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Objective: The aim of this study was to assess the SLN detection rate in presumed early stage, low- and intermediate-risk endometrial cancers, the incidence of SLN metastases, and the negative predictive value of SLN mapping performed with indocyanine green (ICG). Methods: A systematic review with meta-analyses was conducted. Study inclusion criteria were A) low- and intermediate-risk endometrial cancer, B) the use of ICG per cervical injection; C) a minimum of twenty included patients per study. To assess the negative predictive value of SLN mapping, D) a subsequent lymphadenectomy was an additional inclusion criterion. Results: Fourteen studies were selected, involving 2,117 patients. The overall and bilateral SLN detection rates were 95.6% (95% confidence interval [CI]=92.4%-97.9%) and 76.5% (95% CI=68.1%-84.0%), respectively. The incidence of SLN metastases was 9.6% (95% CI=5.1%-15.2%) in patients with grade 1-2 endometrial cancer and 11.8% (95% CI=8.1%-16.1%) in patients with grade 1-3 endometrial cancer. The negative predictive value of SLN mapping was 100% (95% CI=98.8%-100%) in studies that included grade 1-2 endometrial cancer and 99.2% (95% CI=97.9%-99.9%) in studies that also included grade 3. Conclusion: SLN mapping with ICG is feasible with a high detection rate and negative predictive value in low- and intermediate-risk endometrial cancers. Given the incidence of SLN metastases is approximately 10% in those patients, SLN mapping may lead to stage shifting with potential therapeutic consequences. Given the high negative predictive value with SLN mapping, routine lymphadenectomy should be omitted in low- and intermediaterisk endometrial cancer. [ABSTRACT FROM AUTHOR]

To predict the overall pathologic response to neoadjuvant chemotherapy (NACT) of patients with locally advanced cervical cancer (LACC) creating a prediction model based on clinical-pathological factors and biomarkers (p53, Bcl1 and Bcl2) and to evaluate the prognostic outcomes of NACT. This is a retrospective study of 88 consecutive patients with LACC who underwent NACT followed by nerve sparing surgery with retroperitoneal lymphadenectomy at National Cancer Institute of Milan, between January 2000 and June 2013. Clinical pathologic data were retrieved from the institutional database. Biomarkers (p53, Bcl1 and Bcl2) were evaluated before and after NACT in the specimen. To investigate their role as predictors of response, we tried several statistical machine learning algorithms. Responders to NACT showed a 5-years survival between 100%(CR) and 85.7%(PR). Clinical factors were the most important predictor of response. Age, BMI and grade represented the most important predictors of response at random forest analysis. Tree-based boosting revealed that after adjusting for other prognostic factors, age, grade, BMI and tumor size were independent predictors of response to NACT, while p53 was moderately related to response to NACT. Area under the curve (crude estimate): 0.871. Whereas Bcl1 and Bcl2, were not predictors for response to NACT. The final logistic regression reported that grade was the only significant predictor of response to NACT. Combined model that included clinical pathologic variables plus p53 cannot predict response to NACT. Despite this, NACT remain a safe treatment in chemosensitive patients avoiding collateral sequelae related to chemo-radiotherapy. [ABSTRACT FROM AUTHOR]

The role of nodal dissection in patients with endometrial cancer has been intensively studied in several studies. Historically, systematic pelvic and para-aortic lymphadenectomy represented the gold standard surgical treatment to assess potential nodal involvement and consequently define the appropriate stage of the tumor. Over the last years, sentinel node biopsy (SLNB) has been introduced as a more targeted alternative to lymph node dissection for lymph node staging and it has become popular among gynecologic oncologists. However, no level A evidence is still available, and several features of the SLNB technique have been matter of discussion among clinicians and a universally accepted methodology is still not currently available. This narrative review aims to summarize the body of knowledge on SLNB to offer the reader a complete picture about the evolution of this technique over the last decades. [ABSTRACT FROM AUTHOR]

Objective: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. Methods: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy "LND" vs. those who underwent hysterectomy alone "NO-LND". Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). Results: One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32-1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02-1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08-12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31- 13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38; 95% CI=0.17-0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07; 95% CI=1.02-1.13; p<0.001). Conclusions: Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype. [ABSTRACT FROM AUTHOR]

