B Access to cancer care and oncology outcomes comment

Access to cancer care and oncology outcomes
Joseph Ragaz MD, FRCPC, William Hryniuk, MD, FRCPC
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.
VOL. 9, No. 4, november 2010
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
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
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.
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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
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:
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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.
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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.
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The authors report no potential conflicts of interest pertaining to this article.
©2010 Parkhurst, publisher of Oncology Exchange. All rights reserved.
VOL. 9, No. 4, november 2010