Evidence of inequitable use of chemotherapy in New Zealand colorectal cancer patients
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New Zealand has one of the highest incidence rates of colorectal cancer in the world, and has higher colorectal cause-specific mortality than Australia.1,2
The most effective intervention to improve survival after diagnosis of colorectal cancer is surgery. For many patients, survival can be further increased when chemotherapy is added to surgery, so-called “adjuvant” treatment. It can reduce the risk of recurrence.5 Some patients also have neoadjuvant chemotherapy prior to surgery to shrink the tumour.6 For metastatic disease, surgery is used to prevent blockage and chemotherapy is given as palliative treatment to prolong survival but not as a cure.7 The publicly funded chemotherapy regimens for colorectal cancer in New Zealand included bolus / infusional 5-fluorouracil [5-FU] as monotherapy or combination chemotherapy including FOLFOX (5-FU, calcium folinate and oxaliplatin), FOLFIRI (5-FU, calcium folinate and irinotecan), FOLFOXIRI (5-FU, calcium folinate, oxaliplatin and irinotecan), capecitabine and the combination of capecitabine and oxaliplatin (CapOx).8–10
The timeliness of chemotherapy has become an increasingly important question in the management of colorectal cancer.11–13 The Standards of Service Provision for Bowel Cancer Patients in New Zealand recommends that patients’ post-operative chemotherapy starts within four weeks of surgical resection.14 In a meta-analysis of 10 studies on time to start of chemotherapy, longer time to chemotherapy was shown to be associated with worse survival among patients with resected colorectal cancer.11 It showed that a four-week delay to chemotherapy could result in a significant decrease in both overall survival (Hazard ratio, 1.14; 95% confidence interval [CI], 1.10–1.17) and cancer-free survival (Hazard ratio, 1.14; 95% CI, 1.10–1.18).11
New Zealand has a free-at-the-point of use public health service that purports to offer near universal coverage to all residents. There is an increasing body of evidence that access to diagnosis and treatment in New Zealand’s health service is inequitably distributed, with Māori at a particular disadvantage. To measure the quality of care and outcomes for people with colorectal cancer in New Zealand and to present opportunities for improving services or care pathways and reducing inequity, the Ministry of Health completed a bowel cancer quality improvement report in 2019.15 It investigated the diagnostic pathway, surgical treatment and radiation therapy, but did not audit the use of chemotherapy. Thus, this study aims to explore the use and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Material and methods
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016, as recorded in the New Zealand Cancer Registry (NZCR). The NZCR was linked to the Pharmaceutical Collection (PHARMS) dataset by National Health Index (NHI) number to identify the publicly funded chemotherapy regimes in 2006–2017. The NHI number is a unique identifier for people who use publicly funded health and disability services in New Zealand. The PHARMS dataset stores claim and payment information from pharmacists for publicly subsidised dispensings. The combined dataset consisted of: 1) patient demographics: date of birth, gender and ethnicity; 2) tumour characteristics: date of diagnosis, cancer site, cancer extent and number of positive lymph nodes; and 3) medication dispensing information: chemical name, brand name, date of dispensing and quantity dispensed. The cancer extent recorded in the NZCR used the Surveillance Epidemiology and End Results (SEER) programme (A: localised within organ wall, B: limited to organ of origin, C: extension to adjacent organs, D: extension to regional lymph nodes and E: distant metastases).4 While the New Zealand Cancer Registry do have some T, N and M staging data, this is far from complete, while 81% of the colorectal cancer patients had SEER cancer extent information available. Consequently we have used the SEER cancer extent information in our analyses.
The publicly funded regimes of chemotherapy for colorectal cancer were grouped to FOLFOX, FOLFIRI, 5-FU with calcium folinate, capecitabine, CapOx and others. The first chemotherapy regime within 12 months post-colorectal cancer diagnosis was identified from the medication dispensing records as the primary chemotherapy regime. Because we could not ascertain whether the chemotherapy was for primary colorectal cancer or regional /distant recurrence, we used within one year post-diagnosis as time cut-off to identify the primary chemotherapy regime for the primary colorectal cancer. Timeliness of the chemotherapy was stratified into five groups: 1) less than five weeks after cancer diagnosis, 2) ≥5 weeks and <10 weeks, 3) ≥10 weeks and < 15 weeks, 4) ≥15 weeks and <20 weeks, and 5) 20+ weeks post-diagnosis. Surgery dates were not available to examine the relationship of surgery with timeliness of chemotherapy.
Use of different chemotherapy regimes and timeliness of chemotherapy was described by gender, age group (<60, 60–64, 65–69, 70–74, 75–79, 80–84 and 85+ years), ethnicity (New Zealand European, Māori, Pacific, Asian and others), cancer extent, cancer grade (1–4), lymph node (had positive lymph nodes, no positive lymph node), year of diagnosis and cancer network (Northern, Mid Central, Midland and Southern Cancer Network). The analysis was stratified by site of cancer (colon cancer and rectal cancer). Subgroup differences were examined with Chi-square test. Logistic regression model was used to estimate the odds ratio of having chemotherapy by subgroup after adjustment for gender, age, ethnicity, deprivation quintile (NZDep2013), year of diagnosis, cancer extent, grade and cancer network. To identify possible reasons for not having chemotherapy, we examined patients diagnosed with advanced colorectal cancer who had no chemotherapy by age and follow-up time before death. Of the patients who had chemotherapy, we also estimated the adjusted odds ratio of having chemotherapy in less than 10 weeks post-diagnosis by subgroup after adjustment for gender, age, ethnicity, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network.
All data analyses were performed in IBM SPSS statistics 25 (New York, US). The study is covered under ethics approval from the Health and Disability Ethics Committee (HDEC)—Approval Number: 17/NTB/156.
Results
During the study period 6,737/24,217 (27.8%) of patients diagnosed with colon cancer received publicly funded chemotherapy (Table 1) and 3,582/8,170 (43.8%) of patients with rectal cancer (Table 2). The proportion of patients having chemotherapy increased with cancer extent and grade. The use of chemotherapy decreased with increasing age, with only 4.4% of colon cancer patients aged 80+ years and 8.6% rectal cancer patients aged 80+ years receiving chemotherapy.
Table 1: Use of publicly funded chemotherapy for colon cancer patients by subgroup.
Table 2: Use of chemotherapy for rectal cancer patients by subgroup.
The pattern of chemotherapy regimes varied by subgroup. Older patients were more likely to receive Capecitabine and 5-FU, and younger patients were more likely to receive CapOx and FOLFOX. Patients with advanced cancer and patients with positive lymph nodes were more likely to have CapOx. The use of Capecitabine has been increasing over time, while the use of 5-FU has been reducing. CapOx were more commonly used in the Mid Central Cancer Network than in other cancer networks.
After adjustment for age, ethnicity, year of diagnosis, cancer extent, grade and cancer network (Table 3), men were more likely to have chemotherapy than women (OR1.19 for colon cancer; 1.31 for rectal cancer). There were also ethnic differences, with Pacific people being the least likely to receive chemotherapy after adjustment for gender, age, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network (OR compared to Europeans: 0.47 for colon cancer; 0.63 for rectal cancer), followed by Māori (OR: 0.63 for colon cancer; 0.85 for rectal cancer) and Asian (OR: 0.69 for colon cancer; 0.79 for rectal cancer).
Table 3: Adjusted odds ratio of having chemotherapy by logistic regression.
For patients with extent D and E colon cancer not receiving chemotherapy, 44.4% (2547/5734) were aged 80+ years, and another 15.9% (914/5,734) were aged less than 80 years but died within three months post-diagnosis. For extent D and E rectal cancer patients not receiving chemotherapy, 34.9% (390/1,116) of them were aged 80+ years, and another 16.2% (181/1,116) of patients were aged less than 80 years and died within three months post-diagnosis.
More than half of patients commenced their chemotherapy within the first 10 weeks post-diagnosis (Table 4 and 5), with around a quarter of the patients with metastatic disease starting chemotherapy within the first five weeks. The likelihood of starting chemotherapy in less than 10 weeks post-diagnosis has been increasing over time, with an adjusted odds ratio of 1.11 for colon cancer and 1.19 for rectal cancer (Table 6). Younger patients, New Zealand Europeans, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy earlier.
Table 4: Timing of chemotherapy for colon cancer.
Table 5: Timing of chemotherapy for rectal cancer.
Table 6: Adjusted odds ratio of having chemotherapy in less than 10 weeks by logistic regression.
Discussion
This study found that the use of chemotherapy in patients with colorectal cancer is not only influenced by the site and stage of disease but that there are also variations due to age, gender, ethnicity and the centre where treatment is provided. It is important to constantly review our management of cancer to ensure that New Zealand patients have equitable access to care. This study shows that despite the limitations of not having detailed individual clinical data, that routinely collected data can provide useful information when records are linked. In particular the comprehensive New Zealand Pharmaceutical data site provides valuable information on the use of chemotherapy for cancer patients in the absence of a prospectively collected registers of chemotherapy treatment. The findings from this study are consistent with those of the PIPER study—a retrospective study of 5,594 patients with colorectal cancer. Thus this study shows that overall 43.2% (2,836/6,559) of metastatic colorectal cancer patients received chemotherapy within one year after cancer diagnosis compared to 49% (532/1,086) in the PIPER study.1,16 The 5% discrepancy in use of chemotherapy may be explained by the inclusion of privately funded chemotherapy agents in PIPER.
