Impact of gated FDG PET/CT on the staging of patients with suspected or proven newly diagnosed advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer: results from a non-randomized, phase II clinical trial.

OBJECTIVE: Imaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT. METHODS: The IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques. RESULTS: A total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients. CONCLUSIONS: Gated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients. TRIAL REGISTRATION NUMBER: NCT02258165.

Vaginal vault smear cytology in detection of recurrence after hysterectomy for early cervical cancer.

OBJECTIVE: To determine the role of vaginal vault cytology as a surveillance tool for the detection of recurrence in patients with early stage cervical cancer treated with hysterectomy without adjuvant therapy. METHODS: A retrospective cohort study was conducted of all women with cervical cancer treated with a hysterectomy from January 2000 to July 2016 at the Royal Brisbane & Women's Hospital, Australia. Women included were diagnosed with the equivalent of International Federation of Gynecology and Obstetrics (FIGO) 2018 stage 1A1 to 1B3 squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, received either simple or radical hysterectomy with or without pelvic lymph node dissection, and did not receive adjuvant therapy. Age, stage, histology, surgical procedure, and details of individual surveillance regimens including examination findings and indications and results for all vault cytology tests performed in the first 5 years following surgical management were collected. RESULTS: A total of 155 women met the inclusion criteria. Most cases were FIGO 2018 stage 1B1 (61.9%) and squamous cell carcinoma (64.5%). Included women underwent a median of 80 months of surveillance (range 25-200, IQR 64-108). In the first 5 years of surveillance, there were a total of 1001 vault cytology smears performed, with a median of 6 smears (IQR 5-9) per woman. A total of 19 smears were abnormal (1.9%). Of the cohort of 155 women, 19 (12.3%) had an abnormality detected; 1 (0.65%) had a high-grade intraepithelial abnormality and 2 (1.3%) had recurrences detected on cytology; however, a lesion was also seen and biopsied in all three women. A total of 16 of 1001 smears (1.6%) had low-grade abnormalities detected, all of which resolved with clinical observation only. All were alive and well at last review. There were in total 6 (3.9%) recurrences, 2 (33%) of which had abnormal cytology as above, and all of which had a lesion to biopsy and/or abnormal medical imaging. CONCLUSIONS: The routine use of vaginal vault cytology in surveillance following hysterectomy for early stage cervical cancer did not appear to alter the detection of recurrent malignancy.

Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial.

PURPOSE: Intrauterine levonorgestrel (LNG-IUD) is used to treat patients with endometrial adenocarcinoma (EAC) and endometrial hyperplasia with atypia (EHA) but limited evidence is available on its effectiveness. The study determined the extent to which LNG-IUD with or without metformin (M) or weight loss (WL) achieves a pathological complete response (pCR) in patients with EAC or EHA. PATIENTS AND METHODS: This phase II randomized controlled clinical trial enrolled patients with histologically confirmed, clinically stage 1 FIGO grade 1 EAC or EHA; a body mass index > 30 kg/m2; a depth of myometrial invasion of less than 50% on MRI; a serum CA125 ≤ 30 U/mL. All patients received LNG-IUD and were randomized to observation (OBS), M (500 mg orally twice daily), or WL (pooled analysis). The primary outcome measure was the proportion of patients developing a pCR (defined as absence of any evidence of EAC or EHA) after 6 months. RESULTS: From December 2012 to October 2019, 165 patients were enrolled and 154 completed the 6-months follow up. Women had a mean age of 53 years, and a mean BMI of 48 kg/m2. Ninety-six patients were diagnosed with EAC (58%) and 69 patients with EHA (42%). Thirty-five participants were randomized to OBS, 36 to WL and 47 to M (10 patients were withdrawn). After 6 months the rate of pCR was 61% (95% CI 42% to 77%) for OBS, 67% (95% CI 48% to 82%) for WL and 57% (95% CI 41% to 72%) for M. Across the three treatment groups, the pCR was 82% and 43% for EHA and EAC, respectively. CONCLUSION: Complete response rates at 6 months were encouraging for patients with EAC and EHA across the three groups. TRIAL REGISTRATION: U.S. National Library of Medicine, NCT01686126.

Development of a surgical competency assessment tool for sentinel lymph node dissection by minimally invasive surgery for endometrial cancer.

INTRODUCTION: Sentinel lymph node dissection is widely used in the staging of endometrial cancer. Variation in surgical techniques potentially impacts diagnostic accuracy and oncologic outcomes, and poses barriers to the comparison of outcomes across institutions or clinical trial sites. Standardization of surgical technique and surgical quality assessment tools are critical to the conduct of clinical trials. By identifying mandatory and prohibited steps of sentinel lymph node (SLN) dissection in endometrial cancer, the purpose of this study was to develop and validate a competency assessment tool for use in surgical quality assurance. METHODS: A Delphi methodology was applied, included 35 expert gynecological oncology surgeons from 16 countries. Interviews identified key steps and tasks which were rated mandatory, optional, or prohibited using questionnaires. Using the surgical steps for which consensus was achieved, a competency assessment tool was developed and subjected to assessments of validity and reliability. RESULTS: Seventy percent consensus agreement standardized the specific mandatory, optional, and prohibited steps of SLN dissection for endometrial cancer and informed the development of a competency assessment tool. Consensus agreement identified 21 mandatory and three prohibited steps to complete a SLN dissection. The competency assessment tool was used to rate surgical quality in three preselected videos, demonstrating clear separation in the rating of the skill level displayed with mean skills summary scores differing significantly between the three videos (F score=89.4; P<0.001). Internal consistency of the items was high (Cronbach α=0.88). CONCLUSION: Specific mandatory and prohibited steps of SLN dissection in endometrial cancer have been identified and validated based on consensus among a large number of international experts. A competency assessment tool is now available and can be used for surgeon selection in clinical trials and for ongoing, prospective quality assurance in routine clinical care.

Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (LACC): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: In the phase 3 LACC trial and a subsequent population-level review, minimally invasive radical hysterectomy was shown to be associated with worse disease-free survival and higher recurrence rates than was open radical hysterectomy in patients with early stage cervical cancer. Here, we report the results of a secondary endpoint, quality of life, of the LACC trial. METHODS: The LACC trial was a randomised, open-label, phase 3, non-inferiority trial done in 33 centres worldwide. Eligible participants were women aged 18 years or older with International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with lymphovascular space invasion, IA2, or IB1 adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who were scheduled to have a type 2 or 3 radical hysterectomy. Participants were randomly assigned (1:1) to receive open or minimally invasive radical hysterectomy. Randomisation was done centrally using a computerised minimisation program, stratified by centre, disease stage according to FIGO guidelines, and age. Neither participants nor investigators were masked to treatment allocation. The primary endpoint of the LACC trial was disease-free survival at 4·5 years, and quality of life was a secondary endpoint. Eligible patients completed validated quality-of-life and symptom assessments (12-item Short Form Health Survey [SF-12], Functional Assessment of Cancer Therapy-Cervical [FACT-Cx], EuroQoL-5D [EQ-5D], and MD Anderson Symptom Inventory [MDASI]) before surgery and at 1 and 6 weeks and 3 and 6 months after surgery (FACT-Cx was also completed at additional timepoints up to 54 months after surgery). Differences in quality of life over time between treatment groups were assessed in the modified intention-to-treat population, which included all patients who had surgery and completed at least one baseline (pretreatment) and one follow-up (at any timepoint after surgery) questionnaire, using generalised estimating equations. The LACC trial is registered with ClinicalTrials.gov, NCT00614211. FINDINGS: Between Jan 31, 2008, and June 22, 2017, 631 patients were enrolled; 312 assigned to the open surgery group and 319 assigned to the minimally invasive surgery group. 496 (79%) of 631 patients had surgery completed at least one baseline and one follow-up quality-of-life survey and were included in the modified intention-to-treat analysis (244 [78%] of 312 patients in the open surgery group and 252 [79%] of 319 participants in the minimally invasive surgery group). Median follow-up was 3·0 years (IQR 1·7-4·5). At baseline, no differences in the mean FACT-Cx total score were identified between the open surgery (129·3 [SD 18·8]) and minimally invasive surgery groups (129·8 [19·8]). No differences in mean FACT-Cx total scores were identified between the groups 6 weeks after surgery (128·7 [SD 19·9] in the open surgery group vs 130·0 [19·8] in the minimally invasive surgery group) or 3 months after surgery (132·0 [21·7] vs 133·0 [22·1]). INTERPRETATION: Since recurrence rates are higher and disease-free survival is lower for minimally invasive radical hysterectomy than for open surgery, and postoperative quality of life is similar between the treatment groups, gynaecological oncologists should recommend open radical hysterectomy for patients with early stage cervical cancer. FUNDING: MD Anderson Cancer Center and Medtronic.

Survival outcomes after delayed cytoreduction surgery following neoadjuvant chemotherapy in advanced epithelial ovarian cancer.

OBJECTIVE: Interval cytoreduction following neoadjuvant chemotherapy is a well-recognized treatment alternative to primary debulking surgery in the treatment of advanced epithelial ovarian cancer where patient and/or disease factors prevent complete macroscopic disease resection to be achieved. More recently, the strain of the global COVID-19 pandemic on hospital resources has forced many units to alter the timing of interval surgery and extend the number of neoadjuvant chemotherapy cycles. In order to support this paradigm shift and provide more accurate counseling during these unprecedented times, we investigated the survival outcomes in advanced epithelial ovarian cancer patients with the intent of maximal cytoreduction following neoadjuvant chemotherapy with respect to timing of surgery and degree of cytoreduction. METHODS: A retrospective review of all patients aged 18 years and above with FIGO (2014) stage III/IV epithelial ovarian cancer treated with neoadjuvant chemotherapy and the intention of interval cytoreduction surgery between January 2008 and December 2017 was conducted. Overall and progression-free survival outcomes were analyzed and compared with patients who only received chemotherapy. Outcome measures were correlated with the number of neoadjuvant chemotherapy cycles and amount of residual disease following surgery. RESULTS: Six hundred and seventy-one patients (median age 67 (range 20-91) years) were included in the study with 572 patients treated with neoadjuvant chemotherapy and surgery and 99 patients with chemotherapy only. There was no difference in the proportion of patients in whom complete cytoreduction was achieved based on number of cycles of neoadjuvant chemotherapy (2-4 cycles: 67.7%, n=337/498); ≥5 cycles: 62.2%, n=46/74). Patients undergoing cytoreduction surgery after neoadjuvant chemotherapy had a median 5-year progression-free and overall survival of 24 and 38 months, respectively. No significant difference in overall survival between surgical groups was observed (interval cytoreduction: 41 months vs delayed cytoreduction: 43 months, p=0.52). Those who achieved complete cytoreduction to R0 (no macroscopic disease) had a significant median overall survival advantage compared with those with any macroscopic residual disease (R0: 49-51 months vs R<1: 22-39 months, p<0.001 vs R≥1: 23-26 months, p<0.001). CONCLUSIONS: Survival outcomes do not appear to be worse for patients treated with neoadjuvant chemotherapy if cytoreduction surgery is delayed beyond three cycles. In advanced epithelial ovarian cancer patients the imperative to achieve complete surgical cytoreduction remains gold standard, irrespective of surgical timing, for best survival benefit.

The shift toward neo-adjuvant chemotherapy and interval debulking surgery for management of advanced ovarian and related cancers in a population-based setting: Impact on clinical outcomes.

OBJECTIVES: The aim of this study was to determine the proportion of patients with advanced ovarian and related cancers (EOC+RC), treated with neoadjuvant chemotherapy and interval debulking surgery (NACT - IDS), and to determine if there was any relationship with optimal cytoreduction rates and overall survival (OS) in a state-wide gynaecologic oncology service over time. METHODS: A retrospective review was undertaken using a population-based database of patients with stages 3 and 4 EOC+RC treated from 1982 till 2013 at the Queensland Centre for Gynaecological Cancer (QCGC). The proportion of patients treated with NACT - IDS compared with primary debulking surgery (PDS) was determined and compared with debulking rates and with the moving five-year OS probability. RESULTS: From 1982-2013, 2601 patients with advanced EOC+RC were managed at QCGC. No patients received NACT - IDS till 1995 when the first two patients received this treatment, rising to 55% of patients in 2013. Surgical cytoreduction rates to no macroscopic residual (R0) were achieved 32% of the time by 2006, rising to 48% in 2009, and 62% in 2013. Despite the increase in utilisation of NACT - IDS, our unit has noted a continued rise in the OS probability at five years to 45%. CONCLUSIONS: The increasing utilisation of NACT - IDS in the setting of a large centralised clinical service has been associated with increasing rates of optimal cytoreduction and survival rates have continued to rise in excess of those achieved in the trials reported to date.

Effect of Total Laparoscopic Hysterectomy vs Total Abdominal Hysterectomy on Disease-Free Survival Among Women With Stage I Endometrial Cancer: A Randomized Clinical Trial.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

Quality of life after early enteral feeding versus standard care for proven or suspected advanced epithelial ovarian cancer: Results from a randomised trial.

BACKGROUND: Malnutrition is common in patients with advanced epithelial ovarian cancer (EOC), and is associated with impaired quality of life (QoL), longer hospital stay and higher risk of treatment-related adverse events. This phase III multi-centre randomised clinical trial tested early enteral feeding versus standard care on postoperative QoL. METHODS: From 2009 to 2013, 109 patients requiring surgery for suspected advanced EOC, moderately to severely malnourished were enrolled at five sites across Queensland and randomised to intervention (n=53) or control (n=56) groups. Intervention involved intraoperative nasojejunal tube placement and enteral feeding until adequate oral intake could be maintained. Despite being randomised to intervention, 20 patients did not receive feeds (13 did not receive the feeding tube; 7 had it removed early). Control involved postoperative diet as tolerated. QoL was measured at baseline, 6weeks postoperatively and 30days after the third cycle of chemotherapy. The primary outcome measure was the difference in QoL between the intervention and the control group. Secondary endpoints included treatment-related adverse event occurrence, length of stay, postoperative services use, and nutritional status. RESULTS: Baseline characteristics were comparable between treatment groups. No significant difference in QoL was found between the groups at any time point. There was a trend towards better nutritional status in patients who received the intervention but the differences did not reach statistical significance except for the intention-to-treat analysis at 7days postoperatively (11.8 intervention vs. 13.8 control, p 0.04). CONCLUSION: Early enteral feeding did not significantly improve patients' QoL compared to standard of care but may improve nutritional status.

Adenoma malignum presenting as urinary incontinence.

Adenoma malignum is a rare malignancy of the cervix that often presents, as in this case, as urinary incontinence (UI). Due to this symptomatology, women with adenoma malignum are often referred to urogynecologists for investigation and management. Without a high degree of suspicion, the diagnosis is easy to overlook due to the atypical presentation for a gynecological malignancy and the deceptively benign histopathology. Adenoma malignum is highly malignant, and a late diagnosis is often fatal. An early diagnosis is therefore crucial for curative management, and the following paper provides a timely reminder of this rare but potentially devastating condition.

Feasibility and outcomes of ureteroureterostomy and extravesical ureteroneocystostomy as part of radical surgery for infiltrating gynecologic disease.

OBJECTIVE: Abdominopelvic infiltrative disease may require aggressive surgical procedures. This study reports on our experience with distal ureterectomy, ureteroureterostomy, and extravesical ureteroneocystostomy as part of radical surgery for infiltrating gynecologic disease. PATIENTS AND METHODS: Twenty-one women required surgery to the distal ureter at the Queensland Centre for Gynecological Cancer, Australia, from January 2006 to September 2012. Details of the patient's history, operation record, inpatient notes, and follow-up data were obtained through chart review. RESULTS: Patients' median age was 57.8 ± 14.7 years (range, 30-80 years). Seventeen patients had gynecologic cancer. Mean operating time was 3.9 ± 0.9 hours (range, 2.5-5.5 hours). Restoration of continuity was achieved through extravesical ureteroneocystostomy and ureteroureterostomy in 18 and 3 patients, respectively. Boari flap was used in 3 patients, and psoas hitch was the technique chosen in 11 patients. Urinary tract infection was the most common clinical adverse event. Albeit clinically irrelevant, 38% of the patients showed structural renal tract changes postoperatively. CONCLUSIONS: To achieve maximal surgical radicalness, resection of the distal ureter with subsequent ureteroureterostomy or extravesical ureteroneocystostomy is feasible and safe. Radical surgery to the urinary tract should be considered as a legitimate part of a gynecologic oncologist's surgical armamentarium to increase a patient's probability of survival and its positive effect on kidney function.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer.

Nomograms to predict isolated loco-regional or distant recurrence among women with uterine cancer.

OBJECTIVE: While there is ample literature on prognostic factors for uterine cancer, currently there are nomeans to estimate an individual's risk for recurrence or to differentiate the risk of loco-regional recurrence from distant recurrence. We addressed this gap by developing nomograms to individualize the risk of recurrence. METHODS: A total of 2097 consecutive patients who underwent primary surgery between 1997 and 2007 were included. Sixteen covariates were evaluated for their prognostic significance and modeled using multivariable competing risks regression to predict three-year outcomes as part of a nomogram. Each covariate in the nomogram is assigned a value, and a sum of these values form the overall risk score from which three-year incidence probabilities can be predicted for each individual. Predictive accuracy was assessed with concordance index and then corrected for optimism. RESULTS: The median follow-up time (inter-quartile range, IQR) was 50.0 (28.3-77.5) months and 221 patients developed a recurrence (127 patients with isolated loco-regional recurrence, 94 patients with distant recurrence). The nomograms included the following covariates: age at diagnosis, FIGO stage (2009), grade, lymphovascular invasion, histological type, depth of myometrial invasion, and peritoneal cytology. Concordance indices for isolated loco-regional and distant recurrences were 0.73 and 0.86, respectively. CONCLUSIONS: Our nomograms quantify an individual patient's risk of isolated loco-regional and distant recurrence, using factors that are routinely collected. They may assist clinicians to assess an individual's prognosis, individualize treatment and also assist in the risk stratification in prospective randomized clinical trials evaluating the effectiveness of treatments for uterine cancer.

Validation of the FIGO 2009 staging system for carcinoma of the vulva.

BACKGROUND: The previous (1988) International Federation of Gynecology and Obstetrics (FIGO) vulval cancer staging system failed in 3 important areas: (1) stage 1 and 2 disease showed similar survival; (2) stage 3 represented a most heterogeneous group of patients with a wide survival range; and (3) the number and morphology of positive nodes were not taken into account. OBJECTIVE: To compare the 1988 FIGO vulval carcinoma staging system with that of 2009 with regard to stage migration and prognostication. METHODS: Information on all patients treated for vulval cancer at the Queensland Centre for Gynecological Cancers, Australia, between 1988 to the present was obtained. Data included patients' characteristics as well as details on histopathology, treatments, and follow-up. We recorded the original 1988 FIGO stage, reviewed all patients' histopathology information, and restaged all patients to the 2009 FIGO staging system. Data were analyzed using the Kaplan-Meier method to compare relapse-free survival and overall survival. RESULTS: Data from 394 patients with primary vulval carcinoma were eligible for analysis. Patients with stage IA disease remained unchanged. Tumors formerly classified as stage II are now classified as stage IB. Therefore, FIGO 2009 stage II has become rare, with only 6 of 394 patients allocated to stage II. Stage III has been broken down into 3 substages, thus creating distinct differences in relapse-free survival and overall survival. Prognosis of patients with stage IIIC disease is remarkably poor. CONCLUSION: The FIGO 2009 staging system for vulval carcinoma successfully addresses some concerns of the 1988 system. Especially, it identifies high-risk patients within the heterogeneous group of lymph node-positive patients.

Hospital costs associated with adverse events in gynecological oncology.

BACKGROUND AND OBJECTIVE: Treatment for gynecological malignancies is complex and may cause unintended or accidental adverse events (AE). We evaluated the costs of hospitalization associated with those AEs among patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center in Australia. METHODS: Data on AEs were prospectively collected and matched with cost data (AU$ 2008) from the hospital's clinical costing unit and linked to demographical, clinical and histopathological data. Total costs were adjusted for various clinical factors and estimated using log-transformed ordinary least squared regression. Back-transformation was achieved using smearing factors. From epidemiological data, we also estimated the costs of AEs Australia-wide and undertook scenario and probabilistic sensitivity analyses to investigate the potential cost impact of reducing AEs. RESULTS: A total of 369 patients had surgical procedures of which 95 patients (26%) had at least one AE. Patients with AEs incurred an extra AU$12,780 on average, adjusted for age, co-morbidities, ovarian cancer, major or minor complications, surgical complexity, presence of malignancy and abdominal surgery. Mean adjusted costs (95% CI) for patients with intra-operative, minor post-operative and major post-operative AEs were AU$40,746 (11,582-71,859) AU$18,459 (17,270-19,713) and AU$67,656 (5324-131,761), respectively. Up to an estimated AU$20.6 million/year could be saved if the AEs were reduced by 40%. CONCLUSION: Adverse events are associated with significantly increased hospitalization costs and appropriate evidence-based interventions are justified to minimize AEs.

Evaluation of tumor-free distance and depth of myometrial invasion as prognostic factors for lymph node metastases in endometrial cancer.

INTRODUCTION: Concurrent uterine lesions or an irregular endomyometrial junction can make accurate assessment of depth of myometrial invasion (DOI) and percentage of myometrial invasion (%MI) difficult, leading to patients being staged and or treated suboptimally. An alternative measurement, known as the tumor-free distance (TFD), which measures the distance between maximal myometrial invasion and the uterine serosa, has been proposed. Previous studies comparing the predictive abilities of DOI and TFD were underpowered and inconclusive. Our objective was to compare TFD, DOI, and %MI as predictors for lymph node involvement in surgically staged endometrial cancer patients. METHODS: Patients with endometrioid adenocarcinoma of the endometrium treated between January 1997 and December 2007 were included. Tumor-free distance, DOI, and %MI were evaluated along with other pathological variables to determine their predictive ability for nodal involvement. Depth of myometrial invasion was measured between the endomyometrial junction and the maximal myometrial invasion. Tumor-free distance was calculated by subtracting the DOI from myometrial thickness (MT). Percentage MI was derived by dividing DOI by MT and expressed as a percentage of MT invaded. These 3 variables were transformed to z scores, and their ability to predict nodal involvement was compared. RESULTS: A total of 338 patients were eligible for analysis. Mean (SD) MT was 18.7 (5.9) mm. Median DOI was 6 mm, and median TFD was 10.3 mm. On univariate analysis, all 3 variables showed significant associations with nodal involvement. On multivariate analysis, after adjusting for lymphovascular space invasion, cervical involvement, serosal/adnexal involvement, grade, %MI, and TFD, DOI retained its statistical significance along with lymphovascular space invasion and cervical involvement. CONCLUSIONS: Depth of myometrial invasion predicts nodal involvement independently when compared with TFD.

Clinical audit in gynecological cancer surgery: development of a risk scoring system to predict adverse events.

BACKGROUND: Advanced gynecological surgery undertaken in a specialized gynecologic oncology unit may be associated with significant perioperative morbidity. Validated risk prediction models are available for general surgical specialties but currently not for gynecological cancer surgery. OBJECTIVE: The objective of this study was to evaluate risk factors for adverse events (AEs) of patients treated for suspected or proven gynecological cancer and to develop a clinical risk score (RS) to predict such AEs. METHODS: AEs were prospectively recorded and matched with demographical, clinical and histopathological data on 369 patients who had an abdominal or laparoscopic procedure for proven or suspected gynecological cancer at a tertiary gynecological cancer center. Stepwise multiple logistic regression was used to determine the best predictors of AEs. For the risk score (RS), the coefficients from the model were scaled using a factor of 2 and rounded to the nearest integer to derive the risk points. Sum of all the risk points form the RS. RESULTS: Ninety-five patients (25.8%) had at least one AE. Twenty-nine (7.9%) and 77 (20.9%) patients experienced intra- and postoperative AEs respectively with 11 patients (3.0%) experiencing both. The independent predictors for any AE were complexity of the surgical procedure, elevated SGOT (serum glutamic oxaloacetic transaminase, > or /=35 U/L), higher ASA scores and overweight. The risk score can vary from 0 to 14. The risk for developing any AE is described by the formula 100 / (1 + e((3.697 - (RS /2)))). CONCLUSION: RS allows for quantification of the risk for AEs. Risk factors are generally not modifiable with the possible exception of obesity.

Disease-free survival after vaginal vault brachytherapy versus observation for patients with node-negative intermediate-risk endometrial adenocarcinoma.

PURPOSE: To compare the disease-free survival (DFS) of patients with surgical stage 1, intermediate-risk endometrial adenocarcinoma (EAC) treated with primary surgery with or without adjuvant vaginal vault brachytherapy (VVBT). PATIENTS AND METHODS: A retrospective chart review identified 575 patients with stage 1B, 1C or 2A endometrial cancer who had surgery between 1990 and 2004. All patients were surgically staged and 259 patients received postoperative VVBT. The date and site of first recurrence were considered the primary statistical endpoints and were analysed by univariate and multivariate Cox models. Subgroups of patients stratified by substage and grade were created and Log-rank tests using vaginal recurrence as the endpoint were calculated within these groups. RESULTS: After a mean follow-up period of 72 months (95%-confidence interval (CI): 68 to 75 months) a total of 43 (7.5%) patients developed recurrence. Multivariate analysis demonstrated that increasing patient's age at diagnosis and stage 1C or 2A disease were independent risk factors for recurrence whereas the grade of differentiation and the type of treatment (surgery alone vs. surgery followed by postoperative VVBT) were not associated with a change in DFS. Analysis within the subgroups stratified by substage and grade did not even reveal a trend towards improved local control with VVBT. CONCLUSION: Postoperative VVBT was not associated with a measurable reduction in the risk of recurrence in surgical stage 1, intermediate-risk endometrial cancer.