Approximately 80% of lung cancers are classified as non-small cell, which includes squamous carcinoma, large-cell carcinoma, and adenocarcinoma.1 Of these, 25% are considered to be early stage tumors (including stage IB, IIA, IIB) at the time of diagnosis.2 In the fall of 2004, two combination chemotherapy regimens were approved for full coverage in Alberta for stage IB, IIA, and IIB non-small cell lung cancer (NSCLC) patients. This decision was based on the review of several clinical trials.3,4 Five-year survival in the patients who received adjuvant therapy was improved by 4 to 15% over surgery alone in these clinical trials.
There are many issues that are discussed, in addition to survival, when determining whether a drug should be approved for coverage. The number of patients to benefit, the cost of the drug per patient, and the total annual cost are a few. It is, therefore, important to have good estimates for these factors during the review of the drug and after the approval to determine whether the effect on patient care and costs were as expected or whether interventions, to optimize patient care or modify costs, are needed. In this study, we focus on aspects of patient care and factors that might relate to access and uptake to the newly approved regimen for early stage NSCLC.
Uptake of a new treatment is a function of several factors, including patient-specific and clinician-specific characteristics.1,5,6 In order for a patient to be eligible for one of the adjuvant chemotherapy regimens approved in 2004 in Alberta, they must have stage IB, IIA, or IIB NSCLC (coverage for stage IIIA patients occurred prior to 2004), have had surgery with negative margins, and be able to begin chemotherapy within 12 weeks of the surgery. In order for a patient to receive adjuvant chemotherapy, therefore, he/she must receive surgery and then be referred to a cancer facility for a consult with an oncologist. Other than patient choice, receipt of surgery and referral to an oncologist are, therefore, the key factors external to the Alberta Cancer Board (ACB) that effect uptake of adjuvant chemotherapy.
In Alberta, all cancer care except surgery is provided by the ACB via two tertiary facilities and several smaller facilities throughout the province. Surgery is provided by fellowship trained thoracic surgeons in tertiary care centers located in Edmonton or Calgary. Although thoracic surgeons are not employed by the ACB, they are an integral part of a team approach with oncologists for discussing and approving new drug therapies and treatment guidelines for lung cancer patients. In Calgary, the clinics which patients attend for consults with the surgeons before their surgery are held within the cancer facility, whereas in Edmonton they are held at other tertiary hospitals. The proximity of clinics in Calgary between surgeons and oncologists creates a particularly good environment for team care.
The purpose of this study was to measure the proportion of early stage NSCLC patients diagnosed between 2004 and 2006 who received surgery and subsequently had a consult with an oncologist at a cancer facility and identify factors that were associated with having surgery and subsequent consult with an oncologist that could potentially be addressed by the ACB to improve access to care.
All residents of Alberta who were diagnosed in 2004, 2005 and 2006 with stage IB, IIA, or IIB NSCLC were identified from the Alberta Cancer Registry and included in the study. Patients were excluded if they were not residents of Alberta, had another cancer diagnosis within 6 months of the lung cancer, or did not have stage IB, IIA or IIB disease. Gender, postal code at diagnosis, age at diagnosis, and date of surgery for curative intent were also obtained from the Alberta Cancer Registry. A conversion table was used to determine residence by Regional Health Authority (RHA) at time of diagnosis from the postal code. In Alberta, medical care, other than cancer care, is coordinated through nine RHAs (Figure 1). There is large variation across RHAs with respect to the number and types of specialists available locally (such as pulmonologists) which may impact referral patterns and ultimately the type of care and/or timeliness of care patients receive. RHA was, therefore, examined as a predictive factor for both outcomes of interest: surgery and consult with an oncologist.
The Alberta Cancer Registry is routinely recognized by the North American Association of Comprehensive Cancer Registries for the completeness and timeliness of its data reporting. Since 1997 North American Association of Comprehensive Cancer Registries has administered a program that annually reviews member registries for their ability to produce complete, accurate, and timely data. Each year, members of the Data Evaluation and Certification Committee evaluate cancer incidence data for the most recent data year, based on predetermined registry certification criteria established by the Committee.7 The Alberta Cancer Registry is regularly awarded the highest level of certification for the quality of its data.
