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Factors associated with the suboptimal treatment of women less than 55 years of age with early-stage ovarian cancer
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Gynecologic Oncology 108 (2008) 95 – 99 www.elsevier.com/locate/ygyno
Factors associated with the suboptimal treatment of women less than 55 years of age with early-stage ovarian cancer John K. Chan a,⁎, Daniel S. Kapp b , Jacob Y. Shin a , Kathryn Osann c , Gary S. Leiserowitz d , Rosemary D. Cress e , Cynthia O'Malley f a
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine, UCSF Comprehensive Cancer Center, 1600 Divisadero Street, Box 1702, San Francisco, California 94143-1702, USA b Division of Radiation Therapy, Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Drive, MC 5827, Stanford, CA 94305, USA c Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 City Drive, Orange, CA 92868, USA d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Davis-Medical Center, Davis, CA, USA e California Cancer Registry, 1700 Tribute Rd, Suite 100, Sacramento, CA 95815, USA f Northern California Cancer Center, 2201 Walnut Avenue, Suite 300, Fremont, CA, 94538, USA Received 4 July 2007 Available online 18 October 2007
Abstract Objectives. A significant number of young patients with early-stage ovarian cancer did not receive chemotherapy based on standard practice guidelines. We investigated factors associated with the suboptimal treatment in these women. Materials and Methods. Data were obtained from California Cancer Registry from 1994 to 1996. Kaplan–Meier and Cox proportional hazard methods were used. Results. Of 135 younger (b 55 years) patients with stages IC–II epithelial ovarian cancers, 29 (21.5%) did not receive chemotherapy (group A) while the remaining 106 (78.5%) had adjuvant chemotherapy (group B). Women in group A were more likely to live in poor neighborhoods (58.6% vs. 38.7%; p = 0.055), less likely to be seen by a gynecologic oncologist (13.8% vs. 39.6%; p = 0.009), and had more grade 1 and 2 tumors (58.6% vs. 37.8%; p = 0.049). The 5-year disease-specific survival of group A was 70.5% compared to 76.5% in group B (p = 0.252). Of note, patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy, but this difference was not noted for women in non-poor neighborhoods (77.1% vs. 70.9%; p = 0.574). On multivariate analysis, those treated by gynecologic oncologists were more likely to receive chemotherapy (95% CI:1.33–12.63; p = 0.006). Discussion. A significant number of young women with stages IC–II epithelial ovarian cancer did not receive chemotherapy. The factors associated with this suboptimal treatment of young women with stages IC–II ovarian cancer include living in poor neighborhoods and lack of care by a gynecologic oncologist. © 2007 Elsevier Inc. All rights reserved. Keywords: Ovarian cancer; Chemotherapy; Younger women
Introduction In 2006, there were an estimated 20,180 epithelial ovarian cancers diagnosed in the United States with approximately onethird having FIGO (International Federation of Obstetrics and Gynecology) stages I and II disease [1]. Although the survival ⁎ Corresponding author. Fax: +1 415 885 3586. E-mail address: [email protected] (J.K. Chan). 0090-8258/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2007.08.087
of early-stage disease is significantly higher than those with advanced cancers, nearly 20% and 50% of stages I and II cancer patients, respectively, will succumb to their disease [2–6]. The standard treatment for early-stage high-risk epithelial ovarian cancer involves primary surgical staging followed by adjuvant chemotherapy. In fact, the National Cancer Institute Consensus Conference strongly recommends the use of chemotherapy for patients with ovarian cancer except those with early-stage and low grade cancers.
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However, there are an increasing number of studies that have demonstrated treatment disparities in cancer care based on age, race, and socioeconomic status. Prior reports have shown that older patients were less likely to receive adjuvant chemotherapy for ovarian cancers [7,8]. An analysis of enrollment in clinical trials has also demonstrated a substantial under-representation of women 65 years or older [9]. Moreover, others have shown that African Americans were more likely to receive suboptimal treatment compared to Caucasians. In fact, one study revealed that only 61% of African Americans with ovarian cancer underwent surgery and adjuvant chemotherapy compared to 70% of Caucasians [10]. Furthermore, Goff et al. found that only 24.7% of the patients with advanced stage ovarian cancer who had lower (≤ $25,000) annual income received lymph node dissection compared to 40.6% of those more affluent (N$45,000) [11]. Few studies have evaluated the pattern of care in younger women with early-stage epithelial ovarian cancer. A recent analysis on the trends in surgery and chemotherapy for women diagnosed with ovarian cancer in California showed that over 20% of young (b 55 years) patients with early-stage ovarian cancer did not receive chemotherapy as recommended by standard practice guidelines [12]. This current study analyzes the demographic, socioeconomic, and other clinico-pathologic factors that may be associated with the suboptimal treatment in these women. The results of these findings may provide guidance for intervention to improve the treatment for this suboptimal treated group of patients. Materials and methods The study population included women residing in Northern California who were diagnosed with primary invasive epithelial ovarian cancer from January 1, 1994, to December 31, 1996 [12]. Patients with tumors of low-malignant potential were excluded. The study subjects were identified within a surveillance region of 10.5 million people using three population-based databases from the California Cancer Registry. The original study received approval from the Human Subjects Protection Committees at the Northern California Cancer Center, the Public Health Institute, and the State of California Health and Human Services Agency. This current study was exempt from Institutional Review Board approval. Details on the data collection are described in a prior report [12]. Briefly, the tumor registry collects data on tumor (stage, histology, grade), treatment (chemotherapy use, radiation, type of surgery with in the first 4 months following diagnosis), and demographic characteristics (age, sex, race, ethnicity, residential address at time of diagnosis, vital status). Tumor registry data were primarily obtained from hospital registries and supplemented with information from death certificates, physician offices, pathology laboratories, and radiation oncology centers. To supplement registry treatment data, we identified patients for whom the registry had no record of chemotherapy and sent a questionnaire to the patient's attending physician. Race/ethnicity and geographical regions were grouped as previously defined (Table 1) [12]. Using census-based socioeconomic (SES) and race-specific measures for each block group, dichotomous variables were employed to classify each neighborhood as poor/not poor, educated/less educated, and “white vs. blue-collar worker.” The SES measures were obtained for each case by matching records to census data based on blocked group and census tract corresponding to the address at the time of diagnosis. If ≥20% of the population lived below the poverty level, this block was considered poor. If ≥25% of the population lacked a high school education, this block was considered as low education. If N66% of the population over 16 years of age worked in blue-collar jobs, this block was considered “blue-collar.” These census-based socioeconomic measures have been previously employed in public
Table 1 Demographic characteristics of all patients (n = 135)
Age Median (years) Range (years) Race White Hispanic Asian/Pacific islander Black Unknown
Total (n = 135)
Chemotherapy Yes (n = 106)
No (n = 29)
47 23–54
47 23–54
47 30–54
92 (68.1%) 14 (10.4%) 24 (17.8%)
75 (70.8%) 11 (10.4%) 16 (15.1%)
17 (58.6%) 3 (10.3%) 8 (27.6%)
4 (3.0%) 1 (0.7%)
4 (3.8%) 0 (0.0%)
0 (0.0%) 1 (3.4%)
Neighborhood socioeconomic status Not poor 77 (57.0%) Poor 58 (43.0%) More educated 105 (77.8%) Less educated 30 (22.2%) White-collar 95 (70.4%) Blue-collar 40 (29.6%) Region San Francisco Sacramento Rural Northern California Santa Clara Year of diagnosis 1994 1995 1996
65 41 83 23 74 32
p-value (chi-square)
p = 0.304
(61.3%) (38.7%) (78.3%) (21.7%) (69.8%) (30.2%)
12 (41.4%) 17 (58.6%) 22 (75.9%) 7 (24.1%) 21 (72.4%) 8 (27.6%)
p = 0.055
25 (18.5%) 30 (22.2%) 26 (19.3%)
22 (20.8%) 24 (22.6%) 18 (17.0%)
3 (10.3%) 6 (20.7%) 8 (27.6%)
p = 0.437
54 (40.0%)
42 (39.6%)
12 (41.4%)
59 (43.7%) 34 (25.2%) 42 (31.1%)
44 (41.5%) 29 (27.4%) 33 (31.1%)
15 (51.7%) 5 (17.2%) 9 (31.0%)
p = 0.779 p = 0.786
p = 0.480
health research and have been validated in prior studies based in the San Francisco Bay area [13]. All patients underwent surgery for invasive epithelial ovarian cancer and were found to have International Federation of Gynecology and Obstetrics (FIGO) stage IC or II disease. Moreover, all patients with stages IC–II cancers who survived at least 12 days after diagnosis were considered candidates for adjuvant chemotherapy. Histologic cell types were categorized into the following groups: serous, mucinous, endometrioid, clear cell, and other. Women with low malignant potential, germ cell, stromal, and other non-epithelial ovarian tumors were excluded. A patient was classified as having seen a gynecologic oncologist if any of her physicians were members of the Society of Gynecologic Oncology. The use of adjuvant chemotherapy was dichotomized as yes/no. Since chemotherapy is typically administered in an outpatient setting, registry treatment data were supplemented with data from a physician survey, and medical record review. The questionnaire sent to the patient's attending physician asked whether the patient received chemotherapy and the type of agents administered. Those attending physicians who did not have the requested information were asked to provide referral to another physician involved in the patient's management. Furthermore, clinical information was obtained from the medical records at the physician's offices upon request. Follow-up data, including the date and cause of death or censoring, were obtained via Vital Statistics [14]. The outcome variable was death from ovarian cancer (disease-specific survival); deaths from other or unknown causes were censored at the time of death. Pearson's chi-square test was used to evaluate associations between factors and risk of death. Survival time was measured in months from the time of diagnosis until censoring or death. Survival analyses and predictors of outcome were analyzed using Kaplan–Meier and Cox proportional hazard methods. Statistical analyses were performed using SPSS 14.0 [15].
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Results Of 135 younger (b55 years) patients with stages IC–II epithelial ovarian cancers, 29 (21.5%) did not receive chemotherapy (group A) while the remaining 106 (78.5%) underwent adjuvant chemotherapy (group B). The median age of the entire cohort was 47 years (range: 23–54 years). Ninety-two (68.1%) were White, 14 (10.4%) were Hispanic, 24 (17.8%) were Asian, 4 (3.0%) were Black, and 1 (0.7%) was unknown. Based on socioeconomic status [12], 58 (43.0%) were lived in poor neighborhoods, 30 (22.2%) were less educated, and 40 (29.6%) were blue-collar workers. Twenty-eight (18.5%), 30 (22.2%), 26 (19.3%), and 54 (40.0%) were from San Francisco, Sacramento, rural California, and Santa Clara, respectively (Table 1). Seventy-four (54.8%) had stage IC and 61 (45.2%) had stage II disease (Table 2). Endometrioid, serous, and clear cell cancers were found in 42 (31.1%), 40 (29.6%), and 19 (14.1%) of patients, respectively. Grade 1, 2, and 3 disease were noted in 22 (16.3%), 35 (25.9%), and 42 (31.1%) women, respectively. In the overall study group, 46 (34.1%) women received care by a gynecologic oncologist. The demographic and clinico-pathologic factors for patients who did not receive (Group A) or underwent (Group B) chemotherapy were compared (Tables 1 and 2). Women in group A were more likely to reside in poor neighborhoods (58.6% vs. 38.7%; p = 0.055), less likely to be seen by a gynecologic oncologist (13.8% vs. 39.6%; p = 0.009), and had more grade 1 and 2 tumors (58.6% vs. 37.8%; p = 0.049). On multivariate analysis, those treated by gynecologic oncologists had a 4.1-fold increase Table 2 Clinico-pathologic characteristics of all patients (n = 135)
Primary surgery Yes No Unknown
Total (n = 135)
Chemotherapy Yes (n = 106)
No (n = 29)
p-value (chi-square)
130 (96.3%) 4 (3.0%) 1 (0.7%)
104 (98.1%) 2 (1.9%) 0 (0.0%)
26 (89.7%) 2 (6.9%) 1 (3.4%)
p = 0.146
Fig. 1. Kaplan–Meier disease-specific survival of patients living in poor neighborhoods by chemotherapy (n = 58).
