Reducing overtreatment of prostate cancer by radical prostatectomy in Eastern Ontario: a population-based cohort study.

BACKGROUND: Canadian guidelines recommend against population-based screening for prostate cancer because of the risk of overdiagnosis and overtreatment. We sought to assess whether a higher proportion of patients receiving surgery had clinically significant cancer over time. METHODS: All hospitals in Eastern Ontario that perform prostatectomy participate in a Prostate Cancer Community of Practice, which prospectively maintains a database for the region. Using these data, we conducted a retrospective cohort study that included all patients who underwent prostatectomy from 2009 to 2015 in the region. We examined trends in biopsy findings, clinical stage, prostate-specific antigen level and Gleason score. We then determined whether the proportion of patients with clinically significant cancer (Gleason score ≥ 7 or stage pT3) increased over time. RESULTS: During the study period, 1897 patients underwent prostatectomy in Eastern Ontario (mean 271 surgeries/yr). The proportion of patients who were determined to have National Comprehensive Cancer Network intermediate or high-risk disease increased from 46.7% in 2009 to 90.2% in 2015. The proportion of men with clinically significant cancer on prostatectomy increased from 59.7% in 2009 to 93.1% in 2015. Adjusted analyses suggested that the proportion of patients with clinically significant cancer increased by 5% per year during the study period. INTERPRETATION: There has been a change in the tumour characteristics of patients who undergo prostatectomy in Eastern Ontario. In recent years, almost all patients have had clinically significant cancer, which suggests that overtreatment of prostate cancer has decreased.

Addressing fear of cancer recurrence among women with cancer: a feasibility and preliminary outcome study.

BACKGROUND: Evidence suggests that fear of cancer recurrence (FCR) is one of the most frequently cited unmet needs among cancer survivors and is associated with psychological distress, stress-response symptoms, and lower quality of life, as well as increased use of health care resources. Despite these factors, few manualized interventions exist to address FCR among cancer survivors. PURPOSE: To develop, manualize, and pilot test the feasibility and preliminary efficacy of a 6-week cognitive-existential (CE) group intervention designed to address FCR in women with breast or ovarian cancer. METHODS: This study was a single-arm multi-site study with pre-, post-, and 3-month follow-up measurement occasions. RESULTS: A total of 56 breast or ovarian cancer survivors enrolled in the study; 44 completed the CE group intervention. Following the intervention, women experienced a reduction in the primary study outcome measure of FCR and secondary study outcome measures of cancer-specific distress and uncertainty. They also reported improvements in secondary study outcome measures of quality of life and coping. The effect sizes of the observed changes were for the most part in the medium to large effect range; furthermore, almost all changes were sustained at 3-month follow-up. CONCLUSION: This brief intervention appears feasible and has shown promising results in addressing FCR and related secondary outcomes of cancer-specific distress, uncertainty, quality of life, and coping; however, it should be further tested using a randomized controlled study design to more definitively assess its efficacy. IMPLICATIONS FOR CANCER SURVIVORS: FCR is a near-universal worry for cancer survivors that, when left unaddressed, tends to remain stable over time. This study has important implications for all cancer survivors as it is the first published intervention that provides preliminary evidence of its efficacy in decreasing fear of cancer recurrence.

Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations.

Although gynecologic cancers account for only 10% of all new cancer cases in women, these cancers account for 20% of all female cancer survivors. Improvements in cancer care have resulted in almost 10 million cancer survivors, and this number is expected to grow. Therefore, determining the most cost-effective clinical surveillance for detection of recurrence is critical. Unfortunately, there has been a paucity of research in what are the most cost-effective strategies for surveillance once patients have achieved a complete response. Currently, most recommendations are based on retrospective studies and expert opinion. Taking a thorough history, performing a thorough examination, and educating cancer survivors about concerning symptoms is the most effective method for the detection of most gynecologic cancer recurrences. There is very little evidence that routine cytologic procedures or imaging improves the ability to detect gynecologic cancer recurrence at a stage that will impact cure or response rates to salvage therapy. This article will review the most recent data on surveillance for gynecologic cancer recurrence in women who have had a complete response to primary cancer therapy.

Intraperitoneal chemotherapy in the first-line treatment of women with stage III epithelial ovarian cancer: a systematic review with metaanalyses.

