Most women with ovarian cancer are not receiving adequate treatment, as specified in National Comprehensive Cancer Network (NCCN) Guidelines,¹ and as a result are being deprived of the survival benefits correlated with guideline-recommended treatment, according to a study presented at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer in Los Angeles (see The ASCO Post, April 15, page 117).² Adherence to the NCCN Guidelines “was one of the strongest independent predictors of improved ovarian-specific survival,” the study’s lead author, Robert E. Bristow, MD, MBA, said in an interview with The ASCO Post. Dr. Bristow is the Director of the Division of Gynecologic Oncology, University of California, Irvine.

The retrospective population-based study reviewed the medical records of 13,321 patients extracted from the California Cancer Registry. All patients were diagnosed with epithelial ovarian cancer between the beginning of 1999 and the end of 2006. Overall, 37.2% received NCCN guideline-adherent care, defined by stage-appropriate surgical procedures and recommended chemotherapy.

High-volume surgeons, defined as those who treated 10 or more cases of ovarian cancer per year, were significantly more likely to deliver guideline-adherent care—47.6% compared to 34.5% of those treating fewer cases (P < .001). High-volume hospitals, defined as those with a case volume of 20 or more per year, were significantly more likely to deliver guideline-adherent care—50.8% compared to 34.1% of hospitals with fewer cases (P < .001). Hospitals with an American College of Surgeons—approved cancer program were also more likely to administer NCCN guideline–adherent care.

Disease-specific Survival

The 5-year ovarian cancer–specific survival for all patients was 45.3%, and univariate survival analysis revealed a statistically significant difference in disease-specific survival between patients receiving NCCN guideline–adherent vs nonadherent care. For patients with stage I/II disease, the 5-year disease-specific survival rates were 86% for patients receiving guideline–adherent care vs 81% for those receiving nonadherent care (P = .0003). For patients with stage III/IV disease, the 5-year disease-specific survival rates were 35% for patients receiving guideline-adherent care vs 25% for those receiving nonadherent care (P < .0001).

Multivariate survival analysis controlling for patient, disease-related, and health-care system factors found that non–guideline adherent care was independently associated with inferior overall survival (hazard ratio [HR] = 1.34, 95% confidence interval [CI] = 1.26 – 1.42].

“Compared to patients treated according to NCCN Guidelines, patients receiving substandard care experienced more than a 30% increase in the risk of ovarian cancer–related death. Among provider characteristics, both low-volume hospitals and low-volume physicians were also significantly negatively associated with survival, independent of overall treatment adherence to NCCN Guidelines,” Dr. Bristow reported.

“The type of research I do is looking at trying to get people to the right settings for care,” Dr. Bristow said. “If we were able to do that in a more effective fashion, we could probably have a much greater impact on ovarian cancer survival than developing any new drug or biologic agent.”

Dr. Bristow said that it is still too early to tell if the study and the attention directed to the study by national media coverage will serve to improve adherence to guidelines or direct women to high-volume physicians and facilities. While the research has “some nuances to it that are new, the underlying principle that patients do better when they are treated by people specifically trained and in hospitals that have the capability to take the best care of them is not a new observation,” Dr. Bristow noted.

“It is gratifying that it took this paper to start piquing people’s interest about it and it is getting the attention it deserves,” he continued. “One of the sidelights of this is that patients will see these findings and then become empowered to help direct their care and make sure they are getting taken care of in an environment that is optimized to try to give them the best outcome.”

Other Factors Affecting Guideline Adherence

Age ≥ 70 and early-stage disease were associated with a decreased likelihood that treatment would follow the NCCN Guidelines. The median age of the patients was 61, but ages ranged from 18 to 104.

“A number of studies have shown that age in and of itself is not necessarily a contraindication to standard therapy. It really depends more on performance status and what the medical comorbidities are,” Dr. Bristow said. The California Cancer Registry doesn’t contain specific information on medical comorbidities, he noted, “So in our study, age was probably more of a proxy for a compilation of medical morbidities than just chronologic age.”

Adherence to guidelines was less likely when the patients had stage III or IV disease, primarily due to the staging procedures required and complexity of treatment. “Patients with advanced-stage ovarian cancer are also more likely to be medically compromised because of their disease status,” Dr. Bristow explained. “So that is an additional challenge that comes with more advanced-stage disease in terms of being able to adhere to the recommended guidelines.”