in likelihood of receiving chemotherapy (odds ratio = 4.1; 95% CI: 1.33–12.63; p = 0.006). The five-year disease-specific survival for those that did not receive chemotherapy (group A) was 70.5% compared to 76.5% in those who did (group B) (p = 0.252). Of note, patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy (Fig. 1), but this difference was not noted in the women residing in non-poor neighborhoods (77. 1% vs. 70.9%; p = 0.574). The median follow-up was 59 months. On multivariate analysis, primary surgery (no vs. yes) (HR = 0.08, 95% CI = 0.02–0.29; p b 0.0005) and race (White vs. Asian/Pacific Islander vs. Black and Hispanic) (HR = 1.87, 95% CI = 1.23–2.83; p b 0.003) were significant prognostic factors for improved disease-specific survival. Other variables including chemotherapy, ACOS hospital certification, and gynecologic oncologist treatment were not statistically significant on multivariate analysis for disease-specific survival. Discussion
Stage IC II
74 (54.8%) 61 (45.2%)
54 (50.9%) 52 (49.1%)
20 (69.0%) 9 (31.0%)
p = 0.084
Histology Serous Endometrioid Mucinous Clear cell NOS/other
40 (29.6%) 42 (31.1%) 16 (11.9%) 19 (14.1%) 18 (13.3%)
34 (32.1%) 31 (29.2%) 12 (11.3%) 16 (15.1%) 13 (12.3%)
6 11 4 3 5
(20.7%) (37.9%) (13.8%) (10.3%) (17.3%)
p = 0.653
Grade 1 2 3 Unknown
22 (16.3%) 35 (25.9%) 42 (31.1%) 36 (26.7%)
15 (14.2%) 25 (23.6%) 38 (35.9%) 28 (26.4%)
7 10 4 8
(24.1%) (34.5%) (13.8%) (27.6%)
p = 0.049
Gynecologic oncologist Yes 46 (34.1%) No 89 (65.9%)
42 (39.6%) 64 (60.4%)
4 (13.8%) 25 (86.2%)
p = 0.009
Current treatment guidelines for high-risk early-stage epithelial ovarian cancer recommend adjuvant chemotherapy [16]. Several randomized trials have shown a survival advantage associated with adjuvant therapy in these patients [17–19]. The failure rate of high-risk patients with early-stage epithelial ovarian cancer who did not receive adjuvant chemotherapy has been reported to be as high as 20 to 50% [2–6,20]. Furthermore, a prior study showed that the salvage rates for those patients with stage I epithelial ovarian cancers who recurred following surgery alone were poor [21]. Based on a recently published population-based study of 2150 women with epithelial ovarian cancer in California, 21.5% of women less than 55 years with early-stage high-risk (stages IC–II) cancers did not receive chemotherapy [12]. This deviation from the standard treatment guidelines stimulated us to investigate the factors associated with the suboptimal care in these young patients.
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Another population-based study also showed that more young women with ovarian cancer were treated by nongynecologic oncologists (64% vs. 36%) [22]. It is likely that pelvic masses are more difficult to characterize as benign or malignant in the younger cohort, and thus subspecialists are often not involved in their surgeries. In addition, Noumoff et al. [23] showed that the public is poorly informed about gynecologic oncologists and that general physicians may have a misconception about advanced ovarian cancer as one of a rapidly progressing fatal disease with poor response to any treatment. Le et al. showed that the lack of a proper staging surgery led to both overtreatment and undertreatment of patients. After adjusting for confounding variables, the lack of proper staging surgery increased the risk for disease recurrence by three-fold [24]. Furthermore, Goff et al. [11] reported that younger patients (21–50 years) were less likely to undergo debulking/omentectomy. Our current analyses shows that patients who did not get chemotherapy were more likely to be classified as living in poor neighborhoods based on census socioeconomic measures. Goff et al. [11] also showed that poor patients had a significantly higher likelihood of not receiving optimal care with a lower likelihood of having a lymph node dissection. Likewise, Harlan et al. [25] reported that women with private health insurance received guideline therapy significantly more often (66%) than did women with public insurance, no insurance, or unknown insurance status (54%). Women with higher incomes are likely to have private insurance, access to cancer specialists, and quality medical care. Schrag et al. [26] also showed that high volume surgeons, many of whom are gynecologic oncologists, were less likely to treat those who resided in low income census tracts or in rural areas. In addition, those who did not get treatment from gynecologic oncologists had a lower likelihood of receiving chemotherapy. In this current analysis, we also found that patients living in poor neighborhoods were less likely to receive chemotherapy, and this had a significant impact on their overall outcome. It is interesting to note that patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy (Fig. 1), but this difference was not noted in women living in neighborhoods that were not classified as poor (77.1% vs. 70.9%; p = 0.574). One explanation for this finding may be that women from non-poor census blocks were accurately staged with early-stage cancers whereas the women from poor neighborhoods were understaged and had more advanced cancers, which resulted in a survival benefit associated with chemotherapy in these patients from poorer neighborhoods. The results of a prior analysis on the role of gynecologic oncologists in the management of patients with epithelial ovarian cancer demonstrated that women who underwent treatment by a gynecologic oncologist were more likely to receive chemotherapy [27]. Others have also shown that women who were treated by a gynecologic oncologist had a higher likelihood of receiving recommended surgery and adjuvant therapy [11,22, 28–34]. Recently, Giede et al. [33] performed an evidencebased review on the potential benefits of subspecialty care in
patients with ovarian cancer. After an extensive review of 18 studies, these authors found that gynecologic oncologists were more likely to perform optimal staging surgeries (p b 0.01). In these early-stage patients, their analysis suggested that an increased survival could be explained by improved identification of true stage I patients. In addition, of those with advanced disease, there was good quality evidence to support a 6- to 9month median survival advantage for women operated on by gynecologic oncologists rather than general gynecologists and/ or general surgeons (p b 0.01). Thus, they concluded that women receiving initial surgical management for ovarian epithelial cancer should receive care from gynecologic oncologists [33]. Women with low grade disease were less likely to receive chemotherapy. Prior studies showed that patients with stage I grade 1 or 2 disease may not benefit from adjuvant chemotherapy [17]. However, it is important to note that all patients in this current analysis had stage IC or II disease with high-risk for recurrence. Nevertheless, a significant proportion of patients with high-risk disease under non-specialist care did not receive chemotherapy. This suggests that some physicians who lack subspecialty training in ovarian cancer may not appreciate the risk of recurrence and failure in this aggressive cancer. This study was unique in that it provides an opportunity to observe the outcomes of a group of young patients with high-risk early-stage ovarian cancer who did not receive appropriate treatment. The strengths of our study include the availability of chemotherapy data, involvement of multiple institutions, generalized population, supplementation of adjuvant chemotherapy data, and detailed demographics including race and socioeconomic background. However, as the tumor registry collects racial/ethnic data from medical records, it is not known if the patient reported her race or if it was assigned by medical staff. In addition, our study was limited by the lack of information on the extent of cytoreductive surgery and residual disease after primary surgery. In addition, we do not have detailed information on the specific type of chemotherapy, number of cycles of treatment, or whether the patient was offered chemotherapy and refused. There was also no detailed information on the physician subspecialists that administered the chemotherapy. The data were obtained from 1994 to 1996. We arbitrarily selected for this time period in order to provide an extended follow-up of these patients. Furthermore, the current management of early-stage ovarian cancer has not changed significantly over this time period. The relatively small number of patients in the various subgroups suggests that these results should be interpreted with caution, even where the differences were of statistical significance. In summary, this study showed that young patients who did not receive appropriate treatment were more likely to live in poor neighborhoods, less likely to be treated by a gynecologic oncologist, and had more early-grade cancers. The lack of appropriate adjuvant therapy was associated with a poorer outcome. Further studies are warranted to identify the obstacles to appropriate care of young women with ovarian cancer and subsequent implementation of programs to overcome these barriers to improve the outcomes of these women. Patient and
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physician education may be needed to assure that standard treatment guidelines are followed in the treatment of young women diagnosed with high-risk early-stage ovarian cancer. Acknowledgments The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred.
