Danish Gynecological Cancer Database Research Articles

Are we ready for translational research based on material and data from the Danish CancerBiobank and can we gain new knowledge from biobank registration?

Bio-and GenomeBank, Denmark (RBGB) is a nationwide infra-structure. Danish CancerBiobank (DCB) is a biobank in RBGB. The aim is to describe the degree of biological material collected and stored in DCB for patients diagnosed with primary ovarian cancer registered in The Danish Gynecologic Cancer Database (DGCD). Furthermore, to investigate the concordance between predicted organ of disease registered in RBGB at time of sampling (presumed diagnosis) with final diagnosis for patient. Data extraction from DGCD and DCB. Biological materials are present for 1.347 (62%) of 2.172 patients with primary ovarian cancer (OC). The median age of OC patients were 68 years (range: 18-90 years). Median age of patients with biological material in DCB was 67 years and for patients without biological material in DCB 69 years (p ≤ 0.0001). The histological subtypes for the 1347 OC patients with biological material were 911 (68%) serous adenocarcinoma, 97 (7%) endometrioid adenocarcinoma, 80 (6%) mucinous adenocarcinoma, 58 (4%) clear cell carcinoma, and for 201 (15%) no information were registered. For 327 patients (24%), the presumed diagnosis was hematological with a final diagnosis of OC. Using clinical data and biological material including pre-analytical data regarding the biological material the possibility for translational research is optimal. Furthermore, information registered through daily working procedures may propose the need for additional biomarkers to aid clinicians to stratify patients to treatment in correct fast-track packages.

Prognostic impact of molecular profiles and molecular signatures in clear cell ovarian cancer

ObjectiveOvarian Clear cell carcinomas (OCCC) are characterized by low response to chemotherapy and a poor prognosis in advanced stages. Several studies have demonstrated that OCCC are heterogenous entities. We have earlier identified four molecular profiles based on the mutational status of ARID1A and PIK3CA. In this study we aimed to examine the association between molecular profiles, Tumor Mutational Burden (TMB), and molecular signatures with the clinical outcome in OCCC MethodsWe identified 55 OCCC cases with corresponding data and biological tissue samples in the Danish Gynecological Cancer Database during 2005-2016. Mutational profiling and TMB were performed using the Oncomine Tumor Mutational Load Assay. Chi-square and Cox regression analyses were used. P-values < 0.05 were considered statistically significant. ResultsMutations in the PIK3CA gene (p=0.04) and low TMB (p=0.05) were associated with disease progression. In multivariate analyses adjusted for stage, patients with tumor mutations in the ARID1A and/or PIK3CA genes had a significantly impaired Progression Free Survival (PFS) and Overall Survival (OS) compared to patients who were wildtype ARID1A and PIK3CA (undetermined subgroup) (HR= 5.42 and HR= 2.77, respectively). High TMB status was associated with an improved PFS (HR= 0.36) and OS (HR= 0.46). A trend towards an improved PFS in patients with APOBEC enrichment was observed (HR 0.45). ConclusionTMB-High was associated with decreased risk of progression and with an improved PFS and OS. Furthermore, OCCC with mutations in either ARID1A and/or PIK3CA genes had a significantly impaired prognosis compared to the undetermined subgroup in stage adjusted analyses.

A federated approach to identify women with early-stage cervical cancer at low risk of lymph node metastases

