Changing trends in prostatic cancer

BJU International (1999), 83, 786–791

Changing trends in prostatic cancerM. MURPHY, C. JOHNSTON*, P. WHELAN, L. RIDER* and S.N. L LOYDPyrah Department of Urology, St James’s University Hospital, and *Northern and Yorkshire Cancer Registry and Information Service,Leeds, UK

Objectives To examine the diagnosis and treatment of Results In all, 8118 patients with prostatic cancer wereregistered, of whom 6587 had histological confir-prostatic cancer in a population-based study, reporting

incidence trends and survival, in the decade before mation. There was a 30% increase in the age-standardized incidence of prostatic cancer during thethe introduction of prostate-specific antigen (PSA)

testing, and thus determine whether the overall inci- study period (P<0.001). The mortality from prostaticcancer increased by 35% (P<0.001) and the percent-dence of prostatic cancer is increasing or not.

Patients and methods The study included all men regis- age of patients known to have metastases at the timeof presentation increased from 18% to 24%. Thesetered as having prostatic cancer in the Yorkshire

region between 1981 and 1990. The Northern and changes were seen in all age groups. The overallsurvival was 49% at 5 years and 34% at 10 years.Yorkshire Cancer Registry and Information Service

has an active registration policy and after notification, Conclusions There has been a real increase in theincidence of prostatic cancer which pre-dates the usethe information received is validated by histopathology

reports and case-note review. Of the patients regis- of serum PSA testing. The percentage relative survivalof patients with prostatic cancer in Yorkshire duringtered, 68% were over 70 years old at the time of

diagnosis (mean age 74 years). Prostatic cancer was the study period is similar to that seen in other partsof the UK, but compares badly with reported survivaloften diagnosed incidentally, after prostatectomy for

presumed benign disease. Indications for treatment in other countries.Keywords Prostatic cancer, incidence, survival, trendswere not recorded, but most patients had treatment

which was designed to control outlet bladder symp-toms rather than with intent to cure cancer.

study were to document the changes occurring in aIntroduction

well-defined study population for prostatic cancer and toreport on patient survival.There are many unresolved issues in the diagnosis and

treatment of both early and advanced prostatic cancer[1,2]. PSA testing and changes in public awareness and

Patients and methodsexpectations have significantly altered the managementof prostatic cancer in recent years [3,4]. We have All patients with prostatic cancer registered in Yorkshire

between 1981 and 1990 were identified from Theexamined the incidence and mortality trends in thedecade before the introduction of PSA testing, which Northern and Yorkshire Cancer Registry and Information

Service (NYCRIS) records. Histology reports, death cer-became generally available in Leeds in 1990.Prostatic cancer is a diagnosis of variable significance tificates and all other reports on patients with cancer

are automatically issued to the registry. After notifi-and the goals of treatment diCer depending on theindividual situation. At postmortem, 70% of men over cation, dedicated registry staC visit hospitals and abstract

clinical information from the case notes of those patients.70 years old have histological evidence of prostaticcancer [5], but only a proportion of these men are Yorkshire residents treated outside the region are notified

to the registry by other regional cancer registries.symptomatic and die from this disease. Worldwide, pros-tatic cancer is changing from a disease which tradition- Data were collected consistently during the study

period on a standard Cancer Registry form. This includedally presented late and required symptomatic treatment,to a disease increasingly seen in younger men who seek information on tumour site, histological type and grade,

presence of metastases at initial diagnosis if known,a cure for their cancer. Thus the aims of the presenttreatment administered within 3 months of diagnosis,survival and cause of death. Tumours were classified byAccepted for publication 8 January 1999

786 © 1999 BJU International

CHANGING TRENDS IN PROSTATIC CANCER 787

histological grade as well, moderately or poorly diCeren- of diagnosis confirmed that these changes were indepen-dent of changes in the male population. The change intiated adenocarcinomas. Those with no histological con-

firmation were included in incidence rates but excluded incidence was paralleled by an increase in the overallmortality from prostatic cancer from 21 to 28.4 perfrom survival analyses.

Incidence data were analysed by both birth cohort 100 000 (P<0.001) (Fig. 1).Overall, 20.8% of the patients had documented metast-and age at the time of diagnosis. The age-standardized

incidence and mortality rates were calculated using the ases at the time of presentation (Table 1). However, theproportion of men known to have metastases increased‘European Standard Population’ as the standard popu-

lation and mortality data were provided by the OBce for during the decade (Fig. 2). This increase was statisticallysignificant when the percentage known to have metast-National Statistics [6]. Trends were examined using

generalized linear regression and proportional hazard ases in the first 5 years of the study were compared withthose in the second 5 years (P<0.05). A greater pro-regression analysis.

