Socio-demographic variation in stage at diagnosis of breast, bladder, colon, endometrial, lung, melanoma, prostate, rectal, renal and ovarian cancer in England and its population impact.

BACKGROUND: Stage at diagnosis strongly predicts cancer survival and understanding related inequalities could guide interventions. METHODS: We analysed incident cases diagnosed with 10 solid tumours included in the UK government target of 75% of patients diagnosed in TNM stage I/II by 2028. We examined socio-demographic differences in diagnosis at stage III/IV vs. I/II. Multiple imputation was used for missing stage at diagnosis (9% of tumours). RESULTS: Of the 202,001 cases, 57% were diagnosed in stage I/II (an absolute 18% 'gap' from the 75% target). The likelihood of diagnosis at stage III/IV increased in older age, though variably by cancer site, being strongest for prostate and endometrial cancer. Increasing level of deprivation was associated with advanced stage at diagnosis for all sites except lung and renal cancer. There were, inconsistent in direction, sex inequalities for four cancers. Eliminating socio-demographic inequalities would translate to 61% of patients with the 10 studied cancers being diagnosed at stage I/II, reducing the gap from target to 14%. CONCLUSIONS: Potential elimination of socio-demographic inequalities in stage at diagnosis would make a substantial, though partial, contribution to achieving stage shift targets. Earlier diagnosis strategies should additionally focus on the whole population and not only the high-risk socio-demographic groups.

Stage-specific incidence trends of renal cancers in the East of England, 1999-2016.

OBJECTIVES: To determine stage-specific time-trends in renal cancer incidence. METHODS: We used population-based East Anglia data 1999-2016 (population ∼2 million) on 5,456 primary renal cancer diagnoses, estimating stage-specific annual incidence using Poisson regression, allowing for changing time-trends, and adjusting for sex, age, and socioeconomic deprivation. RESULTS: Renal cancer incidence increased from 9.8-16.4 cases per 100,000 during 1999-2016. Incidence of Stage I, II, and III cases increased over time, most steeply for Stage I, with annual Incidence Rate Ratio [IRR] for Stage I of 1.09 (95 % CI 1.07-1.12) during 1999-2010; and 1.03 (1.00-1.05) during 2011-2016. In contrast, the annual incidence of Stage IV renal cancer decreased during most years, IRR of 0.99 (0.98-1.00) during 2003-2016. CONCLUSION: The findings are consistent with both earlier detection of symptomatic renal cancer and increasing identification of asymptomatic lesions. However, the decreasing incidence of late-stage disease suggests genuine shifts towards earlier diagnosis.

Stage-specific incidence trends of melanoma in an English region, 1996-2015: longitudinal analyses of population-based data.

The aim of this study was to examine temporal trends in overall and stage-specific incidence of melanoma. Using population-based data on patients diagnosed with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized time trends in annual incidence rates for each stage at diagnosis. Negative binomial regression was used to model trends over time adjusted for sex, age group and deprivation, and to subsequently examine variation in stage-specific trends by sex and age group. The age-standardized incidence increased from 14 to 29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was apparent across all stages but was steepest for stage I [adjusted annual increase: 5%, 95% confidence interval (CI): 5-6%, and more gradual for stage II-IV disease (stage II: 3%, 95% CI: 2-4%; stage III/IV: 2%, 95% CI: 1-3%)]. Stage II-IV increase was apparent in men across age groups and in women aged 50 years or older. Increases in incidence were steeper in those aged 70 years or older, and in men. The findings suggest that both a genuine increase in the incidence of consequential illness and a degree of overdiagnosis may be responsible for the observed increasing incidence trends in melanoma in our population during the study period. They also suggest the potentially lower effectiveness of public health awareness campaigns in men and older people.

The influence of patient case mix on public health area statistics for cancer stage at diagnosis: a cross-sectional study.

