Eva Morris

Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995–2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data

Summary Background Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. Methods Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995–2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985–2005. Findings Relative survival improved during 1995–2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2–6% at 1 year and by 2–3% at 5 years. Interpretation Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. Funding Department of Health, England; and Cancer Research UK.

Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study

BACKGROUND High-quality rectal cancer surgery is known to improve patient outcome. We aimed to assess the quality of colon cancer surgery by studying the extent of variation in the plane of surgical resection, the amount of tissue removed, and its association with survival. METHODS All resections for primary colon adenocarcinoma done at Leeds General Infirmary (Leeds, UK) between Jan 1, 1997, and June 30, 2002, were identified. The specimens were photographed and graded according to the plane of mesocolic dissection. Tissue morphometry was done on 253 tumours. Univariate and multivariate models were used to ascertain whether there was an association with 5-year survival. The primary outcome measure was overall survival defined as death from any cause. FINDINGS 521 cancers were identified, 122 were excluded because of either no photographic images or insufficient images to allow retrospective grading, leaving 399 specimens for analysis. There was marked variation in the proportion of each plane of surgery: muscularis propria in 95 of 399 (24%) specimens, intramesocolic in 177 of 399 (44%) specimens, and mesocolic in 127 of 399 (32%) specimens. Mean cross-sectional tissue area outside the muscularis propria was significantly higher with mesocolic plane surgery (mean 2181 [SD 895] mm(2)) compared with intramesocolic (mean 2109 [1273] mm(2)) and muscularis propria plane (mean 1447 [913] mm(2)) surgery (p=0.0003). There was also a significant increase in the distance from the muscularis propria to the mesocolic resection margin with mesocolic plane surgery (mean 44 [21] mm) compared with intramesocolic (mean 30 [16] mm) and muscularis propria plane (mean 21 [12] mm) surgery, which was independent of tumour site (all excisions p<0.0001). We noted a 15% (95% CI) overall survival advantage at 5 years with mesocolic plane surgery compared with surgery in the muscularis propria plane (HR 0.57 [0.38-0.85], p=0.006) in univariate analysis. However, this association was no longer significant in the multivariate model (HR 0.86 [95% CI 0.56-1.31], p=0.472), but was especially noted in patients with stage III cancers (HR 0.45 [95% CI 0.24-0.85], p=0.014; multivariate analysis). The plane of surgery and amount of mesocolon removed varied between the different sites with better planes in left-sided resections than right-sided ones, which were better than transverse resection (p<0.0001). INTERPRETATION As previously shown in the rectum, we have now shown there is marked variability in the plane of surgery achieved in colon cancer. Improving the plane of dissection might improve survival, especially in patients with stage III disease. If confirmed by clinical trial data, such as from the ongoing National Cancer Research Institute Fluoropyrimidine, Oxaliplatin and Targeted Receptor pre-Operative Therapy for colon cancer (FOxTROT) trial of neoadjuvant chemotherapy in advanced resectable colon cancer, improvement of the plane of dissection might be a new cost-effective method of decreasing morbidity and mortality in patients with colon cancer.

Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?

Objective: To determine the variation in the rates of use of abdominoperineal excision (APE) by cancer network, hospital trust and surgeon across England between 1998 and 2004 and determine if any variation could be explained by differences in patient characteristics such as stage of disease, age, gender or socioeconomic deprivation. Design: Retrospective study of a population-based dataset comprised of cancer registry and hospital episode statistics data. Setting: All NHS providers of rectal cancer surgery within England. Patients: 31 223 patients diagnosed with rectal cancer and receiving a major abdominal procedure within the NHS in England between 1998 and 2004. Main outcome measure: Rates and odds of use of APE were determined in relation to patient case-mix and each patient’s managing surgeon, trust and cancer network. Results: The rate of use of APE decreased from 30.5% in 1998 to 23.0% in 2004. Males, the economically deprived and those managed by surgeons operating on fewer than seven rectal cancer cases per year were all significantly more likely to receive an APE. There were also significant variations in the odds of receiving an APE over time and between individual surgeons and hospital trusts independently of patient case-mix. Conclusions: Over the study period the use of APE decreased but statistically significant variation was observed in its application independently of case mix. Reducing this variation will remove inequalities, reduce colostomy rates, and improve outcomes in rectal cancer. Rates of APE use could be a national performance measure.

Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction.

Background A variety of stent designs has been studied for endoscopic stenting of the bile duct in patients with malignant biliary obstruction. Although metal stents are associated with longer patency, their costs are significantly higher than plastic stents. Aims To compare clinical outcome and cost-effectiveness of endoscopic metal and plastic stents for malignant biliary obstruction by a systematic review and meta-analysis of all randomized controlled trials in this area. Methods We conducted searches to identify all randomized controlled trials in any language from 1966 to 2006 using electronic databases and hand-searching of conference abstracts. Meta-analysis was performed with RevMan software [Review Manager (RevMan) version 4.2 for Windows. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2003]. Results Seven randomized controlled trials were identified that met the inclusion criteria, and 724 participants were randomized to either metal or plastic endoscopic stents. No significant difference between the two stent types in terms of technical success, therapeutic success, 30-day mortality or complications was observed. Metal stents were associated with a significantly less relative risk (RR) of stent occlusion at 4 months than plastic stents [RR, 0.44; 95% confidence interval (CI) 0.3, 0.63; P<0.01]. The overall risk of recurrent biliary obstruction was also significantly lower in patients treated with metal stents (RR, 0.52; 95% confidence interval 0.39, 0.69; P<0.01). The median incremental cost-effectiveness ratio of metal stents was

Identifying stage III colorectal cancer patients : The influence of the patient, surgeon, and pathologist

1820 per endoscopic retrograde cholangiopancreatography prevented. Conclusion Endoscopic metal stents for malignant biliary obstruction are associated with significantly higher patency rates than plastic stents as early as 4 months after insertion. Metal stents will be cost-effective if the unit cost of additional endoscopic retrograde cholangiopancreatographies per patient exceeds

Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology

1820.

