G Lawrence

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.

Correcting for Lead Time and Length Bias in Estimating the Effect of Screen Detection on Cancer Survival

Determination of survival time among persons with screen-detected cancer is subject to lead time and length biases. The authors propose a simple correction for lead time, assuming an exponential distribution of the preclinical screen-detectable period. Assuming two latent categories of tumors, one of which is more prone to screen detection and correspondingly less prone to death from the cancer in question, the authors have developed a strategy of sensitivity analysis for various magnitudes of length bias. Here they demonstrate these methods using a series of 25,962 breast cancer cases (1988-2004) from the West Midlands, United Kingdom.

PREDICT: a new UK prognostic model that predicts survival following surgery for invasive breast cancer

IntroductionThe aim of this study was to develop and validate a prognostication model to predict overall and breast cancer specific survival for women treated for early breast cancer in the UK.MethodsUsing the Eastern Cancer Registration and Information Centre (ECRIC) dataset, information was collated for 5,694 women who had surgery for invasive breast cancer in East Anglia from 1999 to 2003. Breast cancer mortality models for oestrogen receptor (ER) positive and ER negative tumours were derived from these data using Cox proportional hazards, adjusting for prognostic factors and mode of cancer detection (symptomatic versus screen-detected). An external dataset of 5,468 patients from the West Midlands Cancer Intelligence Unit (WMCIU) was used for validation.ResultsDifferences in overall actual and predicted mortality were <1% at eight years for ECRIC (18.9% vs. 19.0%) and WMCIU (17.5% vs. 18.3%) with area under receiver-operator-characteristic curves (AUC) of 0.81 and 0.79 respectively. Differences in breast cancer specific actual and predicted mortality were <1% at eight years for ECRIC (12.9% vs. 13.5%) and <1.5% at eight years for WMCIU (12.2% vs. 13.6%) with AUC of 0.84 and 0.82 respectively. Model calibration was good for both ER positive and negative models although the ER positive model provided better discrimination (AUC 0.82) than ER negative (AUC 0.75).ConclusionsWe have developed a prognostication model for early breast cancer based on UK cancer registry data that predicts breast cancer survival following surgery for invasive breast cancer and includes mode of detection for the first time. The model is well calibrated, provides a high degree of discrimination and has been validated in a second UK patient cohort.

The Clinical Effectiveness and Cost-Effectiveness of Different Surveillance Mammography Regimens After the Treatment for Primary Breast Cancer: Systematic Reviews, Registry Database Analyses and Economic Evaluation

