Superparamagnetic iron oxide (SPIO) for sentinel lymph node detection in vulvar cancer.

OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.

Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?

BACKGROUND: We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). METHODS: This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. RESULTS: After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p < 0.001). Nodal (regional) recurrences were more frequently observed in PALND patients (noPALND:2.4%, PALND: 11.2%, p < 0.001). Among those who recurred regionally, 57.1% recurred at the pelvic nodes, 37.1% recurred at the aortic nodes, and 5.7% recurred simultaneously at both the pelvic and aortic nodes. Patients who underwent a staging PALND were more frequently diagnosed with a distant recurrence (noPALND: 7.0%, PALND: 15.6%, p < 0.001). PALND patients presented poorer overall, cancer-specific, and disease-free survival when compared to patients in the noPALND group. CONCLUSION: After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates.

Prognostic factors in young women with epithelial ovarian cancer: the Young Ovarian Cancer-Care (YOC-Care) study.

OBJECTIVE: To determine oncological outcomes and to identify prognostic factors in women aged <45 years with epithelial ovarian cancer. METHODS: A multicenter retrospective study was performed of patients treated for epithelial ovarian cancer aged <45 years between January 2010 and December 2019. RESULTS: A total of 998 patients with epithelial ovarian cancer from 55 different institutions in Spain were collected. The median age of the study population was 40.8 years (range 35.6-43.4). The grouped International Federation of Gynecology and Obstetrics (FIGO) stage distribution was 508 (50.9%) patients in initial stages (I and II) and 490 (49.1%) with advanced stages (III and IV). Three hundred and twenty-five (32.6%) patients presented with recurrent disease after a median follow-up of 33.1 months (range 16.1-66.4). The type of staging surgery (incomplete vs complete), type of initial treatment modality (primary cytoreduction vs interval surgery), and amount of residual disease were all significantly associated with overall survival. Tumor rupture was noted in 288 (27.9%) cases, but it was not associated with oncologic outcomes (p=0.11 for overall survival). In the multivariate analysis, the response based on radiological findings (HR 3.24, 95% CI 2.14 to 4.91 for partial response; HR 6.93, 95% CI 4.79 to 10.04 for progression), neoadjuvant chemotherapy (HR 1.42, 95% CI 1.04 to 1.94), and FIGO stage (HR 1.68, 95% CI 1.40 to 2.02) were identified as independent prognostic factors associated with worse oncologic outcomes (p<0.001). CONCLUSION: The partial and progression radiology-based response after chemotherapy, neoadjuvant chemotherapy, and advanced FIGO stage are independent prognostic factors associated with worse oncological outcomes in women aged <45 years with epithelial ovarian cancer.

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 Hospital Case Volume on Uterine Sarcoma Prognosis: SARCUT Study Subanalysis.

BACKGROUND: High-complexity and low-prevalence procedures benefit from treatment by referral centers. The volume of cases necessary to maintain high training in the treatment of gynecologic sarcoma is currently unknown. This study aimed to determine differences in survival and recurrence as a function of the volume of patients treated per center. METHODS: The multicentric cross-sectional SARComa of the Uterus (SARCUT) study retrospectively collected cases of uterine sarcomas from 44 centers in Europe from January 2001 to December 2007. The survival of patients treated in high case-volume (HighCV) centers was compared with the survival of patients treated in low case-volume (LowCV) centers. RESULTS: The study enrolled 966 patients: 753 in the LowCV group and 213 in the HighCV. Overall survival (OS) was 117 months, and cancer-specific survival (CSS) was 126 months. The difference was significant (respectively p = 0.0003 and 0.0004, log rank). After adjustment for other confounding factors, the remaining significant factors were age (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.03-1.05), histology (HR, 1.19; 95% CI, 1.06-1.34), extrauterine involvement (HR, 1.61; 95% CI, 1.24-2.10) and persistent disease after treatment (HR, 3.22; 95% CI, 2.49-4.18). The cytoreduction performed was significantly associated with the CSS and OS in both groups. The log rank for surgical cytoreduction was a p value lower than 0.0001 for OS, lower than 0.0001 for the LowCV centers, and 0.0032 for the HighCV centers. CONCLUSIONS: The prognosis for patients with uterine sarcoma is directly related to complete tumor cytoreduction, histologic type, and FIGO stage, with significant differences between low and high case-volume centers. Patients with uterine sarcomas should be centralized in HighCV centers to improve their oncologic outcomes.