ObjectiveLymph node metastases (pN+) in presumed early-stage cervical cancer negatively impact prognosis. Using federated learning, we aimed to develop a tool to identify a group of women at low risk of pN+, to guide the shared decision-making process concerning the extent of lymph node dissection. MethodsWomen with cervical cancer between 2005 and 2020 were identified retrospectively from population-based registries: the Danish Gynaecological Cancer Database, Swedish Quality Registry for Gynaecologic Cancer and Netherlands Cancer Registry. Inclusion criteria were: squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma; The International Federation of Gynecology and Obstetrics 2009 IA2, IB1 and IIA1; treatment with radical hysterectomy and pelvic lymph node assessment. We applied privacy-preserving federated logistic regression to identify risk factors of pN+. Significant factors were used to stratify the risk of pN+. ResultsWe included 3606 women (pN+ 11%). The most important risk factors of pN+ were lymphovascular space invasion (LVSI) (odds ratio [OR] 5.16, 95% confidence interval [CI], 4.59–5.79), tumour size 21–40 mm (OR 2.14, 95% CI, 1.89–2.43) and depth of invasion>10 mm (OR 1.81, 95% CI, 1.59–2.08). A group of 1469 women (41%)—with tumours without LVSI, tumour size ≤20 mm, and depth of invasion ≤10 mm—had a very low risk of pN+ (2.4%, 95% CI, 1.7–3.3%). ConclusionEarly-stage cervical cancer without LVSI, a tumour size ≤20 mm and depth of invasion ≤10 mm, confers a low risk of pN+. Based on an international privacy-preserving analysis, we developed a useful tool to guide the shared decision-making process regarding lymph node dissection.

Preoperative predictors of inguinal lymph node metastases in vulvar cancer – A nationwide study

BackgroundA combination of tumour size, differentiation grade and location may identify a group of vulvar squamous cell cancer (VSCC) patients with a very low risk of inguinal lymph node metastasis. We aim to examine these findings in a large national cohort of VSCC patients. Materials and methodsPopulation based prospective data on VSCC patients treated with vulvectomy and primary groin surgery was obtained from the Danish Gynaecological Cancer Database. Univariate chi-square and multivariate logistic regression analysis were used. Statistical tests were 2-sided. P-values of <0.05 were considered statistically significant. ResultsIn all, 388 VSCC patients were identified. Of these 264 (63.3%) were node negative and 121 (36.7%) node positive. Increasing tumour size (diameter ≤ 2 cm vs. > 2 to 4 cm), grade (1 vs. 2–3) and location of tumour to clitoris were all associated with a significantly increased risk of inguinal lymph node metastasis OR 2.81(95% CI 1.52–5.20), OR 3.19 (95% CI 1.77–5.74) and OR 2.74 (95% CI 1.56–5.20), respectively. Previous vulvar disease was not associated with lymph node metastasis.No lymph node metastasis was demonstrated in patients with grade 1 tumours, tumour size less than 2 cm and located outside the clitoris area (n = 51). ConclusionsVSCC patients with grade 1 tumours, ≤ 2 cm and without clitoral involvement have a very low risk of inguinal lymph node metastasis. These patients may be spared inguinal lymph node staging to decrease operating time and peri- and postoperative morbidity in the future. However, studies validating our findings are needed.

Prognostic value of the 2018 FIGO staging system for cervical cancer

ObjectiveTo compare the prognostic performance of the FIGO 2009 and FIGO 2018 staging systems for cervical cancer (CC) in regards to risk stratification, survival and treatment outcome. MethodsA total of 4461 CC patients diagnosed in Denmark during 2005–2018 were identified through the Danish Gynaecological Cancer Database and restaged from the 2009 FIGO to the 2018 FIGO staging system. 5-year survival estimates were made for each group. Also, association between lymphovascular space invasion (LVSI) and lymph node metastasis (LNM) was assesed for tumors with a horizontal spread >7 mm and depth of invasion ≤5 mm. ResultsOverall, stage migration was observed in 41.4% of our cases due to the introduction of stage IIIC (20.1%), refined tumor size criteria within stage I (76.2%), and use of radiological findings to define stage IV (3.7%). 5-year overall survival increased for all stages except IA2, IIA2, IIIA and IIIB. Restaging of 2009 IB1 to 2018 FIGO resulted in significant stage allocations. Furthermore, an association between LVSI and LNM was observed in squamous cell carcinomas with a depth of invasion of 3–5 mm and a horizontal spread >7 mm (p = 0.03). ConclusionThe 2018 FIGO staging system provided improved discriminatory ability for stage I and IV. Grouping all patients with positive pelvic or paraortal lymph nodes to stage IIIC led to pronounced heterogenous survival rates within these stages. Lymph node assessment was proven imperative in FIGO 2018 IA2 squamous cell carcinomas with a depth of invasion of 3-5 mm, a horizontal spread >7 mm and LVSI.