[13]
[14]
[15] [16] [17]
[18]
[19]
[20]
[21]
[22]
References [23] [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106–30. [2] Hoskins PJ, Swenerton KD, Manji M, et al. ‘Moderate-risk' ovarian cancer (stage I, grade 2; stage II, grade 1 or 2) treated with cisplatin chemotherapy (single agent or combination) and pelvi-abdominal irradiation. Int J Gynecol Cancer 1994;4:272–8. [3] Partridge EE, Phillips JL, Menck HR. The National Cancer Data Base report on ovarian cancer treatment in United States hospitals. Cancer 1996; 78:2236–46. [4] Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. Int J Gynaecol Obstet 2003;83(Suppl 1):135–66. [5] Averette HE, Janicek MF, Menck HR. The National Cancer Data Base report on ovarian cancer. American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1995;76:1096–103. [6] Kosary CL. FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973–87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina. Semin Surg Oncol 1994;10: 31–46. [7] Janssen-Heijnen ML, Houterman S, Lemmens VE, et al. Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach. Crit Rev Oncol Hematol 2005;55:231–40. [8] Sundararajan V, Hershman D, Grann VR, et al. Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. J Clin Oncol 2002;20:173–8. [9] Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341: 2061–7. [10] Parham G, Phillips JL, Hicks ML, et al. The National Cancer Data Base report on malignant epithelial ovarian carcinoma in African-American women. Cancer 1997;80:816–26. [11] Goff BA, Matthews BJ, Wynn M, et al. Ovarian cancer: patterns of surgical care across the United States. Gynecol Oncol 2006;103:383–90. [12] Cress RD, O'Malley CD, Leiserowitz GS, et al. Patterns of chemotherapy
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
99
use for women with ovarian cancer: a population-based study. J Clin Oncol 2003;21:1530–5. Krieger N. Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 1992;82:703–10. O'Malley CD, Cress RD, Campleman SL, et al. Survival of Californian women with epithelial ovarian cancer, 1994–1996: a population-based study. Gynecol Oncol 2003;91:608–15. SPSS, Inc. Chicago, IL, 2006. NCCN Clinical Practice Guidelines in Oncology. Ovarian Cancer 1, 2007: National Comprehensive Cancer Network; 2007. Young RC, Walton LA, Ellenberg SS, et al. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 1990;322:1021–7. Trimbos JB, Vergote I, Bolis G, et al. Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst 2003;95:113–25. Colombo N, Guthrie D, Chiari S, et al. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 2003;95:125–32. Nguyen HN, Averette HE, Hoskins W, et al. National survey of ovarian carcinoma. VI. Critical assessment of current International Federation of Gynecology and Obstetrics staging system. Cancer 1993;72: 3007–11. Kolomainen DF, A'Hern R, Coxon FY, et al. Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy? J Clin Oncol 2003;21:3113–8. Carney ME, Lancaster JM, Ford C, et al. A population-based study of patterns of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not? Gynecol Oncol 2002;84:36–42. Noumoff J, Morgan M, King S, et al. The specialty of gynecologic oncology as perceived by the public. Gynecol Oncol 1992;47:48–52. Le T, Adolph A, Krepart GV, et al. The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma. Gynecol Oncol 2002;85:351–5. Harlan LC, Abrams J, Warren JL, et al. Adjuvant therapy for breast cancer: practice patterns of community physicians. J Clin Oncol 2002;20: 1809–17. Schrag D, Earle C, Xu F, et al. Associations between hospital and surgeon procedure volumes and patient outcomes after ovarian cancer resection. J Natl Cancer Inst 2006;98:163–71. Chan JK, Kapp DS, Shin JY, et al. Influence of the gynecologic oncologist on the survival of ovarian cancer patients. Obstet Gynecol June 2007;109(6):1342–50. Eisenkop SM, Spirtos NM, Montag TW, et al. The impact of subspecialty training on the management of advanced ovarian cancer. Gynecol Oncol 1992;47:203–9. Nguyen HN, Averette HE, Hoskins W, et al. National survey of ovarian carcinoma. Part V. The impact of physician's specialty on patients' survival. Cancer 1993;72:3663–70. Kehoe S, Powell J, Wilson S, et al. The influence of the operating surgeon's specialisation on patient survival in ovarian carcinoma. Br J Cancer 1994;70:1014–7. Earle CC, Schrag D, Neville BA, et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst 2006;98:172–80. Engelen MJ, Kos HE, Willemse PH, et al. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer 2006;106:589–98. Giede KC, Kieser K, Dodge J, et al. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol Oncol 2005;99: 447–61. Munstedt K, von Georgi R, Misselwitz B, et al. Centralizing surgery for gynecologic oncology—a strategy assuring better quality treatment? Gynecol Oncol 2003;89:4–8.