BACKGROUND Following primary breast cancer treatment, the early detection of ipsilateral breast tumour recurrence (IBTR) or ipsilateral secondary cancer in the treated breast and detection of new primary cancers in the contralateral breast is beneficial for survival. Surveillance mammography is used to detect these cancers, but the optimal frequency of surveillance and the length of follow-up are unclear. OBJECTIVES To identify feasible management strategies for surveillance and follow-up of women after treatment for primary breast cancer in a UK setting, and to determine the effectiveness and cost-effectiveness of differing regimens. METHODS A survey of UK breast surgeons and radiologists to identify current surveillance mammography regimens and inform feasible alternatives; two discrete systematic reviews of evidence published from 1990 to mid 2009 to determine (i) the clinical effectiveness and cost-effectiveness of differing surveillance mammography regimens for patient health outcomes and (ii) the test performance of surveillance mammography in the detection of IBTR and metachronous contralateral breast cancer (MCBC); statistical analysis of individual patient data (West Midlands Cancer Intelligence Unit Breast Cancer Registry and Edinburgh data sets); and economic modelling using the systematic reviews results, existing data sets, and focused searches for specific data analysis to determine the effectiveness and cost-utility of differing surveillance regimens. RESULTS The majority of survey respondents initiate surveillance mammography 12 months after breast-conserving surgery (BCS) (87%) or mastectomy (79%). Annual surveillance mammography was most commonly reported for women after BCS or after mastectomy (72% and 53%, respectively). Most (74%) discharge women from surveillance mammography, most frequently 10 years after surgery. The majority (82%) discharge from clinical follow-up, most frequently at 5 years. Combining initiation, frequency and duration of surveillance mammography resulted in 54 differing surveillance regimens for women after BCS and 56 for women following mastectomy. The eight studies included in the clinical effectiveness systematic review suggest surveillance mammography offers a survival benefit compared with a surveillance regimen that does not include surveillance mammography. Nine studies were included in the test performance systematic review. For routine IBTR detection, surveillance mammography sensitivity ranged from 64% to 67% and specificity ranged from 85% to 97%. For magnetic resonance imaging (MRI), sensitivity ranged from 86% to 100% and specificity was 93%. For non-routine IBTR detection, sensitivity and specificity for surveillance mammography ranged from 50% to 83% and from 57% to 75%, respectively, and for MRI from 93% to 100% and from 88% to 96%, respectively. For routine MCBC detection, one study reported sensitivity of 67% and specificity of 50% for both surveillance mammography and MRI, although this was a highly select population. Data set analysis showed that IBTR has an adverse effect on survival. Furthermore, women experiencing a second tumour measuring >20 mm in diameter were at a significantly greater risk of death than those with no recurrence or those whose tumour was <10 mm in diameter. In the base-case analysis, the strategy with the highest net benefit, and most likely to be considered cost-effective, was surveillance mammography alone, provided every 12 months at a societal willingness to pay for a quality-adjusted life-year of either £20,000 or £30,000. The incremental cost-effectiveness ratio for surveillance mammography alone every 12 months compared with no surveillance was £4727. LIMITATIONS Few studies met the review inclusion criteria and none of the studies was a randomised controlled trial. The limited and variable nature of the data available precluded any quantitative analysis. There was no useable evidence contained in the Breast Cancer Registry database to assess the effectiveness of surveillance mammography directly. The results of the economic model should be considered exploratory and interpreted with caution given the paucity of data available to inform the economic model. CONCLUSIONS Surveillance is likely to improve survival and patients should gain maximum benefit through optimal use of resources, with those women with a greater likelihood of developing IBTR or MCBC being offered more comprehensive and more frequent surveillance. Further evidence is required to make a robust and informed judgement on the effectiveness of surveillance mammography and follow-up. The utility of national data sets could be improved and there is a need for high-quality, direct head-to-head studies comparing the diagnostic accuracy of tests used in the surveillance population. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Explaining the difference in prognosis between screen-detected and symptomatic breast cancers

Background:We analysed 10-year survival data in 19 411 women aged 50–64 years diagnosed with invasive breast cancer in the West Midlands region of the United Kingdom. The aim was to estimate the survival advantage seen in cases that were screen detected compared with those diagnosed symptomatically and attribute this to shifts in prognostic variables or survival differences specific to prognostic categories.Methods:We studied tumour size, histological grade and the Nottingham Prognostic Index in very narrow categories and investigated the distribution of these prognostic factors within screen-detected and symptomatic tumours. We also adjusted for lead time bias.Results:The unadjusted 10-year breast cancer survival in screen-detected cases was 85.5% and in symptomatic cases 62.8%; after adjustment for lead time bias, survival in the screen-detected cases was 79.3%. Within narrow categories of prognostic variables, survival differences were small, indicating that the majority of the survival advantage of screen detection is due to differences in the distributions of size and node status.Conclusion:Our results suggested that a combination of lead time with size and node status in 10 categories explained almost all (97%) of the survival advantage. Only a small proportion remained to be explained by biological differences, manifested as length bias or overdiagnosis.

The effect of DCIS grade on rate, type and time to recurrence after 15 years of follow-up of screen-detected DCIS

Background:The incidence of ductal carcinoma in situ (DCIS) rose rapidly when the NHS Breast Screening Programme (NHSBSP) started in 1988. Some authorities consider that this represents both over-diagnosis and over-treatment. We report long-term follow-up of DCIS diagnosed in the first 10 years (April 1988 to March 1999) of the West Midlands NHSBSP.Methods:840 noninvasive breast cancers were recorded on the national breast screening computer system. Following exclusions, and thorough case note and pathology review, 700 DCIS cases were identified for follow-up.Results:After a median follow-up of 183 (range 133 to 259) months, 102 (14.6%) first local recurrences were identified, 49 (48%) were invasive. Median time to first noninvasive recurrence was 15 months, and 60 months for invasive recurrence. Median time to invasive recurrence was 76 months from initially high-grade DCIS, and 131 months from low/intermediate grade DCIS. For the seven women, presenting with metastasis as their first event, the median time was 82 (range 15 to 188) months. The cumulative proportion developing recurrence at 180 months was twice as high as at 60 months.Interpretation:Short-term follow-up of patients diagnosed with DCIS will miss significant numbers of events, especially invasive local recurrences.