Chemotherapy for lung cancer patients in Alberta is only available within ACB facilities, therefore, consults with oncologists to identify a treatment plan, occur in ACB facilities. The date of the consult with an oncologist was extracted from the electronic medical record of the ACB. We are not able to identify situations in which a patient is referred to an oncologist but does not have a consult scheduled; that is, instances in which the patient refuses to see an oncologist, but we are able to identify whether a consult with an oncologist occurred. If a referral was made but the patient did not attend the consult, by default, the case was categorized as not having had a consult. The electronic medical record has been in place since 2002 and is used for all appointment scheduling for ACB facilities.
Analyses were conducted using SAS. Percentages were calculated to describe the population for each categorical variable of interest. Univariate analyses were conducted using χ2 tests for each outcome. Multiple logistic regression was performed to obtain estimates for odds ratios, 95% confidence intervals, and corresponding p-values for variables that were significant in the univariate analyses.
There were 592 stage IB–IIB NSCLC patients identified from the Alberta Cancer Registry who were diagnosed in the years 2004, 2005, and 2006. There were 24 nonresidents of Alberta, two multiple cancer cases (bladder, kidney), two cases who had pretreatment with chemo, one case who has never come to ACB for consult or treatment, one case with positive cytology but no mass seen in surgery, and one case who upon further review was found to have metastases who were excluded from this study, leaving 561 that were included. Table 1 shows the distribution of all patients, by stage, age, gender, year of diagnosis, and health region of residence at time of diagnosis. Due to small numbers of patients in certain regions, some health regions were combined as indicated in Table 1. The median age at diagnosis was 70 years, most patients had stage IB disease (70%), and slightly more than half were men. Figure 1 is a map of Alberta showing the geographical boundaries of the RHAs and the locations of the different types of ACB facilities. Almost 70% of patients resided in one of the two RHAs that contain the only two tertiary cancer facilities in the province, Calgary and Edmonton.
Of the 561stage IB–IIB NSCLC patients, 165 (29%) did not receive surgery but were referred to an ACB facility for a consult with an oncologist, 44 (8%) did not receive surgery or have a consult with an oncologist, and 352 (63%) of them had surgery. Neither stage at diagnosis nor gender was associated with having surgery (Table 1). Age at diagnosis was significantly associated with surgery (p = < 0.001) with younger patients incrementally more likely to receive surgery than older patients. Residence of RHA at diagnosis was marginally associated with surgery (p = 0.077) with those in the southern/central parts of the province least likely to receive surgery (Table 1). All except 47 patients had microscopically confirmed stage IB–IIB disease, 38 of whom did not receive any sort of treatment and nine of whom received radiation only. Results of the univariate analysis and the multiple logistic regression remained the same when these patients were excluded.
Of the 352 patients who had surgery, 255 (72%) of them subsequently had a consult with an oncologist (Table 1). Age at diagnosis was the factor most strongly associated with having a consult with an oncologist. Younger patients were much more likely to have a consult with an oncologist postsurgery than older patients; 81% of those under age 65 had a consult but only 45% of those age 75 or more (p = < 0.001) did. Women (79%) were more likely than men (67%) to have an oncology consult (p = 0.011). Residence at diagnosis was associated with having a consult with an oncologist after surgery: patients living in RHA 3 (76%) and 4 (92%) were most likely to have a consult with an oncologist and patients in RHA 8 and 9 (43%) were least likely (p = 0.028). Year of diagnosis was not associated with receiving surgery but was associated with receiving a consult with an oncologist (p = 0.011).
Tables 2 and 3 show the results of the multiple logistic regression models for factors predicting surgery and having a consult with an oncologist, respectively. Age and RHA of residence were significantly associated with both receipt of surgery and consult with an oncologist. Residents living in southern and central Alberta were less likely to have surgery than those in northern Alberta, but residents in the far north were least likely to have a consult with an oncologist subsequent to surgery. Year of diagnosis was strongly associated with receiving a consult with an oncologist, with patients diagnosed in 2005 being most likely to have an oncology consult (p = 0.006).
The overall percentage of stage IB–IIB NSCLC patients who received surgery who were diagnosed between 2004 and 2006 was 63%. This is comparable to surgical rates reported in other studies, which range from 28 to 85%.2,6,8 Other studies have found that roughly 25 to 30% of early stage NSCLC patients are not eligible for or decline surgery for various reasons.6 Reasons for not conducting surgery include medical comorbidities, patient preference, and location of tumor. These factors were not addressed in this study. Of the 209 patients who did not have surgery, however, 109 (52%) did receive some other sort of treatment, primarily radiation (105). Based on further review, of those patients who received radiation but did not have surgery, 43 received palliative doses suggesting, although originally diagnosed with early stage disease, they may have had a rapidly growing tumor that became unresectable and/or metastatic. Given the relatively large percentage of patients who received palliative radiation, further investigation of treatment and rate of progression for early stage lung cancer is warranted. It is likely that the remaining 66 patients who received chemotherapy and/or higher dose radiation had unresectable tumors or refused surgery.
A significant decrease in surgical resection and decreased likelihood of consult with an oncologist was seen with increasing patient age. Patients under the age of 65 were more likely to have surgery than those over 75 (OR = 13.3, 95% CI: 7.8–22.7) and more likely to have a consult with an oncologist (OR = 5.1, 95% CI: 2.6–9.9). Similarly, many studies have shown that older patients are less likely to receive surgery and adjuvant chemotherapy than younger patients. Reasons for this have been due to less willingness to accept possibility of toxicity for small perceived survival benefits, concerns related to quality of life, prolonged recovery postoperatively, and shorter life expectancy.9–11 It was not possible in this study to determine if the lower proportion of older patients having a consult with an oncologist is due to patient choice not to attend the consult or clinician’s choice not to refer the patient. Further investigation into this is warranted as there is mounting evidence that less aggressive treatment of older patients is common, however, it is less clear as to whether or not less aggressive treatment is appropriate.12–14
Our study demonstrated significant temporal trends in having a consult with an oncologist for treatment of localized NSCLC postsurgery in Alberta. About 64% of patients diagnosed in 2004 who had surgery also had a consult to discuss adjuvant chemotherapy versus 82% in 2005, likely reflecting a delay in the implementation and uptake of the policy change regarding adjuvant chemotherapy for these patients. Interestingly, in 2006 there was a decline in the percentage of patients having a consult for adjuvant chemotherapy postsurgery. Table 4 shows the percentage of patients who had surgery and those who had surgery and consult with an oncologist by year and tumor stage. The overall decline in oncology consults in 2006 is due to a decrease in the percentage of stage IB patients that had a consult. The percentage of stage II patients who received an oncology consult remained fairly constant over the study period. The change in percentage of stage IB patients having a consult with an oncologist likely reflects ongoing uncertainty in the management of these patients and changes in treatment policy that occurred in 2006. At the 2006 ASCO meeting several abstracts were presented that suggested not only decreased efficacy but also potential harm of adjuvant chemotherapy in stage IB NSCLS patients.15,16 As a follow-up to this meeting, in 2007 Cancer Care Ontario presented another update and review of the evidence for adjuvant chemotherapy in NSCLC.17 The revised guidelines no longer recommend adjuvant therapy for patients with stage IB tumors.
Another phenomenon observed in this study was the variation for both surgery and subsequent consult with an oncologist by area of residence. Patients living in southern and central Alberta were less likely to have surgery than those living in northern Alberta, (56 versus 69%, respectively) but more likely to have a consult with an oncologist post surgery (79 versus 72%, respectively). The difference in surgeries is an unexpected finding and requires further investigation. The patient population in terms of demographics is comparable across the province and there is no reason to think that comorbidities or other factors that would prevent surgery for medical reasons would differ regionally. It is possible that the lower proportion of patients who received surgery in central and southern Alberta is due to issues related to referral patterns and/or access to the surgeons themselves; reasons for the regional differences will be investigated.
The higher proportion of patients who had a consult with an oncologist postsurgery in central and southern Alberta than in northern Alberta is a bit surprising, although there are some reasonable explanations. The thoracic surgeons in the south work literally side-by-side the medical oncologists during patient consults. The higher degree of face-to-face interactions between specialties may lead to higher referral rates; we plan to investigate this possibility. Additionally, the regions with the lowest proportion of patients that had a consult with an oncologist after surgery were those in the far north (RHAs 8 and 9). These regions are very rural and there is only one facility within either of these regions that provides both treatment planning and delivery of chemotherapy. Most patients living in these regions, therefore, have very long commutes with respect to both time and distance to attend a consult with an oncologist and ultimately receive chemotherapy. The ACB has implemented a telehealth program to overcome distance barriers and increase access to oncologists. This year we will also pilot a home chemotherapy administration program to further address access issues for patients living in rural/remote areas.