BACKGROUND: statistics comparing the stage at diagnosis of geographically defined populations of cancer patients are increasingly used in public reporting to monitor geographical inequalities but may be confounded by patient case mix. We explore the impact of case-mix adjustment on a publicly reported measure of early stage at diagnosis in England. METHODS: We analyzed data used for publicly reported statistics about the stage of patients diagnosed with 1 of 11 solid tumours in 2015 in England, including information on cancer site (bladder, breast, colon, rectum, kidney, lung, melanoma, non-Hodgkin lymphoma, ovarian, prostate, endometrial), age, gender, income deprivation and population-based commissioning organization. We investigated how cancer site and other patient characteristics influence organizational comparisons and attainment of early-stage targets (≥60% of all cases diagnosed in TNM stages I-II). RESULTS: Adjusting for patient case mix reduced between-organization variance by more than 50%, resulting in appreciable discordance in organizational ranks (Kendall's tau = 0.53), with 18% (37/207) of organizations being reclassified as meeting/failing the early-stage target due to case mix. CONCLUSION: Summary statistics on stage of cancer diagnosis for geographical populations currently used as public health surveillance tools to monitor organizational inequalities need to account for patient sociodemographic characteristics and cancer site case mix.

Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model.

BACKGROUND: Prognostic stratification is the cornerstone of management in nonmetastatic prostate cancer (PCa). However, existing prognostic models are inadequate-often using treatment outcomes rather than survival, stratifying by broad heterogeneous groups and using heavily treated cohorts. To address this unmet need, we developed an individualised prognostic model that contextualises PCa-specific mortality (PCSM) against other cause mortality, and estimates the impact of treatment on survival. METHODS AND FINDINGS: Using records from the United Kingdom National Cancer Registration and Analysis Service (NCRAS), data were collated for 10,089 men diagnosed with nonmetastatic PCa between 2000 and 2010 in Eastern England. Median follow-up was 9.8 years with 3,829 deaths (1,202 PCa specific). Totals of 19.8%, 14.1%, 34.6%, and 31.5% of men underwent conservative management, prostatectomy, radiotherapy (RT), and androgen deprivation monotherapy, respectively. A total of 2,546 men diagnosed in Singapore over a similar time period represented an external validation cohort. Data were randomly split 70:30 into model development and validation cohorts. Fifteen-year PCSM and non-PCa mortality (NPCM) were explored using separate multivariable Cox models within a competing risks framework. Fractional polynomials (FPs) were utilised to fit continuous variables and baseline hazards. Model accuracy was assessed by discrimination and calibration using the Harrell C-index and chi-squared goodness of fit, respectively, within both validation cohorts. A multivariable model estimating individualised 10- and 15-year survival outcomes was constructed combining age, prostate-specific antigen (PSA), histological grade, biopsy core involvement, stage, and primary treatment, which were each independent prognostic factors for PCSM, and age and comorbidity, which were prognostic for NPCM. The model demonstrated good discrimination, with a C-index of 0.84 (95% CI: 0.82-0.86) and 0.84 (95% CI: 0.80-0.87) for 15-year PCSM in the UK and Singapore validation cohorts, respectively, comparing favourably to international risk-stratification criteria. Discrimination was maintained for overall mortality, with C-index 0.77 (95% CI: 0.75-0.78) and 0.76 (95% CI: 0.73-0.78). The model was well calibrated with no significant difference between predicted and observed PCa-specific (p = 0.19) or overall deaths (p = 0.43) in the UK cohort. Key study limitations were a relatively small external validation cohort, an inability to account for delayed changes to treatment beyond 12 months, and an absence of tumour-stage subclassifications. CONCLUSIONS: 'PREDICT Prostate' is an individualised multivariable PCa prognostic model built from baseline diagnostic information and the first to our knowledge that models potential treatment benefits on overall survival. Prognostic power is high despite using only routinely collected clinicopathological information.

Missing data and chance variation in public reporting of cancer stage at diagnosis: Cross-sectional analysis of population-based data in England.