Gynecologic Oncology 108 (2008) 95 – 99 www.elsevier.com/locate/ygyno
Factors associated with the suboptimal treatment of women less than 55 years of age with early-stage ovarian cancer John K. Chan a,⁎, Daniel S. Kapp b , Jacob Y. Shin a , Kathryn Osann c , Gary S. Leiserowitz d , Rosemary D. Cress e , Cynthia O'Malley f a
Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco School of Medicine, UCSF Comprehensive Cancer Center, 1600 Divisadero Street, Box 1702, San Francisco, California 94143-1702, USA b Division of Radiation Therapy, Department of Radiation Oncology, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Drive, MC 5827, Stanford, CA 94305, USA c Division of Hematology and Oncology, Department of Medicine, Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 City Drive, Orange, CA 92868, USA d Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of California, Davis-Medical Center, Davis, CA, USA e California Cancer Registry, 1700 Tribute Rd, Suite 100, Sacramento, CA 95815, USA f Northern California Cancer Center, 2201 Walnut Avenue, Suite 300, Fremont, CA, 94538, USA Received 4 July 2007 Available online 18 October 2007
Abstract Objectives. A significant number of young patients with early-stage ovarian cancer did not receive chemotherapy based on standard practice guidelines. We investigated factors associated with the suboptimal treatment in these women. Materials and Methods. Data were obtained from California Cancer Registry from 1994 to 1996. Kaplan–Meier and Cox proportional hazard methods were used. Results. Of 135 younger (b 55 years) patients with stages IC–II epithelial ovarian cancers, 29 (21.5%) did not receive chemotherapy (group A) while the remaining 106 (78.5%) had adjuvant chemotherapy (group B). Women in group A were more likely to live in poor neighborhoods (58.6% vs. 38.7%; p = 0.055), less likely to be seen by a gynecologic oncologist (13.8% vs. 39.6%; p = 0.009), and had more grade 1 and 2 tumors (58.6% vs. 37.8%; p = 0.049). The 5-year disease-specific survival of group A was 70.5% compared to 76.5% in group B (p = 0.252). Of note, patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy, but this difference was not noted for women in non-poor neighborhoods (77.1% vs. 70.9%; p = 0.574). On multivariate analysis, those treated by gynecologic oncologists were more likely to receive chemotherapy (95% CI:1.33–12.63; p = 0.006). Discussion. A significant number of young women with stages IC–II epithelial ovarian cancer did not receive chemotherapy. The factors associated with this suboptimal treatment of young women with stages IC–II ovarian cancer include living in poor neighborhoods and lack of care by a gynecologic oncologist. © 2007 Elsevier Inc. All rights reserved. Keywords: Ovarian cancer; Chemotherapy; Younger women
Introduction In 2006, there were an estimated 20,180 epithelial ovarian cancers diagnosed in the United States with approximately onethird having FIGO (International Federation of Obstetrics and Gynecology) stages I and II disease [1]. Although the survival ⁎ Corresponding author. Fax: +1 415 885 3586. E-mail address: [email protected] (J.K. Chan). 0090-8258/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2007.08.087
of early-stage disease is significantly higher than those with advanced cancers, nearly 20% and 50% of stages I and II cancer patients, respectively, will succumb to their disease [2–6]. The standard treatment for early-stage high-risk epithelial ovarian cancer involves primary surgical staging followed by adjuvant chemotherapy. In fact, the National Cancer Institute Consensus Conference strongly recommends the use of chemotherapy for patients with ovarian cancer except those with early-stage and low grade cancers.
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However, there are an increasing number of studies that have demonstrated treatment disparities in cancer care based on age, race, and socioeconomic status. Prior reports have shown that older patients were less likely to receive adjuvant chemotherapy for ovarian cancers [7,8]. An analysis of enrollment in clinical trials has also demonstrated a substantial under-representation of women 65 years or older [9]. Moreover, others have shown that African Americans were more likely to receive suboptimal treatment compared to Caucasians. In fact, one study revealed that only 61% of African Americans with ovarian cancer underwent surgery and adjuvant chemotherapy compared to 70% of Caucasians [10]. Furthermore, Goff et al. found that only 24.7% of the patients with advanced stage ovarian cancer who had lower (≤ $25,000) annual income received lymph node dissection compared to 40.6% of those more affluent (N$45,000) [11]. Few studies have evaluated the pattern of care in younger women with early-stage epithelial ovarian cancer. A recent analysis on the trends in surgery and chemotherapy for women diagnosed with ovarian cancer in California showed that over 20% of young (b 55 years) patients with early-stage ovarian cancer did not receive chemotherapy as recommended by standard practice guidelines [12]. This current study analyzes the demographic, socioeconomic, and other clinico-pathologic factors that may be associated with the suboptimal treatment in these women. The results of these findings may provide guidance for intervention to improve the treatment for this suboptimal treated group of patients. Materials and methods The study population included women residing in Northern California who were diagnosed with primary invasive epithelial ovarian cancer from January 1, 1994, to December 31, 1996 [12]. Patients with tumors of low-malignant potential were excluded. The study subjects were identified within a surveillance region of 10.5 million people using three population-based databases from the California Cancer Registry. The original study received approval from the Human Subjects Protection Committees at the Northern California Cancer Center, the Public Health Institute, and the State of California Health and Human Services Agency. This current study was exempt from Institutional Review Board approval. Details on the data collection are described in a prior report [12]. Briefly, the tumor registry collects data on tumor (stage, histology, grade), treatment (chemotherapy use, radiation, type of surgery with in the first 4 months following diagnosis), and demographic characteristics (age, sex, race, ethnicity, residential address at time of diagnosis, vital status). Tumor registry data were primarily obtained from hospital registries and supplemented with information from death certificates, physician offices, pathology laboratories, and radiation oncology centers. To supplement registry treatment data, we identified patients for whom the registry had no record of chemotherapy and sent a questionnaire to the patient's attending physician. Race/ethnicity and geographical regions were grouped as previously defined (Table 1) [12]. Using census-based socioeconomic (SES) and race-specific measures for each block group, dichotomous variables were employed to classify each neighborhood as poor/not poor, educated/less educated, and “white vs. blue-collar worker.” The SES measures were obtained for each case by matching records to census data based on blocked group and census tract corresponding to the address at the time of diagnosis. If ≥20% of the population lived below the poverty level, this block was considered poor. If ≥25% of the population lacked a high school education, this block was considered as low education. If N66% of the population over 16 years of age worked in blue-collar jobs, this block was considered “blue-collar.” These census-based socioeconomic measures have been previously employed in public
