By Robert L. Coleman, MD, Professor, University of Texas; M.D. Anderson Cancer Center, Houston. Dr. Coleman reports no financial relationships relevant to this field of study.
Synopsis: Clinically significant disparities exist in the quality of ovarian cancer care delivered and in overall survival along both racial and socioeconomic status. These effects appear to persist despite adherence to National Comprehensive Cancer Network guidelines; however, deviation in guideline adherence is common and further impacts survivorship and represents key opportunities for further investigation and study.
Source: Bristow RE, et al. Disparities in ovarian cancer care quality and survival according to race and socioeconomic status. J Natl Cancer Inst 2013 Apr 4; [Epub ahead of print].
The relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care have been evaluated in previous studies but were limited by small cohort numbers and lack of a quality control benchmarks, such as guideline adherence or overall outcomes. The current population-based analysis of National Cancer Data Base (NCDB) records evaluated these factors in invasive primary epithelial ovarian cancer patients diagnosed between 1998 and 2002. Adherence to National Comprehensive Cancer Network (NCCN) guidelines was defined by stage-appropriate surgical procedures and outlined standards for adjuvant chemotherapy. The primary outcome endpoints were NCCN guideline adherence and overall survival. The context in which these outcomes were considered were race, SES, insurance payer status, household income, age, stage, histology, center where care was delivered, and education. A total of 47,160 patients (white = 43,995; black = 3165) were identified. Factors associated with inferior overall survival were non-NCCN-guideline-adherent care, black race, and Medicaid and non-insurance payer status. Tumor-specific factors, such as stage, grade, and subtype as well as hospital case volume of ovarian cancer cases, also were significantly associated with overall survival in a multilevel survival analysis. Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.25-1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12-1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19-1.49). After controlling for disease- and treatment-related variables, independent racial and SES predictors of survival were black race (hazard ratio [HR], 1.29; 95% CI, 1.22-1.36), Medicaid payer status (HR, 1.29; 95% CI, 1.20-1.38), not insured payer status (HR, 1.32; 95% CI, 1.20-1.44), and median household income < $35,000 (HR, 1.06; 95% CI, 1.02-1.11). These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, exist independent of NCCN guideline adherence, and divide along racial and SES parameters. More work is necessary to define at-risk populations and strategies to ameliorate factors leading to these observed disparities, as well as further biological characteristics that may also impact cohort survivorship.
“Study Criticizes Care in Cancer of the Ovaries...Experienced Surgeons Can Extend Lives,” was a front-page headline in the New York Times on March 12, 2013. The piece covered a scientific presentation made at the 2013 annual meeting of the Society of Gynecologic Oncology by gynecologic oncologist, Robert E. Bristow, MD, from the University of California, Irvine, who profiled survivorship in California ovarian cancer patients who were treated either in or out of compliance with established publically available guidelines to care. This included access to gynecologic oncologists for accurate staging and primary debulking procedures, and optimized use of effective adjuvant treatment strategies, such as dose-dense or intraperitoneal chemotherapy. The NCCN guidelines are established by a committee of disease-specific experts and generally outline sequential decision-making practices under a variety of clinical scenarios (http://www.nccn.org). Although they don’t dictate practice, the guidelines provide acceptable considerations at multiple steps in care of patients. In addition, they are reported with the degree of consensus and strength of evidence-based science for these practice recommendations. Some of these algorithms are controversial, particularly when limited or poor quality data are available in the literature. However, strong consensus frequently follows level I evidence (randomized clinical trials) or from repeated historical support.1,2 The data presented by Dr. Bristow were provocative because they demonstrated that these guidelines for ovarian cancer management were also prognostic, that is, compliance was associated with significantly better survival.
