Is there any therapeutic role of pelvic and para-aortic lymphadenectomy in apparent early stage epithelial ovarian cancer?

OBJECTIVE: The therapeutic role of pelvic and para-aortic lymphadenectomy in surgical staging of apparent early-stage epithelial ovarian cancer (eEOC) is still under debate. The aim of this study was to evaluate the potential therapeutic role of systematic lymphadenectomy in patients with eEOC. METHODS: Multi-center retrospective cohort study, comparing women with apparent eEOC who underwent comprehensive bilateral pelvic and para-aortic lymphadenectomy (defined as ≥20 lymph nodes) versus patients receiving no lymphadenectomy or lymph node sampling, from 05/1985 to 12/2016. Patients with bulky nodes at CT-scan and those without complete intra-peritoneal surgical staging were excluded. Only patients who received at least 3 cycles of platinum-based adjuvant chemotherapy were included. RESULTS: Out of 2559 patients with FIGO stage IA-IIIA1 ovarian cancer, 639 (25.0%) met inclusion criteria. 360 (56.3%) underwent comprehensive lymphadenectomy, 150 (23.5%) lymph node sampling and 129 (20.2%) no lymphadenectomy. Patients who underwent comprehensive lymphadenectomy were younger (p < 0.001), experienced a higher number of severe post-operative complications (p = 0.008) and had a longer time to start chemotherapy (p = 0.034). There was no difference in intra-operative complications. Median follow-up was 63 months (range, 5-342). The 5-year disease-free survival (DFS) was 79.7% vs. 76.5% vs. 68.3% (p = 0.006), and 5-year overall survival (OS) was 92.3% vs. 94.5% vs. 89.8% (p = 0.165) in women who received comprehensive lymphadenectomy vs. lymph node sampling vs. no lymphadenectomy, respectively. Lymphadenectomy represented an independent factor for DFS improvement, HR 0.52 (95%CI 0.37-0.73) (p < 0.001). CONCLUSION: Pelvic and para-aortic lymphadenectomy in surgical staging of eEOC improves DFS for the price of increasing post-operative complications and time to chemotherapy but does not affect OS. Better understanding of tumor biology may help to identify those patients in whom lymphadenectomy should still play a role.

Combining positron emission tomography/computed tomography, radiomics, and sentinel lymph node mapping for nodal staging of endometrial cancer patients.

OBJECTIVE: To evaluate the combination of positron emission tomography/computed tomography (PET/CT) and sentinel lymph node (SLN) biopsy in women with apparent early-stage endometrial carcinoma. The correlation between radiomics features extracted from PET images of the primary tumor and the presence of nodal metastases was also analyzed. METHODS: From November 2006 to March 2019, 167 patients with endometrial cancer were included. All women underwent PET/CT and surgical staging: 60/167 underwent systematic lymphadenectomy (Group 1) while, more recently, 107/167 underwent SLN biopsy (Group 2) with technetium-99m +blue dye or indocyanine green. Histology was used as standard reference. PET endometrial lesions were segmented (n=98); 167 radiomics features were computed inside tumor contours using standard Image Biomarker Standardization Initiative (IBSI) methods. Radiomics features associated with lymph node metastases were identified (Mann-Whitney test) in the training group (A); receiver operating characteristic (ROC) curves, area under the curve (AUC) values were computed and optimal cut-off (Youden index) were assessed in the test group (B). RESULTS: In Group 1, eight patients had nodal metastases (13%): seven correctly ridentified by PET/CT true-positive with one false-negative case. In Group 2, 27 patients (25%) had nodal metastases: 13 true-positive and 14 false-negative. Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PET/CT for pelvic nodal metastases were 87%, 94%, 93%, 70%, and 98% in Group 1 and 48%, 97%, 85%, 87%, and 85% in Group 2, respectively. On radiomics analysis a significant association was found between the presence of lymph node metastases and 64 features. Volume-density, a measurement of shape irregularity, was the most predictive feature (p=0001, AUC=0,77, cut-off 0.35). When testing cut-off in Group B to discriminate metastatic tumors, PET false-negative findings were reduced from 14 to 8 (-43%). CONCLUSIONS: PET/CT demonstrated high specificity in detecting nodal metastases. SLN and histologic ultrastaging increased false-negative PET/CT findings, reducing the sensitivity of the technique. PET radiomics features of the primary tumor seem promising for predicting the presence of nodal metastases not detected by visual analysis.