Aortic sentinel node detection in endometrial cancer: 6 year prospective study.

OBJECTIVE: The aim of this study was to describe our final results using dual cervical and fundal indocyanine green injection for the detection of sentinel lymph nodes (SLNs) in endometrial cancer along parametrial and infundibular drainage pathways. METHODS: We conducted a prospective observational study between 26 June 2014 and 31 December 2020 enrolling 332 patients that underwent laparoscopic surgery for endometrial cancer at our hospital. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection identifying pelvic and aortic SLNs. All SLNs were processed with an ultrastaging technique. A total of 172 patients also underwent total pelvic and para-aortic lymphadenectomy. RESULTS: The detection rates were as follows: 94.0% overall for SLNs; 91.3% overall for pelvic SLNs; 70.5% for bilateral SLNs; 68.1% for para-aortic SLNs, and 3.0% for isolated paraaortic SLNs. We found lymph node involvement in 56 (16.9%) cases, macrometastasis in 22, micrometastasis in 12 and isolated tumor cells in 22. Fourteen patients had isolated aortic nodal involvement, representing 25% of the positive cases. There was one false negative (SLN biopsy negative but lymphadenectomy positive). Applying the SLN algorithm, the sensitivity of the dual injection technique for SLN detection was 98.3% (95% CI 91-99.7), specificity 100% (95% CI 98.5-100), negative predictive value 99.6% (95% CI 97.8-99.9), and positive predictive value 100% (95% CI 93.8-100). Overall survival at 60 months was 91.35%, with no differences between patients with negative nodes, isolated tumor cells and treated nodal micrometastasis. CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer account for as many as a quarter of the positive cases and should be considered, especially in high-risk patients.

Oncological outcomes among young women with non-epithelial ovarian cancer: the YOC-Care study (Young Ovarian Cancer - Care).

OBJECTIVE: To determine oncological outcomes and associated prognostic factors in women younger than 45 years diagnosed with non-epithelial ovarian cancer. METHODS: A retrospective, multicenter Spanish study was performed including women with non-epithelial ovarian cancer younger than 45 years between January 2010 and December 2019. All types of treatments and stages at diagnosis with at least 12 months of follow-up were collected. Women with missing data, epithelial cancers, borderline or Krukenberg tumors, and benign histology, as well as patients with previous or concomitant cancer, were excluded. RESULTS: A total of 150 patients were included in this study. The mean±SD age was 31.45±7.45 years. Histology subtypes were divided into germ cell (n=104, 69.3%), sex-cord (n=41, 27.3%), and other stromal tumors (n=5, 3.3%). Median follow-up time was 58.6 (range: 31.10-81.91) months. Nineteen (12.6%) patients presented with recurrent disease with a median time to recurrence of 19 (range: 6-76) months. Progression-free survival and overall survival did not significantly differ among histology subtypes (p=0.09 and 0.26, respectively) and International Federation of Gynecology and Obstetrics (FIGO) stage (I-II vs III-IV) with p=0.08 and p=0.67, respectively. Univariate analysis identified sex-cord histology with the lowest progression-free survival. Multivariate analysis showed that body mass index (BMI) (HR=1.01; 95% CI 1.00 to 1.01) and sex-cord histology (HR=3.6; 95% CI 1.17 to 10.9) remained important independent prognostic factors for progression-free survival. Independent prognostic factors for overall survival were BMI (HR=1.01; 95% CI 1.00 to 1.01) and residual disease (HR=7.16; 95% CI 1.39 to 36.97). CONCLUSIONS: Our study showed that BMI, residual disease, and sex-cord histology were prognostic factors associated with worse oncological outcomes in women younger than 45 years diagnosed with non-epithelial ovarian cancers. Even though the identification of prognostic factors is relevant to identify high-risk patients and guide adjuvant treatment, larger studies with international collaboration are essential to clarify oncological risk factors in this rare disease.