Because women with advanced ovarian cancer have poor outcomes, it is imperative to continue exploring for novel therapies. The opportunity for intraperitoneal treatment, especially in the subgroup of patients with minimal residual disease, in which the intraperitoneal approach may have a biologic rationale for benefit over and above the standard intravenous route, needs to be explored to the fullest extent. The MEDLINE, EMBASE, and Cochrane Library databases were searched up to January 2006 for randomized trials that compared first-line intraperitoneal-containing chemotherapy with first-line intravenous chemotherapy in the treatment of women with stage III epithelial ovarian cancer. Seven randomized, controlled trials were identified, including 3 large Phase III trials and 4 smaller randomized trials. The 3 large Phase III trials detected statistically significant overall survival benefits with intraperitoneal cisplatin-containing chemotherapy compared with intravenous chemotherapy alone. The improvements in survival were 8 months, 11 months, and 16 months, respectively. Pooled analysis from 6 of the 7 randomized trials confirmed the survival effect with intraperitoneal chemotherapy compared with intravenous chemotherapy alone (relative risk, 0.88; 95% confidence interval, 0.81-0.95). Severe adverse events and catheter-related complications with intraperitoneal chemotherapy were significantly more common and often were dose-limiting. The results from this review indicated that cisplatin-containing intraperitoneal chemotherapy should be offered to patients on the basis of significant improvements in overall survival. The appropriate clinical and institutional multidisciplinary facilities are needed for the safe delivery of this treatment in optimally debulked patients. Further research is needed concerning specific aspects of the treatment, such as optimal agent, dose, and scheduling.

Prognostic significance of postoperative morbidities in patients with advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy and delayed primary surgical debulking.

BACKGROUND: To examine the prognostic significance of postoperative morbidities in patients with ovarian cancer treated with neoadjuvant chemotherapy and interval surgical debulking. METHODS: Retrospective chart reviews of all patients treated with neoadjuvant chemotherapy and interval debulking were performed from 1999 to 2002. Descriptive statistics were used to summarize the distributions of important clinical variables. Logistic regression was used to identify statistically significant predictors of postoperative morbidities. Cox regression was used to model time to first clinical progression. Survivals were estimated by the Kaplan-Meier method and compared with the log rank test. P < .05 was considered to be statistically significant. RESULTS: Fifty-eight patients were treated with neoadjuvant platinum-taxane combination chemotherapy. Major surgical complications were observed in four patients (6.8%). There were no perioperative deaths. The presence of concurrent medical comorbidities was associated with the development of significant postoperative morbidities (P = .038). Cox regression showed any macroscopic residual disease (P = .04) and the presence of significant postoperative morbidities (odds ratio, 4.7, 95% confidence interval, 1.8-12.7, P = .002) to be predictive of a shorter progression-free interval. CONCLUSIONS: Neoadjuvant chemotherapy followed by interval surgical debulking carried a low risk for postoperative morbidity. The adverse influence of marked postoperative morbidity on progression-free survival needs further study.

Palliative radiotherapy for recurrent granulosa cell tumor of the ovary: a report of 3 cases with radiological evidence of response.

BACKGROUND: The role of radiotherapy for recurrent or residual granulosa cell tumor of the ovary (GCTO) is controversial. One reason for this controversy may be that most published studies on this topic have not utilized sectional imaging to assess response to radiotherapy. We report on three cases of recurrent or residual GCTO that were treated with radiotherapy for which pre- and post-treatment CT scans were available to assess response. CASE REPORTS: Case #1: A 77-year-old woman with a 7 x 10-cm pelvic mass post-surgery was treated with radiotherapy to a dose of 45 Gy in 25 fractions followed by a boost of 10 Gy in 5 fractions. Post-treatment scans revealed a decrease in tumor size to 4 x 2.5 cm. The reduction in tumor volume was 86%, and the duration of response was 13 months. Case #2: A 73-year-old woman with multiple abdominal recurrences was treated with radiotherapy to a dose of 30 Gy in 20 fractions. The dominant mass shrank from 13 x 17 cm to 5.1 x 6.6 cm. The reduction in volume was 85%, and the duration of response has been 5 months. Her symptom of abdominal bloating and early satiety abated. Case #3: An 83-year-old woman with a 20 x 20 x 15-cm mass in the left abdomen was treated with radiotherapy to a dose of 45 Gy in 25 fractions. The mass decreased in size to 3.7 x 2.5 cm post-treatment. The duration of response has been 21 months. Her symptom of left leg swelling disappeared after therapy. CONCLUSION: Radiotherapy is highly effective in treating recurrent or residual GCTO. In these three cases, the tumor volume decreased by 85 to 90%, and the duration of response has, up to now, been 5 to 21 months.

