comment Access to cancer care and oncology outcomes Joseph Ragaz MD, FRCPC, William Hryniuk, MD, FRCPC B oth technologic developments and the organization of cancer care are paying outcome dividends. Overall, cancer mortality rates have been decreasing for most cancer sites, and in most regions of the Western world including Canada.1,2 However, provision of timely access to optimal cancer care for all Canadians presents an increasing challenge, both for oncologists and for those in charge of provincial budgets. If access to optimal cancer care is defined as receiving the most updated optimal diagnostic tools and curative therapeutic interventions in a timely manner, then their delay (or their “non-access”) will automatically result, to some degree, in lower cure rates. Is this phenomenon infrequent? Not at all. In Canada, even with the Health Act guaranteeing universal access to healthcare, we are increasingly faced with suboptimal cancer care to varying degrees in different provinces. Not having access to potentially curative therapy or optimal diagnostic approaches is a serious issue, as thousands of lives each month are affected — lives either lost, or lived with substantially lower quality of life. Thus, avoidable poor access to optimal cancer care should be considered a societal emergency. It should become a publicized issue, with calls for urgent remedy — similar to any other disaster. The suboptimal access to care occurs due to at least 2 categories of related problems — organizational and socioeconomic. Organizational problems Organizational problems have been identified at institutional, regional, provincial and federal levels, and have resulted in lack of funding and the slow rate of acceptance of potentially curative approaches into practice guidelines. As a consequence, prohibitive delays — or actual lack of access to therapies already proven to be effective — occur. Koo et al3 and Hryniuk et al4 systematically summarized access to new agents and to general cancer funding, according to provincial policies in different regions of Canada. After reading Koo’s and Hryniuk’s work, some cynics concluded: “Tell me your zip code, and I will predict your outcome.” Most cancer agents reviewed by Koo et al were “targeted” antibodies or molecules designed to hit genetically identified cancer molecular targets. Most are prohibitively expensive, and careful cost-benefit assessment is required. However, Joseph Ragaz MD, FRCPC, is a Medical Oncologist, Clinical professor, Faculty of Medicine and School of Population and Public Health, University of British Columbia. E-mail: [email protected]; William Hryniuk, MD, FRCPC is a Medical Oncologist and past Chair of the Cancer Advocacy Coalition of Canada (CACC). E-mail: [email protected] there are problems also with less expensive approaches, which may cause even larger outcome differences. There is, for example, important non-access to the more conventional agents such as bisphosphonates for early breast cancer.5,6 These agents are approved in Canada for bone loss in the general population but not for patients with early breast cancer. Yet if given in the adjuvant setting, they have the potential to reduce breast cancer recurrences by 30-40%, in addition to preventing bone fractures in a significant number of breast cancer patients.5,6 There are also very soft policies regarding tamoxifen/ raloxifene prevention guidelines in most regions of Canada, despite the good levels of evidence for breast cancer rate reduction by 30–50%.7,8 There should be high appeal for tamoxifen prevention among young patients <55 years old, due to substantially lower rates of uterine cancer and thromboembolism compared to postmenopausal women.9 Other examples exist. The 21-gene assay (OncotypeDx), which has been evaluated in peer literature, could disqualify over 30–40% of well-differentiated early breast cancer tumours from adjuvant chemotherapy.10,11 Yet this test is not incorporated in any guidelines in Canada and thus not funded in most parts of the country,12 even though it is covered by virtually every insurance company in the US. Access delays are also seen with agents that show great promise in confirmatory trials. Cyclooxygenase-2 (COX-2) inhibitors, despite their documented potential in preventing breast cancer13-18 and confirmation of their safety, are not being tested in clinical trials. Lapatinib needs to be evaluated