Residual tumor and primary debulking surgery vs interval debulking surgery in stage IV epithelial ovarian cancer.

It is debated whether women with FIGO (International Federation of Gynecology and Obstetrics) Stage IV epithelial ovarian cancer should be offered primary debulking surgery (PDS) or interval debulking surgery (IDS). Furthermore, the impact of complete resection of intra-abdominal disease (R0) despite their extra-abdominal metastases is questioned. The objective of this study was to investigate the impact of intra-abdominal residual tumor, Stage IVA vs IVB, the localization and number of metastases defining Stage IV disease on overall survival (OS) comparing PDS and IDS in FIGO Stage IV epithelial ovarian cancer. We included 2091 women registered with Stage IIIC-IV ovarian cancer in the Danish Gynecological Cancer Database during 2009-2016. The impact of residual tumor was evaluated using univariate and multivariate analyses. In total, 681 patients had stage IV disease, of whom 26% underwent PDS, 38% IDS, and 36% chemotherapy only. Overall survival for PDS and IDS were similar. Patients achieving R0 at PDS showed a tendency towards a higher OS than patients achieving R0 at IDS, though the difference was non-significant. In women with Stage IVA and IVB disease there was a survival benefit in achieving R0 both when treated with PDS and IDS. Women with Stage IVB disease treated with chemotherapy only had a significantly lower OS than patients achieving R0 at both PDS and IDS. Malignant pleural effusion and having five metastatic sites compared with having one was associated with a poorer OS. Our study shows similar OS in patients with Stage IV disease treated with IDS compared with PDS. Complete intra-abdominal tumor resection improves the prognosis in both PDS and IDS in Stage IV ovarian cancer. Malignant pleural effusion seems to be a negative prognostic factor and should have more focus in future studies.

Prognostic relevance of the molecular classification in high-grade endometrial cancer for patients staged by lymphadenectomy and without adjuvant treatment

IntroductionThe clinical role of the molecular endometrial cancer (EC) classification has not been fully explored in patients staged with lymphadenectomy or without adjuvant treatment, conditions that could potentially moderate the prognostic value of the classification. We aimed to evaluate the clinical outcome of the molecular subgroups in patients with high-grade EC staged by lymphadenectomy and those without adjuvant treatment. MethodsDNA-sequencing for the detection of pathogenic POLE-exonuclease domain mutations and immunohistochemistry for mismatch repair (MMR) proteins and p53 expression were performed on 412 high-grade EC from the Danish Gynaecological Cancer Database (2005–2012) to classify them as POLE-ultramutated (POLEmut), MMR-deficient (MMRd), p53-mutant (p53abn), or no specific molecular profile (NSMP). Patients with stage IV or residual disease after surgery were excluded. Kaplan-Meier method, log-rank test and Cox proportional hazard models were used for analysis. ResultsMolecular analysis was successful in 367 EC; 251 patients had undergone lymphadenectomy. Five-year recurrence rates in this subgroup of patients was 36.7% for women with p53abn EC, 0.0% for POLEmut EC, 13.4% for MMRd EC and 42.9% for NSMP EC (p < 0.001). Similar results were observed among stage IA-IB patients. Among patients without adjuvant treatment (n = 264), none with POLEmut EC (n = 26) had a recurrence. ConclusionThe molecular EC classification has strong prognostic value, independent of clinicopathological factors, also among high-grade EC patients staged by lymphadenectomy and those without adjuvant treatment. The unfavourable prognosis of early-stage p53abn EC is not due to undetected lymph node metastasis, and the indolent behaviour of POLEmut EC is independent of adjuvant treatment.