Table 1 Demographic characteristics of all patients (n = 135)
Age Median (years) Range (years) Race White Hispanic Asian/Pacific islander Black Unknown
Total (n = 135)
Chemotherapy Yes (n = 106)
No (n = 29)
47 23–54
47 23–54
47 30–54
92 (68.1%) 14 (10.4%) 24 (17.8%)
75 (70.8%) 11 (10.4%) 16 (15.1%)
17 (58.6%) 3 (10.3%) 8 (27.6%)
4 (3.0%) 1 (0.7%)
4 (3.8%) 0 (0.0%)
0 (0.0%) 1 (3.4%)
Neighborhood socioeconomic status Not poor 77 (57.0%) Poor 58 (43.0%) More educated 105 (77.8%) Less educated 30 (22.2%) White-collar 95 (70.4%) Blue-collar 40 (29.6%) Region San Francisco Sacramento Rural Northern California Santa Clara Year of diagnosis 1994 1995 1996
65 41 83 23 74 32
p-value (chi-square)
p = 0.304
(61.3%) (38.7%) (78.3%) (21.7%) (69.8%) (30.2%)
12 (41.4%) 17 (58.6%) 22 (75.9%) 7 (24.1%) 21 (72.4%) 8 (27.6%)
p = 0.055
25 (18.5%) 30 (22.2%) 26 (19.3%)
22 (20.8%) 24 (22.6%) 18 (17.0%)
3 (10.3%) 6 (20.7%) 8 (27.6%)
p = 0.437
54 (40.0%)
42 (39.6%)
12 (41.4%)
59 (43.7%) 34 (25.2%) 42 (31.1%)
44 (41.5%) 29 (27.4%) 33 (31.1%)
15 (51.7%) 5 (17.2%) 9 (31.0%)
p = 0.779 p = 0.786
p = 0.480
health research and have been validated in prior studies based in the San Francisco Bay area [13]. All patients underwent surgery for invasive epithelial ovarian cancer and were found to have International Federation of Gynecology and Obstetrics (FIGO) stage IC or II disease. Moreover, all patients with stages IC–II cancers who survived at least 12 days after diagnosis were considered candidates for adjuvant chemotherapy. Histologic cell types were categorized into the following groups: serous, mucinous, endometrioid, clear cell, and other. Women with low malignant potential, germ cell, stromal, and other non-epithelial ovarian tumors were excluded. A patient was classified as having seen a gynecologic oncologist if any of her physicians were members of the Society of Gynecologic Oncology. The use of adjuvant chemotherapy was dichotomized as yes/no. Since chemotherapy is typically administered in an outpatient setting, registry treatment data were supplemented with data from a physician survey, and medical record review. The questionnaire sent to the patient's attending physician asked whether the patient received chemotherapy and the type of agents administered. Those attending physicians who did not have the requested information were asked to provide referral to another physician involved in the patient's management. Furthermore, clinical information was obtained from the medical records at the physician's offices upon request. Follow-up data, including the date and cause of death or censoring, were obtained via Vital Statistics [14]. The outcome variable was death from ovarian cancer (disease-specific survival); deaths from other or unknown causes were censored at the time of death. Pearson's chi-square test was used to evaluate associations between factors and risk of death. Survival time was measured in months from the time of diagnosis until censoring or death. Survival analyses and predictors of outcome were analyzed using Kaplan–Meier and Cox proportional hazard methods. Statistical analyses were performed using SPSS 14.0 [15].
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Results Of 135 younger (b55 years) patients with stages IC–II epithelial ovarian cancers, 29 (21.5%) did not receive chemotherapy (group A) while the remaining 106 (78.5%) underwent adjuvant chemotherapy (group B). The median age of the entire cohort was 47 years (range: 23–54 years). Ninety-two (68.1%) were White, 14 (10.4%) were Hispanic, 24 (17.8%) were Asian, 4 (3.0%) were Black, and 1 (0.7%) was unknown. Based on socioeconomic status [12], 58 (43.0%) were lived in poor neighborhoods, 30 (22.2%) were less educated, and 40 (29.6%) were blue-collar workers. Twenty-eight (18.5%), 30 (22.2%), 26 (19.3%), and 54 (40.0%) were from San Francisco, Sacramento, rural California, and Santa Clara, respectively (Table 1). Seventy-four (54.8%) had stage IC and 61 (45.2%) had stage II disease (Table 2). Endometrioid, serous, and clear cell cancers were found in 42 (31.1%), 40 (29.6%), and 19 (14.1%) of patients, respectively. Grade 1, 2, and 3 disease were noted in 22 (16.3%), 35 (25.9%), and 42 (31.1%) women, respectively. In the overall study group, 46 (34.1%) women received care by a gynecologic oncologist. The demographic and clinico-pathologic factors for patients who did not receive (Group A) or underwent (Group B) chemotherapy were compared (Tables 1 and 2). Women in group A were more likely to reside in poor neighborhoods (58.6% vs. 38.7%; p = 0.055), less likely to be seen by a gynecologic oncologist (13.8% vs. 39.6%; p = 0.009), and had more grade 1 and 2 tumors (58.6% vs. 37.8%; p = 0.049). On multivariate analysis, those treated by gynecologic oncologists had a 4.1-fold increase Table 2 Clinico-pathologic characteristics of all patients (n = 135)
Primary surgery Yes No Unknown
Total (n = 135)
Chemotherapy Yes (n = 106)
No (n = 29)
p-value (chi-square)
130 (96.3%) 4 (3.0%) 1 (0.7%)
104 (98.1%) 2 (1.9%) 0 (0.0%)
26 (89.7%) 2 (6.9%) 1 (3.4%)
p = 0.146
Fig. 1. Kaplan–Meier disease-specific survival of patients living in poor neighborhoods by chemotherapy (n = 58).
in likelihood of receiving chemotherapy (odds ratio = 4.1; 95% CI: 1.33–12.63; p = 0.006). The five-year disease-specific survival for those that did not receive chemotherapy (group A) was 70.5% compared to 76.5% in those who did (group B) (p = 0.252). Of note, patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy (Fig. 1), but this difference was not noted in the women residing in non-poor neighborhoods (77. 1% vs. 70.9%; p = 0.574). The median follow-up was 59 months. On multivariate analysis, primary surgery (no vs. yes) (HR = 0.08, 95% CI = 0.02–0.29; p b 0.0005) and race (White vs. Asian/Pacific Islander vs. Black and Hispanic) (HR = 1.87, 95% CI = 1.23–2.83; p b 0.003) were significant prognostic factors for improved disease-specific survival. Other variables including chemotherapy, ACOS hospital certification, and gynecologic oncologist treatment were not statistically significant on multivariate analysis for disease-specific survival. Discussion
Stage IC II
74 (54.8%) 61 (45.2%)
54 (50.9%) 52 (49.1%)
20 (69.0%) 9 (31.0%)
p = 0.084
Histology Serous Endometrioid Mucinous Clear cell NOS/other
40 (29.6%) 42 (31.1%) 16 (11.9%) 19 (14.1%) 18 (13.3%)
34 (32.1%) 31 (29.2%) 12 (11.3%) 16 (15.1%) 13 (12.3%)
6 11 4 3 5
(20.7%) (37.9%) (13.8%) (10.3%) (17.3%)
p = 0.653
Grade 1 2 3 Unknown
22 (16.3%) 35 (25.9%) 42 (31.1%) 36 (26.7%)
15 (14.2%) 25 (23.6%) 38 (35.9%) 28 (26.4%)
7 10 4 8
(24.1%) (34.5%) (13.8%) (27.6%)
p = 0.049
Gynecologic oncologist Yes 46 (34.1%) No 89 (65.9%)
42 (39.6%) 64 (60.4%)
4 (13.8%) 25 (86.2%)
p = 0.009
Current treatment guidelines for high-risk early-stage epithelial ovarian cancer recommend adjuvant chemotherapy [16]. Several randomized trials have shown a survival advantage associated with adjuvant therapy in these patients [17–19]. The failure rate of high-risk patients with early-stage epithelial ovarian cancer who did not receive adjuvant chemotherapy has been reported to be as high as 20 to 50% [2–6,20]. Furthermore, a prior study showed that the salvage rates for those patients with stage I epithelial ovarian cancers who recurred following surgery alone were poor [21]. Based on a recently published population-based study of 2150 women with epithelial ovarian cancer in California, 21.5% of women less than 55 years with early-stage high-risk (stages IC–II) cancers did not receive chemotherapy [12]. This deviation from the standard treatment guidelines stimulated us to investigate the factors associated with the suboptimal care in these young patients.
