Ovarian cancer prevention by opportunistic salpingectomy is a new de facto standard in Germany.

PURPOSE: The most prevalent and aggressive subtype of epithelial ovarian carcinoma (EOC), high-grade serous carcinoma (HGSC), originates in many cases from the fallopian tubes. Because of poor prognosis and lack of effective screening for early detection, opportunistic salpingectomy (OS) for prevention of EOC is being implemented into clinical routine in several countries worldwide. Taking the opportunity of a gynecological surgery in women at average cancer risk, extramural fallopian tubes are completely resected preserving the ovaries with their infundibulopelvic blood supply. Until recently, only 13 of the 130 national partner societies of the International Federation of Obstetrics and Gynecology (FIGO) have published a statement on OS. This study aimed to analyze the acceptance of OS in Germany. METHODS: (1) Survey of German gynecologists in 2015 and 2022 by the Department of Gynecology of the Jena University Hospital in co-operation with the Department of Gynecology at Charité-University Medicine Berlin with support of NOGGO e. V. and AGO e. V. (2) Salpingectomy numbers in Germany for years 2005-2020 as retrieved from the Federal Statistical Office of Germany (Destatis). RESULTS: (1) Survey: Number of participants was 203 in 2015 and 166 in 2022, respectively. Nearly all respondents (2015: 92%, 2022: 98%) have already performed bilateral salpingectomy without oophorectomy in combination with benign hysterectomy with the intention to reduce the risk for malignant (2015: 96%, 2022: 97%) and benign (2015: 47%, 2022: 38%) disorders. Compared to 2015 (56.6%), considerably more survey participants performed OS in > 50% or in all cases in 2022 (89.0%). Recommendation of OS for all women with completed family planning at benign pelvic surgery was approved by 68% in 2015 and 74% in 2022. (2) Case number analysis: In 2020, four times more cases of salpingectomy were reported by German public hospitals compared to 2005 (n = 50,398 vs. n = 12,286). Of all inpatient hysterectomies in German hospitals in 2020, 45% were combined with salpingectomy, and more than 65% in women at the age of 35 to 49 years. CONCLUSION: Mounting scientific plausibility regarding involvement of fallopian tubes in the pathogenesis of EOC led to change of clinical acceptance of OS in many countries including in Germany. Case number data and widespread expert judgment demonstrate that OS has become a routine procedure in Germany and a de facto standard for primary prevention of EOC.

Concordance of the molecular subtype classification between core needle biopsy and surgical specimen in primary breast cancer.

BACKGROUND: Molecular profiling of breast cancer (BC) classifies several intrinsic subtypes based on different patterns of gene expression. Multigene assays estimate the risk of recurrence and help to select high-risk patients for adjuvant chemotherapy. However, these tests are associated with significant costs. Immunohistochemistry (IHC) offers a surrogate classification for molecular subtypes by determining estrogen (ER) and progesterone receptors (PR), human epidermal growth factor (Her2neu), as well as the proliferation marker Ki67. Core needle biopsy (CNB) is well established in BC diagnosis and allows a pre-operative assessment of biomarkers. The aim of this study was to analyze the concordance of these markers between CNB and surgical specimens to assess whether re-testing of the surgical specimen is mandatory. MATERIALS AND METHODS: Within a 3-year period, patients with primary BC and paired samples of CNB and surgical specimens were analyzed retrospectively. Concordance rates of ER, PR, Her2neu, Ki67, and the surrogate classification for molecular subtypes were calculated using the Landis and Koch agreement grades. RESULTS: Out of 2254 patients with primary breast cancer, 1307 paired specimens without pre-operative treatment were available for analysis Concordance rates for ER, PR, Her2neu, and Ki67 status showed substantial-to-almost perfect agreement grades (κ = 0.91, 0.75, 0.89, and 0.61, respectively). Though substantial concordance was also found for the subtype classification (κ = 0.70), the molecular subtype changed in 18.5% of patients based on the testing of the surgical specimen, mainly from luminal A-like to luminal B-like. CONCLUSIONS: Though the concordance rates for single markers were convincing, a significant proportion of the molecular subtypes differed between CNB and the surgical specimen. Re-testing of PR and Ki67 is mandatory to ensure optimal treatment decisions. Further research is necessary to define safe, efficient, and cost-effective predictive models in adjuvant breast cancer therapy.

Sentinel lymph node mapping with indocyanine green compared to blue dye tracer in gynecologic malignancies-A single center experience of 218 patients.

BACKGROUND AND OBJECTIVES: To compare the detection rates of sentinel lymph nodes after converting the tracer technique from blue dye to indocyanine green (ICG). METHODS: Patients with uterine or cervical cancer were enrolled for sentinel lymph node (SLN) dissection. A total of 109 consecutive patients were analyzed and compared to a historical cohort of 109 consecutive patients with the sentinel blue dye technique. SLNs were analyzed by ultrastaging. RESULTS: The bilateral mapping rate of sentinel nodes was significantly higher with the ICG (78%; n = 85) compared to the blue dye tracer (61%; n = 67; p = .006). Neither the mean number of SLN nor the rate of low volume metastases showed significant differences between both cohorts. In the subgroup of endometrial cancer patients, the number of systematic lymph node dissection (LND) was significantly lower in the ICG cohort compared to the blue dye cohort (9% vs. 28%, p = .001). CONCLUSIONS: ICG improved the detection rate of pelvic SLN compared to blue dye and may be considered as the superior technique. In clinical practice, the rate of systematic LND further decreased after incorporating SLN mapping with ICG. Reliable safety data are still pending.