much more assertively since it is likely to have a major impact in trastuzumab-resistant patients19 both in Stage IV and in the adjuvant settings. Most of these initiatives could be accepted into the clinical trial arena and into guidelines virtually overnight, were it not for lack of focus, asymmetric attention to side effects rather than benefits, and sheer inertia, which is not uncommon in government or scientific institutions forced to cope with rapidly emerging issues while operating with an obsolete infrastructure. Poor socioeconomic status Higher mortality rates among those who are socioeconomically disadvantaged has been well documented and is the subject of the commentary breast cancer survival rates in African Americans (AA) in this issue of Oncology Exchange. Based on the Southwest Oncology Group trials, Albain et al20 have shown lower survival among AAs due to both lower socioeconomic (SE) status, and tumour biology, using the 21-gene OncotypeDx assay. Albain et al showed that AAs in estrogen receptor-positive early breast cancer trials have worse survival than others, due largely to tumours with higher proliferation and not to differences in endocrine responsiveness.20 The poorer survival rates of socioeconomically disadvantaged ©2010 Parkhurst, publisher of Oncology Exchange. All rights reserved. oe VOL. 9, No. 4, november 2010 7 comment minorities are unquestionably the consequence of poor access to care,21,22 with fewer screening mammograms, later diagnosis and less access to optimal therapeutic post-diagnostic therapies such as chemotherapy or tamoxifen. Consider also that those with low SE status not only receive less, but seek less, of the best-recommended treatments. Thus, poor access to cancer care could lead to a chain of events that adversely affects outcome — from delays in diagnosis, which means larger and possibly more aggressive tumours resulting in greater systemic spread, to limited access to treatment, and a possibility of a higher transition towards either disease aggressivity or therapeutic resistance.23,24 consequences of inferior cancer care organization A recent comparison of long-term cancer mortality trends between 1950–2004 in BC, Ontario and the Atlantic provinces demonstrated substantially lower mortality rates in BC. Specifically, a drop in mortality from breast cancer occurred in BC a decade earlier than in Ontario, and 2 decades earlier than in the Atlantic provinces. Principal reasons for these differences are related to more curative interventions being delivered more expeditiously, more uniformly and more consistently to a larger part of the population in BC during the 1970–1990s compared to Ontario and Atlantic Canada, as judged from the different levels of provincial diagnostic and therapy guideline implementation during this time.2,25 Recent evidence from Quebec also showed that mortality rates in rural populations, treated less uniformly with guideline-based policies, were more than double (hazard ratio [HR]=2.3, p<0.005) the rates in academic urban centers.26 Consistent provincial funding of new cancer initiatives Hryniuk and Miller in the 2003–2005 series of Cancer Advocacy Coalition of Canada Annual Report Cards documented significant and consistent variation in all-cause cancer mortality among the provinces of Canada and showed that these variations correlated most closely with trends of the respective provincial cancer control budgets.4 Vision for the Future Poor access to optimal cancer care, either due to SE factors or inadequate organization of cancer care at many levels, must be addressed. We can no longer justify the continued avoidable loss of lives from cancer in Canada. The comparison of interprovincial funding differences and breast cancer mortality data indicate that while differences in access do exist in Canada, most are avoidable and can be rectified. The transfer of proven positive results into community guidelines has to be expedited, with input of patient advocacy groups a strong consideration. This failure to apply mature results expeditiously for the benefit of patients should be considered a societal crisis. References 1. Jemal A, Center MM, DeSantis C et al. Global patterns of cancer incidence and mortality rates andtrends. Cancer Epidemiol Biomarkers Prev 2010;19(8): 1893-907. 