Ovarian function, fertility, and menopause occurrence after fertility-sparing surgery and chemotherapy for ovarian neoplasms.

BACKGROUND: The effect of chemotherapy exposure (CE) on ovarian function in young women with ovarian neoplasms undergoing fertility-sparing treatment (FST) remains unclear. We investigated whether CE is correlated with the outcomes (1) during-treatment and (2) post-treatment amenorrhea, (3) conception rate, (4) pregnancy outcome, and (5) spontaneous menopausal age. PATIENTS AND METHODS: Eligibility criteria were patients with a diagnosis of epithelial (EOC) or nonepithelial (no-EOC) invasive ovarian neoplasm, premenopausal age, undergoing FST ±â€¯CE, histopathology confirmation, and adequate follow-up. The groups' outcomes were compared by logistic and linear regression analysis. RESULTS: A total of 548 patients diagnosed during 1980 and 2014 were included, 198 in the EOC group and 350 in the no-EOC group, and 44% received chemotherapy, with a median follow-up of 15.9 years. In no-EOC patients, CE conferred a higher risk for Outcomes 1 (adjusted OR [aOR] 27; 95% CI 12 to 61; P < .0001) and 2 (aOR 5.42; 95% CI 1 to 24; P = .0256) and was associated with a younger menopausal age (adjusted ß -5.52; 95% CI -10.53 to -0.52; P = .0313). Overall, 57% of patients attempted pregnancy, with a conception rate of 89%. In EOC patients, no association between CE and a decreased fertility was demonstrated (aOR, 3.05; 95% CI 0.72 to 12.88; P = .1298). CONCLUSIONS: CE in no-EOC was associated with an increased risk of during-treatment amenorrhea, post-treatment amenorrhea, and earlier spontaneous menopausal age; CE in EOC was not associated with any item at study. Patients undergoing FST had reassuringly high conception rates and low premature ovarian failure rates; however, in pretreatment counseling, the risks of this approach in such young population should be discussed.

The impact of the type of nodal assessment on prognosis in patients with high-intermediate and high-risk ESMO/ESGO/ESTRO group endometrial cancer. A multicenter Italian study.

OBJECTIVES: The majority of endometrial cancers (EC) are discovered while the disease is confined to the uterine body. The presence of lymph nodes metastases impairs the prognosis. In this study, we evaluated the possible impact on survival of sentinel lymph node (SLN) mapping algorithm and selective lymphadenectomy (LD) in early stage EC, according to the ESMO-ESGO-ESTRO risk subgroup classification. METHODS: We retrospectively analyzed the database from two collaborative institutions including women with high-intermediate (HI) and high-risk (HR) ESMO/ESGO/ESTRO groups that underwent surgical staging with either SLN mapping, or selective LD. RESULTS: Two-hundred and sixty-six women were overall identified, 121 in HI and 145 in HR group, respectively. LD was performed in 139 patients (52.5%), whereas SLN mapping algorithm in 61 patients (23%). Sixty-six patients in Rome center were not staged (24.8%). Aortic dissection was performed in 29 women (10.9%). The 3-year comparison did not show a significant difference between strategy adopted for nodal staging (SLN mapping, LD, and SLN + LD) on both disease-free survival [HR: 0.82; 95% CI 0.53-1.28; p = 0.390], and overall survival [HR: 0.78; 95% CI 0.47-1.31; p = 0.355]. CONCLUSIONS: In this study focused on women in the HI and HR groups we did not find difference in the 3-years DFS and OS when comparing the SLN strategy with selective lymphadenectomy, or the SLN algorithm. The SLN strategy did not seem to not compromise the prognosis of high risk patients.

18F-FDG PET/CT in preoperative staging of vulvar cancer patients: is it really effective?