BACKGROUND: The percentage of cancer patients diagnosed at an early stage is reported publicly for geographically-defined populations corresponding to healthcare commissioning organisations in England, and linked to pay-for-performance targets. Given that stage is incompletely recorded, we investigated the extent to which this indicator reflects underlying organisational differences rather than differences in stage completeness and chance variation. METHODS: We used population-based data on patients diagnosed with one of ten cancer sites in 2013 (bladder, breast, colorectal, endometrial, lung, ovarian, prostate, renal, NHL, and melanoma). We assessed the degree of bias in CCG (Clinical Commissioning Group) indicators introduced by missing-is-late and complete-case specifications compared with an imputed 'gold standard'. We estimated the Spearman-Brown (organisation-level) reliability of the complete-case specification. We assessed probable misclassification rates against current pay-for-performance targets. RESULTS: Under the missing-is-late approach, bias in estimated CCG percentage of tumours diagnosed at an early stage ranged from -2 to -30 percentage points, while bias under the complete-case approach ranged from -2 to +7 percentage points. Using an annual reporting period, indicators based on the least biased complete-case approach would have poor reliability, misclassifying 27/209 (13%) CCGs against a pay-for-performance target in current use; only half (53%) of CCGs apparently exceeding the target would be correctly classified in terms of their underlying performance. CONCLUSIONS: Current public reporting schemes for cancer stage at diagnosis in England should use a complete-case specification (i.e. the number of staged cases forming the denominator) and be based on three-year reporting periods. Early stage indicators for the studied geographies should not be used in pay-for-performance schemes.

Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study.

INTRODUCTION: Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. METHODS AND FINDINGS: Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator. Using this approach, a new five-stratum risk stratification system was produced, and its prognostic power was compared against the current system, with PCSM as the outcome. The results were analysed using a Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks regression, and concordance indices. In the training set, the new risk stratification system identified distinct subgroups with different risks of PCSM in pair-wise comparison (p < 0.0001). Specifically, the new classification identified a very low-risk group (Group 1), a subgroup of intermediate-risk cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96-2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk (Group 3, HR 3.35 [95% CI 2.04-5.49]) (p < 0.0001). High-risk cancers were also sub-classified by the new system into subgroups with lower and higher PCSM risk: Group 4 (HR 5.03 [95% CI 3.25-7.80]) and Group 5 (HR 17.28 [95% CI 11.2-26.67]) (p < 0.0001), respectively. These results were recapitulated in the testing set and remained robust after inclusion of competing risks. In comparison to the current risk stratification system, the new system demonstrated improved prognostic performance, with a concordance index of 0.75 (95% CI 0.72-0.77) versus 0.69 (95% CI 0.66-0.71) (p < 0.0001). In an external cohort, the new system achieved a concordance index of 0.79 (95% CI 0.75-0.84) for predicting PCSM versus 0.66 (95% CI 0.63-0.69) (p < 0.0001) for the current NICE risk stratification system. The main limitations of the study were that it was registry based and that follow-up was relatively short. CONCLUSIONS: A novel and simple five-stratum risk stratification system outperforms the standard three-stratum risk stratification system in predicting the risk of PCSM at diagnosis in men with primary non-metastatic prostate cancer, even when accounting for competing risks. This model also allows delineation of new clinically relevant subgroups of men who might potentially receive more appropriate therapy for their disease. Future research will seek to validate our results in external datasets and will explore the value of including additional variables in the system in order in improve prognostic performance.

Trends and outcome from radical therapy for primary non-metastatic prostate cancer in a UK population.

BACKGROUND: Increasing proportions of men diagnosed with prostate cancer in the UK are presenting with non-metastatic disease. We investigated how treatment trends in this demographic have changed. PATIENT AND METHODS: Non-metastatic cancers diagnosed from 2000-2010 in the UK Anglian Cancer network stratified by age and risk group were analysed [n = 10,365]. Radiotherapy [RT] and prostatectomy [RP] cancer specific survival [CSS] were further compared [n = 4755]. RESULTS: Over the decade we observed a fall in uptake of primary androgen deprivation therapy but a rise in conservative management [CM] and radical therapy [p<0.0001]. CM in particular has become the primary management for low-risk disease by the decade end [p<0.0001]. In high-risk disease however both RP and RT uptake increased significantly but in an age dependent manner [p<0.0001]. Principally, increased RP in younger men and increased RT in men ≥ 70y. In multivariate analysis of radically treated men both high-risk disease [HR 8.0 [2.9-22.2], p<0.0001] and use of RT [HR 1.9 [1.0-3.3], p = 0.024] were significant predictors of a poorer CSM. In age-stratified analysis however, the trend to benefit of RP over RT was seen only in younger men [≤ 60 years] with high-risk disease [p = 0.07]. The numbers needed to treat by RP instead of RT to save one cancer death was 19 for this group but 67 for the overall cohort. CONCLUSION: This study has identified significant shifts in non-metastatic prostate cancer management over the last decade. Low-risk disease is now primarily managed by CM while high-risk disease is increasingly treated radically. Treatment of high-risk younger men by RP is supported by evidence of better CSM but this benefit is not evident in older men.