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Another population-based study also showed that more young women with ovarian cancer were treated by nongynecologic oncologists (64% vs. 36%) [22]. It is likely that pelvic masses are more difficult to characterize as benign or malignant in the younger cohort, and thus subspecialists are often not involved in their surgeries. In addition, Noumoff et al. [23] showed that the public is poorly informed about gynecologic oncologists and that general physicians may have a misconception about advanced ovarian cancer as one of a rapidly progressing fatal disease with poor response to any treatment. Le et al. showed that the lack of a proper staging surgery led to both overtreatment and undertreatment of patients. After adjusting for confounding variables, the lack of proper staging surgery increased the risk for disease recurrence by three-fold [24]. Furthermore, Goff et al. [11] reported that younger patients (21–50 years) were less likely to undergo debulking/omentectomy. Our current analyses shows that patients who did not get chemotherapy were more likely to be classified as living in poor neighborhoods based on census socioeconomic measures. Goff et al. [11] also showed that poor patients had a significantly higher likelihood of not receiving optimal care with a lower likelihood of having a lymph node dissection. Likewise, Harlan et al. [25] reported that women with private health insurance received guideline therapy significantly more often (66%) than did women with public insurance, no insurance, or unknown insurance status (54%). Women with higher incomes are likely to have private insurance, access to cancer specialists, and quality medical care. Schrag et al. [26] also showed that high volume surgeons, many of whom are gynecologic oncologists, were less likely to treat those who resided in low income census tracts or in rural areas. In addition, those who did not get treatment from gynecologic oncologists had a lower likelihood of receiving chemotherapy. In this current analysis, we also found that patients living in poor neighborhoods were less likely to receive chemotherapy, and this had a significant impact on their overall outcome. It is interesting to note that patients residing in poor neighborhoods had a statistically significant improvement in survival (from 65.5% to 86.0%; p = 0.012) associated with chemotherapy (Fig. 1), but this difference was not noted in women living in neighborhoods that were not classified as poor (77.1% vs. 70.9%; p = 0.574). One explanation for this finding may be that women from non-poor census blocks were accurately staged with early-stage cancers whereas the women from poor neighborhoods were understaged and had more advanced cancers, which resulted in a survival benefit associated with chemotherapy in these patients from poorer neighborhoods. The results of a prior analysis on the role of gynecologic oncologists in the management of patients with epithelial ovarian cancer demonstrated that women who underwent treatment by a gynecologic oncologist were more likely to receive chemotherapy [27]. Others have also shown that women who were treated by a gynecologic oncologist had a higher likelihood of receiving recommended surgery and adjuvant therapy [11,22, 28–34]. Recently, Giede et al. [33] performed an evidencebased review on the potential benefits of subspecialty care in
patients with ovarian cancer. After an extensive review of 18 studies, these authors found that gynecologic oncologists were more likely to perform optimal staging surgeries (p b 0.01). In these early-stage patients, their analysis suggested that an increased survival could be explained by improved identification of true stage I patients. In addition, of those with advanced disease, there was good quality evidence to support a 6- to 9month median survival advantage for women operated on by gynecologic oncologists rather than general gynecologists and/ or general surgeons (p b 0.01). Thus, they concluded that women receiving initial surgical management for ovarian epithelial cancer should receive care from gynecologic oncologists [33]. Women with low grade disease were less likely to receive chemotherapy. Prior studies showed that patients with stage I grade 1 or 2 disease may not benefit from adjuvant chemotherapy [17]. However, it is important to note that all patients in this current analysis had stage IC or II disease with high-risk for recurrence. Nevertheless, a significant proportion of patients with high-risk disease under non-specialist care did not receive chemotherapy. This suggests that some physicians who lack subspecialty training in ovarian cancer may not appreciate the risk of recurrence and failure in this aggressive cancer. This study was unique in that it provides an opportunity to observe the outcomes of a group of young patients with high-risk early-stage ovarian cancer who did not receive appropriate treatment. The strengths of our study include the availability of chemotherapy data, involvement of multiple institutions, generalized population, supplementation of adjuvant chemotherapy data, and detailed demographics including race and socioeconomic background. However, as the tumor registry collects racial/ethnic data from medical records, it is not known if the patient reported her race or if it was assigned by medical staff. In addition, our study was limited by the lack of information on the extent of cytoreductive surgery and residual disease after primary surgery. In addition, we do not have detailed information on the specific type of chemotherapy, number of cycles of treatment, or whether the patient was offered chemotherapy and refused. There was also no detailed information on the physician subspecialists that administered the chemotherapy. The data were obtained from 1994 to 1996. We arbitrarily selected for this time period in order to provide an extended follow-up of these patients. Furthermore, the current management of early-stage ovarian cancer has not changed significantly over this time period. The relatively small number of patients in the various subgroups suggests that these results should be interpreted with caution, even where the differences were of statistical significance. In summary, this study showed that young patients who did not receive appropriate treatment were more likely to live in poor neighborhoods, less likely to be treated by a gynecologic oncologist, and had more early-grade cancers. The lack of appropriate adjuvant therapy was associated with a poorer outcome. Further studies are warranted to identify the obstacles to appropriate care of young women with ovarian cancer and subsequent implementation of programs to overcome these barriers to improve the outcomes of these women. Patient and
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physician education may be needed to assure that standard treatment guidelines are followed in the treatment of young women diagnosed with high-risk early-stage ovarian cancer. Acknowledgments The collection of cancer incidence data used in this study was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract N01-PC-35136 awarded to the Northern California Cancer Center, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Prevention's National Program of Cancer Registries, under agreement #U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Health Services, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred.