The aim of this study was to assess the role of 18F-FDG PET/CT in preoperative staging of vulvar cancer patients.29 pts (69 years, range 51-88) with vulvar cancer (clinical apparent stage I-II), underwent preoperative FDG-PET/CT scan followed by radical vulvectomy and bilateral (or monolateral in case of tumor >2 cm from midline) inguinal lymphadenectomy ± sentinel node biopsy. PET/CT images were analyzed in consensus and correlated to histological findings according to a pt-based and a groin-based analyses. SUVmax of the nodal uptake of each inguinal area (if present) was calculated and correlated to histological findings. The presence of distant metastases was also considered and confirmed.PET/CT analysis in consensus resulted negative at the inguinal LN level in 17 pts (10 true negative, 7 false negative) and positive in 12 pts (7 true positive, 5 false positive). Incidence of LN metastases resulted 48%. On pt-based analysis, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT in detecting LN metastases were 50%, 67%, 59%, 59%, and 58%, respectively. On a groin-based analysis, considering overall 50 LN-sites, sensitivity, specificity, accuracy, and negative and positive predictive value of PET/CT were 53%, 85%, 73%, 67%, and 76%, respectively. The mean value of SUVmax was 6.1 (range 0.7-16.2) for metastatic nodes, whereas 1.6 (range 0.7 - 5.4) for negative lymph-nodes (P = .007). PET/CT detected pelvic (n = 1) and both pelvic/paraortic (n = 1) nodal metastases.In clinical early stage vulvar cancer FDG PET/CT showed low sensitivity and moderate specificity for N-staging; therefore, it is not an accurate tool for the nodal status assessment. PET/CT may not be cost-effective in detecting the rare event of distant metastases, but further studies are needed.

Comparison of V-Y Advancement Flap Versus Lotus Petal Flap for Plastic Reconstruction After Surgery in Case of Vulvar Malignancies: A Retrospective Single Center Experience.

Vulvoperineal defects after demolitive surgery for preneoplastic or malignant vulvar lesions require a reconstruction to restore good sexual functions and to offer a satisfactory cosmetic result. Several techniques of reconstruction have been described in the past, leading to a more conservative and localized treatment. This study retrospectively reviewed patients with primary or recurrent vulvar malignancies that had undergone vulvoperineal reconstruction between 2010 and 2016 using the V-Y advancement flap and the 2 variant of the lotus petal flap (LPF) in terms of surgical outcome and postoperative complications. Two hundred eighty-four (284) women were reviewed, 234 of them having undergone V-Y flap and 128, the LPF. Overall, postoperative complications occurred in 21.5% of patients including 21% (27/128) of the V-Y group and in 13% (14/106) of the LPF group. The 2 techniques are valid and feasible for vulvar reconstruction in case of moderate defects. No statistically significant differences in terms of complications were observed between the 2 groups overall (P = 0.588), or by comparing the primary (P = 0.202) or the recurrent setting (P = 0.281). Lotus petal flap, particularly the tunneled variant, was superior to V-Y advancement flap in terms of functional and cosmetic results in patients undergoing resection for primary vulvar malignancies.

Near-infrared Fluorescence-guided Sentinel Node Mapping of the Ovary With Indocyanine Green in a Minimally Invasive Setting: A Feasible Study.

Sentinel lymph node (SLN) mapping has increased its feasibility in both early-stage cervical and endometrial cancer. There are few SLN studies regarding the ovary because of the risk of tumor dissemination and perhaps because the ovary represents an inconvenient site for injection. In this preliminary study, we have shown the feasibility of SLN mapping of the ovary with indocyanine green during laparoscopic retroperitoneal aortic surgical staging. The 10 women who were included in this study underwent aortic with pelvic laparoscopic staging, which included SLN biopsy, extrafascial total hysterectomy, and bilateral salpingo-oophorectomy in case of an ovarian tumor. The fluorescent dye was injected on the dorsal and ventral side of the proper ovarian ligament and the suspensory ligament, close to the ovary and just underneath the peritoneum. In all cases except 1, SLNs were detected soon after the injection in the aortic compartment and in 3 cases also in the common iliac region. Only 1 intraoperative complication occurred: a superficial lesion of the vena cava that was recovered with a laparoscopic suture. Laparoscopic ovarian SLN mapping performed by means of an injection of indocyanine green fluorescent tracer in the ovarian ligaments seems feasible and promising. Further investigation are encouraged and necessary to evaluate the possible applications of this new technique for staging patients with early-stage ovarian cancer.

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PURPOSE: To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. METHODS: From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. RESULTS: SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. CONCLUSIONS: SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.