2. Ragaz J, Spinelli JJ, Semeniciw R et al. Breast cancer mortality reduction in the western world: therapeutic versus diagnostic interventions. Implications for cancer care organization processes. Cancer Res 2009;69:383s # 6083. 3. Khoo K, Colucci R, Hryniuk W et al. Cancer Drug Access. 2006-2008 Report Card. Cancer Advocacy Coalition of Canada. www.canceradvocacy.ca 4. Hryniuk W, Miller T: Your money your life. Report Card of Cancer in Canada 2003-2005. Cancer Advocacy Coalition of Canada. www.canceradvocacy.ca 5. Brufsky AM, Bosserman LD, Caradonna RR et al. Zoledronic acid effectively prevents aromatase inhibitor-associated bone loss in postmenopausal women with early breast cancer receiving adjuvant letrozole: Z-FAST study 36-month follow-up results. Clin Breast Cancer 2009;9:77-85. 6. Gnant M, Mlineritsch B, Schippinger W et al. Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009;360:679-91. 7. Fisher B, Costantino, Wickerham L et al. Tamoxifen for the prevention of breast cancer: Current status of the national surgical adjuvant breast and bowel project P-1 study. Natl Cancer Inst 2005;97:1652-62. 8. Cuzick J, Powles T, Veronesi U et al.Overview of the main outcomes in breast cancer prevention trials. The Lancet 2003(361):296-300. 9. J.Ragaz, JJ Spinelli, A Coldman, C Mihalciou. Is tamoxifen prevention of breast cancer (BrCa) underutilized in younger women? Analysis of competing cause mortality. J Clin Oncol 2006;(24):39. 10. Paik S, Tang G, Shak S et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006;24:3726-34. 11. Albain K, Barlow W, Shak G et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogenreceptor-positive breast cancer on chemotherapy. Lancet Oncology 2009; 11(1):55-6. 12. Ragaz J: The 21 gene assay: Impact on breast cancer in Canada. Ethically and economically when do we act? Cancer Advocacy Coalition of Canada, 2009-2010 Report Card. www.canceradvocacy.ca 13. Steinbach G, Lynch PM, Phillips RKS et al. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 2000;342: 1946-52. 14. Fitzgerald GA, Patrono C. The coxibs, selective inhibitors of cyclo-oxygenase-2. N Engl J Med 2001;345:433-42. 15. Brueggemeier RW, Quinn AL, Parrett ML et al. Correlation of aromatase and cyclooxygenase gene expression in human breast cancer specimens. Cancer Lett 1999;140:27-35. 16. Ristimaki A, Sivula A, Lundin J et al. Prognostic significance of elevated cyclooxygenase-2 expression in breast cancer. Cancer Res 2002;62:632-35. 17. Ragaz J, Bajdik C, Spinelli JJ et al. Significant expression of Cox-2 according to Aromatase: Long-term follow up of the British Columbia Tissue Microarray project. Breast Ca Res Treat 2004;88 (109):S22. 18. Holmes M, Chen W, Li L. ASA: Aspirin intake and survival after breast cancer. J Clin Oncol 2010;28(9):1467-72. 19. Geyer CE, Forster J, Lindquist D et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. Engl J Med 2006;355(26):2733-43. 20. Albain KS, Barlow WE, Shak S et al. Potential biologic causes of the racial survival disparity in adjuvant trials of ER-positive breast cancer. J Clin Oncol 2010; 28:15s(suppl; abstr 511). 21. Barcenas CH, Wells J, Chong D et al. Race as an independent risk factor for breast cancer survival: breast cancer outcomes from the medical college of Georgia tumor registry. Clin Breast Cancer 2010 Feb;10(1):59-63. 22. Komenaka IK, Martinez ME, Pennington RE Jr et al. Cancer outcomes in an underinsured population. Race and ethnicity and breast cancer. J Natl Cancer Instit 2010;102(15):1178-87. 23. Luria SE, Dulbecco R. Lethal mutations and inactivation of individual genetic determinants in bacteriophage. Genetics 1948;33(6):618. 24. Goldie JH and Coldman AJ. A mathematic model for relating the drug sensitivity of tumors to their spontaneous mutation rate. Cancer Treat Rep 1979;63(11-12):1727-33. 25. Ragaz J, Wong H, Qian H. Comparative analysis of breast cancer (BrCA) mortality reduction among regions of Canada between 1950-2004: Impact of systemic and diagnostic guidelines after 1977, with model definition of potentially avoided annual deaths. Cancer Res 2009; 69:613s. 26. Hébert-Croteau N, Brisson J, Latreille J. Compliance with consensus recommendations for systemic therapy is associated with improved survival of women with node-negative breast cancer. J Clin Oncol 2004;22:3685-3693. Disclosure The authors report no potential conflicts of interest pertaining to this article. ©2010 Parkhurst, publisher of Oncology Exchange. All rights reserved. 8 oe VOL. 9, No. 4, november 2010