Prognosis and pathology of screen-detected carcinomas: how different are they?

It has been observed that screen‐detected breast cancers have a better prognosis than symptomatic tumors, even after taking pathological tumor attributes into account. This has led to the hypothesis that screen‐detected tumors are substantially biologically different from symptomatic cancers.

Radiological and pathological size estimations of pure ductal carcinoma in situ of the breast, specimen handling and the influence on the success of breast conservation surgery: a review of 2564 cases from the Sloane Project

Background:The Sloane Project, an audit of UK screen-detected non-invasive carcinomas and atypical hyperplasias of the breast, has accrued over 5000 cases in 5 years; with paired radiological and pathological data for 2564 ductal carcinoma in situ (DCIS) cases at the point of this analysis. We have compared the radiological estimate of DCIS size with the pathological estimate of DCIS size. We have correlated these sizes with histological grade, specimen-handling methods, particularly the use of specimen slice radiographs, and the success or failure of breast-conserving surgery (BCS).Methods:The Sloane Project database was interrogated to extract information on all patients diagnosed with DCIS with complete radiological and pathological data on the size of DCIS, nuclear grade, specimen handling (with particular reference to specimen radiographs) and whether primary BCS was successful or whether the patient required further conservation surgery or a mastectomy.Results:Of 2564 patients in the study, 2013 (79%) had attempted BCS and 1430 (71%) had a successful single operation. Of the 583 BCS patients who required further surgery, 65% had successful conservation and 97% of them after a single further operation. In successful one-operation BCS patients, there was a close agreement between radiological and pathological DCIS size with radiology tending to marginally overestimate the disease extent. In multiple-operation BCS, radiology underestimated DCIS size in 59% of cases. The agreement between pathological and radiological size of DCIS was poor in mastectomies but was improved by specimen slice radiography, suggesting specimen-handling techniques as a cause.Conclusion:In 30% of patients undergoing BCS for DCIS, preoperative imaging underestimates the extent of disease resulting in a requirement for further surgery. This has implications for the further improvement of preoperative imaging and non-operative diagnosis of DCIS so that second operations are reduced to a minimum.

Radiotherapy following breast-conserving surgery for screen-detected ductal carcinoma in situ: indications and utilisation in the UK. Interim findings from the Sloane Project

Use of radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) varies according to country, precedent and prejudice. Results from a preliminary analysis of the data available within the UK Sloane Project can be appreciated in the context of the uncertainty concerning the selection of adjuvant RT following BCS for DCIS. There was a marked geographical variation in the use of RT within the United Kingdom. However, overall, patients with DCIS treated with BCS were significantly more likely to have RT planned (and given) if they had large (⩾15 mm), intermediate or high-grade tumours or if central comedo-type necrosis was present. Unexpectedly, margin width did not appear to have a significant effect on the decision-making process. However, the Van Nuys Prognostic Index did significantly affect the chances of getting planned RT in the univariate analysis, suggesting that clinicians may be starting to use this scoring system in routine practice to assist in decision making.

Evidence against the proposition that “UK cancer survival statistics are misleading”: simulation study with National Cancer Registry data

Objectives To simulate each of two hypothesised errors in the National Cancer Registry (recording of the date of recurrence of cancer, instead of the date of diagnosis, for registrations initiated from a death certificate; long term survivors who are never notified to the registry), to estimate their possible effect on relative survival, and to establish whether lower survival in the UK might be due to one or both of these errors. Design Simulation study. Setting National Cancer Registry of England and Wales. Population Patients diagnosed as having breast (women), lung, or colorectal cancer during 1995-2007 in England and Wales, with follow-up to 31 December 2007. Main outcome measure Mean absolute percentage change in one year and five year relative survival associated with each simulated error. Results To explain the differences in one year survival after breast cancer between England and Sweden, under the first hypothesis, date of diagnosis would have to have been incorrectly recorded by an average of more than a year for more than 70% of women known to be dead. Alternatively, under the second hypothesis, failure to register even 40% of long term survivors would explain less than half the difference in one year survival. Results were similar for lung and colorectal cancers. Conclusions Even implausibly extreme levels of the hypothesised errors in the cancer registry data could not explain the international differences in survival observed between the UK and other European countries.