Even for the high-volume hospitals, which accounted for 2.8% of all hospitals in the study and18.8% of the total cases, adherence to NCCN Guidelines was just over 50%. For high-volume surgeons, who were just 0.3% of all physicians in the study and treated 20.9% of all cases, adherence to NCCN Guidelines was not even 50%, but 47.6%.

“If you look specifically at the surgery or the chemotherapy, most of the high-volume groups were in the neighborhood of 70% guideline adherence for the individual components,” Dr. Bristow commented. “It is only when you mesh the two together that that number drops down to around 50%, suggesting that a sick patient may have been able to tolerate the proper surgery, but they were too sick to tolerate proper chemotherapy or vice versa.”

While the numbers used to determine high-volume physicians were not very high—just 10 or more cases per year—Dr. Bristow said those numbers “have been studied previously in the literature and are pretty well accepted as defining high-volume providers.” For this study, “the high-volume providers are going to be a surrogate for gynecologic oncologists,” he noted, since the California Cancer Registry doesn’t contain data on physician specialty.

Barriers to ‘Ideal Triage Algorithm’

“The reasons that patients aren’t making it to the appropriate specialists or hospitals are multifactorial,” Dr. Bristow explained. “There are a lot of potential barriers to that ideal triage algorithm. One is just not making the correct diagnosis.” Another reason relates to the patient’s comfort with and loyalty to her general gynecologist, who may have treated her for years and delivered all of her children. When the general gynecologist tells her that she has an ovarian mass and needs a hysterectomy, the patient may opt to have the procedure done by that general gynecologist.

“Specifically with ovary cancer, a gynecologic oncologist really needs to make that initial assessment and determine whether the patient is an appropriate candidate for surgery. If she is, then it should be the gynecologic oncologist that does that surgery, not only because we are trained in the surgical techniques, but also because we have a deeper understanding of the underlying disease process and are able to tailor the surgery to the individual patient’s risk factors,” Dr. Bristow said.

“Most general surgeons don’t routinely take care of a comparable disease process like ovarian cancer, which is largely a chemotherapy-sensitive malignancy in which the surgical debulking status has been shown to be such a good prognostic factor for long-term survival,” he said. “They can do the technical aspect of the surgery, but are often lacking in that broad understanding of the disease process and how the individual procedures work together to optimize patient outcome.”

Role of Third-party Payers

Another barrier is related to third-party payers, particularly those that are profit-driven. “The individual contracts that some third-party payers have with hospitals do not make the referral process easy for patients,” Dr. Bristow said. Those contracts may specify that certain procedures be done at community hospitals with which particular payers have contracts, he said, rather than at large tertiary referral centers, which tend to also be the high-volume centers.

“The control that the payers have over determining where the patient actually undergoes a procedure is definitely one of the factors that determines patient access to what we would call a high-volume ovarian cancer center,” Dr. Bristow remarked.

“We are entering into a time where clinical practice patterns are going to need to be driven by data, and with current concerns about health-care expenditures, reimbursement is going to be tightly linked to following guidelines, with built-in exceptions,” Dr. Bristow stated.

An example of an exception to the ovarian cancer guidelines might be an 87-year-old woman in a nursing home who has had hypertension and congestive heart failure and is not in good medical condition. “She is probably not going to be a great candidate for guideline therapy because it will end up being too toxic and hasten her demise. So there need to be built-in exceptions or deviations from guidelines care, and that is probably our next challenge—to figure out how to risk-adjust adherence to guidelines.” ■

Disclosure: Dr. Bistrow reported no potential conflicts of interest.

References

1. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Ovarian Cancer, Including Fallopian Tube Cancer and Primary Peritoneal Cancer. Version 1.2013. Available at www.nccn.org. Accessed April 19, 2013.

2. Bristow R, Chang J, Ziogas A, et al: NCCN treatment guidelines for ovarian cancer: A population-based validation study of structural and process quality measures. Society of Gynecologic Oncology Annual Meeting on Women’s Cancer. Abstract 45. Presented March 11, 2013.