SUCCOR quality: validation of ESGO quality indicators for surgical treatment of cervical cancer.

OBJECTIVE: To evaluate whether compliance with European Society of Gynaecological Oncology (ESGO) surgery quality indicators impacts disease-free survival in patients undergoing radical hysterectomy for cervical cancer. METHODS: In this retrospective cohort study, 15 ESGO quality indicators were assessed in the SUCCOR database (patients who underwent radical hysterectomy for International Federation of Gynecology and Obstetrics (FIGO) stage 2009 IB1, FIGO 2018 IB1, and IB2 cervical cancer between January 2013 and December 2014), and the final score ranged between 0 and 16 points. Centers with more than 13 points were classified as high-quality indicator compliance centers. We constructed a weighted cohort using inverse probability weighting to adjust for the variables. We compared disease-free survival and overall survival using Cox proportional hazards regression analysis in the weighted cohort. RESULTS: A total of 838 patients were included in the study. The mean number of quality indicators compliance in this cohort was 13.6 (SD 1.45). A total of 479 (57.2%) patients were operated on at high compliance centers and 359 (42.8%) patients at low compliance centers. High compliance centers performed more open surgeries (58.4% vs 36.7%, p<0.01). Women who were operated on at centers with high compliance with quality indicators had a significantly lower risk of relapse (HR=0.39; 95% CI 0.25 to 0.61; p<0.001). The association was reduced, but remained significant, after further adjustment for conization, surgical approach, and use of manipulator surgery (HR=0.48; 95% CI 0.30 to 0.75; p=0.001) and adjustment for adjuvant therapy (HR=0.47; 95% CI 0.30 to 0.74; p=0.001). Risk of death from disease was significantly lower in women operated on at centers with high adherence to quality indicators (HR=0.43; 95% CI 0.19 to 0.97; p=0.041). However, the association was not significant after adjustment for conization, surgical approach, use of manipulator surgery, and adjuvant therapy. CONCLUSIONS: Patients with early cervical cancer who underwent radical hysterectomy in centers with high compliance with ESGO quality indicators had a lower risk of recurrence and death.

Transperitoneal vs extraperitoneal approach for aortic sentinel node detection in endometrial cancer.

BACKGROUND: Although the sentinel lymph node technique in endometrial cancer is currently replacing pelvic and aortic lymphadenectomy for the evaluation of lymph node status in endometrial cancer, its performance is not yet standardized. OBJECTIVE: This study aimed to describe the detection rates and locations of aortic sentinel lymph node detection after dual cervical and fundal indocyanine green injection in patients with endometrial cancer, using the transperitoneal and extraperitoneal approaches. STUDY DESIGN: Between June 26, 2014 and December 31, 2019, 278 patients underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed sentinel lymph node biopsy with dual cervical and fundal indocyanine green injection, and back-up lymphadenectomy in high-risk cases. A post hoc analysis was performed to evaluate differences between the transperitoneal and extraperitoneal approach to aortic sentinel lymph nodes. RESULTS: The detection rates were as follows: overall detection rate: 93.2% (259/278); pelvic detection rate: 90.3% (251/278); bilateral pelvic detection rate: 68.0% (189/278); aortic detection rate: 66.9% (186/278); and isolated aortic detection rate: 2.88% (8/278). Transperitoneal and extraperitoneal aortic detection rates were similar (65.0% and 69.6%, respectively), with no significant differences (P=.441). Isolated aortic metastases were similar in both groups (2% vs 4.7%, respectively; P=.185). The laterality of aortic sentinel lymph node detection was influenced by the surgical approach (P=.002), but not its location above or below the inferior mesenteric artery (P=.166 and P=.556, respectively). CONCLUSION: The detection rates at the aortic level were similar between the transperitoneal and extraperitoneal approaches, with no impact on subsequent pelvic detection. The transperitoneal approach detected more laterocaval, precaval, and interaortocaval nodes, whereas the extraperitoneal approach detected more preaortic and left lateroaortic nodes.