Incidence of glioma in a northwestern region of England, 2006-2010.

BACKGROUND: Gliomas are important because they affect disproportionately high numbers of people of working age and have a poor prognosis. Neurosurgeons were concerned about a possible recent cluster of glioma cases in a northwestern region in England. METHODS: All patients aged 18-89 years in Lancashire and South Cumbria with a histologically confirmed glioma diagnosed at the Royal Preston Hospital between January 1, 2006, and December 31, 2010, were ascertained. Clinical information was extracted from hospital records. Completeness of case referral to Royal Preston Hospital was checked against the National Cancer Registry and National Brain Tumour Registry records for the same period. For a comprehensive assessment of regional incidence, age-standardized incidence rates of all gliomas diagnosed in adults (aged 15 years and older) in the study area were then compared with those for the North West region and England as a whole. Rates for the North West region in defined small area-units ("Middle Super Output Areas") were also investigated to assess any small-area variation in the region during the decade to 2010. RESULTS: There were 435 glioma patients from Lancashire and South Cumbria diagnosed at the Royal Preston Hospital between 2006 and 2010, with case ascertainment verified to be complete by the National Cancer Registration Service. The age-standardized incidence rate of gliomas in the study area was 7.10 per 100,000 in 2006-2010, which was minimally different from the rate for all cancer networks in England over the 10 years from 2001. Small-area analysis confirmed lack of major variation in glioma rates in the North West region of England. CONCLUSION: Glioma incidence rates in England have remained stable by region and over time during the last decade.

Serum albumin and survival in glioblastoma multiforme.

Serum albumin is an established predictor of survival in numerous cancers but its prognostic value in central nervous system tumours has not been established. Here we have examined prognostic factors in 685 patients with histologically proven glioblastoma multiforme (GBM), the majority of which (n = 549) had pre-operative serum albumin assayed. Mean serum albumin was 34.7 g/l (SD 5.2). Post-operative survival was significantly less for patients with hypoalbuminaemia (<30 g/l, n = 82) than for patients with normal albumin level (median 2.3 vs. 5.6 months, P < 0.001 Log-rank test). Furthermore, patients with lower normal albumin (30-40 g/l, n = 371) had significantly shorter survival compared against patients with albumin in the upper normal range (40-50 g/l, n = 96; median 5.1 vs. 8.8 months, P < 0.001). Multivariate Cox regression showed the independent predictors of survival were age, debulking surgery, chemoradiotherapy, and serum albumin (Hazard Ratio 0.97 per g/l, P < 0.005). This study suggests pre-operative serum albumin level is a significant predictor of survival in patients with GBM. Further studies are needed to examine the relationship between albumin and other known prognostic factors, and to determine if pre-operative serum albumin is a clinically useful predictor of survival.

Population-based trends in use of surgery for non-small cell lung cancer in a UK region, 1995-2006.

OBJECTIVE: To assess time trends in use of surgery in patients with non-small cell lung cancer (NSCLC) in a UK region. METHODS: Cancer registration data for patients diagnosed with NSCLC between 1995 and 2006 in the East of England were analysed. Rates of surgery use for different age, gender, diagnosis period, tumour subtype and deprivation quintile groups were examined. RESULTS: The analysis included 18,767 patients with NSCLC. During the study period, 13% of patients were treated by surgery. Use of surgery decreased over time from 15% in 1995-1997 to 11% in 2004-2006 (p=0.022). Initial socioeconomic differences in surgery use narrowed significantly over time (p=0.028) and became non-apparent at the end of the study period. CONCLUSIONS: Use of surgery in patients with NSCLC decreased during the study period, possibly reflecting increasing quality of preoperative staging processes. Initial socioeconomic inequalities in surgery use became undetectable at the end of the study period. The findings provide baseline information to support comparisons with patterns of clinical management in more recent years.