We have shown that the use of chemotherapy for patients with colorectal cancer has been increasing by 6% per year as well as showing improvements in the timeliness of treatment. The likelihood of colorectal cancer patients having chemotherapy decreased with increasing age, with only 5% of patients aged 80+ years receiving chemotherapy (10% if with extent D and 9% if extent E disease). It is well established that older cancer patients are less likely to receive chemotherapy.17–19 Older patients have more comorbidities and poorer performance status, and are at greater risk of toxicity from chemotherapy than younger patients.20,21
A Denmark study showed that older patients were more frequently treated with single-agent therapy.20 This was also found in our study, with 89.5% of colon cancer patients aged 80+ years and 95.5% of rectal cancer patients aged 80+ years receiving 5-FU or capecitabine alone as the primary chemotherapy regime. More than half of the patients with advanced colorectal cancer (extent D and E) who did not receive chemotherapy were aged 80+ years or had a short life expectancy. Age was also a barrier in timely access to chemotherapy with an adjusted odds ratio of 0.98 per year for both colon cancer and rectal cancer.
Māori, Pacific and Asian patients were less likely to receive chemotherapy for colorectal cancer. We also have noted differences in the timing of chemotherapy for Maori, Pacific and Asian patients when compared to New Zealand Europeans. This finding is consistent with the results from a local cohort study that found Māori patients with stage III colon cancer were less likely to receive chemotherapy than non-Māori patients (relative risk: 0.69; 95% CI (0.53–0.91)).23 The findings that the variation in care applies to both colonic and rectal cancer and apply to pacific and Asian patients are of concern and suggest that the variations in care are not restricted just to the management of Māori with stage III colon cancer.
This study has also shown that there are variations in both the use and timing of chemotherapy depending on the Cancer Region where patients are treated. It seems that after adjustment for patient characteristics that patients in the Midland and Southern Region are more likely to be treated with chemotherapy. However, while patients in the Southern Region are more likely to be treated in a timely manner those in the Midland Region seem to be more likely to have delay before receiving treatment. These findings suggest that investigation of the regional variation in of surgery and radiotherapy as noted in the Bowel Cancer Quality Improvement Report can also extend to the use of chemotherapy.15 It is worth noting that not only has the use of chemotherapy been increasing but also the time taken to start chemotherapy has been reducing. This is likely due to the effect of the faster cancer treatment programme in New Zealand which was introduced in July 201227 and Standards of Service Provision for Bowel Cancer Patients in December 2013.14
One of the strengths of this study is that it was based on national datasets with 11 years data including 30,954 colorectal cancer patients. We have showed the most recent chemotherapy usage in New Zealand, and have demonstrated the changes over time. This study has its own limitations. Firstly the National Cancer Register does have missing data on staging on almost 20% of cases so matching chemotherapy regimens to both site and stage of disease would have missed some patients. On the other hand by including all cases of cancer we can have a better overall understanding of how chemotherapy is being used in New Zealand. The PHARMS dataset collects the dispensing records of pharmaceuticals that are publicly funded, but does not records data on pharmaceuticals that are privately funded. We used a long follow-up period of one year post-diagnosis as time cut-off to try and ensure a complete recording of chemotherapy. We recognise such a time is well outside the guidelines that post-operative chemotherapy starts within four weeks of surgical resection.14 We also did not have the data pertaining to other treatments including surgery and radiotherapy, and therefore could not discuss the relation of timeliness of chemotherapy with other treatments including surgery.
Conclusions
Chemotherapy is more likely to be used in younger patients with colorectal cancer and in men. Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in less than 10 weeks post-diagnosis. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Summary
Abstract
Aim
To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Method
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors.
Results
27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Māori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy.
Conclusion
Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1. Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, Sarfati D, et al. The New Zealand PIPER Project: colorectal cancer survival according to rurality, ethnicity and socioeconomic deprivation-results from a retrospective cohort study. The New Zealand medical journal. 2018; 131(1476):24–39.
2. Aye PS, Elwood JM, Stevanovic V. Comparison of cancer survival in New Zealand and Australia, 2006-2010. The New Zealand medical journal. 2014; 127(1407):14–26.
3. Ministry of Health. Cancer: New registrations and deaths 2013. Wellington: Ministry of Health; 2016.
4. Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Annals of Oncology. 2008;19(3):487–95.
5. New Zealand Guidelines Group. Clinical practice guidelines for the management of early colorectal cancer. Wellington: New Zealand Guidelines Group.; 2011.
6. Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ, Jr. Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management. Clin Colorectal Cancer. 2018; 17(1):1–12.
7. Best L, Simmonds P, Baughan C, Buchanan R, Davis C, Fentiman I, et al. Palliative chemotherapy for advanced or metastatic colorectal cancer. Cochrane Database of Systematic Reviews. 2000(1).
8. Carethers JM. Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor. Therap Adv Gastroenterol. 2008; 1(1):33–42.
9. Sandhu J, Lavingia V, Fakih M. Systemic treatment for metastatic colorectal cancer in the era of precision medicine. J Surg Oncol. 2019; 119(5):564–82.
10. Boyne DJ, Cuthbert CA, O’Sullivan DE, Sajobi TT, Hilsden RJ, Friedenreich CM, et al. Association Between Adjuvant Chemotherapy Duration and Survival Among Patients With Stage II and III Colon Cancer: A Systematic Review and Meta-analysis. JAMA Network Open. 2019; 2(5):e194154-e.
11. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer: A Systematic Review and Meta-analysis. JAMA. 2011; 305(22):2335–42.
12. Dos Santos LV, Faria TM, Lima AB, Abdalla KC, de Moraes ED, Cruz MR, et al. Timing of adjuvant chemotherapy in colorectal cancer. Colorectal Dis. 2016; 18(9):871–6.
13. Bos AC, van Erning FN, van Gestel YR, Creemers GJ, Punt CJ, van Oijen MG, et al. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer. 2015; 51(17):2553–61.
14. National Bowel Cancer Tumour Standards Working Group. Standards of Service Provision for Bowel Cancer Patients in New Zealand – Provisional. Wellington: Ministry of Health; 2013.
15. Ministry of Health. Bowel Cancer Quality Improvement Report. Wellington: Ministry of Health; 2019.
16. Jackson CG, Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, et al. The PIPER Project: An Internal Examination of Colorectal Cancer Management in New Zealand. 2015.
17. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001; 93(11):850–7.
18. Blackmore T, Lawrenson R, Lao C, Edwards M, Kuper-Hommel M, Elwood M, et al. The characteristics, management and outcomes of older women with breast cancer in New Zealand. Maturitas. 2018; 112:64–70.
19. Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002; 20(5):1192–202.
20. Lund CM, Nielsen D, Dehlendorff C, Christiansen AB, Rønholt F, Johansen JS, et al. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study. ESMO Open. 2016; 1(5):e000087.
21. Hoeben KWJ, van Steenbergen LN, van de Wouw AJ, Rutten HJ, van Spronsen DJ, Janssen-Heijnen MLG. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Annals of Oncology. 2012; 24(4):974–9.
22. Biskup E, Vetter M, Wedding U. Fighting diagnostic and therapeutic nihilism in the elderly with cancer. Ann Palliat Med. 2019.
23. Hill S, Sarfati D, Blakely T, Robson B, Purdie G, Dennett E, et al. Ethnicity and management of colon cancer in New Zealand: do indigenous patients get a worse deal? Cancer. 2010; 116(13):3205–14.
24. Lawrenson R, Lao C, Campbell I, Harvey V, Brown C, Seneviratne S, et al. The use of trastuzumab in New Zealand women with breast cancer. Asia-Pacific Journal of Clinical Oncology. 2017.
25. Lawrenson R, Lao C, Campbell I, Harvey V, Seneviratne S, Edwards M, et al. Treatment and survival disparities by ethnicity in New Zealand women with stage I-III breast cancer tumour subtypes. Cancer causes & control : CCC. 2017; 28(12):1417–27.
26. Metcalfe S, Laking G, Arnold J. Variation in the use of medicines by ethnicity during 2006/07 in New Zealand: a preliminary analysis. The New Zealand medical journal. 2013; 126(1384):14–41.
