A Fritz

A Shah

B Rachet

C Percy

CA Stiller

CL Percy

E Lynge

E Mitry

F Berrino

H Brenner

J Schillinger

JM Kaldor

JM Stellman

M P Coleman

MJ Quinn

MP Coleman

N Cooper

English

PubMed

Milligan, D W

HEFT Repository

Survival from adult leukaemia in England and Wales up to 2001.

Rachet, B

Mitry, E

Shah, A

Cooper, N

Coleman, MP

LSHTM Research Online

Shah, A; Rachet, B; Mitry, E; Cooper, N; Brown, CM; Coleman,MP (2008) Survival from bladder cancer in England and Wales up to2001. British journal of cancer, 99 Suppl 1. S86-9. ISSN 0007-0920Downloaded from: http://researchonline.lshtm.ac.uk/6973/Usage GuidelinesPlease refer to usage guidelines at http://researchonline.lshtm.ac.uk/policies.html or alterna-tively contact researchonline@lshtm.ac.uk.Available under license: Creative Commons Attribution Non-commercial No Derivativeshttp://creativecommons.org/licenses/by-nc-nd/2.5/Survival AnalysisSurvival from bladder cancer in England and Wales up to 2001A Shah1, B Rachet1, E Mitry2, N Cooper3, CM Brown4, MP Coleman*,11Cancer Research UK Cancer Survival Group, Non-Communicable Disease Epidemiology Unit, Department of Epidemiology and Population Health,London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK ; 2De´partement d’He´patogastroente´rologie et OncologieDigestive, Centre Hospitalo-Universitaire Ambroise-Pare´, 9 avenue Charles de Gaulle, F-92100 Boulogne, France; 3Social and Health Analysis andReporting Division, Off ice for National Statistics (Room FG/114) 1 Myddelton Street, London EC1R 1UW, UK; 4Medical Director, Eastern Cancer Registry,Addenbrooke’s Hospital, Box 193 Oncology, Hills Road, Cambridge CB2 2QQ, UKBritish Journal of Cancer (2008) 99, S86 – S89. doi:10.1038/sj.bjc.6604599 www.bjcancer.comPublished online 23 September 2008& 2008 Cancer Research UKApproximately 9200 cancers of the urinary bladder are registeredin England and Wales each year, of which 6500 in men (8% of allmalignancies) and 2700 in women (3%) (Office for NationalStatistics, 2003). Bladder cancer ranks as the fourth most commonin men and ninth in women, and it causes approximately 4300deaths (2800 in men) a year in England and Wales.Incidence increases with age, most steeply above the age of 60years. The two-fold or greater excess in men is world-wide (Ferlayet al, 2004), and the excess is three-fold above the age of 60 years.Bladder cancer is uncommon below the age of 50 years, except incountries where it is linked with chronic schistosomal infestationof the bladder. Both incidence and mortality show deprivationgradients, with higher rates in more deprived areas, but thedifferences are small (Quinn et al, 2001).Incidence rose steadily in both sexes during the 1970s and 1980s,reaching a peak of approximately 31 cases per 100 000 per year inmen and 9 per 100 000 in women by 1990. Incidence has fallen byapproximately 10% since then in both sexes. Annual death rates inmen have fallen by a third since the early 1990s (from 12 to 8 per100 000), but the death rate in women (3 per 100 000) has notchanged (Quinn et al, 2001).Most bladder cancers (90%) are urothelial (transitional cell)carcinomas, often arising on the surface of small papillary tumours.The remaining 10% comprise mainly squamous cell carcinomas andadenocarcinomas. European recommendations for coding bladdertumours changed in 1995 to exclude some urothelial papillarytumours of the bladder that would previously have been classified asinvasive (Pheby et al, 1995). Similar recommendations wereimplemented by UK cancer registries, but only for tumoursregistered from 2000 (UK Association of Cancer Registries, 2004).Tobacco smoking confers a two- to three-fold risk. Occupationalexposure to aromatic amines and polycyclic aromatic hydro-carbons in the chemical, rubber, transport and dye industries canalso cause bladder cancer. Chemotherapeutic drugs, such ascyclophosphamide, and therapeutic irradiation of the pelvic regionalso increase the risk (Silverman et al, 2006).Haematuria or pain often leads to the diagnosis. Approximately75% of tumours are superficial (confined to the bladder mucosa orsubmucosal layer without muscle invasion) and these can be treatedby transurethral resection. Tumours that have invaded muscle mayrequire open surgery and a combination of intravesical or systemicchemotherapy, immunotherapy and radiotherapy.Approximately 12% (21 000) of all the bladder tumoursregistered in