Tumor Size and Oncological Outcomes in Patients with Early Cervical Cancer Treated by Fertility Preservation Surgery: A Multicenter Retrospective Cohort Study.

Background: The aim of this study was to analyze the impact of tumor size > 2 cm on oncological outcomes of fertility-sparing surgery (FSS) in early cervical cancer in a Spanish cohort. Methods: A multicenter, retrospective cohort study of early cervical cancer (stage IA1 with lymphovascular space invasion -IB1 (FIGO 2009)) patients with gestational desire who underwent FSS at 12 tertiary departments of gynecology oncology between 01/2005 and 01/2019 throughout Spain. Results: A total of 111 patients were included, 82 (73.9%) with tumors < 2 cm and 29 (26.1%) with tumors 2−4 cm. Patients' characteristics were balanced except from lymphovascular space invasion. All were intraoperative lymph node-negative. Median follow-up was 55.7 and 30.7 months, respectively. Eleven recurrences were diagnosed (9.9%), five (6.0%) and six (21.4%) (p < 0.05). The 3-year progression-free survival (PFS) was 95.7% (95%CI 87.3−98.6) and 76.9% (95% CI 55.2−89.0) (p = 0.011). Only tumor size (<2 cm vs. 2−4 cm) was found to be significant for recurrence. After adjusting for the rest of the variables, tumor size 2−4 cm showed a Hazard Ratio of 5.99 (CI 95% 1.01−35.41, p = 0.036). Conclusions: Tumor size ≥ 2 cm is the most important negative prognostic factor in this multicenter cohort of patients with early cervical cancer and gestational desire who underwent FSS in Spain.

Role of fluorescence imaging for intraoperative intestinal assessment in gynecological surgery: a systematic review.

BACKGROUND: Our aim was to review the current knowledge of the role of fluorescence imaging for intraoperative intestinal assessment in gynecological surgery. MATERIAL AND METHODS: A computer-based systematic review was performed from 2000 to 2020. All articles describing the use of indocyanine green (ICG) applied to bowel assessments in gynecology or endometriosis surgery were considered for review. RESULTS: ICG is an effective tool for assessing bowel vascularization, potentially preventing anastomotic leakage and recto-vaginal fistula and can therefore be useful for endometriosis surgery or bowel assessment in gynecological oncology procedures. Real-time characterization of the hypovascular pattern of endometriotic nodules has been associated with a larger nodule size and lower microvessel density, helping surgeons choose the best transecting line and the most appropriate technique. ICG angiography allows for a laparoscopic and intrarectal bowel assessment, which can act as a double check of bowel perfusion, enabling the assessment of mucosa vascularization. ICG fluorescence can guide intraoperative decision-making after intestinal anastomosis, discoid resection, and rectal shaving, preventing anastomotic leakage and postoperative recto-vaginal fistula in low anterior resections. CONCLUSIONS: ICG angiography provides a better intestinal assessment. Larger, prospective, randomized controlled studies are needed to validate the technique and confirm these encouraging results.

Maximizing sentinel node detection in endometrial cancer with dual cervical and transcervical fundal indocyanine green injection: 5-year single-center prospective study.

OBJECTIVE: The aim of this study was to describe our latest results using dual cervical and fundal indocyanine green injection for detection of sentinel lymph node (SLN) in endometrial cancer. METHODS: A prospective observational study was conducted between 26 June 2014 and 31 December 2019 with 278 patients that underwent laparoscopic surgery for endometrial cancer at our institution. In all cases, we performed SLN biopsy with dual cervical and fundal indocyanine green injection. All SLNs were processed with an ultrastaging technique. A total of 128 patients also underwent total pelvic and paraaortic lymphadenectomy. RESULTS: The detection rates were as follows: 93.5 % (260/278) overall for SLNs; 90.7 % (252/278) overall for pelvic SLNs; 68.0 % (189/278) for bilateral SLNs; 66.9 % (186/278) for paraaortic SLNs, and 2.9 % (8/278) for isolated paraaortic SLNs. We found macroscopic lymph node metastasis in 26 patients (10.0 %) and microdisease in lymph nodes in another 48 patients, raising the overall rate of lymph node involvement to 16.2 %. There was one false negative (negative SLN biopsy but positive lymphadenectomy). Applying the SLN algorithm, the sensitivity of detection was 97.9 % (95 % CI 89.1-99.6), specificity 100 % (95 % CI 98.2-100), negative predictive value 99.5 % (95 % CI 97.4-99.9), and positive predictive value 100 % (95 % CI 92.4-100). CONCLUSIONS: Dual sentinel node injection is a feasible technique that achieves adequate detection rates. Additionally, this technique allows a high rate of aortic detection, identifying a non-negligible percentage of isolated aortic metastases. Aortic metastases in endometrial cancer are possible and we should not give up actively looking for them.