27. Ministry of Health. Faster Cancer Treatment Wellington, New Zealand.2018 [Available from: http://www.health.govt.nz/our-work/diseases-and-conditions/national-cancer-programme/cancer-initiatives/faster-cancer-treatment
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Evidence of inequitable use of chemotherapy in New Zealand colorectal cancer patients
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New Zealand has one of the highest incidence rates of colorectal cancer in the world, and has higher colorectal cause-specific mortality than Australia.1,2
The most effective intervention to improve survival after diagnosis of colorectal cancer is surgery. For many patients, survival can be further increased when chemotherapy is added to surgery, so-called “adjuvant” treatment. It can reduce the risk of recurrence.5 Some patients also have neoadjuvant chemotherapy prior to surgery to shrink the tumour.6 For metastatic disease, surgery is used to prevent blockage and chemotherapy is given as palliative treatment to prolong survival but not as a cure.7 The publicly funded chemotherapy regimens for colorectal cancer in New Zealand included bolus / infusional 5-fluorouracil [5-FU] as monotherapy or combination chemotherapy including FOLFOX (5-FU, calcium folinate and oxaliplatin), FOLFIRI (5-FU, calcium folinate and irinotecan), FOLFOXIRI (5-FU, calcium folinate, oxaliplatin and irinotecan), capecitabine and the combination of capecitabine and oxaliplatin (CapOx).8–10
The timeliness of chemotherapy has become an increasingly important question in the management of colorectal cancer.11–13 The Standards of Service Provision for Bowel Cancer Patients in New Zealand recommends that patients’ post-operative chemotherapy starts within four weeks of surgical resection.14 In a meta-analysis of 10 studies on time to start of chemotherapy, longer time to chemotherapy was shown to be associated with worse survival among patients with resected colorectal cancer.11 It showed that a four-week delay to chemotherapy could result in a significant decrease in both overall survival (Hazard ratio, 1.14; 95% confidence interval [CI], 1.10–1.17) and cancer-free survival (Hazard ratio, 1.14; 95% CI, 1.10–1.18).11
New Zealand has a free-at-the-point of use public health service that purports to offer near universal coverage to all residents. There is an increasing body of evidence that access to diagnosis and treatment in New Zealand’s health service is inequitably distributed, with Māori at a particular disadvantage. To measure the quality of care and outcomes for people with colorectal cancer in New Zealand and to present opportunities for improving services or care pathways and reducing inequity, the Ministry of Health completed a bowel cancer quality improvement report in 2019.15 It investigated the diagnostic pathway, surgical treatment and radiation therapy, but did not audit the use of chemotherapy. Thus, this study aims to explore the use and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Material and methods
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016, as recorded in the New Zealand Cancer Registry (NZCR). The NZCR was linked to the Pharmaceutical Collection (PHARMS) dataset by National Health Index (NHI) number to identify the publicly funded chemotherapy regimes in 2006–2017. The NHI number is a unique identifier for people who use publicly funded health and disability services in New Zealand. The PHARMS dataset stores claim and payment information from pharmacists for publicly subsidised dispensings. The combined dataset consisted of: 1) patient demographics: date of birth, gender and ethnicity; 2) tumour characteristics: date of diagnosis, cancer site, cancer extent and number of positive lymph nodes; and 3) medication dispensing information: chemical name, brand name, date of dispensing and quantity dispensed. The cancer extent recorded in the NZCR used the Surveillance Epidemiology and End Results (SEER) programme (A: localised within organ wall, B: limited to organ of origin, C: extension to adjacent organs, D: extension to regional lymph nodes and E: distant metastases).4 While the New Zealand Cancer Registry do have some T, N and M staging data, this is far from complete, while 81% of the colorectal cancer patients had SEER cancer extent information available. Consequently we have used the SEER cancer extent information in our analyses.
The publicly funded regimes of chemotherapy for colorectal cancer were grouped to FOLFOX, FOLFIRI, 5-FU with calcium folinate, capecitabine, CapOx and others. The first chemotherapy regime within 12 months post-colorectal cancer diagnosis was identified from the medication dispensing records as the primary chemotherapy regime. Because we could not ascertain whether the chemotherapy was for primary colorectal cancer or regional /distant recurrence, we used within one year post-diagnosis as time cut-off to identify the primary chemotherapy regime for the primary colorectal cancer. Timeliness of the chemotherapy was stratified into five groups: 1) less than five weeks after cancer diagnosis, 2) ≥5 weeks and <10 weeks, 3) ≥10 weeks and < 15 weeks, 4) ≥15 weeks and <20 weeks, and 5) 20+ weeks post-diagnosis. Surgery dates were not available to examine the relationship of surgery with timeliness of chemotherapy.
Use of different chemotherapy regimes and timeliness of chemotherapy was described by gender, age group (<60, 60–64, 65–69, 70–74, 75–79, 80–84 and 85+ years), ethnicity (New Zealand European, Māori, Pacific, Asian and others), cancer extent, cancer grade (1–4), lymph node (had positive lymph nodes, no positive lymph node), year of diagnosis and cancer network (Northern, Mid Central, Midland and Southern Cancer Network). The analysis was stratified by site of cancer (colon cancer and rectal cancer). Subgroup differences were examined with Chi-square test. Logistic regression model was used to estimate the odds ratio of having chemotherapy by subgroup after adjustment for gender, age, ethnicity, deprivation quintile (NZDep2013), year of diagnosis, cancer extent, grade and cancer network. To identify possible reasons for not having chemotherapy, we examined patients diagnosed with advanced colorectal cancer who had no chemotherapy by age and follow-up time before death. Of the patients who had chemotherapy, we also estimated the adjusted odds ratio of having chemotherapy in less than 10 weeks post-diagnosis by subgroup after adjustment for gender, age, ethnicity, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network.
All data analyses were performed in IBM SPSS statistics 25 (New York, US). The study is covered under ethics approval from the Health and Disability Ethics Committee (HDEC)—Approval Number: 17/NTB/156.
Results
During the study period 6,737/24,217 (27.8%) of patients diagnosed with colon cancer received publicly funded chemotherapy (Table 1) and 3,582/8,170 (43.8%) of patients with rectal cancer (Table 2). The proportion of patients having chemotherapy increased with cancer extent and grade. The use of chemotherapy decreased with increasing age, with only 4.4% of colon cancer patients aged 80+ years and 8.6% rectal cancer patients aged 80+ years receiving chemotherapy.
Table 1: Use of publicly funded chemotherapy for colon cancer patients by subgroup.
Table 2: Use of chemotherapy for rectal cancer patients by subgroup.
The pattern of chemotherapy regimes varied by subgroup. Older patients were more likely to receive Capecitabine and 5-FU, and younger patients were more likely to receive CapOx and FOLFOX. Patients with advanced cancer and patients with positive lymph nodes were more likely to have CapOx. The use of Capecitabine has been increasing over time, while the use of 5-FU has been reducing. CapOx were more commonly used in the Mid Central Cancer Network than in other cancer networks.
After adjustment for age, ethnicity, year of diagnosis, cancer extent, grade and cancer network (Table 3), men were more likely to have chemotherapy than women (OR1.19 for colon cancer; 1.31 for rectal cancer). There were also ethnic differences, with Pacific people being the least likely to receive chemotherapy after adjustment for gender, age, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network (OR compared to Europeans: 0.47 for colon cancer; 0.63 for rectal cancer), followed by Māori (OR: 0.63 for colon cancer; 0.85 for rectal cancer) and Asian (OR: 0.69 for colon cancer; 0.79 for rectal cancer).
Table 3: Adjusted odds ratio of having chemotherapy by logistic regression.
For patients with extent D and E colon cancer not receiving chemotherapy, 44.4% (2547/5734) were aged 80+ years, and another 15.9% (914/5,734) were aged less than 80 years but died within three months post-diagnosis. For extent D and E rectal cancer patients not receiving chemotherapy, 34.9% (390/1,116) of them were aged 80+ years, and another 16.2% (181/1,116) of patients were aged less than 80 years and died within three months post-diagnosis.
More than half of patients commenced their chemotherapy within the first 10 weeks post-diagnosis (Table 4 and 5), with around a quarter of the patients with metastatic disease starting chemotherapy within the first five weeks. The likelihood of starting chemotherapy in less than 10 weeks post-diagnosis has been increasing over time, with an adjusted odds ratio of 1.11 for colon cancer and 1.19 for rectal cancer (Table 6). Younger patients, New Zealand Europeans, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy earlier.
Table 4: Timing of chemotherapy for colon cancer.
Table 5: Timing of chemotherapy for rectal cancer.
Table 6: Adjusted odds ratio of having chemotherapy in less than 10 weeks by logistic regression.
Discussion
This study found that the use of chemotherapy in patients with colorectal cancer is not only influenced by the site and stage of disease but that there are also variations due to age, gender, ethnicity and the centre where treatment is provided. It is important to constantly review our management of cancer to ensure that New Zealand patients have equitable access to care. This study shows that despite the limitations of not having detailed individual clinical data, that routinely collected data can provide useful information when records are linked. In particular the comprehensive New Zealand Pharmaceutical data site provides valuable information on the use of chemotherapy for cancer patients in the absence of a prospectively collected registers of chemotherapy treatment. The findings from this study are consistent with those of the PIPER study—a retrospective study of 5,594 patients with colorectal cancer. Thus this study shows that overall 43.2% (2,836/6,559) of metastatic colorectal cancer patients received chemotherapy within one year after cancer diagnosis compared to 49% (532/1,086) in the PIPER study.1,16 The 5% discrepancy in use of chemotherapy may be explained by the inclusion of privately funded chemotherapy agents in PIPER.