Assessment of recurrence rate and risk factors of relapse in stage in IA vulvar carcinoma

ObjectiveTo evaluate recurrence rates and risk factors of relapse in stage IA vulvar squamous cell carcinoma (VSCC) patients. Material and methodsPopulation-based prospectively collected data on stage IA VSCC was retrieved through the Danish Gynecological Cancer Database (DGCD) during 2011–2017. A central pathology review was performed on tumors from women with recurrent disease. Results62 women diagnosed and treated for stage IA VSCC were identified. Nine (14.5%) of the included cases relapsed within the observation period. The recurrences were in the vulva, groins or both in 5 (8.1%), 3 (4.8%) and 1 (1.6%) of the women, respectively. At central pathology review, including all recurrent cases (n = 9), 5 out of 21 reviewed patients were upstaged to stage IB due to depth of invasion >1 mm and two were downstaged to Carcinoma in situ. Two of the upstaged women developed an isolated groin recurrence and one an isolated vulvar relapse. After exclusion of the seven cases the overall recurrence rate decreased to 10.9% (n = 6).Among these cases (n = 55) resection margin <8 mm and tumor size were associated with cancer recurrence. ConclusionPathological assessment of stage IA VSCC (depth of invasion ≤1 mm) may be difficult. This may result in under-staging, which impact the choice of treatment and possibly the prognosis. This suggests a need for further clarification of the FIGO measurement and may require a more radical approach when it comes to treatment and groin exploration in stage IA VSCC.Resection margins <8 mm and tumor size were associated with relapse of the disease.

Substantial Lymphovascular Space Invasion Is an Adverse Prognostic Factor in High-Risk Endometrial Cancer.

Approximately 15% of patients with endometrial cancer present with high-risk disease (HREC). Moreover, assessing the extent of lymphovascular space invasion (LVSI) may provide prognostic insight among patients with HREC. The aim of this study was to determine whether the extent of LVSI can serve as a prognostic factor in HREC. All cases of ESMO-ESGO-ESTRO 2016 classified HREC in the Danish Gynecological Cancer Database (DGCD) diagnosed from 2005 to 2012 were reviewed for the presence and extent of LVSI (categorized using a 3-tiered definition). We used the Kaplan-Meier analysis to calculate actuarial survival rates, both adjusted and unadjusted Cox regression analyses were used to calculate the proportional hazard ratio (HR). A total of 376 patients were included in our analysis. Among 305 patients with stage I/II HREC, 8.2% and 6.2% had focal or substantial LVSI, respectively, compared with 12.7% and 38.0% of 71 patients with stage III/IV HREC, respectively. Moreover, the estimated 5-yr recurrence-free survival rate was significantly lower among patients with substantial LVSI compared with patients with no LVSI for both stage I/II (HR: 2.8; P=0.011) and stage III/IV (HR: 2.9; P=0.003) patients. Similarly, overall survival was significantly lower among patients with substantial LVSI for both stage I/II (HR: 3.1; P<0.001) and stage III/IV (HR: 3.2; P=0.020) patients. In patients with HREC, substantial LVSI is an independent adverse prognostic factor for lymph node and distant metastases, leading to reduced survival. Thus, the extent of LVSI should be incorporated into routine pathology reports in order to guide the appropriate choice of adjuvant treatment.

Defining Substantial Lymphovascular Space Invasion in Endometrial Cancer.

Lymphovascular space invasion (LVSI) occurs in a minority of endometrial cancer (EC) cases, and the extent of LVSI is an important risk factor for recurrence and/or metastases. Our aim was to improve the reproducibility of measuring clinically meaningful LVSI by performing a quantitative analysis of the correlation between LVSI and the risk of pelvic lymph node recurrence in EC. EC samples from PORTEC-1 and PORTEC-2 trials were retrieved and used to collect quantitative data, including the number of LVSI-positive vessels per H&E-stained slide. Using a predefined threshold for clinical relevance, the risk of pelvic lymph node recurrence risk was calculated (Kaplan-Meier method, with Cox regression) using a stepwise adjustment for the number of LVSI-positive vessels. This analysis was then repeated in the Danish Gynecological Cancer Database (DGCD) cohort. Among patients in PORTEC-1 and PORTEC-2 trials who did not receive external beam radiotherapy, the 5-yr pelvic lymph node recurrence risk was 3.3%, 6.7% (P=0.51), and 26.3% (P<0.001), respectively when 0, 1 to 3, or ≥4 vessels had LVSI involvement; similar results were obtained for the DGCD cohort. Furthermore, both the average number of tumor cells in the largest embolus and the number of LVSI-positive H&E slides differed significantly between focal LVSI and substantial LVSI. On the basis of these results, we propose a numeric threshold (≥4 LVSI-involved vessels in at least one H&E slide) for defining clinically relevant LVSI in EC, thereby adding supportive data to the semiquantitative approach. This will help guide gynecologic pathologists to differentiate between focal and substantial LVSI, especially in borderline cases.