England and Wales during the period 1986–1999were coded as in situ (behaviour code 2) or uncertain if benignor malignant (behaviour code 1). The proportion of tumours inthese categories has risen very sharply, from virtually zero during1986– 1990 (Coleman et al, 1999) to approximately 23% during the1990s (data not shown). Large regional variations were also seen.These tumours were considered ab initio as ineligible for inclusionin the survival analyses.Of the 160 614 eligible patients with a tumour explicitly coded asa malignant, invasive (behaviour code 3), primary cancer of thebladder, some 5% were excluded because their recorded durationof survival was zero (date of diagnosis same as date of death).Some of these patients will have been diagnosed on the day ofdeath, but in many cases the cancer registration was based solelyon the death certificate; hence, the date of diagnosis was unknown.It was not possible to distinguish these cases reliably in theavailable data; hence, all patients with ‘zero survival’ wereexcluded. The proportion of patients excluded for this reasonwas the same for all deprivation groups (data not shown). Onlypatients for whom the bladder cancer was the first primarymalignancy were retained in the analyses; 5% of patients known tohave had a previous primary cancer at some time since 1971 wereexcluded. Finally, 1.6% of patients were excluded because theirvital status was unknown on 5 November 2002, when the data wereextracted for analysis. In all, more than 141 500 patients wereincluded in the analyses (88% of those eligible).SURVIVAL TRENDSFor bladder cancer patients diagnosed during 1996–1999, relativesurvival at 1 year was 82 and 71% for men and women,respectively, and 67 and 56% at 5 years (Table 1, Figure 1).Survival barely changed at all between the late 1980s and the late1990s: deprivation-adjusted trends were very close to zero. Ten-year survival for patients diagnosed in the early 1990s was 60% formen and 54% for women.The most striking feature is the persistent 6– 10% survivaladvantage for men at 1, 5 and 10 years after diagnosis.*Correspondence: Professor MP Coleman;E-mail: michel.coleman@lshtm.ac.ukBritish Journal of Cancer (2008) 99, S86 – S89& 2008 Cancer Research UK All rights reserved 0007 – 0920/08 $32.00www.bjcancer.comExamination of patients’ survival experience during 2000–2001with hybrid analysis (Brenner and Rachet, 2004) does not suggestthat survival up to 10 years after diagnosis is likely to increase inthe near future (Table 1).DEPRIVATIONThe deprivation gap in survival at 1, 5 and 10 years between the mostaffluent and the most deprived groups ranged from 4 to 10%.This was remarkably consistent for both men and womendiagnosed from the late 1980s to the late 1990s. All the estimatesof the deprivation gap in survival were statistically significant atthe 1% level (Table 2, Figure 2).The deprivation gap in survival up to 10 years widened slightlyfor both sexes, but the rate of change every 5 years was not itselfstatistically significant.Hybrid analysis does not suggest any imminent change in thedeprivation gap in survival up to 10 years for men, although somereduction of the socioeconomic differences may occur for women(Table 2).COMMENTSurvival for bladder cancer patients diagnosed in England andWales during 1996–1999 seems to have been no higher than forpatients diagnosed during 1986–1990, a decade earlier. Sincesurvival up to 5 years did not increase by more than 2–3%between the early 1980s and the late 1980s either (Coleman et al,1999), it would seem that bladder cancer survival in England andWales as a whole has not increased much for almost 20 years.The large and significant deprivation gap in survival between themost affluent and deprived patients (4 to 10%) has not shrunkeither.The male survival advantage for bladder cancer (6–10%) islarger than for cancers of the upper urinary tract (2–4%). This hasbeen a consistent feature for both cancers since the 1970s(Coleman et al, 1999). It is all the more striking because amongthe other common cancers, only breast cancer shows a survivaladvantage for men.Changes in the spectrum of what is recorded – and treated – asan invasive malignant tumour can affect the interpretation of timetrends in population-based cancer incidence and survival. Trendsare more difficult to interpret for bladder cancer than for manyother cancers, because of difficulties in the