Stage at diagnosis and colorectal cancer survival in six high-income countries: A population-based study of patients diagnosed during 2000–2007

PURPOSE Nodal yields from resected colorectal cancers vary greatly. This study sought to determine what patient, tumor, and management factors influence the number of nodes retrieved and to determine if the extent of lymphadenectomy affects stage allocation and influences survival. PATIENTS AND METHODS Retrospective study of the nodal yields of 7,062 surgically resected colorectal cancer patients for whom colorectal pathology minimum data sets had been collected. The percentage of patients diagnosed as stage III was compared across nodal yield categories. A threshold for an adequate lymphadenectomy was defined as retrieval of 12 nodes. Binary logistic regression was used to determine factors associated with obtaining an adequate lymphadenectomy. RESULTS Median nodal yields increased over the study period from 7 (interquartile range [IQR], 4 to 11) in 1995 to 13 (IQR 8 to 19) in 2003. There was no difference in yield by cancer site or sex, but yields were lower in older patients. Yields increased with increasing local invasion and stage of tumor. The percentage of patients diagnosed as stage III increased as yields increased. Five-year survival was lower in those patients who did not have an adequate lymphadenectomy. Adequate lymphadenectomy was significantly more likely in patients with advanced tumors and when the surgery and pathology was undertaken by a specialist. Older patients were significantly less likely to receive an adequate lymphadenectomy. CONCLUSION Variations in nodal yield are due to idiosyncratic patient and tumor characteristics and differences in the quality of surgery and pathology undertaken. Adequate lymphadenectomy is essential to ensure correct stage allocation and optimal survival.

The impact of the Calman–Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients

Objective: To identify by routine pathology which Dukes B colorectal cancer patients may benefit from chemotherapy. Method: Retrospective study of the five year survival of colorectal cancer patients for whom colorectal pathology minimum datasets had been collected between 1997 and 2000 in the Yorkshire region of the UK. The study population consisted of 1625 Dukes B and 480 Dukes C patients who possessed one positive node treated between 1997 and 2000. The predictive ability of the Petersen prognostic model was investigated and survival of Dukes B patients with potentially high risk pathological features was compared to that of Dukes C patients with one positive node. Results: Only 23.3% of patients had all the pathological variables required for the application of Petersen’s index reported. The index offered a statistically significant survival difference of 24.3% and 30.3% between high and low risk colon (p<0.01) and rectal cancer patients (p<0.01). The size of these effects was smaller than predicted by the original model. Survival of Dukes B patients with any of the high risk pathological factors or low nodal yields was lower than that of Dukes C patients who possessed one positive node. Conclusion: Petersen’s index discriminated between high and low risk Dukes B colorectal tumours, but inadequate pathological reporting diminished its ability to identify all high risk patients. The survival of patients with any high risk feature was lower than the threshold for adjuvant therapy of one lymph node positive Dukes C colorectal cancer. Chemotherapy may benefit patients with such features. Improving the quality of pathological reporting is vital if high risk patients are to be reliably identified.

Patient-reported outcomes of cancer survivors in England 1-5 years after diagnosis: a cross-sectional survey.

Abstract Background. Large international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences. Methods. Data from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000–2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale. Results. International differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of ‘regional’ disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82–84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years. Conclusion. Differences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK.

A retrospective observational study examining the characteristics and outcomes of tumours diagnosed within and without of the English NHS Bowel Cancer Screening Programme.

The 1995 Calman–Hine plan outlined radical reform of the UKs cancer services with the aim of improving outcomes and reducing inequalities in NHS cancer care. Its main recommendation was to concentrate care into the hands of site-specialist, multi-disciplinary teams. This study aimed to determine if the implementation of Calman–Hine cancer teams was associated with improved processes and outcomes of care for colorectal cancer patients. The design included longitudinal survey of 13 colorectal cancer teams in Yorkshire and retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service. The population was all colorectal cancer patients diagnosed and treated in Yorkshire between 1995 and 2000. The main outcome measures were: variations in the use of anterior resection and preoperative radiotherapy in rectal cancer, chemotherapy in Dukes stage C and D patients, and five-year survival. Using multilevel models, these outcomes were assessed in relation to measures of the extent of Calman–Hine implementation throughout the study period, namely: (i) each teams degree of adherence to the Manual of Cancer Service Standards (which outlines the specification of the ‘ideal’ colorectal cancer team) and (ii) the extent of site specialisation of each teams surgeons. Variation was observed in the extent to which the colorectal cancer teams in Yorkshire had conformed to the Calman–Hine recommendations. An increase in surgical site specialisation was associated with increased use of preoperative radiotherapy (OR=1.43, 95% CI=1.04–1.98, P<0.04) and anterior resection (OR=1.43, 95% CI=1.16–1.76, P<0.01) in rectal cancer patients. Increases in adherence to the Manual of Cancer Service Standards was associated with improved five-year survival after adjustment for the casemix factors of age, stage of disease, socioeconomic status and year of diagnosis, especially for colon cancer (HR=0.97, 95% CI=0.94–0.99 P<0.01). There was a similar trend of improved survival in relation to increased surgical site specialisation for rectal cancer, although the effect was not statistically significant (HR=0.93, 95% CI=0.84–1.03, P=0.15). In conclusion, the extent of implementation of the Calman–Hine report has been variable and its recommendations are associated with improvements in processes and outcomes of care for colorectal cancer patients.