Preliminary results of 5% imiquimod cream in the primary treatment of vulva intraepithelial neoplasia grade 2/3.

OBJECTIVE: This study was undertaken to study the tolerability and efficacy of 5% imiquimod cream in the primary treatment of vulva intraepithelial neoplasia (VIN) grade 2/3. STUDY DESIGN: VIN grade 2/3 patients were recruited from regional colposcopy units. Imiquimod cream was applied over the abnormal area by the patient using an escalating dose regime for total treatment duration of 16 weeks. At the end of study, repeat colposcopy and biopsy of the target lesion were performed to assess for response. RESULTS: Twenty-three patients participated. Twenty patients (87%) had VIN grade 3. Nine patients (39%) had multifocal disease on colposcopy. Therapy was well tolerated with the most commonly observed side effects being irritation at the application site. Responses were evaluable in 17 patients. Complete responses were observed in 9 patients with partial responses in another 5 (relative risk 82%). The median time to response was 7 weeks. CONCLUSION: Imiquimod cream can induce histologic regression of high-grade VIN lesions and is well tolerated using a slow dose-escalating regime.

Development of ovarian cancer surgery quality indicators using a modified Delphi approach.

OBJECTIVE: Little performance measurement has been undertaken in the area of oncology, particularly for surgery which is a pivotal event in the continuum of cancer care. This work was conducted to develop indicators of quality ovarian cancer surgery using a modified three-step Delphi approach. METHODS: A multidisciplinary panel, comprised of surgical and methodologic co-chairs, nine surgeons, one medical oncologist, one radiation oncologist, a nurse, and a pathologist, reviewed potential indicators extracted from the medical literature through two consecutive rounds of rating followed by consensus discussion. The panel then prioritized the indicators selected in the previous two rounds. RESULTS: Of 33 possible indicators that emerged from 41 selected articles, 14 were prioritized by the panel as benchmarks for assessing the quality of surgical care. The 14 indicators represent three levels of measurement (provincial/regional, hospital, individual provider) across several phases of care (diagnosis, surgery, pathology, and adjuvant therapy), as well as broad measures of access and outcomes. Some of the indicators selected by the panel were also recommended as standards of care by national initiatives in other countries. CONCLUSIONS: A systematic evidence- and consensus-based approach was used to develop quality indicators of ovarian cancer care, with a focus on pre-, peri-, and postoperative care as well as outcomes, that are applicable in any jurisdiction.

Systemic therapy for advanced uterine sarcoma: a systematic review of the literature.

OBJECTIVE: To conduct a systematic review of the literature regarding the systemic treatment of advanced uterine sarcoma and provide an evidence-based summary of the available literature. METHODS: MEDLINE, EMBASE, and the Cochrane Library databases were searched. "Uterine sarcoma," "leiomyosarcoma," "mixed mesodermal tumor," "chemotherapy," and "systemic therapy" were combined with the search terms for study designs. RESULTS: Three randomized controlled trials and 24 prospective phase II trials were included in the systematic review. In a randomized trial of doxorubicin versus doxorubicin plus cyclophosphamide for advanced or recurrent uterine sarcoma, doxorubicin produced an overall response rate (RR) of 19% and median survival of 11.6 months, which was similar to the response with combination chemotherapy (RR 19%, median survival 10.9 months). A randomized trial comparing ifosfamide plus cisplatin versus ifosfamide alone in mixed mesodermal tumors showed a significant improvement in RR and progression-free survival with the combination compared with ifosfamide alone, however, the combination was associated with increased toxicity including death. A randomized trial comparing doxorubicin to doxorubicin with dacarbazine in women with advanced or recurrent uterine sarcoma demonstrated a significantly higher RR with the combination (P < 0.05), but no significant difference in survival. CONCLUSIONS: Offering palliative chemotherapy to patients with advanced, unresectable uterine sarcoma who are symptomatic from this disease is a reasonable decision. Doxorubicin is an option for women with advanced uterine sarcoma. The combination of cisplatinum and ifosfamide is also an option for women with metastatic mixed mesodermal tumors; however, this combination is associated with significant toxicity when compared to ifosfamide alone.

Coping with ovarian cancer: do coping styles affect outcomes?