pathological definitionof disease, variation between cancer registries in coding practice,and changes over time in both factors. Thus, the proportion ofbladder tumours coded as in situ or of uncertain behaviour inEngland and Wales jumped from virtually zero for 1986– 1990 toan average of 23% for 1996–1999. Similarly, the proportion ofin situ tumours rose from 1 to 7% in the United States during the1970s and has continued to rise since then (Silverman et al, 2006).Small biopsy fragments taken at cystoscopy may not enable thepathologist to determine unequivocally if the tumour is invasive orin situ, but the speed and magnitude of this shift must reflectchanges in the pathological classification and registry coding ofbladder tumours more than true change in the pathology ofdisease.Table 1 Trends in relative survival (%) by sex, time since diagnosis and calendar period of diagnosis: England and Wales, adults (15–99 years) diagnosedduring 1986–1999 and followed up to 2001Calendar period of diagnosisaAverage change (%) Predictionc for patients1986–1990 1991–1995 1996–1999 every 5 yearsb diagnosed during 2000–2001Time sincediagnosisSurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CISurvival(%) 95% CI1 year Men 82.2 (81.7, 82.6) 82.7 (82.3, 83.1) 81.6 (81.1, 82.1) 0.0 (0.9, 0.9) 81.4 (80.6, 82.1)Women 72.2 (71.4, 73.0) 71.2 (70.4, 72.0) 70.6 (69.7, 71.5) 0.2 (1.5, 1.9) 71.1 (69.8, 72.4)5 years Men 66.3 (65.7, 67.0) 66.6 (66.0, 67.2) 66.5 (65.6, 67.4) 0.7 (0.7, 2.2) 66.1 (65.1, 67.2)Women 58.7 (57.7, 59.8) 58.0 (57.1, 59.0) 56.3 (55.0, 57.6) 0.8 (3.0, 1.5) 57.0 (55.4, 58.6)10 years Men 59.1 (58.3, 59.9) 60.3 (59.4, 61.3) 2.7 (0.7, 6.0) 60.9 (59.6, 62.2)Women 53.6 (52.4, 54.8) 53.9 (52.6, 55.2) 3.6 (1.2, 8.3) 53.0 (51.2, 54.9)CI=confidence interval. aSurvival estimated with cohort or complete approach (see Rachet et al, 2008). bMean absolute change (%) in survival every 5 years, adjusted fordeprivation (see Rachet et al, 2008). cSurvival estimated with hybrid approach (see Rachet et al, 2008).020406080100Relative survival (%)0 2 4 6 8 10Years since diagnosisMen020406080100Relative survival (%)0 2 4 6 8 10Years since diagnosis2000 – 20011996 –19991991 –19951986 –1990WomenFigure 1 Relative survival (%) up to 10 years after diagnosis by sex andcalendar period of diagnosis: England and Wales, adults (15–99 years)diagnosed during 1986–1999 and followed up to 2001. Survival estimatedwith cohort or complete approach (1986–1990, 1991–1995, 1996–1999) or hybrid approach (2000–2001) (see Rachet et al, 2008).Survival from bladder cancer in England and WalesA Shah et alS87British Journal of Cancer (2008) 99(S1), S86 – S89& 2008 Cancer Research UKThe declining incidence of invasive cancer of the bladderprobably reflects earlier declines in tobacco smoking, but it mayalso echo this shift in the recorded spectrum of malignantbehaviour. An increasing proportion of bladder tumours is nowbeing coded as in situ or uncertain if benign or malignant. Some ofthese tumours are of low invasive potential (Newling et al, 1995).The recommended change in coding practice by Europeanregistries was made in 1995, but pathological practice may havechanged before that. If a substantial proportion of bladdertumours that were classified by the pathologist (and coded bythe cancer registry) as invasive during the 1980s would have beencoded as in situ or of uncertain malignancy in the late 1990s, thiswould tend to cause both a decline in the recorded incidence ofinvasive cancer of the bladder and – as those low-grade tumourswould also be excluded from survival analysis – a decline insurvival from bladder cancer.Regional variation within England and Wales in the percentageof bladder tumours coded as in situ or of uncertain malignancyis very wide. The overall percentage of in situ tumours during1986– 1999 ranged from less than 1 up to 27% among the 10 cancerregistries (national average 8.1%). In some registries, it rose fromless than 1% in 1986–1990 to 35% by 1996– 1999, whereas inothers it was stable at 1 –2% (data not shown). A similar patternwas seen for tumours of benign or uncertain behaviour, thepercentage ranging from 0.4 to 31% of all bladder tumourregistrations during the period 1986– 1999 (national average3.4%), with similarly disparate trends among registries over thatperiod. This must overstate any true underlying regional variation,and it reflects differences in pathological