Trends in the use of radiotherapy and radical surgery for patients with bladder urothelial cell carcinoma in East Anglia, 1995-2006.

OBJECTIVE: • To examine the use of radiotherapy and radical surgery for bladder urothelial cell carcinoma (UCC) before, during and after national initiatives for reorganization of uro-oncology services. PATIENTS AND METHODS: • Population-based data (1995-2006) from a cancer registry with stable coding practices were analysed. • Bladder UCC was defined using relevant International Classification of Disease site and morphology codes. • Time trends in the use of radiotherapy and radical surgery, and other predictors of their use were examined. RESULTS: • Of 4639 bladder UCC patients aged ≥40 years (76% men), stage information was available for 4303 (93%). • Morphology and stage case mix remained stable during the study period. • Radiotherapy use decreased significantly (from 31% in 1995-1998 to 22% in 2003-2006, P < 0.001) among patients of any stage, whilst radical surgery use increased significantly (from 8 to 13%, P < 0.001), particularly among stage II-IV patients. • The proportion of patients treated by both radiotherapy and surgery also decreased notably (from 4.0 to 1.1%). • Women were significantly more likely to present in stages II-IV [odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.06-1.40, P = 0.005], and less likely to be treated with radiotherapy (OR = 0.84, 95% CI: 0.72-0.99, P = 0.036). CONCLUSIONS: • Use of radical surgery in UCC invading bladder muscle increased and use of radiotherapy decreased during the study period, most probably reflecting the increasing availability of specialist surgical management. Sociodemographic variation in treatment was limited to lower use of radiotherapy in women. • Further research should encompass treatment timeliness and other aspects of care quality, as well as exploring potential differences in endoscopic treatments for disease not invading bladder muscle.

Age-period-cohort analysis of colorectal cancer in East Anglia, 1971-2005.

BACKGROUND: This study aimed to investigate the incidence trends of colorectal cancer by sex and subsite, in East Anglia from 1971 to 2005. METHODS: Using data from the Eastern Cancer Registration and Information Centre, we examined the time trends and the effect of age, period of diagnosis and birth cohort on the incidence of colorectal cancer by sex and subsite. RESULTS: Between 1971 and 2005, 23875 males and 22651 females were registered with colorectal cancer in East Anglia. During this period, the increase in the incidence trends was higher among males, more recent periods of diagnosis, and proximal colon. Cohort effects were statistically significant in distal and rectal cancers in males (p<0.001 and p=0.05, respectively), and in proximal colon in females (p<0.001). Period effects were statistically significant across all subsites and both sexes (p<0.001 for all). CONCLUSIONS: Period effects were significant across all subsites for both sexes, whereas cohort effects varied in their significance levels depending on subsite and sex. We suggest that the period effect may be due to an increase in the use of colonoscopy for diagnostic or opportunistic screening, and the cohort effect may be due to aetiological differences in CRC between sexes and subsites.

Population based time trends and socioeconomic variation in use of radiotherapy and radical surgery for prostate cancer in a UK region: continuous survey.

OBJECTIVE: To examine variation in the management of prostate cancer in patients with different socioeconomic status. DESIGN: Survey using UK regional cancer registry data. SETTING: Regional population based cancer registry. PARTICIPANTS: 35 171 patients aged >or=51 with a diagnosis of prostate cancer, 1995-2006. MAIN OUTCOME MEASURES: Use of radiotherapy and radical surgery. Socioeconomic status according to fifths of small area deprivation index. RESULTS: Over the nine years of the study, information on stage at diagnosis was available for 15 916 of 27 970 patients (57%). During the study period, the proportion of patients treated with radiotherapy remained at about 25%, while use of radical surgery increased significantly (from 2.9% (212/7201) during 1995-7 to 8.4% (854/10 211) during 2004-6, P<0.001). Both treatments were more commonly used in least deprived compared with most deprived patients (28.5% v 21.0% for radiotherapy and 8.4% v 4.0% for surgery). In multivariable analysis, increasing deprivation remained strongly associated with lower odds of radiotherapy or surgery (odds ratio 0.92 (95% confidence interval 0.90 to 0.94), P<0.001, and 0.91 (0.87 to 0.94), P<0.001, respectively, per incremental deprivation group). There were consistently concordant findings with multilevel models for clustering of observations by hospital of diagnosis, with restriction of the analysis to patients with information on stage, and with sequential restriction of the analysis to different age, stage, diagnosis period, and morphology groups. CONCLUSIONS: After a diagnosis of prostate cancer, men from lower socioeconomic groups were substantially less likely to be treated with radical surgery or radiotherapy. The causes and impact on survival of such differences remain uncertain.