There are two main limitations of this study, First, we are not able to determine whether patients did not receive surgery because they were not referred to a surgeon, they were referred but deemed inoperable (e.g., comorbidities), had poor tumor location, or patient refusal. We did conduct a chart review on a subset of patients to determine if we could obtain high-quality data on comorbidities but found that we could not. The comorbidity data we abstracted did not help predict surgery or subsequent consult with an oncologist nor did it change the effect of age or region of residence when evaluated via multiple logistic regression models. With the exception of referral to a surgeon, however, none of the above factors should differ by region, therefore, the lack of information on these factors does not impact the study conclusions. We do plan to investigate whether differences in surgical rates by region have continued and, if so, whether they are related to differences in referral rates to surgeons. Second, we are not able to determine if the reason patients did not have a consult with an oncologist postsurgery is due to lack of referral from the surgeon or is due to patient refusal. Further investigations to determine the reasons are warranted to optimize access to and receipt of recommended treatment.
Overall, this study demonstrated comparable rates of surgical resection as found in other studies and fairly high rates of consult with an oncologist for patients with stage IB, IIA, and IIB NSCLC diagnosed in the province of Alberta soon after the approval of adjuvant chemotherapy for these patients. The strongest demographic factor affecting surgical resection and referral for adjuvant chemotherapy is age. Patients older than 75 were significantly less likely than younger patients to have surgery for early stage NSCLC. Of those undergoing resection, older patients were also significantly less likely to have a consult with an oncologist to discuss adjuvant chemotherapy. Future efforts should focus on whether these decisions are primarily patient preference or related to other factors such as comorbidities or physician perception regarding patient age. Although definitive referral and treatment patterns were not addressed in this study, significant regional variation was observed for both surgery and oncology consults. The information learned by the study is helpful for future planning and for identifying future areas of research.
Supported by the Alberta Cancer Board.
1. Patel N, Adatia R, Mellemgaard A, Jack R, Møller H. Variation in the use of chemotherapy in lung cancer. British J Cancer 2007;96:886–890.
2. Fry W, Phillips JL, Menck HR. Ten-Year Survey of lung cancer treatment and survival in hospitals in the United States. A National Cancer Data Base Report. Cancer 1999;86:1867–1876.
3. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005;352:2589–2597.
4. The International Adjuvant Lung Cancer Trial Collaborative G. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004;350:351–360.
5. Bekelman JE, Rosenzweig KE, Bach PB, Schrag D. Trends in the use of postoperative radiotherapy for resected non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2006;66:492–499.
6. Li WWL, Visser O, Ubbink DT, et al. The influence of provider characteristics on resection rates and survival in patients with localized non-small cell lung cancer. Lung Cancer. In press.
7. The North American Association of Cancer Centre Registries. NAACCR Data Standards for Cancer Registries. Vol. 2008; 2007.
8. Little AG, Rusch VW, Bonner JA, et al. Patterns of surgical care of lung cancer patients. Ann Thorac Surg 2005;80:2051–2056.
9. Wang J, Kuo YF, Freeman J, Markowitz AB, Goodwin JS. Temporal trends and predictors of perioperative chemotherapy use in elderly patients with resected nonsmall cell lung cancer. Cancer 2008;112:382–390.
10. de Rijke JM, Schouten LJ, Ten Velde GP, et al. Influence of age, comorbidity and performance status on the choice of treatment for patients with non-small cell lung cancer; results of a population-based study. Lung Cancer 2004;46:233–245.
11. Janssen-Heijnen MLG, Smulders S, Lemmens VEPP, et al. Effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer. Thorax 2004;59:602–607.
12. Port JL, Kent M, Korst RJ, et al. Surgical Resection for Lung Cancer in the Octogenarian. Chest 2004;126:733–738.
13. Brock MV, Kim MP, Hooker CM, et al. Pulmonary resection in octogenarians with stage I nonsmall cell lung cancer: a 22-year experience. Ann Thorac Surg 2004;77:271–277.
14. Pepe C, Hasan T, Winton L, et al. Adjuvant chemotherapy in elderly patients: an analysis of National Cancer Institute of Canada Clinical Trials Group and Intergroup BR10. Proc Am Soc Clin Oncol 2006;24(18s). Abstract 7009.
15. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung Adjuvant Cisplatin Evaluation (LACE): a pooled analysis of five randomized clinical trials including 4584 patients. J Clin Oncol 2006;24(Suppl 18).
16. Strauss GM, Herndon JE, Maddaus MA, et al. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): update of Cancer and Leukemia Group B (CALGB) protocol 9633. Proc Am Soc Clin Oncol 2006;24(18S). Abstract 7007.
17. Pisters KMW, Evans WK, Azzoli CG, et al. Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I-IIIA resectable non-small cell lung cancer guideline. J Clin Oncol 2007;25:1–13.