[13]
[14]
[15] [16] [17]
[18]
[19]
[20]
[21]
[22]
References [23] [1] Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006;56:106–30. [2] Hoskins PJ, Swenerton KD, Manji M, et al. ‘Moderate-risk' ovarian cancer (stage I, grade 2; stage II, grade 1 or 2) treated with cisplatin chemotherapy (single agent or combination) and pelvi-abdominal irradiation. Int J Gynecol Cancer 1994;4:272–8. [3] Partridge EE, Phillips JL, Menck HR. The National Cancer Data Base report on ovarian cancer treatment in United States hospitals. Cancer 1996; 78:2236–46. [4] Heintz AP, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. Int J Gynaecol Obstet 2003;83(Suppl 1):135–66. [5] Averette HE, Janicek MF, Menck HR. The National Cancer Data Base report on ovarian cancer. American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 1995;76:1096–103. [6] Kosary CL. FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973–87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina. Semin Surg Oncol 1994;10: 31–46. [7] Janssen-Heijnen ML, Houterman S, Lemmens VE, et al. Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach. Crit Rev Oncol Hematol 2005;55:231–40. [8] Sundararajan V, Hershman D, Grann VR, et al. Variations in the use of chemotherapy for elderly patients with advanced ovarian cancer: a population-based study. J Clin Oncol 2002;20:173–8. [9] Hutchins LF, Unger JM, Crowley JJ, et al. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999;341: 2061–7. [10] Parham G, Phillips JL, Hicks ML, et al. The National Cancer Data Base report on malignant epithelial ovarian carcinoma in African-American women. Cancer 1997;80:816–26. [11] Goff BA, Matthews BJ, Wynn M, et al. Ovarian cancer: patterns of surgical care across the United States. Gynecol Oncol 2006;103:383–90. [12] Cress RD, O'Malley CD, Leiserowitz GS, et al. Patterns of chemotherapy
[24]
[25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
99
use for women with ovarian cancer: a population-based study. J Clin Oncol 2003;21:1530–5. Krieger N. Overcoming the absence of socioeconomic data in medical records: validation and application of a census-based methodology. Am J Public Health 1992;82:703–10. O'Malley CD, Cress RD, Campleman SL, et al. Survival of Californian women with epithelial ovarian cancer, 1994–1996: a population-based study. Gynecol Oncol 2003;91:608–15. SPSS, Inc. Chicago, IL, 2006. NCCN Clinical Practice Guidelines in Oncology. Ovarian Cancer 1, 2007: National Comprehensive Cancer Network; 2007. Young RC, Walton LA, Ellenberg SS, et al. Adjuvant therapy in stage I and stage II epithelial ovarian cancer. Results of two prospective randomized trials. N Engl J Med 1990;322:1021–7. Trimbos JB, Vergote I, Bolis G, et al. Impact of adjuvant chemotherapy and surgical staging in early-stage ovarian carcinoma: European Organisation for Research and Treatment of Cancer-Adjuvant ChemoTherapy in Ovarian Neoplasm trial. J Natl Cancer Inst 2003;95:113–25. Colombo N, Guthrie D, Chiari S, et al. International Collaborative Ovarian Neoplasm trial 1: a randomized trial of adjuvant chemotherapy in women with early-stage ovarian cancer. J Natl Cancer Inst 2003;95:125–32. Nguyen HN, Averette HE, Hoskins W, et al. National survey of ovarian carcinoma. VI. Critical assessment of current International Federation of Gynecology and Obstetrics staging system. Cancer 1993;72: 3007–11. Kolomainen DF, A'Hern R, Coxon FY, et al. Can patients with relapsed, previously untreated, stage I epithelial ovarian cancer be successfully treated with salvage therapy? J Clin Oncol 2003;21:3113–8. Carney ME, Lancaster JM, Ford C, et al. A population-based study of patterns of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not? Gynecol Oncol 2002;84:36–42. Noumoff J, Morgan M, King S, et al. The specialty of gynecologic oncology as perceived by the public. Gynecol Oncol 1992;47:48–52. Le T, Adolph A, Krepart GV, et al. The benefits of comprehensive surgical staging in the management of early-stage epithelial ovarian carcinoma. Gynecol Oncol 2002;85:351–5. Harlan LC, Abrams J, Warren JL, et al. Adjuvant therapy for breast cancer: practice patterns of community physicians. J Clin Oncol 2002;20: 1809–17. Schrag D, Earle C, Xu F, et al. Associations between hospital and surgeon procedure volumes and patient outcomes after ovarian cancer resection. J Natl Cancer Inst 2006;98:163–71. Chan JK, Kapp DS, Shin JY, et al. Influence of the gynecologic oncologist on the survival of ovarian cancer patients. Obstet Gynecol June 2007;109(6):1342–50. Eisenkop SM, Spirtos NM, Montag TW, et al. The impact of subspecialty training on the management of advanced ovarian cancer. Gynecol Oncol 1992;47:203–9. Nguyen HN, Averette HE, Hoskins W, et al. National survey of ovarian carcinoma. Part V. The impact of physician's specialty on patients' survival. Cancer 1993;72:3663–70. Kehoe S, Powell J, Wilson S, et al. The influence of the operating surgeon's specialisation on patient survival in ovarian carcinoma. Br J Cancer 1994;70:1014–7. Earle CC, Schrag D, Neville BA, et al. Effect of surgeon specialty on processes of care and outcomes for ovarian cancer patients. J Natl Cancer Inst 2006;98:172–80. Engelen MJ, Kos HE, Willemse PH, et al. Surgery by consultant gynecologic oncologists improves survival in patients with ovarian carcinoma. Cancer 2006;106:589–98. Giede KC, Kieser K, Dodge J, et al. Who should operate on patients with ovarian cancer? An evidence-based review. Gynecol Oncol 2005;99: 447–61. Munstedt K, von Georgi R, Misselwitz B, et al. Centralizing surgery for gynecologic oncology—a strategy assuring better quality treatment? Gynecol Oncol 2003;89:4–8.