Outcomes of a Decade of Routine Cervical Screening in a Canadian Adolescent Obstetrics Clinic.

OBJECTIVE: New recommendations from the Ontario Cervical Cancer Screening Program indicate that initiation of screening should be delayed to age 21. However, there is sparse evidence pertaining to pregnant adolescents. Our objective was to determine whether early cervical cancer screening in pregnant adolescents confers an advantage over delayed screening in the prevention of cervical carcinoma. METHODS: We conducted a retrospective cohort study of cervical cancer screening in all pregnant adolescents receiving antenatal care through an obstetrics clinic for adolescents between 2000 and 2010. Clinic attendees had an antenatal and/or postpartum Pap smear, with follow-up according to standard recommendations. Results were recorded together with information on regression, persistence, or progression of abnormal cytology, colposcopy referrals, and cervical biopsies. There is a single regional colposcopy clinic. RESULTS: At least one Pap smear result was documented in 365 of the 388 patients. Of these 365 smears, 88 had abnormal cytology, 76 (86.4%) of which were reported as atypical cells of undetermined significance/low-grade squamous intraepithelial lesion, 11 (12.5%) high-grade squamous intraepithelial lesion (HSIL), and one atypical glandular cells (1.1%). Follow-up cytology was available for 78 patients. No patient lost to follow-up had subsequent referrals for colposcopic assessment in the region. Overall, cytologic abnormalities regressed in 75 (96.1%), persisted in two (2.6%), and progressed in one patient (1.3%). Twenty-three patients (of 365) required a total of 68 colposcopy visits and 17 biopsies, but ultimately only three loop electrosurgical excision procedures (LEEPs) and one laser vaporization were performed. Only one LEEP in a 20-year-old demonstrated HSIL. CONCLUSION: This population of pregnant adolescents had a high incidence of low-grade cervical abnormalities with a high rate of regression. Routinely screening these pregnant adolescents resulted in numerous repeat visits, repeat Pap smears, and colposcopy referrals, and led to patient anxiety and systemic costs. Not a single case of cervical cancer was prevented that would not otherwise have been identified by adherence to the new guidelines.

Identification of the IGF1/PI3K/NF κB/ERK gene signalling networks associated with chemotherapy resistance and treatment response in high-grade serous epithelial ovarian cancer.

BACKGROUND: Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. The objective of this study was to use gene expression profiling to delineate major deregulated pathways and biomarkers associated with the development of intrinsic chemotherapy resistance upon exposure to standard first-line therapy for ovarian cancer. METHODS: The study cohort comprised 28 patients divided into two groups based on their varying sensitivity to first-line chemotherapy using progression free survival (PFS) as a surrogate of response. All 28 patients had advanced stage, high-grade serous ovarian cancer, and were treated with standard platinum-based chemotherapy. Twelve patient tumours demonstrating relative resistance to platinum chemotherapy corresponding to shorter PFS (< eight months) were compared to sixteen tumours from platinum-sensitive patients (PFS > eighteen months). Whole transcriptome profiling was performed using an Affymetrix high-resolution microarray platform to permit global comparisons of gene expression profiles between tumours from the resistant group and the sensitive group. RESULTS: Microarray data analysis revealed a set of 204 discriminating genes possessing expression levels which could influence differential chemotherapy response between the two groups. Robust statistical testing was then performed which eliminated a dependence on the normalization algorithm employed, producing a restricted list of differentially regulated genes, and which found IGF1 to be the most strongly differentially expressed gene. Pathway analysis, based on the list of 204 genes, revealed enrichment in genes primarily involved in the IGF1/PI3K/NF κB/ERK gene signalling networks. CONCLUSIONS: This study has identified pathway specific prognostic biomarkers possibly underlying a differential chemotherapy response in patients undergoing standard platinum-based treatment of serous epithelial ovarian cancer. In addition, our results provide a pathway context for further experimental validations, and the findings are a significant step towards future therapeutic interventions.

Initial evaluation and referral guidelines for management of pelvic/ovarian masses.

