy. The primary safety endpoint was freedom from device and procedure-related major adverse events (MAEs) through 6-months post-implantation compared to an historical control. The primary performance endpoint was histopathologic evidence of tumor cells capture. RESULTS: Only one major adverse event was attributable to the device. 18 women were free of device and procedure related MAEs (78.3%). However, the primary safety endpoint was not achieved (p = 0.131), primarily attributable to the greater surgical complexity of the M-Trap patient population. 62% of recurrent patients demonstrated tumor cell capture in at least one device with a minimal tumor cell infiltration. No other long-term device-related adverse events were reported. The secondary performance endpoint demonstrated a lack of disease focalization. CONCLUSIONS: The M-Trap technology failed to meet its primary safety objective, although when adjusted for surgical complexity, the study approved it. Likewise, the devices did not demonstrate the anticipated benefits in terms of tumor cell capture and disease focalization in recurrent ovarian cancer.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis.

INTRODUCTION: Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. METHODS: We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. RESULTS: A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). CONCLUSION: In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer.

OBJECTIVE: To assess the survival benefit of primary debulking surgery (PDS) compared to interval debulking surgery (IDS) after complete cytoreduction (CC-0) or cytoreduction to minimal residual disease (CC-1) in advanced ovarian cancer. Secondary objective was to evaluate the effect of tumor load and surgical complexity on patients' survival. METHODS: A retrospective multicentric study was designed, including patients with IIIC-IV FIGO stage ovarian cancer who underwent PDS or IDS with CC-0 or CC-1 from January 2008 to December 2015 in four high-volume institutions. Patients were classified in three groups: PDS, IDS after 3-4 cycles of neoadjuvant chemotherapy (NACT), and IDS after 6 cycles. Disease-free survival (DFS) and overall survival (OS) were estimated. Univariable and multivariable analyses were conducted. RESULTS: We included 549 patients, 175 (31.9%) underwent PDS, 224 (40.8%) had IDS after 3-4 cycles of NACT, and 150 (27.3%) underwent IDS after 6 cycles. Median DFS in PDS, IDS at 3-4 cycles and IDS at 6 cycles were 23.0 months (95%CI = [20.0-29.3]), 18.0 months (95%CI = [15.9-20.0]) and 17.1 months (95%CI = [15.0-20.9]), respectively; p < .001. Median OS were 84.0 months (95%CI = [68.3-111.0]), 50.7 months (95%CI = [44.6-59.5]) and 47.5 months (95%CI = [39.3-52.9]), respectively; p < .001. In multivariable analysis, high peritoneal cancer index score and NACT were negatively associated to DFS and OS. Surgical complexity and CC-1 were negatively associated to DFS. CONCLUSION: PDS offered a survival gain of almost three years compared to IDS in patients with minimal or no residual disease after surgery. PDS should remain the standard of care for advanced ovarian cancer.