Prognostic impact of histological review of high-grade endometrial carcinomas in a large Danish cohort.

The aim of this study was to investigate the outcome of histological subtype review of high-grade endometrial carcinoma (EC) and its prognostic impact in a large well-documented Danish nationwide cohort. From the Danish Gynecological Cancer Database (DGCD) 2005-2012 cohort, we included 425 patients with an original diagnosis of high-grade EC, independent of histologic subtype. Of these, at least one hematoxylin and eosin (H&E)-stained slide from 396 cases (93.2%) was available for review. The histologic subtype was reviewed by specialized gynecopathologists blinded to the original diagnosis and clinical outcome. Interobserver variability between original and revised histologic subtypes was analyzed using simple Kappa statistics. Hazard ratios (HR), recurrence-free survival (RFS), and overall survival were calculated for original and revised subtypes, respectively. Overall histologic subtype agreement was moderate (kappa = 0.42) with the highest agreement for endometrioid-type EC (EEC; 75.5%) and serous-type EC (SEC; 63.8%). For clear cell carcinoma and un-/dedifferentiated EC, agreement was significantly lower: 30.1% and 33.3% respectively. Of the 396 reviewed cases, only two (0.5%) were re-classified as low-grade EEC upon revision. Interestingly, GR3 EEC had better RFS than SEC with stronger significance after revision (HR 2.36 (95% CI 1.43-3.89), p = 0.001), compared to original diagnosis (HR 1.74 (95% CI 1.07-2.81), p = 0.024). In conclusion, this study confirmed that pathology review results in substantial shift in histological subtype in high-grade EC. After review, a stronger prognostic benefit for GR3 EEC as compared to other histological subtypes was observed. This work supports maintaining a low threshold for pathology revision of high-grade EC in clinical practice.

The timing of venous thromboembolism in ovarian cancer patients: A nationwide Danish cohort study

Background and aimVenous thromboembolism (VTE) is associated with excess mortality and morbidity in cancer, and is influenced by patient‐, tumor‐, and treatment‐related factors. We aimed to investigate the impact of such factors in a national cohort of patients with epithelial ovarian cancer (EOC). MethodsPatients in the Danish Gynecologic Cancer Database (DGCD) with EOC from 2005 to 2014 were followed from time of diagnosis to VTE, or censoring. Surgery, chemotherapy, and vascular epithelial growth factor (VEGF)‐inhibitors were included as time‐varying exposures in Cox proportional hazard regression models. ResultsA total of 551 VTE events were registered in 4991 EOC patients. Median follow‐up time was 2.9 years. The 2‐year cumulative incidence of VTE was 7.2%. Patients were at highest risk during the first year after EOC diagnosis. Previous VTE was associated with a hazard ratio (HR) of 3.26 (95% confidence interval [CI] 2.42–4.39). Exposure to major pelvic surgery was associated with a HR of 3.21 (95% CI 2.29–4.50). Exposure to chemotherapy or (VEGF)‐inhibitors were associated with HRs of 1.91 (95% CI 1.56–2.33) and 1.05 (95% CI 0.57–1.93), respectively. Hazard ratios for patients with clear cell histopathology was 1.46 (95% CI 0.97–2.20) and 2.42 for International Federation of Gynaecology and Obstetrics stage III‐‐IV (95% CI 1.93–3.03). ConclusionsEOC is associated with a high risk of VTE, particularly within the first year after diagnosis. Major pelvic surgery and chemotherapy were strongly associated with VTE. Person‐related risk factors were increasing age and previous VTE. Advanced stage was an independent tumor‐related risk factor. These findings support the indication for thrombosis prophylaxis during chemotherapy.