We have shown that the use of chemotherapy for patients with colorectal cancer has been increasing by 6% per year as well as showing improvements in the timeliness of treatment. The likelihood of colorectal cancer patients having chemotherapy decreased with increasing age, with only 5% of patients aged 80+ years receiving chemotherapy (10% if with extent D and 9% if extent E disease). It is well established that older cancer patients are less likely to receive chemotherapy.17–19 Older patients have more comorbidities and poorer performance status, and are at greater risk of toxicity from chemotherapy than younger patients.20,21
A Denmark study showed that older patients were more frequently treated with single-agent therapy.20 This was also found in our study, with 89.5% of colon cancer patients aged 80+ years and 95.5% of rectal cancer patients aged 80+ years receiving 5-FU or capecitabine alone as the primary chemotherapy regime. More than half of the patients with advanced colorectal cancer (extent D and E) who did not receive chemotherapy were aged 80+ years or had a short life expectancy. Age was also a barrier in timely access to chemotherapy with an adjusted odds ratio of 0.98 per year for both colon cancer and rectal cancer.
Māori, Pacific and Asian patients were less likely to receive chemotherapy for colorectal cancer. We also have noted differences in the timing of chemotherapy for Maori, Pacific and Asian patients when compared to New Zealand Europeans. This finding is consistent with the results from a local cohort study that found Māori patients with stage III colon cancer were less likely to receive chemotherapy than non-Māori patients (relative risk: 0.69; 95% CI (0.53–0.91)).23 The findings that the variation in care applies to both colonic and rectal cancer and apply to pacific and Asian patients are of concern and suggest that the variations in care are not restricted just to the management of Māori with stage III colon cancer.
This study has also shown that there are variations in both the use and timing of chemotherapy depending on the Cancer Region where patients are treated. It seems that after adjustment for patient characteristics that patients in the Midland and Southern Region are more likely to be treated with chemotherapy. However, while patients in the Southern Region are more likely to be treated in a timely manner those in the Midland Region seem to be more likely to have delay before receiving treatment. These findings suggest that investigation of the regional variation in of surgery and radiotherapy as noted in the Bowel Cancer Quality Improvement Report can also extend to the use of chemotherapy.15 It is worth noting that not only has the use of chemotherapy been increasing but also the time taken to start chemotherapy has been reducing. This is likely due to the effect of the faster cancer treatment programme in New Zealand which was introduced in July 201227 and Standards of Service Provision for Bowel Cancer Patients in December 2013.14
One of the strengths of this study is that it was based on national datasets with 11 years data including 30,954 colorectal cancer patients. We have showed the most recent chemotherapy usage in New Zealand, and have demonstrated the changes over time. This study has its own limitations. Firstly the National Cancer Register does have missing data on staging on almost 20% of cases so matching chemotherapy regimens to both site and stage of disease would have missed some patients. On the other hand by including all cases of cancer we can have a better overall understanding of how chemotherapy is being used in New Zealand. The PHARMS dataset collects the dispensing records of pharmaceuticals that are publicly funded, but does not records data on pharmaceuticals that are privately funded. We used a long follow-up period of one year post-diagnosis as time cut-off to try and ensure a complete recording of chemotherapy. We recognise such a time is well outside the guidelines that post-operative chemotherapy starts within four weeks of surgical resection.14 We also did not have the data pertaining to other treatments including surgery and radiotherapy, and therefore could not discuss the relation of timeliness of chemotherapy with other treatments including surgery.
Conclusions
Chemotherapy is more likely to be used in younger patients with colorectal cancer and in men. Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in less than 10 weeks post-diagnosis. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Summary
Abstract
Aim
To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Method
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors.
Results
27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Māori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy.
Conclusion
Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1. Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, Sarfati D, et al. The New Zealand PIPER Project: colorectal cancer survival according to rurality, ethnicity and socioeconomic deprivation-results from a retrospective cohort study. The New Zealand medical journal. 2018; 131(1476):24–39.
2. Aye PS, Elwood JM, Stevanovic V. Comparison of cancer survival in New Zealand and Australia, 2006-2010. The New Zealand medical journal. 2014; 127(1407):14–26.
3. Ministry of Health. Cancer: New registrations and deaths 2013. Wellington: Ministry of Health; 2016.
4. Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Annals of Oncology. 2008;19(3):487–95.
5. New Zealand Guidelines Group. Clinical practice guidelines for the management of early colorectal cancer. Wellington: New Zealand Guidelines Group.; 2011.
6. Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ, Jr. Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management. Clin Colorectal Cancer. 2018; 17(1):1–12.
7. Best L, Simmonds P, Baughan C, Buchanan R, Davis C, Fentiman I, et al. Palliative chemotherapy for advanced or metastatic colorectal cancer. Cochrane Database of Systematic Reviews. 2000(1).
8. Carethers JM. Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor. Therap Adv Gastroenterol. 2008; 1(1):33–42.
9. Sandhu J, Lavingia V, Fakih M. Systemic treatment for metastatic colorectal cancer in the era of precision medicine. J Surg Oncol. 2019; 119(5):564–82.
10. Boyne DJ, Cuthbert CA, O’Sullivan DE, Sajobi TT, Hilsden RJ, Friedenreich CM, et al. Association Between Adjuvant Chemotherapy Duration and Survival Among Patients With Stage II and III Colon Cancer: A Systematic Review and Meta-analysis. JAMA Network Open. 2019; 2(5):e194154-e.
11. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer: A Systematic Review and Meta-analysis. JAMA. 2011; 305(22):2335–42.
12. Dos Santos LV, Faria TM, Lima AB, Abdalla KC, de Moraes ED, Cruz MR, et al. Timing of adjuvant chemotherapy in colorectal cancer. Colorectal Dis. 2016; 18(9):871–6.
13. Bos AC, van Erning FN, van Gestel YR, Creemers GJ, Punt CJ, van Oijen MG, et al. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer. 2015; 51(17):2553–61.
14. National Bowel Cancer Tumour Standards Working Group. Standards of Service Provision for Bowel Cancer Patients in New Zealand – Provisional. Wellington: Ministry of Health; 2013.
15. Ministry of Health. Bowel Cancer Quality Improvement Report. Wellington: Ministry of Health; 2019.
16. Jackson CG, Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, et al. The PIPER Project: An Internal Examination of Colorectal Cancer Management in New Zealand. 2015.
17. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001; 93(11):850–7.
18. Blackmore T, Lawrenson R, Lao C, Edwards M, Kuper-Hommel M, Elwood M, et al. The characteristics, management and outcomes of older women with breast cancer in New Zealand. Maturitas. 2018; 112:64–70.
19. Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002; 20(5):1192–202.
20. Lund CM, Nielsen D, Dehlendorff C, Christiansen AB, Rønholt F, Johansen JS, et al. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study. ESMO Open. 2016; 1(5):e000087.
21. Hoeben KWJ, van Steenbergen LN, van de Wouw AJ, Rutten HJ, van Spronsen DJ, Janssen-Heijnen MLG. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Annals of Oncology. 2012; 24(4):974–9.
22. Biskup E, Vetter M, Wedding U. Fighting diagnostic and therapeutic nihilism in the elderly with cancer. Ann Palliat Med. 2019.
23. Hill S, Sarfati D, Blakely T, Robson B, Purdie G, Dennett E, et al. Ethnicity and management of colon cancer in New Zealand: do indigenous patients get a worse deal? Cancer. 2010; 116(13):3205–14.
24. Lawrenson R, Lao C, Campbell I, Harvey V, Brown C, Seneviratne S, et al. The use of trastuzumab in New Zealand women with breast cancer. Asia-Pacific Journal of Clinical Oncology. 2017.
25. Lawrenson R, Lao C, Campbell I, Harvey V, Seneviratne S, Edwards M, et al. Treatment and survival disparities by ethnicity in New Zealand women with stage I-III breast cancer tumour subtypes. Cancer causes & control : CCC. 2017; 28(12):1417–27.
26. Metcalfe S, Laking G, Arnold J. Variation in the use of medicines by ethnicity during 2006/07 in New Zealand: a preliminary analysis. The New Zealand medical journal. 2013; 126(1384):14–41.