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

INTRODUCTION: The 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. METHODS: Using 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. RESULTS: Differences 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). CONCLUSIONS: We 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.

Trends and variation in the management of oesophagogastric cancer patients: a population-based survey.

BACKGROUND: Previous evidence indicates potential variation in the quality of care of cancer patients. We aimed to examine whether recent changes in the treatment of oesophagogastric cancers have been distributed equally among different patient subgroups. METHODS: We analysed population-based cancer registry data about the treatment patterning of oesophagogastric cancer (other than oesophageal squamous cell carcinoma) during 1995-2006. RESULTS: There were 14,077 patients aged > or =40 years (69% men). There was only limited information on stage, and no information on co-morbidity status. During successive triennia, curative surgery use decreased from 28% to 20% (p < 0.001) whilst chemotherapy use increased from 9% to 30% (p < 0.001). Use of palliative surgery and of radiotherapy increased significantly but modestly (7% to 10%, and 9% to 11%, respectively). In multivariable logistic regression adjusting for age group, gender, diagnosis period and tumour type, curative surgery and chemotherapy were used less frequently in more deprived patients [per increasing deprivation group Odds Ratio (OR) = 0.96, 95% Confidence Interval (CI) 0.93-0.99, and OR = 0.90, 95%CI 0.87-0.93, respectively, p < 0.001 for both)]. Chemotherapy was also used less frequently in women (OR = 0.76, p < 0.001). CONCLUSIONS: During the study period, curative surgery decreased by a third and chemotherapy use increased by more than three-fold, reflecting improvements in the appropriateness and quality of management, but chemotherapy use, in particular, was unequal, both by socioeconomic status and gender.

Population-based prostate-specific antigen testing in the UK leads to a stage migration of prostate cancer.

OBJECTIVE: To determine, within the UK, the stage and grade of prostate cancers that would be found through population-based prostate specific antigen (PSA) testing and biopsy. SUBJECTS AND METHODS: In the 'Prostate Testing for Cancer and Treatment' trial (ProtecT), men aged 50-69 years were recruited from nine cities in the UK and from randomly selected practices of general practitioners. Those with a PSA level of >3 ng/mL were offered a prostate biopsy. Age, PSA, stage and grade at diagnosis of ProtecT participants with cancer were compared with contemporaneous incident cases aged 50-69 years (age-restricted Cancer Registry cases) registered with the Eastern Cancer Registration and Information Centre (ECRIC). RESULTS: Within ProtecT, 94,427 men agreed to be tested (50% of men contacted), 8807 ( approximately 9%) had a raised PSA level and 2022 (23%) had prostate cancer; 229 ( approximately 12%) had locally advanced (T3 or T4) or metastatic cancers, the rest having clinically localized (T1c or T2) disease. Within ECRIC, 12,661 cancers were recorded over the same period; 3714 were men aged 50-69 years at diagnosis. Men in ProtecT had a lower age distribution and PSA level, and the cancers were of lower stage and grade (P < 0.001 for all comparisons). If population-based PSA testing were introduced in the UK, approximately 2660 men per 100,000 aged 50-69 years would be found to have prostate cancer, compared to current rates of approximately 130 per 100,000. If half of men accepted PSA testing, approximately 160,000 cancers would be found, compared to 30,000 diagnosed each year at present. CONCLUSIONS: Population-based PSA testing resulted in a significant downward stage and grade migration, and most such cancers were of low stage and grade, which could lead to risks of over-treatment for some men.