Objectives To analyze detection-rate(DR) and diagnostic-accuracy (A) of sentinel-nodes(SLNs) mapping following hysteroscopic-injection of tracer. To compare DR and A between tracers: ICG and Tc99m. Methods Evaluation of endometrial-cancer patients who underwent SLNs mapping after hysteroscopic-peritumoral-injection of tracer ± lymphadenectomy. Analysis of DR (overall-bilateral-aortic) and A in the entire cohort and comparison between tracers. Results 202 procedures were performed from January/2005 to February/2017. Mean age:60 years (28–82); mean BMI: 26.8 kg/m 2 (15–47). In 133 cases (65.8%) hysterectomy and mapping procedure were performed laparoscopically. The overall-DR of the technique was 93.2% (179/192) (10 cases were excluded: 9 for technical-equipment failure; 1 for vagal reaction). Bilateral pelvic mapping was found in 59.7% of cases (107/179) and was more frequent in the ICG group (72.8% vs 53.3%; p: 0.012). In 50.8% of cases (91/179) SLNs were mapped both in pelvic and aortic nodes, and in 5 cases (2.8%) only in the aortic area. The mean number of detected SLNs was 3.7 (1–8). 22 patients (12.3%) had nodal involvement: 10-(45.5%)-macrometastases; 5-(22.7%)-micrometastases; 7-(31.8%)-ITCs. In 6 cases (27.3%) only aortic nodes were positive; in 5 cases (22.7%) both pelvic and aortic nodes and in 11 cases (50%) only pelvic nodes were involved. Three false-negative results were found, all in the Tc99m group. All had isolated aortic metastases with negative pelvic nodes. Overall-sensitivity was 86.4% (95%CI: 68.4–100) and overall-negative-predictive-value (NPV) was 96.4% (95%CI 86.7–100). No differences in terms of overall-DR, overall-sensitivity and overall-NPV were found between the two tracers. Conclusions Hysteroscopic-injection of tracer for SLNs mapping in endometrial cancer is as accurate as cervical injection with a higher DR in the aortic area. ICG improves bilateral-DR. Further investigation is warranted on this topic. [ABSTRACT FROM AUTHOR]

Objective Fertility-sparing surgery (FSS) is a strategy often considered in young patients with low-grade (G1-2) early-stage epithelial ovarian cancer (eEOC), while is still controversial in high-risk patients. We investigated the role of FSS in low and high-risk eEOC patients undergoing comprehensive surgical staging. Methods We analyzed data from patients operated for an eEOC from 1975 to 2011, focusing on patients submitted to FSS. Seventy patients out of 307 with eEOC were identified. Patients underwent FSS were compared with 237 patients underwent radical-comprehensive-staging (RCS) in the same period. Disease free (DFS) and overall (OS) survivals were evaluated using Kaplan-Meier and Cox models. Results Overall, 307 patients had surgery for eEOC: 70 (22.8%) and 237 (77.2%) women had FSS and RCS, respectively. At univariate analysis, the execution of FSS not influenced DFS (HR:1.06 (95%CI: 0.56,2.02); p = 0.84) and OS (HR:1.94 (95%CI: 0.75,4.98); p = 0.16). Stage of disease was the only factor correlating with DFS (HR:4.73; 95%CI: 2.01,11.11; p < 0.001). Independently, increased age (HR per 1-unit of age:1.06 (95%CI: 1.03,1.11); p < 0.001) and high risk disease (HR:3.26; 95%CI: 1.23,8.62; p = 0.01) remained associated with worse OS. Focusing on the high risk group (stage IAG3 or more) we observed that type of surgery (FSS v. RCS) did not influence DFS (p = 0.77, log-rank test) and OS (p = 0.08, log-rank test). Conclusions FSS upholds oncologic effectiveness of RCS, preserving reproductive and endocrine functions. FSS does not increase risk of recurrence among high risk eEOC patients. Further prospective studies on this issue are warranted to improve patients' care. [ABSTRACT FROM AUTHOR]

The role of adopting PET/CT and its cost-effectiveness in the context of sentinel node mapping have to be further validated into prospective trials. As observed for CT scan [[8]], in high-risk patients PET/CT would be useful in identify gross intra-abdominal disease and suspected nodes, thus tailoring surgical plans. Accumulating data suggested that sentinel node mapping improves detection rate of positive nodes in comparison to lymphadenectomy, thanks to the application of ultrastaging on sentinel nodes harvested. [Extracted from the article]