National coverage of biological materials for translational research in the Danish cancerbiobank (RBGB) and of corresponding clinical data in the Danish Gynecological Cancer Database (DGCD)

Objective: Optimal personalized medicine may be based on specific predictive/prognostic biomarkers in order to discern between responders and nonresponders. Knowledge of markers is based on biomarker studies analyzing clinical data and their associated biological materials stored in high-quality biobanks. There is no precise knowledge of the extent of nationwide clinical data and corresponding biological specimens available for translational research in gynecologic cancer diseases in Denmark. The aim was to investigate the coverage of biological materials in the Bio- and GenomeBank, Denmark (RBGB), for patients with primary ovarian cancer (tubal, peritoneal, and ovarian) registered in the nationwide compulsory Danish Gynecological Cancer Database (DGCD) for the period 2015–2018.

Survival after a nationwide adoption of robotic minimally invasive surgery for early-stage cervical cancer – A population-based study

AimLately, the safety of minimally invasive surgery (MIS) in the treatment of cervical cancer (CC) has been questioned. This study aimed to evaluate the risk of recurrence and survival after a nationwide adoption of robotic MIS for the treatment of early-stage CC in Denmark. MethodsPopulation-based data on all Danish women with early-stage CC, who underwent radical hysterectomy January 1st 2005–June 30th 2017 were retrieved from the Danish Gynecologic Cancer Database and enriched with follow-up data on recurrence, death and cause of death. The cohort was divided into two groups according to the year of robotic MIS introduction at each cancer centre. Chi-squared or Fischer test, the Kaplan Meier method and multivariate Cox regression were used for comparison between groups. ResultsOne thousand one hundred twenty-five patients with CC were included; 530 underwent surgery before (group 1) and 595 underwent surgery after (group 2) the introduction of robotic MIS. The 5-year rate of recurrence was low: 8.2% and 6.3% (p = 0.55) in group 1 and 2, respectively. In adjusted analyses, this corresponded to a five-year disease-free survival, hazard ratio (HR) 1.23 [95% confidence interval (CI) 0.79-1.93]. No difference in site of recurrence (P = 0.19) was observed. The cumulative cancer-specific survival was 94.1% and 95.9% (P = 0.10) in group 1 and 2, respectively, corresponding to a HR 0.60 [95% CI 0.32–1.11] in adjusted analyses. ConclusionIn this population-based cohort study, the Danish nationwide adoption of robotic MIS for early-stage CC was not associated with increased risk of recurrence or reduction in survival outcomes.

Recurrence and survival rates in node negative patients after sentinel node biopsy for early-stage vulva cancer – A nationwide study

ObjectiveThe sentinel node (SN) procedure is adopted in selected patients with early-stage vulva cancer (VC) in Denmark. Due to the low incidence of VC, large population-based studies on the safety of SN outside multicenter clinical trials are lacking. The current study evaluated the risk of recurrence and survival in SN- negative VC patients. MethodsNationwide data was collected and registered prospectively in the Danish Gynecologic Cancer Database from January 2011 to July 2017. Patients with clinically stage IB-II unifocal vulva squamous cell carcinoma, tumor <4 cm and no clinically suspicious groin nodes or distant metastases, who underwent SN-procedure, were included. ResultsThe SN-procedure was performed in 286 patients, of these 190 (66.4%) patients were SN-negative. Twenty-three of the 190 SN-negative patients (12.1%) had one or more recurrences during a median follow-up of 30 months (range 1–83). Four patients (2.1%) had an isolated groin recurrence identified from 5 to 17 months after primary surgery. Fourteen patients (7.4%) experienced a local recurrence in vulva, 1 patient (0.5%) had a recurrence in the vulva and the groin and 4 patients (2.1%) had distant recurrences. The 3-year overall (OS) and disease-specific survival (DSS) for SN-negative patients was 84% and 93%, respectively. The 3-year OS for patients with recurrent disease was 58%. ConclusionsThis is the largest prospective nationwide study on SN-procedure in vulva cancer. The study confirms the safety of the SN-procedure in selected early-stage VC patients with a low isolated groin recurrence rate and a good DSS.