UNLABELLED: The majority of patients with ovarian cancer face a long road of persistent hardship and strain. Treatment of this disease is intense, involving aggressive debulking surgery and multiple chemotherapy regimens. Coping with the disease and its treatment challenges patients on many levels. This review was developed to summarize the evidence concerning the impact of coping strategies on outcomes in patients with ovarian cancer. A comprehensive search of the literature in the field of coping and ovarian cancer was undertaken. Using the Ovid interface, 3 electronic databases, including Medline, Cinahl, and PsycINFO, were searched using the search terms "coping," "cancer," and "ovarian cancer." In addition, a critical appraisal of the 2 most widely used scales to assess coping strategies was a component of this work. This review highlights the relative lack of knowledge on coping in ovarian cancer, the methodologic challenges to its study, and the need to develop an instrument that is tailored to evaluate coping strategies used by patients with ovarian cancer. A validated instrument to assess coping strategies used by patients with ovarian cancer is needed. Identification of strategies that are maladaptive or destructive in patients with ovarian cancer could be used to improve quality of care for patients burdened by this disease. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to list the potential coping strategies for patients with ovarian cancer, to explain the various coping assessment scales, and to summarize the evidence concerning the impact of coping strategies on outcomes in ovarian cancer patients.

Systematic review of adjuvant care for women with Stage I ovarian carcinoma.

BACKGROUND: Several adjuvant care interventions to treat women with Stage I ovarian carcinoma have been studied. The aim of the current systematic review was to determine the optimal strategy for adjuvant care for women with Stage I ovarian carcinoma. METHODS: A systematic search was conducted to find randomized controlled trials published between 1965 and April 2004 that examined adjuvant therapy (e.g., chemotherapy and radiotherapy) for women with Stage I ovarian carcinoma. RESULTS: Thirteen randomized controlled trials were identified that compared adjuvant therapies for women with Stage I ovarian carcinoma. Eight of these trials reported results only for patients with Stage I disease. The majority of patients in the five randomized trials that compared adjuvant chemotherapy with no chemotherapy did not receive lymphadenectomy as part of their surgical staging. The pooled results for Stage I patients indicated a survival benefit (relative risk [RR], 0.74; 95% confidence interval [CI], 0.58-0.94; P = 0.01), and a benefit in terms of a reduced risk of developing disease recurrence (RR, 0.70; 95% CI, 0.58-0.86; P = 0.0004) favoring adjuvant chemotherapy. Platinum-based adjuvant chemotherapy was reported to improve overall 5-year survival (absolute survival difference 8%; 95% CI, 2-12%; hazard ratio, 0.67; 95% CI, 0.50-0.90; P = 0.008). CONCLUSIONS: Adjuvant platinum-based chemotherapy for women with Stage I ovarian carcinoma improved survival and reduced the risk of recurrent disease. The optimally staged group accounted for approximately 10% of women with Stage I disease. The role of adjuvant chemotherapy in optimally staged patients (especially those with good prognostic factors) has not been assessed adequately.

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.

Cervical cancer mortality by neighbourhood income in urban Canada from 1971 to 1996.

BACKGROUND: The reduction of socioeconomic inequalities in health is an explicit objective of health policy in Canada, yet rates of death from cervical cancer are known to be higher among women of low socioeconomic status than among those of higher socioeconomic status. To evaluate progress toward the World Health Organization's goal of "Health for All," we examined whether income-related differentials in cervical cancer mortality diminished from 1971 to 1996. METHODS: Death registration data for Canada's census metropolitan areas in 1971, 1986, 1991 and 1996 were assigned to census tracts through postal code, and the tracts were in turn assigned to income quintiles based on their proportion of the population below the Statistics Canada low-income cutoff values. We compared age-standardized death rates (using the 1966 world population standard) in the female population (excluding those in institutions) across the 5 income quintiles and calculated interquintile rate ratios (poorest over richest) and interquintile rate differences (poorest minus richest). RESULTS: From 1971 to 1996, the overall age-standardized cervical cancer death rate per 100 000 women (and 95% confidence interval) declined from 5.0 (4.5-5.6) to 1.9 (1.7-2.1), the interquintile rate ratio diminished from 2.7 (1.8-4.2) to 1.7 (1.1- 2.6), and the interquintile rate difference decreased from 4.6 (2.8- 6.4) to 1.1 (0.2-1.9). INTERPRETATION: The income-related disparity in rates of death from cervical cancer as measured by rate ratios and rate differences diminished markedly in urban Canada from 1971 to 1996. Among the numerous factors that may have contributed to the decline (including decline in fertility and improvement in diet), one important factor was probably the implementation of effective screening programs.

Assisted reproductive technology and the incidence of ovarian cancer: a meta-analysis.