Lymph node dissection in endometrial cancer and clinical outcome: A population-based study in 5546 patients.

BACKGROUND: According to current treatment guidelines, comprehensive surgical staging procedures in endometrial cancer confined to the uterus depend on uterine risk factors: a systematic lymph node dissection (LND) is recommended in high risk patients and should be omitted in low risk patients. Its role in intermediate and high intermediate risk patients is inconclusive. The aim of this analysis was to review the implementation of this risk-adopted strategy. MATERIALS AND METHODS: Data were provided by the population-based Munich Cancer Registry. Patients with endometrial cancer diagnosed between 1998 and 2016 were included. RESULTS: Of 5446 eligible patients, 58.5%, 30.1% and 11.4% belonged to the low risk, intermediate/high-intermediate and high risk group, respectively. Lymph node dissection was performed in 20.2%, 53.0% and 63.7% within these groups. Lymph node involvement was diagnosed in 1.7%, 9.6% and 19.3%, respectively. Within these risk groups, there was no significant difference in the time to local recurrence, lymph node recurrence or distant metastases between patients with and without LND. After adjusting for age and comorbidity-status, no significant difference in overall survival was found. CONCLUSIONS: The application of a risk-adopted management of LND in early endometrial cancer in real-life is associated with a high rate of surgical under- and overtreatment. Corresponding survival data do not show a significant benefit of a systematic lymph node dissection. In order to improve the management and outcome of early endometrial cancer in the future, prospective trials, new surgical concepts and prognostic markers will be primary and necessary.

Cancer of the ovary, fallopian tube, and peritoneum: a population-based comparison of the prognostic factors and outcomes.

PURPOSE: The objective was to compare the prognostic factors and outcomes among primary ovarian cancer (OC), fallopian tube cancer (FC), and peritoneal cancer (PC) patients in a population-based setting. METHODS: We analysed 5399 OC, 327 FC, and 416 PC patients diagnosed between 1998 and 2014 in the catchment area of the Munich Cancer Registry (meanwhile 4.8 million inhabitants). Tumour site differences were examined by comparing prognostic factors, treatments, the time to progression, and survival. The effect of the tumour site was additionally analysed by a Cox regression model. RESULTS: The median age at diagnosis, histology, and FIGO stage significantly differed among the tumour sites (p < 0.001); PC patients were older, more often diagnosed with a serous subtype, and in FIGO stage III or IV. The time to progression and survival significantly differed among the tumour sites. When stratified by FIGO stage, the differences in time to progression disappeared, and the differences in survival considerably weakened. The differences in the multivariate survival analysis showed an almost identical outcome in PC patients (HR 1.07 [0.91-1.25]) and an improved survival of FC patients (HR 0.63 [0.49-0.81]) compared to that of OC patients. CONCLUSION: The comparison of OC, FC, and PC patients in this large-scale population-based study showed differences in the prognostic factors. These differences primarily account for the inferior outcome of PC patients, and for the improved survival of FC compared to OC patients.

HER-2/neu gene amplification by fluorescence in situ hybridization allows risk-group assessment in node-negative breast cancer.

In a collective of 112 node-negative breast cancer patients, we compared the prognostic impact of HER-2/neu gene amplification (AMP) determined by fluorescence in situ hybridization (FISH) and HER-2/neu protein overexpression (EXP) measured by immunohistochemistry (IHC) with traditional prognostic factors (tumor size, grade, steroid hormone receptor status, menopausal status) and tumor invasion markers uPA (urokinase-type plasminogen activator) and its inhibitor PAI-1 determined by enzyme immunoassay (ELISA). Median follow-up in patients still alive at time of analysis was 7 years. Automated FISH and IHC were performed on parallel-cut formalin-fixed paraffin-embedded tissue sections. HER-2/neu AMP was detected by FISH in 31% and HER-2/neu EXP was measured by IHC in 41% of the cases. In 13% of the tumors, both AMP and EXP were found. FISH and IHC results were concordant in 56% of all analyzed cases. In univariate analysis, HER-2/neu AMP significantly predicted both disease-free (DFS) and overall survival (OS). HER-2/neu EXP was significant for OS, only. In multivariate analysis of all analyzed prognostic factors, HER-2/neu AMP was the only independent predictive factor for both DFS and OS. CART analysis revealed that HER-2/neu AMP together with the combination uPA/PAI-1 allowed optimal risk-group assessment after a 7-year median follow-up: patients with low levels of both uPA and PAI-1 and no HER-2/neu AMP had a significantly lower relapse rate (4.6%) than the remaining patients (32%). In conclusion, HER-2/neu gene AMP determined by FISH allowed a more accurate risk-group assessment than HER-2/neu protein EXP measured by IHC. Combining the HER-2/neu gene status measured by FISH with levels of tumor invasion markers uPA and PAI-1 improves clinically relevant risk-group assessment. In addition to its prognostic strength, the significant impact of HER-2/neu AMP on OS may reflect its ability to predict resistance to systemic therapy.