Impact of restaging lymphadenectomy after sentinel node biopsy on endometrial cancer.

INTRODUCTION: Approximately 10 % of patients with an intra-operative diagnosis of low-risk endometrial cancer (EC) will be upstaged after a definitive histological evaluation of hysterectomy and bilateral adnexectomy samples. This study aimed to explore the results associated with the performance of pelvic and para-aortic lymphadenectomy for restaging after upstaging/upgrading these patients, and to compare those who underwent sentinel lymph node biopsy (SNB) in the first procedure with those who did not. MATERIALS AND METHODS: This retrospective cohort study included 27 patients diagnosed with low-risk EC (based on the criteria of the European Society of Medical Oncology/European Society of Gynecological Oncology/European Society for Radiotherapy and Oncology), who underwent surgical laparoscopic restaging due to upstaging based on the final histological result at Hospital Universitario Donostia from April 2013 to September 2018. Surgical and oncological results were compared between patients who underwent hysterectomy and double adnexectomy without any additional procedures (SNB-; n = 17) and patients who also underwent pelvic&aortic sentinel node biopsysen (SNB+; n = 10). The main outcome evaluated in the study was intra-operative complications. Secondary outcomes were mean operative time, length of hospital stay, number of nodes obtained, progression-free survival (PFS) and overall survival (OS). RESULTS: The median duration of restaging surgery was 240 [interquartile range (IQR) 180-300) min in the SNB(-) group and 300 (IQR 247.5-330) min in the SNB(+) group; this difference was significant (one-sided Student's t-test, p = 0.0295). With regard to intra-operative complications, there were 17.65 % and 40 % in the SNB(-) and SNB(+) groups, respectively, all of which were vascular; this difference was not significant. There were no significant difference in the length of hospital stay, number of pelvic nodes obtained, PFS or OS between the groups. CONCLUSION: Women with EC who require lymph node restaging due to upstaging, and have previously undergone SNB, experience more surgical complications and a longer operative time. The authors advise against performing second restaging surgery in these patients.

Utility of Intraoperative Fluorescence Imaging in Gynecologic Surgery: Systematic Review and Consensus Statement.

BACKGROUND: This study aimed to review the current knowledge on the utility of intraoperative fluorescence imaging in gynecologic surgery and to give evidence-based recommendations to improve the quality of care for women who undergo gynecologic surgery. METHODS: A computer-based systematic review of the MEDLINE, CENTRAL, Pubmed, EMBASE, and SciSearch databases as well as institutional guidelines was performed. The time limit was set at 2000-2019. For the literature search, PRISMA guidelines were followed. A modified-Delphi method was performed in three rounds by a panel of experts to reach a consensus of conclusions and recommendations. RESULTS: Indocyanine green (ICG) is used primarily in gynecology for sentinel node-mapping. In endometrial and cervical cancer, ICG is a feasible, safe, time-efficient, and reliable method for lymphatic mapping, with better bilateral detection rates. Experience in vulvar cancer is more limited, with ICG used together with Tc-99 m as a dual tracer and alone in video endoscopic inguinal lymphadenectomy. In early ovarian cancer, results are still preliminary but promising. Indocyanine green fluorescence imaging also is used for ureteral assessment, allowing intraoperative ureteral visualization, to reduce the risk of ureteral injury during gynecologic surgery. CONCLUSIONS: For most gynecologic cancers, ICG fluorescence imaging is considered the tracer of choice for lymphatic mapping. The use of this new technology expands to a better ureteral assessment.