Endometrial cancer does not increase the 30-day risk of venous thromboembolism following hysterectomy compared to benign disease. A Danish National Cohort Study

ObjectivesWe aimed to clarify if endometrial cancer patients are at higher risk of venous thromboembolism (VTE) following hysterectomy, compared to patients undergoing hysterectomy for benign gynecological disease. MethodsIn a nationwide registry-based cohort study, patients undergoing hysterectomy for endometrial cancer or benign disease were followed 30 days after surgery. The Danish Gynecological Cancer Database (DGCD) and the Danish National Patient Register (DNPR) were linked with four other administrative registries to describe the population and retrieve data on venous thromboembolism and mortality.Multivariable logistic regression models were used to estimate odds ratios (ORs) for 30-day postoperative VTE. ResultsWe identified 5513 patients with endometrial cancer, and 45,825 patients with benign disease undergoing hysterectomy in the period 2005–2014.The overall incidence of 30-day VTE following hysterectomy was 0.2% (103/51,338). Thirty (0.5%) patients with endometrial cancer and 73 (0.16%) patients with benign disease developed VTE. In a multivariable logistic regression analysis, significant predictors of 30-day OR for VTE were open surgery (minimally invasive surgery vs. open: OR = 0.46; 95% CI, 0.30–0.71; p < 0.001), lymphadenectomy (OR = 4.00; 95% CI, 1.89–8.46; p < 0.001), BMI > 40 (OR = 2.34;95% CI, 1.10–5.01; p = 0.03) and previous VTE (OR = 34; 95% CI, 22.7–51.3; p < 0.001). There was no statistically significant difference in the 30-day OR for VTE in endometrial cancer compared to benign disease (OR = 1.47; 95% CI, 0.74–2.91; p = 0.27). ConclusionsThis study did not identify endometrial cancer to be an independent risk factor for VTE following hysterectomy compared to benign disease. We identified open surgery, lymphadenectomy, BMI above 40 and previous VTE as independent risk factors for 30-day postoperative VTE.

Nationwide Introduction of Minimally Invasive Robotic Surgery for Early-Stage Endometrial Cancer and Its Association With Severe Complications

ImportanceMinimally invasive laparoscopic surgery (MILS) for endometrial cancer reduces surgical morbidity compared with a total abdominal hysterectomy. However, only a minority of women with early-stage endometrial cancer undergo MILS.ObjectiveTo evaluate the association between the Danish nationwide introduction of minimally invasive robotic surgery (MIRS) and severe complications in patients with early-stage endometrial cancer.Design, Setting, and ParticipantsIn this nationwide prospective cohort study of 5654 women with early-stage endometrial cancer who had undergone surgery during the period from January 1, 2005, to June 30, 2015, data from the Danish Gynecological Cancer Database were linked with national registers on socioeconomic status, deaths, hospital diagnoses, and hospital treatments. The women were divided into 2 groups; group 1 underwent surgery before the introduction of MIRS in their region, and group 2 underwent surgery after the introduction of MIRS. Women with an unknown disease stage, an unknown association with MIRS implementation, unknown histologic findings, sarcoma, or synchronous cancer were excluded, as were women who underwent vaginal or an unknown surgical type of hysterectomy. Statistical analysis was conducted from February 2, 2017, to May 4, 2018.ExposureMinimally invasive robotic surgery, MILS, or total abdominal hysterectomy.Main Outcomes and MeasuresSevere complications were dichotomized and encompassed death within 30 days after surgery and intraoperative and postoperative complications diagnosed within 90 days after surgery.ResultsA total of 3091 women (mean [SD] age, 67 [10] years) were allocated to group 1, and a total of 2563 women (mean [SD] age, 68 [10] years) were allocated to group 2. In multivariate logistic regression analyses, the odds of severe complications were significantly higher in group 1 than in group 2 (odds ratio [OR], 1.39; 95% CI, 1.11-1.74). The proportion of women undergoing MILS was 14.1% (n = 436) in group 1 and 22.2% in group 2 (n = 569). The proportion of women undergoing MIRS in group 2 was 50.0% (n = 1282). In group 2, multivariate logistic regression analyses demonstrated that a total abdominal hysterectomy was associated with increased odds of severe complications compared with MILS (OR, 2.58; 95% CI, 1.80-3.70) and MIRS (OR, 3.87; 95% CI, 2.52-5.93). No difference was found for MILS compared with MIRS (OR, 1.50; 95% CI, 0.99-2.27).Conclusions and RelevanceThe national introduction of MIRS changed the surgical approach for early-stage endometrial cancer from open surgery to minimally invasive surgery. This change in surgical approach was associated with a significantly reduced risk of severe complications.