In some ways, this is not unexpected; it is clear that optimal cytoreduction (no visible residual) and use of the best chemotherapy agents, under optimal infusion schedules and modalities (all supported by positive Phase 3 trials), should provide a patient with the best that we have to offer.3 Deviation from these approaches should (like the control arms of the Phase 3 trials) provide inferior outcomes. However, the adherence or non-adherence to guideline-directed therapy does not consider specific patient factors, underlying nuances that might add to or detract from individual therapeutic modalities, or decisions made in concert with an individual patient’s desire. For example, we know that germline BRCA mutation carriers (BRCA-mt) have improved outcomes relative to those whom are BRCA-wild type (BRCA-wt).4 However, there are differential outcomes seen within the BRCA-mt cohort relative to the modality of chemotherapy delivery. Indeed, while ovarian cancer patients appeared to have improved overall survival with intraperitoneal (IP) delivery of cisplatin and paclitaxel, the BRCA-mt patients appeared to benefit substantially better than their cohorts receiving intravenous infusion of the same agents.5 This kind of nuance, like an audited surgical cytoreduction success variable, is not easily captured in the database from which these data were gathered. Thus, the impact, which might be only captured well by a (an unethical) trial where women were randomized to guideline-directed care vs guideline-avoided care, will not be easily sleuthed.
Added to this are the provocative results presented in the current study by the same study team. In this report, a much larger cohort of ovarian cancer patients were examined in an audited clinical database (NCDB), which reports the outcomes of about 70% of newly diagnosed cancers in the United States. They only included epithelial ovarian cancers and examined several putative prognostic factors of survival such as age, race, stage of disease, grade, payer status, median household income, education, hospital case volume, and care practices adhering to NCCN guidelines. They also looked at how these factors related to the delivery of NCCN-based care. Several striking relationships were found in the analysis. The first was that the overall 5-year survival for ovarian cancer care initiated more than a decade ago is well below 50%. Since this time, many new agents have become available; however, their widespread use is limited by lack of FDA approval and none have affected overall survival. This has greatly reduced the pace of survivorship gains over the last decade compared with the previous two. Next, putative benefit from guideline-adherent care was confirmed. Somewhat surprisingly, there was a strong relationship in survival by race stratification. Indeed, white patients faired far better than blacks in both care categories (adherent or non-adherent care). Black patients also were far less likely to get NCCN guideline-adherent care. Of interest, payer status was strongly associated with overall survival, even when controlled for adherence to guideline care. However, black patients were significantly more likely to be classified as having no insurance/self pay or on Medicare or Medicaid, which were three of the lowest performing cohorts in outcomes among patients getting guideline-adherent care. Several factors could explain these findings, such as imbalanced degree of surgical cytoreduction, access to high-volume surgeons, intensity of chemotherapy, and different treatment strategies for management of recurrent disease. However, it also intimates that there may be intrinsic differences in patient populations, as exemplified by the data from BRCA-mt carrier status. Of interest, racial factors have been recently linked to response to novel targeted agents in other malignancies and to tolerance of chemotherapy.6 This describes an emerging field of science called pharmacogenomics.
These data, although not definitive, are important considerations in the current climate of the Affordable Care Act. Since socioeconomic status factors have been linked to survival in ways being addressed by access to care, some of the complex issues underlying health care disparities may be engaged anew with the focus on improved outcomes to care. The expectation already has been realized in screening and prevention campaigns, where results have crossed all races and socioeconomic levels. However, much more work needs to be done on a population-based scale to understand the intricacies of how these aspects of, and to, health care can be leveraged to optimize treatment outcomes of cancer patients.
1. Chi DS, et al. An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT). Gynecol Oncol 2012;124:10-14.
2. Hennessy BT, et al. Ovarian cancer. Lancet 2009;374: 1371-1382.
3. Armstrong DK, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med 2006;354:34-43.
4. Yang D, et al. Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 2011;306:1557-1565.
5. Lesnock JL, et al. BRCA1 expression and improved survival in ovarian cancer patients treated with intraperitoneal cisplatin and paclitaxel: A Gynecologic Oncology Group study. Br J Cancer 2013;108:1231-1237.
6. Soo RA, et al. Differences in outcome and toxicity between Asian and caucasian patients with lung cancer treated with systemic therapy. Future Oncol 2012;8: 451-462.