27. Ministry of Health. Faster Cancer Treatment Wellington, New Zealand.2018 [Available from: http://www.health.govt.nz/our-work/diseases-and-conditions/national-cancer-programme/cancer-initiatives/faster-cancer-treatment
For the PDF of this article,
contact nzmj@nzma.org.nz
Evidence of inequitable use of chemotherapy in New Zealand colorectal cancer patients
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New Zealand has one of the highest incidence rates of colorectal cancer in the world, and has higher colorectal cause-specific mortality than Australia.1,2
The most effective intervention to improve survival after diagnosis of colorectal cancer is surgery. For many patients, survival can be further increased when chemotherapy is added to surgery, so-called “adjuvant” treatment. It can reduce the risk of recurrence.5 Some patients also have neoadjuvant chemotherapy prior to surgery to shrink the tumour.6 For metastatic disease, surgery is used to prevent blockage and chemotherapy is given as palliative treatment to prolong survival but not as a cure.7 The publicly funded chemotherapy regimens for colorectal cancer in New Zealand included bolus / infusional 5-fluorouracil [5-FU] as monotherapy or combination chemotherapy including FOLFOX (5-FU, calcium folinate and oxaliplatin), FOLFIRI (5-FU, calcium folinate and irinotecan), FOLFOXIRI (5-FU, calcium folinate, oxaliplatin and irinotecan), capecitabine and the combination of capecitabine and oxaliplatin (CapOx).8–10
The timeliness of chemotherapy has become an increasingly important question in the management of colorectal cancer.11–13 The Standards of Service Provision for Bowel Cancer Patients in New Zealand recommends that patients’ post-operative chemotherapy starts within four weeks of surgical resection.14 In a meta-analysis of 10 studies on time to start of chemotherapy, longer time to chemotherapy was shown to be associated with worse survival among patients with resected colorectal cancer.11 It showed that a four-week delay to chemotherapy could result in a significant decrease in both overall survival (Hazard ratio, 1.14; 95% confidence interval [CI], 1.10–1.17) and cancer-free survival (Hazard ratio, 1.14; 95% CI, 1.10–1.18).11
New Zealand has a free-at-the-point of use public health service that purports to offer near universal coverage to all residents. There is an increasing body of evidence that access to diagnosis and treatment in New Zealand’s health service is inequitably distributed, with Māori at a particular disadvantage. To measure the quality of care and outcomes for people with colorectal cancer in New Zealand and to present opportunities for improving services or care pathways and reducing inequity, the Ministry of Health completed a bowel cancer quality improvement report in 2019.15 It investigated the diagnostic pathway, surgical treatment and radiation therapy, but did not audit the use of chemotherapy. Thus, this study aims to explore the use and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Material and methods
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016, as recorded in the New Zealand Cancer Registry (NZCR). The NZCR was linked to the Pharmaceutical Collection (PHARMS) dataset by National Health Index (NHI) number to identify the publicly funded chemotherapy regimes in 2006–2017. The NHI number is a unique identifier for people who use publicly funded health and disability services in New Zealand. The PHARMS dataset stores claim and payment information from pharmacists for publicly subsidised dispensings. The combined dataset consisted of: 1) patient demographics: date of birth, gender and ethnicity; 2) tumour characteristics: date of diagnosis, cancer site, cancer extent and number of positive lymph nodes; and 3) medication dispensing information: chemical name, brand name, date of dispensing and quantity dispensed. The cancer extent recorded in the NZCR used the Surveillance Epidemiology and End Results (SEER) programme (A: localised within organ wall, B: limited to organ of origin, C: extension to adjacent organs, D: extension to regional lymph nodes and E: distant metastases).4 While the New Zealand Cancer Registry do have some T, N and M staging data, this is far from complete, while 81% of the colorectal cancer patients had SEER cancer extent information available. Consequently we have used the SEER cancer extent information in our analyses.
The publicly funded regimes of chemotherapy for colorectal cancer were grouped to FOLFOX, FOLFIRI, 5-FU with calcium folinate, capecitabine, CapOx and others. The first chemotherapy regime within 12 months post-colorectal cancer diagnosis was identified from the medication dispensing records as the primary chemotherapy regime. Because we could not ascertain whether the chemotherapy was for primary colorectal cancer or regional /distant recurrence, we used within one year post-diagnosis as time cut-off to identify the primary chemotherapy regime for the primary colorectal cancer. Timeliness of the chemotherapy was stratified into five groups: 1) less than five weeks after cancer diagnosis, 2) ≥5 weeks and <10 weeks, 3) ≥10 weeks and < 15 weeks, 4) ≥15 weeks and <20 weeks, and 5) 20+ weeks post-diagnosis. Surgery dates were not available to examine the relationship of surgery with timeliness of chemotherapy.
Use of different chemotherapy regimes and timeliness of chemotherapy was described by gender, age group (<60, 60–64, 65–69, 70–74, 75–79, 80–84 and 85+ years), ethnicity (New Zealand European, Māori, Pacific, Asian and others), cancer extent, cancer grade (1–4), lymph node (had positive lymph nodes, no positive lymph node), year of diagnosis and cancer network (Northern, Mid Central, Midland and Southern Cancer Network). The analysis was stratified by site of cancer (colon cancer and rectal cancer). Subgroup differences were examined with Chi-square test. Logistic regression model was used to estimate the odds ratio of having chemotherapy by subgroup after adjustment for gender, age, ethnicity, deprivation quintile (NZDep2013), year of diagnosis, cancer extent, grade and cancer network. To identify possible reasons for not having chemotherapy, we examined patients diagnosed with advanced colorectal cancer who had no chemotherapy by age and follow-up time before death. Of the patients who had chemotherapy, we also estimated the adjusted odds ratio of having chemotherapy in less than 10 weeks post-diagnosis by subgroup after adjustment for gender, age, ethnicity, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network.
All data analyses were performed in IBM SPSS statistics 25 (New York, US). The study is covered under ethics approval from the Health and Disability Ethics Committee (HDEC)—Approval Number: 17/NTB/156.
Results
During the study period 6,737/24,217 (27.8%) of patients diagnosed with colon cancer received publicly funded chemotherapy (Table 1) and 3,582/8,170 (43.8%) of patients with rectal cancer (Table 2). The proportion of patients having chemotherapy increased with cancer extent and grade. The use of chemotherapy decreased with increasing age, with only 4.4% of colon cancer patients aged 80+ years and 8.6% rectal cancer patients aged 80+ years receiving chemotherapy.
Table 1: Use of publicly funded chemotherapy for colon cancer patients by subgroup.
Table 2: Use of chemotherapy for rectal cancer patients by subgroup.
The pattern of chemotherapy regimes varied by subgroup. Older patients were more likely to receive Capecitabine and 5-FU, and younger patients were more likely to receive CapOx and FOLFOX. Patients with advanced cancer and patients with positive lymph nodes were more likely to have CapOx. The use of Capecitabine has been increasing over time, while the use of 5-FU has been reducing. CapOx were more commonly used in the Mid Central Cancer Network than in other cancer networks.
After adjustment for age, ethnicity, year of diagnosis, cancer extent, grade and cancer network (Table 3), men were more likely to have chemotherapy than women (OR1.19 for colon cancer; 1.31 for rectal cancer). There were also ethnic differences, with Pacific people being the least likely to receive chemotherapy after adjustment for gender, age, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network (OR compared to Europeans: 0.47 for colon cancer; 0.63 for rectal cancer), followed by Māori (OR: 0.63 for colon cancer; 0.85 for rectal cancer) and Asian (OR: 0.69 for colon cancer; 0.79 for rectal cancer).
Table 3: Adjusted odds ratio of having chemotherapy by logistic regression.
For patients with extent D and E colon cancer not receiving chemotherapy, 44.4% (2547/5734) were aged 80+ years, and another 15.9% (914/5,734) were aged less than 80 years but died within three months post-diagnosis. For extent D and E rectal cancer patients not receiving chemotherapy, 34.9% (390/1,116) of them were aged 80+ years, and another 16.2% (181/1,116) of patients were aged less than 80 years and died within three months post-diagnosis.
More than half of patients commenced their chemotherapy within the first 10 weeks post-diagnosis (Table 4 and 5), with around a quarter of the patients with metastatic disease starting chemotherapy within the first five weeks. The likelihood of starting chemotherapy in less than 10 weeks post-diagnosis has been increasing over time, with an adjusted odds ratio of 1.11 for colon cancer and 1.19 for rectal cancer (Table 6). Younger patients, New Zealand Europeans, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy earlier.
Table 4: Timing of chemotherapy for colon cancer.
Table 5: Timing of chemotherapy for rectal cancer.
Table 6: Adjusted odds ratio of having chemotherapy in less than 10 weeks by logistic regression.
Discussion
This study found that the use of chemotherapy in patients with colorectal cancer is not only influenced by the site and stage of disease but that there are also variations due to age, gender, ethnicity and the centre where treatment is provided. It is important to constantly review our management of cancer to ensure that New Zealand patients have equitable access to care. This study shows that despite the limitations of not having detailed individual clinical data, that routinely collected data can provide useful information when records are linked. In particular the comprehensive New Zealand Pharmaceutical data site provides valuable information on the use of chemotherapy for cancer patients in the absence of a prospectively collected registers of chemotherapy treatment. The findings from this study are consistent with those of the PIPER study—a retrospective study of 5,594 patients with colorectal cancer. Thus this study shows that overall 43.2% (2,836/6,559) of metastatic colorectal cancer patients received chemotherapy within one year after cancer diagnosis compared to 49% (532/1,086) in the PIPER study.1,16 The 5% discrepancy in use of chemotherapy may be explained by the inclusion of privately funded chemotherapy agents in PIPER.
We have shown that the use of chemotherapy for patients with colorectal cancer has been increasing by 6% per year as well as showing improvements in the timeliness of treatment. The likelihood of colorectal cancer patients having chemotherapy decreased with increasing age, with only 5% of patients aged 80+ years receiving chemotherapy (10% if with extent D and 9% if extent E disease). It is well established that older cancer patients are less likely to receive chemotherapy.17–19 Older patients have more comorbidities and poorer performance status, and are at greater risk of toxicity from chemotherapy than younger patients.20,21
A Denmark study showed that older patients were more frequently treated with single-agent therapy.20 This was also found in our study, with 89.5% of colon cancer patients aged 80+ years and 95.5% of rectal cancer patients aged 80+ years receiving 5-FU or capecitabine alone as the primary chemotherapy regime. More than half of the patients with advanced colorectal cancer (extent D and E) who did not receive chemotherapy were aged 80+ years or had a short life expectancy. Age was also a barrier in timely access to chemotherapy with an adjusted odds ratio of 0.98 per year for both colon cancer and rectal cancer.