Survival after a nationwide introduction of robotic surgery in women with early-stage endometrial cancer: a population-based prospective cohort study

PurposeThe purpose of the study was to evaluate the association between a nationwide introduction of robotic minimally invasive surgery (RMIS) and survival in women with early-stage endometrial cancer. Materials and methodsProspective data on consecutive women with early-stage endometrial cancer who underwent surgery during January 2005 to June 2015 in Denmark were identified in the nationwide Danish Gynaecological Cancer Database. Data were linked with national registries regarding comorbidity, education, income and death. The cohort was divided according to the time they underwent surgery: Group 1 before RMIS introduction in their respective region and Group 2 after RMIS introduction. Five-year overall survival was compared by multivariate Cox proportional hazards models stratified by histopathological risk between Groups 1 and 2 and between surgical modalities within Group 2: total abdominal hysterectomy (TAH), laparoscopic minimally invasive surgery (LMIS) and RMIS. ResultsWomen in Group 1 (N = 3091) had significantly lower overall survival compared with those in Group 2 (N = 2563; hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.05–1.42). Age, smoking, socioeconomic status, American Society of Anaesthesiologists (ASA) score, comorbidity and histopathological risk influenced the overall survival. Following RMIS adoption, TAH was associated with higher mortality compared with LMIS and RMIS (HR, 1.42; 95% CI 1.02–1.97 and HR, 1.70; 95% CI 1.31–2.19 for LMIS and RMIS, respectively). There was no significant survival difference between RMIS and LMIS (HR, 1.19; 95% CI 0.85–1.68). ConclusionThe national introduction of robotic surgery for early-stage endometrial cancer was associated with improved survival irrespective of age, body mass index, ASA score, comorbidity, smoking, socioeconomic status and histopathological risk.

The effect of introducing pelvic lymphadenectomy on survival and recurrence rates in Danish endometrial cancer patients at high risk: a Danish Gynecological Cancer Group study.

To evaluate the rate of survival and recurrence related to the introduction of pelvic lymphadenectomy in Danish high-risk endometrial cancer patients. Data on 713 high-risk patients defined as grade 3 with >50% myometrial invasion or serous/clear/undifferentiated carcinomas stage I-IV endometrial cancer patients diagnosed from 2005 to 2012 were retrieved from the Danish Gynecological Cancer Database. Of these, 305 were high-risk stage I. Five year Kaplan-Meier survival estimates and actuarial recurrence rates were calculated, and adjusted Cox used for comparison. Findings were compared with earlier Danish results. Lymphadenectomy in 390 radically operated high-risk patients resulted in upstaging of 31 patients from stage I to IIIC and 19 patients from stage II to IIIC corresponding to 12.8%. Upstaging from stage I to IIIC had a cancer-specific survival of 77%, almost comparable to lymph node-negative high-risk stage I patients (81%). Lymphadenectomy patients had a significant higher overall survival as compared with non-lymph node resected for all patients, but not for stage I patients. Lymphadenectomy, however, did not significantly affect cancer-specific survival, progression-free survival, recurrence rate or risk of local, distant, or lymph node recurrence. When the survival of high-risk stage I patients was compared with earlier Danish results, a small improvement in overall survival (7%) and cancer-specificsurvival (8%) was demonstrated. Only a small number of high-risk patients were upstaged from stage I to III due to lymphadenectomy. These patients showed a surprisingly good survival possibly due to correct stage identification and subsequent relevant adjuvant therapy. However, even though introduction of lymphadenectomy in the Danish high-risk population seems to increase overall survival, no significant change in cancer-specific survival, progression-free survival or recurrence patterns was demonstrated.

Influence of Prior Psychiatric Disorders on the Treatment Course of Gynaecological Cancer – A Nationwide Cohort Study

AimsTo examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer. Materials and methodsThe analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment. ResultsIn the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54). ConclusionsWe did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis.