Optimizing the adenoma detection rate – a never-ending story? Or does the outcome quality depend on the follow-up?
Thomas Rösch, Hamburg
Increased Rate of Adenoma Detection Associates With Reduces Risk of Colorectal Cancer and Death
|Michal F. Kaminski,1, 2, 3, 4,* Paulina Wieszczy,1, 2, 4, * Maciej Rupinski,1, 2 Urszula Wojciechowska,5 Joanna Didkowska,4 Ewa Kraszewska,2 Ewa Kraszewska,2 Jaroslaw Kobiela, 2, 6 Robert Franczyk,1, 2 Maria Rupinksa,1, 2 Bartlomiej Kocot,2 Anna Chaber-Ciopinska,1, 2 Jacek Pachlewski,1 Marcin Polkowski,1, 2 and Jaroslaw Regula,1, 2|
|1 Department of Gastroenterological Oncology, 4 Department of Cancer Prevention, 5 National Cancer, Registry of Poland, Maria-Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland; 2 Department of Gastroenterology, Hepatotology and Oncology, Medical Center to Health and Society, University of Oslo, Oslo. Norway;
6 Department of general, Endocrine and Tarnsplant Surgery, medical University of Gdansk- Invasive Medicine Centre, Gdansk, Poland
Background and Aims
The quality of endoscopists’ colonoscopy performance is measured by adenoma detection rate (ADR). Although ADR is associated inversely with interval colorectal cancer and colorectal cancer death, the effects of an increasing ADR have not been shown. We investigated whether increasing ADRs from individual endoscopists is associated with reduced risks of interval colorectal cancer and subsequent death.
We performed a prospective cohort study of individuals who underwent a screening colonoscopy within the National Colorectal Cancer Screening Program in Poland, from January 1, 2004, through December 31, 2008. We collected data from 146,860 colonoscopies performed by 294 endoscopists, with each endoscopist having participated at least twice in annual editions of primary colonoscopy screening. We used annual feedback and quality benchmark indicators to improve colonoscopy performance. We used ADR quintiles in the whole data set to categorize the annual ADRs for each endoscopist. An increased ADR was defined as an increase by at least 1 quintile category, or the maintenance of the highest category in subsequent screening years. Multivariate frailty models were used to evaluate the effects of increased ADR on the risk of interval colorectal
cancer and death.
Throughout the enrollment period, 219 endoscopists (74.5%) increased their annual ADR category. During 895,916 person-years of follow-up evaluation through the National Cancer Registry, we identified 168 interval colorectal cancers and 44 interval cancer deaths. An increased ADR was associated with an adjusted hazard ratio for interval colorectal cancer of 0.63 (95% confidence interval [CI], 0.45–0.88; P ¼ .006), and for cancer death of 0.50 (95% CI, 0.27–0.95; P ¼ .035). Compared with no increase in ADR, reaching or maintaining the highest quintile ADR category (such as an ADR > 24.56%) decreased the adjusted hazard ratios for interval colorectal cancer to 0.27 (95% CI, 0.12–0.63; P ¼ .003), and 0.18 (95% CI, 0.06–0.56; P ¼ .003), respectively.
In a prospective study of individuals who underwent screening colonoscopy within a National Colorectal Cancer Screening Program, we associated increased ADR with a reduced risk of
interval colorectal cancer and death.
Lancet Oncology 2017; 18: 823–34
|Adenoma surveillance and colorecteral cancer incidence: a retrospective, multicentre, cohort study|
|Wendy Atkin, Kate Wooldrage, Amy Brenner, Jesscia Martin, Urvi Shah, Sajith Perena, Fiona Luca, Jeremy P Brown, Ines Kralj-Hans, Paul Greliak,Kevon Pack, Jill Wood, Ann Thomson, Andrew Veitch, Stephen W. Duffy, Amanda J Cross|
Removal of adenomas reduces colorectal cancer incidence and mortality; however, the benefit of surveillance colonoscopy on colorectal cancer risk remains unclear. We examined heterogeneity in colorectal cancer incidence in intermediate-risk patients and the effect of surveillance on colorectal cancer incidence.
We did this retrospective, multicentre, cohort study using routine lower gastrointestinal endoscopy and pathology data from patients who, after baseline colonoscopy and polypectomy, were diagnosed with intermediate-risk adenomas mostly (>99%) between Jan 1, 1990, and Dec 31, 2010, at 17 hospitals in the UK. These patients are currently offered surveillance colonoscopy at intervals of 3 years. Patients were followed up through to Dec 31, 2014. We assessed the effect of surveillance on colorectal cancer incidence using Cox regression with adjustment for patient, procedural, and polyp characteristics. We defined lower-risk and higher-risk subgroups on the basis of polyp and procedural characteristics identified as colorectal cancer risk factors. We estimated colorectal cancer incidence and standardised incidence ratios (SIRs) using as standard the general population of England in 2007. This trial is registered, number ISRCTN15213649.
253 798 patients who underwent colonic endoscopy were identified, of whom 11 944 with intermediate-risk adenomas were included in this analysis. After a median follow-up of 7·9 years (IQR 5·6–11·1), 210 colorectal cancers were diagnosed. 5019 (42%) patients did not attend surveillance and 6925 (58%) attended one or more surveillance visits. Compared to no surveillance, one or two surveillance visits were associated with a significant reduction in colorectal cancer incidence rate (adjusted hazard ratio 0·57, 95% CI 0·40–0·80 for one visit; 0·51, 0·31–0·84 for two visits). Without surveillance, colorectal cancer incidence in patients with a suboptimal quality colonoscopy, proximal polyps, or a high-grade or large adenoma (≥20 mm) at baseline (8865 [74%] patients) was significantly higher than in the general population (SIR 1·30, 95% CI 1·06–1·57). By contrast, in patients without these features, colorectal cancer incidence was lower than that of the general population (SIR 0·51, 95% CI 0·29–0·84).
Colonoscopy surveillance benefits most patients with intermediate-risk adenomas. However, some patients are already at low risk after baseline colonoscopy and the value of surveillance for them is unclear.
What you need to know about these papers
The adenoma detection rate (ADR) is the holy grail of quality assurance in colonoscopy. It is the main parameter for outcome quality — or more precisely, it is a surrogate parameter, or even a surrogate surrogate parameter. The main aim is to reduce the mortality rate in patients with colorectal cancer (CRC). This is also reflected in a reduction in the incidence of CRC and the rate of interval cancers (equivalent to missed cancers, at least partly, since the correlation is not 1 : 1). Two studies — one in Poland1 and one in California2 — have shown that the rate of interval cancers correlates with the ADR in endoscopy. Several methodological objections can be raised against these studies, especially the one from California; most importantly, neither of the studies analyzed the rate of advanced adenomas as a possible outcome parameter. The patients with these adenomas are the ones who ought to be able to benefit most from screening colonoscopy.
The Polish group have now backed up their hypothesis with another paper from their large screening database.3 A total of 294 colonoscopists were observed over 5 years (2004–2008) and classified into five groups (quintiles) depending on their ADR at the start of the study. Among the five groups/quintiles formed, the poorest had an ADR of < 11% and the best had a rate of > 25% (similar to the average ADR in the registry in Germany, currently 28%). After 2004, the ADR in the various groups developed differently, stayed the same, or improved or worsened. All improvements in the ADR were associated with a reduced rate of interval cancers overall (hazard ratio/HR 0.67). Colonoscopists who reached the highest quintile had an HR of 0.27. Three-quarters of the endoscopists improved, and the mean number of annual screening colonoscopies ranged from 88 to 125. Overall, 169 interval cancers were detected after 146,860 colonoscopies over a follow-up period of 5.8 years, representing a rate of 0.1%. So far, so good. As in the previous paper(s), the rate of advanced adenomas was not analyzed.
What do advanced adenomas mean for the overall prognosis after screening colonoscopy? The other paper discussed here looked at 11,944 polypectomies of intermediate-risk adenomas out of 253,798 colonoscopies with unclear selection criteria (apparently for all indications) over a 20-year period.4 “Intermediate risk” is a category unfortunately newly introduced by the British Society of Gastroenterology in contrast to advanced adenomas. It is defined as one or two larger adenomas (≥ 10 mm) or three or four smaller adenomas. This sort of definition naturally makes the study difficult to compare with other papers. About half of the patients had one or more follow-up or surveillance endoscopies. Follow-up endoscopies were associated with a substantially reduced CRC rate (HR 0.57 for one surveillance colonoscopy and 0.51 for two).
In the group without surveillance, clear risk factors were identified for a higher CRC rate during the follow-up in comparison with the general population. These factors were: poorer-quality colonoscopy, adenoma size larger than 2 cm, or the presence of high-grade dysplasia. For these factors, the increase in risk (standardized incidence ratio, SIR) was 1.3. In other words, this important risk group did not experience any reduction in risk as a result of colonoscopy — although these patients are in particular need of it. The group does of course have a substantially increased risk in comparison with the general population (to what extent we will never know, since adenomas are removed and not observed). However, it ought to be possible to reduce the risk in this group more clearly.
Unfortunately, this was also not the first study of this type. The Norwegian research group of Michael Bretthauer and colleagues analyzed a database of 40,826 adenomas removed during colonoscopies for various indications (but mostly not during screening). The authors found that patients with low-risk adenomas have a lower risk in comparison with the general population (standardized incidence-based mortality ratio/SMR = 0.75). In contrast, the group with high-risk adenomas (multiple adenomas, villous components, high-grade dysplasia; the sizes of the adenomas were not available in the database) had a higher risk (SMR 1.16)5 — results that are similar to those of the UK study discussed above. The recommended follow-up period in Norway for these high-risk adenomas at that time (1993–2007) was still 10 years — well below current international guidelines. A French study on the national CRC screening program (n = 5779 polypectomies) showed similar results, with an SIR of 1.26 for the carcinoma rate in patients after polypectomies for all types of adenoma.6 Again, there were clear and contrasting differences between non-advanced adenomas (SIR 0.68) and advanced adenomas (SIR 2.23). Patients who received surveillance had a significantly lower risk than those without (SIR 1.10 vs. 4.26).
What conclusions can be drawn from this?
- The mean adenoma detection rate of 28% in Germany is in the top category (> 25%) relative to the Polish standard for cancer prevention. That appears to represent a sufficient cancer prevention effect for colonoscopists. Whether the ADR — as suggested by the Californian study2 — then needs to be further increased up to 50% or more in order to optimize the effect may be doubted, for the reasons outlined.
- However, even the best possible ADR is no use if sufficient surveillance is not carried out. The possible risk groups are clearly distinct here — even without surveillance, patients with non-advanced, low-risk adenomas have a better prognosis (relative to CRC) after polypectomy than the general population, possibly because the pathology is genuinely benign. In patients with advanced, high-risk adenomas, by contrast, polypectomy is not sufficient and careful surveillance is exceptionally important — otherwise the risk in these patients is greater than that in the general population. So endoscopists need to ensure that proper surveillance continues to be provided.
- In the end, of course, the quality of the polypectomy also plays a role. It can be assumed that smaller adenomas are easier to remove and are removed more successfully than larger, advanced ones.
- Kaminski MF, Regula J, Kraszewska E, et al. Quality indicators for colonoscopy and the risk of interval cancer. The New England journal of medicine 2010;362:1795-803.
- Corley DA, Jensen CD, Marks AR, et al. Adenoma detection rate and risk of colorectal cancer and death. The New England journal of medicine 2014;370:1298-306.
- Kaminski MF, Wieszczy P, Rupinski M, et al. Increased Rate of Adenoma Detection Associates With Reduced Risk of Colorectal Cancer and Death. Gastroenterology 2017;153:98-105.
- Atkin W, Wooldrage K, Brenner A, et al. Adenoma surveillance and colorectal cancer incidence: a retrospective, multicentre, cohort study. The Lancet Oncology 2017;18:823-34.
- Loberg M, Kalager M, Holme O, Hoff G, Adami HO, Bretthauer M. Long-term colorectal-cancer mortality after adenoma removal. The New England journal of medicine 2014;371:799-807.
- Cottet V, Jooste V, Fournel I, Bouvier AM, Faivre J, Bonithon-Kopp C. Long-term risk of colorectal cancer after adenoma removal: a population-based cohort study. Gut 2012;61:1180-6.