Māori, Pacific and Asian patients were less likely to receive chemotherapy for colorectal cancer. We also have noted differences in the timing of chemotherapy for Maori, Pacific and Asian patients when compared to New Zealand Europeans. This finding is consistent with the results from a local cohort study that found Māori patients with stage III colon cancer were less likely to receive chemotherapy than non-Māori patients (relative risk: 0.69; 95% CI (0.53–0.91)).23 The findings that the variation in care applies to both colonic and rectal cancer and apply to pacific and Asian patients are of concern and suggest that the variations in care are not restricted just to the management of Māori with stage III colon cancer.
This study has also shown that there are variations in both the use and timing of chemotherapy depending on the Cancer Region where patients are treated. It seems that after adjustment for patient characteristics that patients in the Midland and Southern Region are more likely to be treated with chemotherapy. However, while patients in the Southern Region are more likely to be treated in a timely manner those in the Midland Region seem to be more likely to have delay before receiving treatment. These findings suggest that investigation of the regional variation in of surgery and radiotherapy as noted in the Bowel Cancer Quality Improvement Report can also extend to the use of chemotherapy.15 It is worth noting that not only has the use of chemotherapy been increasing but also the time taken to start chemotherapy has been reducing. This is likely due to the effect of the faster cancer treatment programme in New Zealand which was introduced in July 201227 and Standards of Service Provision for Bowel Cancer Patients in December 2013.14
One of the strengths of this study is that it was based on national datasets with 11 years data including 30,954 colorectal cancer patients. We have showed the most recent chemotherapy usage in New Zealand, and have demonstrated the changes over time. This study has its own limitations. Firstly the National Cancer Register does have missing data on staging on almost 20% of cases so matching chemotherapy regimens to both site and stage of disease would have missed some patients. On the other hand by including all cases of cancer we can have a better overall understanding of how chemotherapy is being used in New Zealand. The PHARMS dataset collects the dispensing records of pharmaceuticals that are publicly funded, but does not records data on pharmaceuticals that are privately funded. We used a long follow-up period of one year post-diagnosis as time cut-off to try and ensure a complete recording of chemotherapy. We recognise such a time is well outside the guidelines that post-operative chemotherapy starts within four weeks of surgical resection.14 We also did not have the data pertaining to other treatments including surgery and radiotherapy, and therefore could not discuss the relation of timeliness of chemotherapy with other treatments including surgery.
Conclusions
Chemotherapy is more likely to be used in younger patients with colorectal cancer and in men. Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in less than 10 weeks post-diagnosis. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Summary
Abstract
Aim
To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Method
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors.
Results
27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Māori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy.
Conclusion
Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Author Information
Acknowledgements
Correspondence
Correspondence Email
Competing Interests
1. Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, Sarfati D, et al. The New Zealand PIPER Project: colorectal cancer survival according to rurality, ethnicity and socioeconomic deprivation-results from a retrospective cohort study. The New Zealand medical journal. 2018; 131(1476):24–39.
2. Aye PS, Elwood JM, Stevanovic V. Comparison of cancer survival in New Zealand and Australia, 2006-2010. The New Zealand medical journal. 2014; 127(1407):14–26.
3. Ministry of Health. Cancer: New registrations and deaths 2013. Wellington: Ministry of Health; 2016.
4. Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Annals of Oncology. 2008;19(3):487–95.
5. New Zealand Guidelines Group. Clinical practice guidelines for the management of early colorectal cancer. Wellington: New Zealand Guidelines Group.; 2011.
6. Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ, Jr. Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management. Clin Colorectal Cancer. 2018; 17(1):1–12.
7. Best L, Simmonds P, Baughan C, Buchanan R, Davis C, Fentiman I, et al. Palliative chemotherapy for advanced or metastatic colorectal cancer. Cochrane Database of Systematic Reviews. 2000(1).
8. Carethers JM. Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor. Therap Adv Gastroenterol. 2008; 1(1):33–42.
9. Sandhu J, Lavingia V, Fakih M. Systemic treatment for metastatic colorectal cancer in the era of precision medicine. J Surg Oncol. 2019; 119(5):564–82.
10. Boyne DJ, Cuthbert CA, O’Sullivan DE, Sajobi TT, Hilsden RJ, Friedenreich CM, et al. Association Between Adjuvant Chemotherapy Duration and Survival Among Patients With Stage II and III Colon Cancer: A Systematic Review and Meta-analysis. JAMA Network Open. 2019; 2(5):e194154-e.
11. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer: A Systematic Review and Meta-analysis. JAMA. 2011; 305(22):2335–42.
12. Dos Santos LV, Faria TM, Lima AB, Abdalla KC, de Moraes ED, Cruz MR, et al. Timing of adjuvant chemotherapy in colorectal cancer. Colorectal Dis. 2016; 18(9):871–6.
13. Bos AC, van Erning FN, van Gestel YR, Creemers GJ, Punt CJ, van Oijen MG, et al. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer. 2015; 51(17):2553–61.
14. National Bowel Cancer Tumour Standards Working Group. Standards of Service Provision for Bowel Cancer Patients in New Zealand – Provisional. Wellington: Ministry of Health; 2013.
15. Ministry of Health. Bowel Cancer Quality Improvement Report. Wellington: Ministry of Health; 2019.
16. Jackson CG, Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, et al. The PIPER Project: An Internal Examination of Colorectal Cancer Management in New Zealand. 2015.
17. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001; 93(11):850–7.
18. Blackmore T, Lawrenson R, Lao C, Edwards M, Kuper-Hommel M, Elwood M, et al. The characteristics, management and outcomes of older women with breast cancer in New Zealand. Maturitas. 2018; 112:64–70.
19. Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002; 20(5):1192–202.
20. Lund CM, Nielsen D, Dehlendorff C, Christiansen AB, Rønholt F, Johansen JS, et al. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study. ESMO Open. 2016; 1(5):e000087.
21. Hoeben KWJ, van Steenbergen LN, van de Wouw AJ, Rutten HJ, van Spronsen DJ, Janssen-Heijnen MLG. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Annals of Oncology. 2012; 24(4):974–9.
22. Biskup E, Vetter M, Wedding U. Fighting diagnostic and therapeutic nihilism in the elderly with cancer. Ann Palliat Med. 2019.
23. Hill S, Sarfati D, Blakely T, Robson B, Purdie G, Dennett E, et al. Ethnicity and management of colon cancer in New Zealand: do indigenous patients get a worse deal? Cancer. 2010; 116(13):3205–14.
24. Lawrenson R, Lao C, Campbell I, Harvey V, Brown C, Seneviratne S, et al. The use of trastuzumab in New Zealand women with breast cancer. Asia-Pacific Journal of Clinical Oncology. 2017.
25. Lawrenson R, Lao C, Campbell I, Harvey V, Seneviratne S, Edwards M, et al. Treatment and survival disparities by ethnicity in New Zealand women with stage I-III breast cancer tumour subtypes. Cancer causes & control : CCC. 2017; 28(12):1417–27.
26. Metcalfe S, Laking G, Arnold J. Variation in the use of medicines by ethnicity during 2006/07 in New Zealand: a preliminary analysis. The New Zealand medical journal. 2013; 126(1384):14–41.
27. Ministry of Health. Faster Cancer Treatment Wellington, New Zealand.2018 [Available from: http://www.health.govt.nz/our-work/diseases-and-conditions/national-cancer-programme/cancer-initiatives/faster-cancer-treatment
Contact diana@nzma.org.nz
for the PDF of this article
Evidence of inequitable use of chemotherapy in New Zealand colorectal cancer patients
View Article PDF
New Zealand has one of the highest incidence rates of colorectal cancer in the world, and has higher colorectal cause-specific mortality than Australia.1,2
The most effective intervention to improve survival after diagnosis of colorectal cancer is surgery. For many patients, survival can be further increased when chemotherapy is added to surgery, so-called “adjuvant” treatment. It can reduce the risk of recurrence.5 Some patients also have neoadjuvant chemotherapy prior to surgery to shrink the tumour.6 For metastatic disease, surgery is used to prevent blockage and chemotherapy is given as palliative treatment to prolong survival but not as a cure.7 The publicly funded chemotherapy regimens for colorectal cancer in New Zealand included bolus / infusional 5-fluorouracil [5-FU] as monotherapy or combination chemotherapy including FOLFOX (5-FU, calcium folinate and oxaliplatin), FOLFIRI (5-FU, calcium folinate and irinotecan), FOLFOXIRI (5-FU, calcium folinate, oxaliplatin and irinotecan), capecitabine and the combination of capecitabine and oxaliplatin (CapOx).8–10
The timeliness of chemotherapy has become an increasingly important question in the management of colorectal cancer.11–13 The Standards of Service Provision for Bowel Cancer Patients in New Zealand recommends that patients’ post-operative chemotherapy starts within four weeks of surgical resection.14 In a meta-analysis of 10 studies on time to start of chemotherapy, longer time to chemotherapy was shown to be associated with worse survival among patients with resected colorectal cancer.11 It showed that a four-week delay to chemotherapy could result in a significant decrease in both overall survival (Hazard ratio, 1.14; 95% confidence interval [CI], 1.10–1.17) and cancer-free survival (Hazard ratio, 1.14; 95% CI, 1.10–1.18).11
New Zealand has a free-at-the-point of use public health service that purports to offer near universal coverage to all residents. There is an increasing body of evidence that access to diagnosis and treatment in New Zealand’s health service is inequitably distributed, with Māori at a particular disadvantage. To measure the quality of care and outcomes for people with colorectal cancer in New Zealand and to present opportunities for improving services or care pathways and reducing inequity, the Ministry of Health completed a bowel cancer quality improvement report in 2019.15 It investigated the diagnostic pathway, surgical treatment and radiation therapy, but did not audit the use of chemotherapy. Thus, this study aims to explore the use and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Material and methods
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016, as recorded in the New Zealand Cancer Registry (NZCR). The NZCR was linked to the Pharmaceutical Collection (PHARMS) dataset by National Health Index (NHI) number to identify the publicly funded chemotherapy regimes in 2006–2017. The NHI number is a unique identifier for people who use publicly funded health and disability services in New Zealand. The PHARMS dataset stores claim and payment information from pharmacists for publicly subsidised dispensings. The combined dataset consisted of: 1) patient demographics: date of birth, gender and ethnicity; 2) tumour characteristics: date of diagnosis, cancer site, cancer extent and number of positive lymph nodes; and 3) medication dispensing information: chemical name, brand name, date of dispensing and quantity dispensed. The cancer extent recorded in the NZCR used the Surveillance Epidemiology and End Results (SEER) programme (A: localised within organ wall, B: limited to organ of origin, C: extension to adjacent organs, D: extension to regional lymph nodes and E: distant metastases).4 While the New Zealand Cancer Registry do have some T, N and M staging data, this is far from complete, while 81% of the colorectal cancer patients had SEER cancer extent information available. Consequently we have used the SEER cancer extent information in our analyses.
