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.

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.

Malignant ovarian germ cell tumours in the post-menopausal population.

BACKGROUND: Malignant ovarian germ cell tumours (MOGCT) are uncommon in the general population and very rare in post-menopausal women. AIMS: To evaluate the demographics, treatment and survival of post-menopausal women with MOGCT treated at the Queensland Centre for Gynaecological Cancer (QCGC) and compare these with pre-menopausal women. MATERIALS AND METHODS: Retrospective analysis was performed of the QCGC database from January 1981 to February 2017. The disease course of post-menopausal women was compared with pre-menopausal women affected by MOGCT over the same period and compared with the world literature. RESULTS: There were six post-menopausal women with MOGCT treated at the QCGC compared with 166 pre-menopausal women. In the post-menopausal group of women, there was no mortality directly attributed to germ cell ovarian disease compared with 10 (6.0%) women in the pre-menopausal group. CONCLUSIONS: Malignant ovarian germ cell tumours are a very rare condition in post-menopausal women. Despite some suggestion in the world literature that survival outcomes are worse in this population, this was not found in our study.

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.

Cervical cancer in women under 25 years of age in Queensland, Australia: To what extent is the diagnosis made by screening cytology?

INTRODUCTION: The current Australian National Cervical Screening Program (NCSP) involves biennial, cytology-based screening of women from the age of 18 years. From December, 2017 this will change to a five-yearly human papilloma virus-based screening commencing at age 25. There is some concern that the new program may delay the opportunistic detection of cervical cancers in women under 25 years. AIM: (1) To review all cases of invasive cervical cancer in Queensland women under the age of 25 over the last 28 years. (2) To determine symptoms and screening history prior to diagnosis. METHODS: A retrospective cohort study was undertaken at the Queensland Centre for Gynaecological Cancer (QCGC) and the Queensland Cancer Registry (QCR) of all women aged between 13 and 25 years diagnosed with cervical cancer in Queensland between 1984 and 2012. Demographic data and symptoms prior to diagnosis were extracted from the QCGC and QCR databases. RESULTS: A total of 56 women aged 13-25, were diagnosed with cervical cancer and treated at the QCGC between 1984 and 2012. The commonest reason for the diagnosis of cancer was investigation of abnormal symptoms (n = 22, 39%) rather than routine Pap smear abnormalities (n = 15, 26%). CONCLUSIONS: Consistent with the world literature, there is a very low incidence of cervical cancer in women under 25 years of age, irrespective of the age of commencement of screening, or the screening interval. Our study lends some support to the proposed commencement age of 25 years in the new NCSP.

Outcomes of women diagnosed and treated for low-risk gestational trophoblastic neoplasia at the Queensland Trophoblast Centre (QTC).

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is classified as a highly curable group of pregnancy-related malignancies; however, approximately 15% will be persistent and require chemotherapy. Up to 25% of these women will develop resistance and 2% will develop disease relapse after initial chemotherapy. Despite the need for further chemotherapy in these women, cure rates are high. OBJECTIVE: To evaluate the outcomes of women diagnosed with low-risk GTN, assessing the type of treatment, the number of chemotherapy cycles received, development of resistance or disease relapse, survival, and to assess the feasibility of changing to a new drug regimen. METHODS: From March 2012 until February 2015, a retrospective study was conducted and 38 cases with low-risk GTN were reviewed. The number of cycles, type of treatment received, duration of treatment, development of resistance and disease relapse, and adverse side effects were analysed. RESULTS: The median duration of follow-up was 12 months. Disease-free survival was 100% and primary complete remission rates were achieved in 85.3% of patients who were treated with actinomycin D and 25% patients who were treated with methotrexate (MTX). A change in chemotherapy was required for nine patients. One patient developed disease relapse. Nausea, fatigue and constipation were the most frequent adverse events reported with actinomycin D. All women were cured of their disease. CONCLUSION: All women were successfully treated and achieved complete remission. Changing from MTX to actinomycin D as first-line chemotherapy for women with low-risk GTN was feasible and safe.

Squamous cell carcinoma of the vulva: a comparison between women 35 years or younger and 90 years or older.

OBJECTIVE: This study aimed to compare clinical features, diagnosis, management, and outcomes between women 35 years or younger and 90 years or older with vulvar squamous cell carcinoma referred to Queensland Centre for Gynaecological Cancer between 1983 and 2010. MATERIALS AND METHODS: Fifty-seven case records, including pathology reports for these 2 groups were reviewed and analyzed using the computer software SPSS 11.0. RESULTS: Of the cases, 34 were 35 years or younger (mean = 31.6 years), and 23 90 years or older (mean = 92.6 years). International Federation of Gynecology and Obstetrics classification showed grade 1 for 74% in the younger group and 55% for the older group. Patient status showed 22 alive (65%) in the younger group and 4 alive (17%) in the older group. Three younger patients (9%) were dead of disease and 8 (35%) in the older group. Three patients (9%) died of another disease in the younger group and 10 patients (43%) in the older group. Initial treatment was surgical in 30 younger cases (88%) and 18 older cases (78%). CONCLUSIONS: We demonstrated a trend toward younger women presenting with vulvar squamous cell carcinoma and a history of human papillomavirus and vulvar intraepithelial neoplasia. Immune deficiency diseases occurred in 23% of the younger group, but none occurred in the older group, where Alzheimer disease, heart disease, and renal failure (57%) were present. Poorly differentiated tumors and an International Federation of Gynecology and Obstetrics classification of 2 or more resulted in a worse outcome than did better differentiated lesions, irrespective of additional medical conditions.

Paget's disease of the vulva: Diagnosis and follow-up key to management; a retrospective study of 50 cases from Queensland.

OBJECTIVE: To review the clinical features, diagnosis, management, and outcomes for the 50 cases of Paget's disease (PD) of the vulva referred to Queensland Centre for Gynaecological Cancer between 1986 and 2009. METHODS: Vulvar PD cases from QCGC were reviewed and analyzed using the computer software Statistical Package for the Social Sciences (SPSS) 11.0. RESULTS: Paget's disease (PD) of the vulva is uncommon. Of the 50 patients, 2 have died of their PD, 1 patient that had coexisting PD died of squamous cell vulva cancer, and 11 died of unrelated causes. The mean age at diagnosis was 67.6 years (range, 31 to 91). All cases were Caucasian. Time from onset of symptoms to diagnosis averaged 21 months. Not until a biopsy was performed was the diagnosis made. The most common presenting complaint was pruritis (27 cases, 54%). There was no identifiable "favored" site on the vulva for PD. Positive groin lymph nodes were found in 4 of the 10 cases who underwent node biopsy. Two who had poorly differentiated carcinoma in the nodes and PD died of disease within a year of diagnosis, one is alive three years later. The fourth case had coincidental PD and vulvar squamous cell carcinoma with squamous carcinoma groin nodes. Initial treatment was surgical. CONCLUSIONS: The prognosis for primary extra-mammary PD of the vulva confined to the epidermis (IEP) is excellent. Early diagnosis and long term follow-up are the keys to successful management. The status of disease at the margins of surgical specimens does not reliably equate to patient long term outcomes.

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.