classification and registrycoding practice. The relevance of these patterns is that the nationaldata for the period 1986– 1999 do not comprise a consistentlydefined group of bladder cancers.Thus, a study of 1500 bladder cancer patients diagnosed in theWest Midlands in 1990–1991 (Begum et al, 2004) found asocioeconomic gradient in crude (all-cause) survival, but not incause-specific survival (deaths certified as due to bladder cancer),which should be very close to relative survival if death certificationis accurate. The difference in crude survival at 5 years betweenthe most affluent and most deprived groups (7%) was similar tothat seen for West Midlands and for England as a whole during1986– 1990 (Coleman et al, 1999), but the survival estimatesthemselves (56–63%) were some 15% higher. These discrepanciessuggest both errors in attribution of the cause of death and/orselection bias: fewer tumours were classified as in situ or benign inthe West Midlands during 1986–1999 than in other regions ofEngland (data not shown).Bladder cancer survival rates observed in the late 1990s maytherefore reflect a more aggressive spectrum of bladder tumoursthan those retained in survival analyses for the 1980s. This mighthelp to explain why survival from bladder cancer seems to haveimproved so little between the 1980s and the 1990s.More robustly interpretable information on population-based bladder cancer survival trends will require greaterconsistency in pathological definition and coding than seemsto be available at present; this will take some time. In themeantime, examination of survival trends by stage of disease atdiagnosis should prove informative, particularly if early-stagedisease were excluded.50607080905-year relative survival (%)Affluent 2 3 4 DeprivedDeprivation categoryMen40506070805-year relative survival (%)Affluent 2 3 4 DeprivedDeprivation category2000– 20011996–19991991–19951986–1990WomenFigure 2 Trends in the deprivation gap in 5-year relative survival (%) bysex and calendar period of diagnosis: England and Wales, adults (15–99years) diagnosed during 1986–1999 and followed up to 2001.Table 2 Trends in the deprivation gap in relative survival (%) by sex, time since diagnosis and calendar period of diagnosis: England and Wales, adults(15–99 years) diagnosed during 1986–1999 and followed up to 2001Calendar period of diagnosisaAverage change (%) Predictionc for patients1986 –1990 1991–1995 1996–1999 every 5 yearsb diagnosed during 2000–2001Time sincediagnosisDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CIDeprivationgap (%) 95% CI1 year Men 4.1** (5.5, 2.8) 5.3** (6.6, 4.1) 4.6** (6.1, 3.1) 0.3 (1.4, 0.7) 4.8** (6.9, 2.6)Women 4.3** (6.8, 1.9) 7.0** (9.4, 4.7) 6.5** (9.2, 3.8) 1.2 (3.1, 0.7) 5.3** (9.2, 1.5)5 years Men 4.4** (6.3, 2.4) 6.5** (8.4, 4.7) 5.7** (8.2, 3.1) 0.9 (2.5, 0.8) 6.1** (9.1, 3.0)Women 5.3** (8.3, 2.3) 9.7** (12.5, 6.8) 5.8** (9.5, 2.0) 0.7 (3.2, 1.8) 3.4 (8.1, 1.4)10 years Men 3.8** (6.2, 1.3) 5.9** (8.8, 3.1) 2.2 (5.9, 1.5) 6.5** (10.2, 2.8)Women 6.0** (9.6, 2.5) 10.2** (14.1, 6.2) 4.1 (9.4, 1.2) 2.5 (8.0, 3.1)CI=confidence interval. aSurvival estimated with cohort or complete approach (see Rachet et al, 2008). bMean absolute change (%) in the deprivation gap in survival every 5 years,adjusted for the underlying trend in survival (see Rachet et al, 2008). cSurvival estimated with hybrid approach (see Rachet et al, 2008). **Po0.01.Survival from bladder cancer in England and WalesA Shah et alS88British Journal of Cancer (2008) 99(S1), S86 – S89 & 2008 Cancer Research UKThe shift since the mid-1990s towards a more malignantspectrum of bladder tumours that have been classified andcoded as invasive in most registries may partly explain theoverall lack of improvement in bladder cancer survival inEngland and Wales, but it does not explain why the widesocioeconomic inequalities in survival have not been reduced;nor does it explain the persistent sex difference in survival frombladder cancer.REFERENCESBegum G, Dunne JA, Bryan RT, Bathers S, Wallace MA, West MidlandsUrological Research Group (2004) Socio-economic deprivation andsurvival in bladder cancer. 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Survival from adult leukaemia in England and Wales up to 2001

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Survival from adult leukaemia in England and Wales up to 2001.

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