OBJECTIVE: To systematically evaluate the available literature regarding the relationship between assisted reproductive technology and ovarian cancer. DATA SOURCES: Computerized search of 6 databases from 1966 (or closest) to present: Cochrane Controlled Trials Register, Cancerlit, CINHAL, Current Contents, PubMed in process (formerly called PreMEDLINE), and MEDLINE. We collected references from the bibliographies of reviews, original research articles, content experts, and conference proceedings to find published and unpublished literature. METHODS OF STUDY SELECTION: Case-control and cohort studies are included. The population of interest is treated infertile women, the control population is untreated infertile women, and the intervention or exposure of interest includes the following fertility medications: clomiphene citrate, gonadotropins, human chorionic gonadotropin, and gonadotropin releasing hormone agonists. The primary outcome is incident, primary ovarian cancer. Three cohort and 7 case-control studies were included in the quantitative analyses. TABULATION, INTEGRATION, AND RESULTS: The Newcastle-Ottawa Quality Assessment Scales were used. Two investigators independently extracted study methods, sources of bias, and outcomes. The following information was recorded: publication information, subject characteristics, intervention information and outcomes. Studies combined were sufficiently homogeneous for quantitative summary. Case-control and cohort data showed a significantly elevated risk for exposure of infertility medications and ovarian cancer in subjects who underwent assisted reproductive technology compared with general population controls (1.52; 95% confidence interval [CI] 1.18 to 1.97). When cases of ovarian cancer were compared with infertile controls for exposure to infertility medications, the odds ratio (0.99; 95% CI 0.67, 1.45) was not elevated. However, cohort data comparing outcome in treated infertile patients with untreated infertile patients suggests that treated patients may tend to a lower incidence of ovarian cancer-odds ratio = 0.67 (95% CI 0.32, 1.41). CONCLUSION: Ovarian cancer does not appear to be increased in treated infertile patients versus untreated infertile patients. Treated infertile patients may have a lower incidence of ovarian cancer than untreated infertile patients.

Prospective longitudinal study of ultrasound screening for endometrial abnormalities in women with breast cancer receiving tamoxifen.

OBJECTIVE: The goal of this work was to study the role of transvaginal ultrasonography (TVUS) together with colorflow Doppler imaging (CFDI) in the detection of significant endometrial abnormalities induced by tamoxifen. METHODS: Over a 6-year period, 304 women on tamoxifen as adjuvant therapy for breast cancer were recruited into the current study. Standard demographic data as well as duration of tamoxifen use were collected. Patients were assessed at study entry and at yearly intervals with TVUS together with CFDI. All patients had an endometrial biopsy at the time of study entry, and repeat endometrial evaluations were done subsequently only if there were abnormal ultrasound findings or the presence of irregular vaginal bleeding. All ultrasonic characteristics and Doppler flow measurements were recorded. Descriptive statistics were used to describe the study group. Logistic regression was used to identify significant treatment- and ultrasound-related factors associated with the presence of significant uterine pathology. RESULTS: One thousand and sixty-one ultrasound assessments were performed on 304 patients over a 6-year period. The mean age was 52.33 (range, 29-79). Seventy-two percent of the patients were postmenopausal at the time of breast cancer diagnosis. The median concentrations of estrogen and progesterone receptor were 75 and 73 fmol/L, respectively. Fifty-eight percent of the patients had received cytotoxic chemotherapy. The mean duration of tamoxifen use was 48.2 months. Thirty-two percent of the ultrasound examinations had associated significant uterine pathology defined as conditions that required further medical or surgical investigation and treatment. However, 80% of the abnormalities represented benign polyps. Six cases of primary endometrial cancer were detected. All cases presented with irregular bleeding. No recurrence of disease was detected at a median follow-up of 48 months. One case of metastatic breast cancer to the uterus was encountered. By setting the endometrial thickness cutoff at more than 9 mm to represent significant abnormality in this patient population, the sensitivity was 63.3%, specificity was 60.4%, positive predictive value was 43.3%, and negative predictive value was 77.5%. To detect endometrial cancer, the endometrial thickness cutoff at 9 mm had a positive predictive value of only 1.4%. Logistic regression analysis showed only endometrial thickness greater than 9 mm (OR 3.99, CI = 1.26-12.65, P = 0.018) and spiral artery pulsatility index measurement (OR 4.18, CI = 1.25-13.92, P = 0.02) to be associated with significant uterine abnormalities. CONCLUSIONS: Routine sequential ultrasound surveillance in asymptomatic women on tamoxifen is not useful because of its low specificity and positive predictive value. A significant portion of screened asymptomatic women would need to undergo needless surgical evaluations of their endometrium if widespread use of ultrasound is implemented in this patient population.