The publicly funded regimes of chemotherapy for colorectal cancer were grouped to FOLFOX, FOLFIRI, 5-FU with calcium folinate, capecitabine, CapOx and others. The first chemotherapy regime within 12 months post-colorectal cancer diagnosis was identified from the medication dispensing records as the primary chemotherapy regime. Because we could not ascertain whether the chemotherapy was for primary colorectal cancer or regional /distant recurrence, we used within one year post-diagnosis as time cut-off to identify the primary chemotherapy regime for the primary colorectal cancer. Timeliness of the chemotherapy was stratified into five groups: 1) less than five weeks after cancer diagnosis, 2) ≥5 weeks and <10 weeks, 3) ≥10 weeks and < 15 weeks, 4) ≥15 weeks and <20 weeks, and 5) 20+ weeks post-diagnosis. Surgery dates were not available to examine the relationship of surgery with timeliness of chemotherapy.
Use of different chemotherapy regimes and timeliness of chemotherapy was described by gender, age group (<60, 60–64, 65–69, 70–74, 75–79, 80–84 and 85+ years), ethnicity (New Zealand European, Māori, Pacific, Asian and others), cancer extent, cancer grade (1–4), lymph node (had positive lymph nodes, no positive lymph node), year of diagnosis and cancer network (Northern, Mid Central, Midland and Southern Cancer Network). The analysis was stratified by site of cancer (colon cancer and rectal cancer). Subgroup differences were examined with Chi-square test. Logistic regression model was used to estimate the odds ratio of having chemotherapy by subgroup after adjustment for gender, age, ethnicity, deprivation quintile (NZDep2013), year of diagnosis, cancer extent, grade and cancer network. To identify possible reasons for not having chemotherapy, we examined patients diagnosed with advanced colorectal cancer who had no chemotherapy by age and follow-up time before death. Of the patients who had chemotherapy, we also estimated the adjusted odds ratio of having chemotherapy in less than 10 weeks post-diagnosis by subgroup after adjustment for gender, age, ethnicity, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network.
All data analyses were performed in IBM SPSS statistics 25 (New York, US). The study is covered under ethics approval from the Health and Disability Ethics Committee (HDEC)—Approval Number: 17/NTB/156.
Results
During the study period 6,737/24,217 (27.8%) of patients diagnosed with colon cancer received publicly funded chemotherapy (Table 1) and 3,582/8,170 (43.8%) of patients with rectal cancer (Table 2). The proportion of patients having chemotherapy increased with cancer extent and grade. The use of chemotherapy decreased with increasing age, with only 4.4% of colon cancer patients aged 80+ years and 8.6% rectal cancer patients aged 80+ years receiving chemotherapy.
Table 1: Use of publicly funded chemotherapy for colon cancer patients by subgroup.
Table 2: Use of chemotherapy for rectal cancer patients by subgroup.
The pattern of chemotherapy regimes varied by subgroup. Older patients were more likely to receive Capecitabine and 5-FU, and younger patients were more likely to receive CapOx and FOLFOX. Patients with advanced cancer and patients with positive lymph nodes were more likely to have CapOx. The use of Capecitabine has been increasing over time, while the use of 5-FU has been reducing. CapOx were more commonly used in the Mid Central Cancer Network than in other cancer networks.
After adjustment for age, ethnicity, year of diagnosis, cancer extent, grade and cancer network (Table 3), men were more likely to have chemotherapy than women (OR1.19 for colon cancer; 1.31 for rectal cancer). There were also ethnic differences, with Pacific people being the least likely to receive chemotherapy after adjustment for gender, age, deprivation quintile, year of diagnosis, cancer extent, grade and cancer network (OR compared to Europeans: 0.47 for colon cancer; 0.63 for rectal cancer), followed by Māori (OR: 0.63 for colon cancer; 0.85 for rectal cancer) and Asian (OR: 0.69 for colon cancer; 0.79 for rectal cancer).
Table 3: Adjusted odds ratio of having chemotherapy by logistic regression.
For patients with extent D and E colon cancer not receiving chemotherapy, 44.4% (2547/5734) were aged 80+ years, and another 15.9% (914/5,734) were aged less than 80 years but died within three months post-diagnosis. For extent D and E rectal cancer patients not receiving chemotherapy, 34.9% (390/1,116) of them were aged 80+ years, and another 16.2% (181/1,116) of patients were aged less than 80 years and died within three months post-diagnosis.
More than half of patients commenced their chemotherapy within the first 10 weeks post-diagnosis (Table 4 and 5), with around a quarter of the patients with metastatic disease starting chemotherapy within the first five weeks. The likelihood of starting chemotherapy in less than 10 weeks post-diagnosis has been increasing over time, with an adjusted odds ratio of 1.11 for colon cancer and 1.19 for rectal cancer (Table 6). Younger patients, New Zealand Europeans, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy earlier.
Table 4: Timing of chemotherapy for colon cancer.
Table 5: Timing of chemotherapy for rectal cancer.
Table 6: Adjusted odds ratio of having chemotherapy in less than 10 weeks by logistic regression.
Discussion
This study found that the use of chemotherapy in patients with colorectal cancer is not only influenced by the site and stage of disease but that there are also variations due to age, gender, ethnicity and the centre where treatment is provided. It is important to constantly review our management of cancer to ensure that New Zealand patients have equitable access to care. This study shows that despite the limitations of not having detailed individual clinical data, that routinely collected data can provide useful information when records are linked. In particular the comprehensive New Zealand Pharmaceutical data site provides valuable information on the use of chemotherapy for cancer patients in the absence of a prospectively collected registers of chemotherapy treatment. The findings from this study are consistent with those of the PIPER study—a retrospective study of 5,594 patients with colorectal cancer. Thus this study shows that overall 43.2% (2,836/6,559) of metastatic colorectal cancer patients received chemotherapy within one year after cancer diagnosis compared to 49% (532/1,086) in the PIPER study.1,16 The 5% discrepancy in use of chemotherapy may be explained by the inclusion of privately funded chemotherapy agents in PIPER.
We have shown that the use of chemotherapy for patients with colorectal cancer has been increasing by 6% per year as well as showing improvements in the timeliness of treatment. The likelihood of colorectal cancer patients having chemotherapy decreased with increasing age, with only 5% of patients aged 80+ years receiving chemotherapy (10% if with extent D and 9% if extent E disease). It is well established that older cancer patients are less likely to receive chemotherapy.17–19 Older patients have more comorbidities and poorer performance status, and are at greater risk of toxicity from chemotherapy than younger patients.20,21
A Denmark study showed that older patients were more frequently treated with single-agent therapy.20 This was also found in our study, with 89.5% of colon cancer patients aged 80+ years and 95.5% of rectal cancer patients aged 80+ years receiving 5-FU or capecitabine alone as the primary chemotherapy regime. More than half of the patients with advanced colorectal cancer (extent D and E) who did not receive chemotherapy were aged 80+ years or had a short life expectancy. Age was also a barrier in timely access to chemotherapy with an adjusted odds ratio of 0.98 per year for both colon cancer and rectal cancer.
Māori, Pacific and Asian patients were less likely to receive chemotherapy for colorectal cancer. We also have noted differences in the timing of chemotherapy for Maori, Pacific and Asian patients when compared to New Zealand Europeans. This finding is consistent with the results from a local cohort study that found Māori patients with stage III colon cancer were less likely to receive chemotherapy than non-Māori patients (relative risk: 0.69; 95% CI (0.53–0.91)).23 The findings that the variation in care applies to both colonic and rectal cancer and apply to pacific and Asian patients are of concern and suggest that the variations in care are not restricted just to the management of Māori with stage III colon cancer.