OBJECTIVES: To optimize the management of adnexal masses and to assist primary care physicians and gynaecologists determine which patients presenting with an ovarian mass with a significant risk of malignancy should be considered for gynaecologic oncology referral and management. OPTIONS: Laparoscopic evaluation, comprehensive surgical staging for early ovarian cancer, or tumour debulking for advanced stage ovarian cancer. OUTCOMES: To optimize conservative versus operative management of women with possible ovarian malignancy and to optimize the involvement of gynaecologic oncologists in planning and delivery of treatment. EVIDENCE: Published literature was retrieved through searches of PubMed or MEDLINE, CINAHL, and the Cochrane Library, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified by searching the web sites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. RECOMMENDATIONS: 1. Primary care physicians and gynaecologists should always consider the possibility of an underlying ovarian cancer in patients in any age group who present with an adnexal or ovarian mass. (II-2B) 2. Appropriate workup of a perimenopausal or postmenopausal woman presenting with an adnexal mass should include evaluation of symptoms and signs suggestive of malignancy, such as persistent pelvic/abdominal pain, urinary urgency/frequency, increased abdominal size/bloating, and difficulty eating. In addition, CA125 measurement should be considered. (II-2B) 3. Transvaginal or transabdominal ultrasound examination is recommended as part of the initial workup of a complex adnexal/ovarian mass. (II-2B) 4. Ultrasound reports should be standardized to include size and unilateral/bilateral location of the adnexal mass and its possible origin, thickness of septations, presence of excrescences and internal solid components, vascular flow distribution pattern, and presence or absence of ascites. This information is essential for calculating the risk of malignancy index II score to identify pelvic mass with high malignant potential. (IIIC) 5. Patients deemed to have a high risk of an underlying malignancy should be reviewed in consultation with a gynaecologic oncologist for assessment and optimal surgical management. (II-2B).

An evidence-based estimate of the appropriate rate of utilization of radiotherapy for cancer of the cervix.

PURPOSE: Current estimates of the proportion of cancer patients who will require radiotherapy (RT) are based almost entirely on expert opinion. The objective of this study was to calculate the proportion of incident cases of cervical cancer that should receive RT by application of an evidence-based approach. METHODS AND MATERIALS: A systematic review of the literature was done to identify indications for RT for cervical cancer and to ascertain the level of evidence that supported each indication. A survey of Canadian gynecologic oncologists and radiation oncologists who treat cervical cancer was done to determine the level of acceptance of each indication among doctors who practice in the field. An epidemiologic approach was then used to estimate the incidence of each indication for RT in a typical North American population of patients with cervical cancer. RESULTS: The systematic review of the literature identified 29 different indications for RT for cervical cancer. The majority of the 75 experts who responded to the mail survey stated that they "usually" or "always" recommended RT in all but one of the clinical situations that were identified as indications for RT on the basis of the systematic review. The analysis of epidemiologic data revealed that, in a typical North American population, 65.4% +/- 2.5% of cervical cancer cases will develop one or more indications for RT at some point in the course of the illness, 63.4% +/- 2.3% will develop indications for RT as part of their initial management, and 2.0% +/- 0.9% will develop indications for RT for progressive or recurrent disease. The effects of variations in case mix on the need for RT was examined by sensitivity analysis, which suggested that the maximum plausible range for the appropriate rate of utilization of RT was 54.3% to 67.9%. The proportion of cases that required RT was stage dependent: 10.6% +/- 1.2% in Stage IA, 74.9% +/- 1.3% in Stage IB, 100% in Stages II and III, and 97.2% +/- 1.1% in Stage IV. CONCLUSIONS: This evidence-based estimate of the appropriate rate of use of RT for cervical cancer adds to the growing pool of knowledge about the need for RT that will ultimately provide a rational basis for long-term planning for RT programs and for auditing access to RT in the general population.

A comparison of endometrial cancer outcomes in Ontario.