Sentinel node mapping is increasingly being utilized for endometrial cancer staging. However, only limited evidence supporting the adoption of sentinel node mapping instead of conventional lymphadenectomy is still available. Here, we aimed to review the current evidence comparing sentinel node mapping and lymphadenectomy in endometrial cancer staging. This systematic review was registered in the International Prospective Register of Systematic Reviews. Six comparative studies were included. Overall, 3536 patients were included: 1249 (35.3%) and 2287 (64.7%), undergoing sentinel node mapping and lymphadenectomy, respectively. Pooled data suggested that positive pelvic nodes were detected in 184 out of 1249 (14.7%) patients having sentinel node mapping and 228 out of 2287 (9.9%) patients having lymphadenectomy (OR: 2.03; (95%CI: 1.30 to 3.18); p = 0.002). No difference in detection of positive nodes located in the paraaortic was observed (OR: 93 (95%CI: 0.39 to 2.18); p = 0.86). Overall recurrence rate was 4.3% and 7.3% after sentinel node mapping and lymphadenectomy, respectively (OR: 0.90 (95%CI: 0.58 to 1.38); p = 0.63). Similarly, nodal recurrences were statistically similar between groups (1.2% vs. 1.7%; OR: 1.51 (95%CI: 0.70 to 3.29); p = 0.29). In conclusion, our meta-analysis underlines that sentinel node mapping is non-inferior to standard lymphadenectomy in term of detection of paraaortic nodal involvement and recurrence rates (any site and nodal recurrence); while, focusing on the ability to detect positive pelvic nodes, sentinel node mapping could be consider superior to lymphadenectomy. Further randomized studies are needed to asses long term effectiveness of sentinel node mapping. • Sentinel node mapping allows an accurate identification of nodal disease in the pelvic area in comparison to lymphadenectomy. • Sentinel node mapping is non inferior to lymphadenectomy in terms of para-aortic detection rate. • Sentinel node mapping does not increase nodal-specific recurrence. [ABSTRACT FROM AUTHOR]

Objective To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Methods Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Results Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively ( p = 0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement ( p < 0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Conclusions Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. [ABSTRACT FROM AUTHOR]

Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed. • Back-up lymphadectomy does not improve disease-free survival of high-risk EC undergoing SNM. • Back-up lymphadectomy does not improve overall survival of high-risk EC undergoing SNM. • Back-up lymphadenectomy increases positive node detection rate by 1%. [ABSTRACT FROM AUTHOR]

• Sentinel node mapping allows a more accurate identification of patients with nodal disease compared to lymphadenectomy. • Patients having sentinel node mapping experience similar outcomes than patients having lymphadenectomy. • Even in high-risk group sentinel node mapping ensures the oncologic safety of lymphadenectomy. [ABSTRACT FROM AUTHOR]

To evaluate the long-term outcomes of young early stage cervical cancer patients wishing to preserve their childbearing potential. Data of young (aged <40 years) patients with early stage cervical cancer were prospectively collected. All patients with stage IA2, IB1 and IB2 cervical cancer were included; they have cervical conization and pelvic node dissection performed via minimally invasive surgery. Survival outcomes were assessed with the Kaplan-Meier model. Overall, 32 patients met the inclusion criteria. Mean (SD) age of the population included was 33 (±4). According to the FIGO 2018 staging system, the stage of disease was IA2, IB1 and IB2 in 9 (28%), 21 (66%) and 2 (6%) cases, respectively. All patients included had cervical conization and laparoscopic pelvic node assessment, including systematic pelvic lymphadenectomy (N = 30, 94%) and sentinel node mapping (N = 2, 6%). In six (19%) patients the planned conservative treatment was discontinued. Median follow-up was 75 (range, 12–184) months. No recurrent disease was diagnosed among patients undergoing conservative treatment; while 2 out of 6 patients having definitive surgical or radiotherapy treatments developed recurrent disease. Five-year disease free and overall survivals were 94% and 97%, respectively. Considering reproductive outcomes, 11 (69%) out of 16 patients who attempted to conceive got pregnant. Cervical conization and pelvic nodes assessment could be considered a valid treatment modality for early-stage cervical cancer patients who are wishing to preserve their childbearing potential. • Cervical conization plus lymph node dissection is a valuable option for early-stage stage cervical cancer. • About 20% for patients initially submitted to fertility sparing procedure required radical treatments. • In case of negative margins, cervical conization guarantees a good local disease control rate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of full lymphadenectomy in patients with isolated nodal recurrence of ovarian cancer.Methods: In a retrospective study, the data of women undergoing secondary cytoreduction at the National Cancer Institute, Milan, Italy, between January 1, 2001, and December 31, 2015, were collected and patients with isolated nodal recurrence were identified. Factors predicting for disease-free interval (DFI) and overall survival were estimated using Kaplan-Meier survival analysis and Cox regression analysis.Results: Of the 199 consecutive patients whose data were collected, isolated nodal recurrence (defined as the presence of lymphatic disease) was observed in 35 women. Among this study cohort, lymphadenectomy and bulky node removal were performed in 11 (31%) and 24 (69%) patients, respectively. Women who underwent lymphadenectomy experienced better DFI compared with those who had bulky node removal only (median 21 and 12 months, respectively; P=0.019), and lymphadenectomy, but not bulky node removal, significantly improved rates of DFI (P=0.043). No factors were independently associated with overall survival; however, a trend toward an improved overall survival rate was observed in patients undergoing complete resection at the time of primary surgery (P=0.055).Conclusion: Lymphadenectomy at the time of secondary cytoreduction improved DFI but did not have a significant effect on overall survival. [ABSTRACT FROM AUTHOR]