This study has also shown that there are variations in both the use and timing of chemotherapy depending on the Cancer Region where patients are treated. It seems that after adjustment for patient characteristics that patients in the Midland and Southern Region are more likely to be treated with chemotherapy. However, while patients in the Southern Region are more likely to be treated in a timely manner those in the Midland Region seem to be more likely to have delay before receiving treatment. These findings suggest that investigation of the regional variation in of surgery and radiotherapy as noted in the Bowel Cancer Quality Improvement Report can also extend to the use of chemotherapy.15 It is worth noting that not only has the use of chemotherapy been increasing but also the time taken to start chemotherapy has been reducing. This is likely due to the effect of the faster cancer treatment programme in New Zealand which was introduced in July 201227 and Standards of Service Provision for Bowel Cancer Patients in December 2013.14
One of the strengths of this study is that it was based on national datasets with 11 years data including 30,954 colorectal cancer patients. We have showed the most recent chemotherapy usage in New Zealand, and have demonstrated the changes over time. This study has its own limitations. Firstly the National Cancer Register does have missing data on staging on almost 20% of cases so matching chemotherapy regimens to both site and stage of disease would have missed some patients. On the other hand by including all cases of cancer we can have a better overall understanding of how chemotherapy is being used in New Zealand. The PHARMS dataset collects the dispensing records of pharmaceuticals that are publicly funded, but does not records data on pharmaceuticals that are privately funded. We used a long follow-up period of one year post-diagnosis as time cut-off to try and ensure a complete recording of chemotherapy. We recognise such a time is well outside the guidelines that post-operative chemotherapy starts within four weeks of surgical resection.14 We also did not have the data pertaining to other treatments including surgery and radiotherapy, and therefore could not discuss the relation of timeliness of chemotherapy with other treatments including surgery.
Conclusions
Chemotherapy is more likely to be used in younger patients with colorectal cancer and in men. Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in less than 10 weeks post-diagnosis. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Summary
Abstract
Aim
To explore variations in the use of and timeliness of chemotherapy in patients diagnosed with colorectal cancer in New Zealand.
Method
This study included patients diagnosed with colorectal cancer in New Zealand between 1 January 2006 and 31 December 2016. The first chemotherapy regime was identified from Pharmaceutical Collection dataset. Logistic regression model was used to estimate the adjusted odds ratio of having chemotherapy by subgroup after adjustment for other factors.
Results
27.8% (6,737/24,217) of colon cancer patients and 43.8% (3,582/8,170) of rectal cancer patients received publicly funded chemotherapy. The uptake and timeliness of chemotherapy has been improving over time. Pacific people were the least likely to receive chemotherapy, followed by Māori and Asian. Younger patients, New Zealand European, patients with metastatic disease and patients in the Southern Cancer Network were more likely to have chemotherapy in less than 10 weeks post-diagnosis. Over half of the advanced colorectal cancer patients who did not receive chemotherapy were aged 80+ years or had a short life expectancy.
Conclusion
Although the uptake and timeliness of chemotherapy for colorectal cancer has been improving, Māori, Pacific, Asian and older patients were less likely to receive chemotherapy and less likely to receive chemotherapy in a timely manner. There is a variation in use of chemotherapy by Region with patients in the Southern Cancer region appearing to be the most likely to receive chemotherapy and to receive it within a timely period.
Author Information
Acknowledgements
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Competing Interests
1. Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, Sarfati D, et al. The New Zealand PIPER Project: colorectal cancer survival according to rurality, ethnicity and socioeconomic deprivation-results from a retrospective cohort study. The New Zealand medical journal. 2018; 131(1476):24–39.
2. Aye PS, Elwood JM, Stevanovic V. Comparison of cancer survival in New Zealand and Australia, 2006-2010. The New Zealand medical journal. 2014; 127(1407):14–26.
3. Ministry of Health. Cancer: New registrations and deaths 2013. Wellington: Ministry of Health; 2016.
4. Lidgren M, Jönsson B, Rehnberg C, Willking N, Bergh J. Cost-effectiveness of HER2 testing and 1-year adjuvant trastuzumab therapy for early breast cancer. Annals of Oncology. 2008;19(3):487–95.
5. New Zealand Guidelines Group. Clinical practice guidelines for the management of early colorectal cancer. Wellington: New Zealand Guidelines Group.; 2011.
6. Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ, Jr. Total Neoadjuvant Therapy: A Shifting Paradigm in Locally Advanced Rectal Cancer Management. Clin Colorectal Cancer. 2018; 17(1):1–12.
7. Best L, Simmonds P, Baughan C, Buchanan R, Davis C, Fentiman I, et al. Palliative chemotherapy for advanced or metastatic colorectal cancer. Cochrane Database of Systematic Reviews. 2000(1).
8. Carethers JM. Systemic treatment of advanced colorectal cancer: tailoring therapy to the tumor. Therap Adv Gastroenterol. 2008; 1(1):33–42.
9. Sandhu J, Lavingia V, Fakih M. Systemic treatment for metastatic colorectal cancer in the era of precision medicine. J Surg Oncol. 2019; 119(5):564–82.
10. Boyne DJ, Cuthbert CA, O’Sullivan DE, Sajobi TT, Hilsden RJ, Friedenreich CM, et al. Association Between Adjuvant Chemotherapy Duration and Survival Among Patients With Stage II and III Colon Cancer: A Systematic Review and Meta-analysis. JAMA Network Open. 2019; 2(5):e194154-e.
11. Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer: A Systematic Review and Meta-analysis. JAMA. 2011; 305(22):2335–42.
12. Dos Santos LV, Faria TM, Lima AB, Abdalla KC, de Moraes ED, Cruz MR, et al. Timing of adjuvant chemotherapy in colorectal cancer. Colorectal Dis. 2016; 18(9):871–6.
13. Bos AC, van Erning FN, van Gestel YR, Creemers GJ, Punt CJ, van Oijen MG, et al. Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer. Eur J Cancer. 2015; 51(17):2553–61.
14. National Bowel Cancer Tumour Standards Working Group. Standards of Service Provision for Bowel Cancer Patients in New Zealand – Provisional. Wellington: Ministry of Health; 2013.
15. Ministry of Health. Bowel Cancer Quality Improvement Report. Wellington: Ministry of Health; 2019.
16. Jackson CG, Sharples KJ, Firth MJ, Hinder VA, Hill AG, Jeffery M, et al. The PIPER Project: An Internal Examination of Colorectal Cancer Management in New Zealand. 2015.
17. Schrag D, Cramer LD, Bach PB, Begg CB. Age and adjuvant chemotherapy use after surgery for stage III colon cancer. J Natl Cancer Inst. 2001; 93(11):850–7.
18. Blackmore T, Lawrenson R, Lao C, Edwards M, Kuper-Hommel M, Elwood M, et al. The characteristics, management and outcomes of older women with breast cancer in New Zealand. Maturitas. 2018; 112:64–70.
19. Potosky AL, Harlan LC, Kaplan RS, Johnson KA, Lynch CF. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002; 20(5):1192–202.
20. Lund CM, Nielsen D, Dehlendorff C, Christiansen AB, Rønholt F, Johansen JS, et al. Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study. ESMO Open. 2016; 1(5):e000087.
21. Hoeben KWJ, van Steenbergen LN, van de Wouw AJ, Rutten HJ, van Spronsen DJ, Janssen-Heijnen MLG. Treatment and complications in elderly stage III colon cancer patients in the Netherlands. Annals of Oncology. 2012; 24(4):974–9.
22. Biskup E, Vetter M, Wedding U. Fighting diagnostic and therapeutic nihilism in the elderly with cancer. Ann Palliat Med. 2019.
23. Hill S, Sarfati D, Blakely T, Robson B, Purdie G, Dennett E, et al. Ethnicity and management of colon cancer in New Zealand: do indigenous patients get a worse deal? Cancer. 2010; 116(13):3205–14.
24. Lawrenson R, Lao C, Campbell I, Harvey V, Brown C, Seneviratne S, et al. The use of trastuzumab in New Zealand women with breast cancer. Asia-Pacific Journal of Clinical Oncology. 2017.
25. Lawrenson R, Lao C, Campbell I, Harvey V, Seneviratne S, Edwards M, et al. Treatment and survival disparities by ethnicity in New Zealand women with stage I-III breast cancer tumour subtypes. Cancer causes & control : CCC. 2017; 28(12):1417–27.
26. Metcalfe S, Laking G, Arnold J. Variation in the use of medicines by ethnicity during 2006/07 in New Zealand: a preliminary analysis. The New Zealand medical journal. 2013; 126(1384):14–41.
27. Ministry of Health. Faster Cancer Treatment Wellington, New Zealand.2018 [Available from: http://www.health.govt.nz/our-work/diseases-and-conditions/national-cancer-programme/cancer-initiatives/faster-cancer-treatment
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Evidence of inequitable use of chemotherapy in New Zealand colorectal cancer patients
New Zealand has one of the highest incidence rates of colorectal cancer in the world, and has higher colorectal cause-specific mortality than Australia.
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