OBJECTIVE: To compare endometrial cancer treatment strategies and outcomes across the province of Ontario, Canada. METHODS: A retrospective cohort study was conducted of 195 women diagnosed with endometrial cancer in Ontario between 1996 and 1998, as a sample of the population. The women's charts were randomly selected by the medical records departments at 5 tertiary care centres in Ontario. The outcomes measured included 5-year overall survival (OS) and disease-free survival (DFS), use of adjuvant radiotherapy, treatment complications, and prognostic factors for survival. RESULTS: The 2 main treatment strategies were (1) total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH BSO) and (2) surgical staging (defined as TAH BSO and pelvic lymph node dissection with or without cytology, peritoneal biopsies, and omentectomy). Surgical staging rates across the province ranged from 0% to 88%. Stratified survival analysis revealed a significant difference in OS among centres (log rank P =.039). Crude survival analysis revealed no difference in 5-year OS or DFS between the 2 treatment strategies. The Cox proportional hazards model identified advanced stage of tumour as being the most predictive factor of DFS, and the woman's age at diagnosis and tumour grade as predictive of OS. DISCUSSION: There was a significant difference in 5-year OS among the 5 tertiary care centres. There was no significant difference between surgical staging and TAH BSO with respect to 5-year DFS or OS. CONCLUSION: As there were significant differences in the treatment of endometrial carcinoma and OS across the province, a population-based study of endometrial cancer treatment strategies and outcomes is required.

Screening postmenopausal women for ovarian cancer: a systematic review.

OBJECTIVES: To assess ovarian cancer screening in asymptomatic, general-risk postmenopausal women. Outcomes of interest were the screening tests assessed (predictive values, sensitivity, and specificity), the stage of screen-detected disease at diagnosis, psychological effects of screening, and survival. METHODS: MEDLINE, CANCERLIT, and the Cochrane Library databases were searched to June 2003 using the terms "ovarian," "cancer," "neoplasms," "screening," "clinical trial," "meta-analysis," and "systematic review." Studies were included if they were clinical trials, meta-analyses, or systematic reviews that evaluated tests used to detect ovarian cancer in asymptomatic women in the general population. Studies investigating women at increased risk for ovarian cancer (e.g., family history) and those with symptoms suggestive of ovarian cancer were excluded. TABULATION, INTEGRATION, AND RESULTS: Seventeen prospective cohort studies and 3 pilot randomized controlled trials were included in this review. Screening tests for cancer antigen 125 (CA125) and ultrasound had low positive predictive values, resulting in healthy women being recalled and a false-positive rate of 0.01% to 5.8%. Of every 10,000 women participating in an annual screening program with CA125 for 3 years, 800 will have an ultrasound scan because of an elevated CA125, 30 will undergo surgery because of an abnormal ultrasound, and 6 will have ovarian cancer detected at surgery (3 will be diagnosed at early-stage disease and have a chance of a cure). CONCLUSION: There is insufficient evidence to support the introduction of screening for ovarian cancer in the asymptomatic general-risk postmenopausal population. Screening is associated with increased rates of surgery and patient anxiety.

Systematic review of first-line chemotherapy for newly diagnosed postoperative patients with stage II, III, or IV epithelial ovarian cancer.

OBJECTIVE: The aim of this study was to determine the optimal postoperative chemotherapy regimen for women with newly diagnosed stage II, III (micro or macro), or IV epithelial ovarian cancer. METHODS: A systematic search was conducted to find randomized controlled trials and meta-analyses published between 1980 and April 2001. RESULTS: A published meta-analysis found that, compared with non-platinum-based regimens, platinum, alone or in combination with other agents, improved survival when used as first-line chemotherapy for ovarian cancer. The meta-analysis did not detect a difference in efficacy between cisplatin and carboplatin. A published randomized trial of cisplatin plus paclitaxel versus carboplatin plus paclitaxel did not detect a significant difference in survival between these regimens. In two randomized trials, treatment with paclitaxel plus cisplatin resulted in improved survival compared with cyclophosphamide plus cisplatin. A randomized trial of paclitaxel plus cisplatin versus paclitaxel alone versus cisplatin alone detected no differences in survival among the three treatment groups. While hematologic adverse effects were more frequent with carboplatin than with cisplatin, nonhematologic adverse effects were less frequent with carboplatin. The addition of paclitaxel to cisplatin did not appear to increase the incidence of serious adverse effects. CONCLUSIONS: Intravenous carboplatin plus paclitaxel is the recommended postoperative chemotherapy regimen for newly diagnosed stage II-IV epithelial ovarian cancer. Intravenous cisplatin plus paclitaxel may also be considered a treatment option. Intravenous carboplatin as a single agent may be considered a treatment option in patients for whom paclitaxel is contraindicated or in patients who are unwilling to accept the adverse effects of paclitaxel chemotherapy.