Patients were grouped according to whether they had portion of young patients were found to have metastases,possibly reflecting their greater level of investigationundergone surgical treatment, hormonal manipulation,

or no active management. However, because indications (Table 1). At the time of diagnosis, 5% of patients wereaged <60 years, 27% 60–69 years, 47% were >70for treatment were not recorded, those in the surgical

treatment group include those with a preoperative diag- years old and 21% were aged >80 years; the mean agewas 74 years. The association of age with metastases,nosis of prostatic cancer, and others whose cancer was

diagnosed incidentally as a consequence of their ‘treat- tumour grade and treatment is outlined in Table 1. Thedegree of tumour diCerentiation was similar in all agement’ for presumed benign disease. Rarely, patients

underwent radical surgery for localized prostatic cancer groups.Data collected included the treatment administeredbut the exact number is unknown. The hormonal

manipulation group included those treated by during the first 3 months after diagnosis, but specificindications for treatment were not available (Table 1).orchidectomy.

The overall percentage relative survival was estimated In all, 5227 patients underwent prostatectomy, of which96% were TURPs. In 2082 of these men surgery wasand survival compared according to age group, tumour

grade and presence or absence of metastases. Relative combined with another treatment modality. Manypatients would have undergone TURP for presumedsurvival is the ratio of the observed and expected sur-

vival, with expected survival calculated from life-tables benign disease but histology later revealed foci of cancer.Others would have undergone TURP to relieve obstruc-for England and Wales [6].

Copies of death certificates are routinely received from tion, either from known or suspected cancer. There were931 patients initially treated by hormonal manipulationthe OBce of National Statistics and those issued for

patients with prostatic cancer were examined. When without prostatectomy and 355 patients who were notactively treated within 3 months of diagnosis. Seventy-this is the first notification of cancer, the registry sends

an inquiry to the GP or to the hospital where the patient four patients were treated with radiotherapy and/orchemotherapy, with no surgery or hormone manipu-died. Where death occurred from a cause other than

cancer, or if it occurred outside the region, the Registry lation; 141 patients were identified as receiving morethan two treatment modalities during their illness butis notified by the NHS Central Register, where all patients

with cancer are ‘flagged’. this is probably an underestimate (data not shown).Radiotherapy was administered to 368 patients in total,either with or without another treatment modality. This

Resultswas usually to treat symptomatic metastatic disease,although a few younger men with localized cancer wereThere were 8118 patients with prostatic cancer regis-

tered between 1981 and 1990, of whom 6587 (81%) treated with intent to cure.Survival data were available for 6573 of the 6587were confirmed histologically. The remaining 1531

patients were diagnosed as having prostatic cancer on men with histologically confirmed disease. The overallpercentage relative survival was 49.4% at 5 years andclinical grounds alone. Prostatic cancer represented

>10% of all malignancies in males and was the third 34.5% at 10 years. As expected, survival was similar inthe diCerent age groups (Fig. 3a). However, survival wasmost frequently registered cancer in men in Yorkshire.

Between 1981 and 1990 the age-standardized inci- significantly altered by tumour grade (Fig. 3b) and bythe presence of metastases (Fig. 3c), as shown by bothdence of prostatic cancer increased from 38.7 to 50.4

per 100 000 (P<0.001) (Fig. 1). This is in keeping with univariate and multivariate analysis. Death certificatesissued for patients with a diagnosis of prostatic cancer,the incidence rate elsewhere within Britain for the same

period [7]. Analysis by birth cohort and age at the time listed it as the main (1a) or immediate (1b) cause of

© 1999 BJU International 83, 786–791

788 M. MURPHY et al.

Fig. 1. The age-standardized incidence(green, P<0.001) and mortality (red,P<0.001) rates for all cases of prostaticcancer in Yorkshire in 1981–90.

Table 1 Stage, grade and treatment of all histologically confirmed prostatic cancer registrations by age, 1981–90

Number (%) at age (years)Variable <60 60–69 70–79 80+ Total

Metastatic status;M0/MX 228 (70) 1356 (75) 2467 (80) 1166 (85) 5217 (79)M1 98 (30) 450 (25) 611 (20) 211 (15) 1370 (21)

Tumour diCerentiation;Well 81 (25) 509 (28) 918 (30) 392 (29) 1900 (29)Moderate 93 (26) 485 (27) 834 (27) 399 (29) 1811 (28)Poor 97 (30) 549 (30) 860 (28) 388 (28) 1894 (29)Unknown 55 (17) 263 (15) 466 (15) 198 (14) 982 (15)

TreatmentSurgery only 109 (33) 747 (41) 1510 (49) 779 (57) 3145 (48)Surgery + other 125 (38) 649 (36) 972 (32) 336 (24) 2082 (32)Hormonal manipulation 63 (19) 288 (16) 425 (14) 155 (11) 931 (14)Radio- and/or chemotherapy 16 (5) 29 (2) 23 (1) 6 (1) 74 (1)No active treatment 13 (4) 93 (5) 148 (5) 101 (7) 355 (5)

Total 326 1806 3078 1377 6587

Fig. 2. The total (green) number ofhistologically confirmed cases of prostaticcancer and the number known to havemetastases (red) at the time of presentationin Yorkshire, 1981–90.



Fig. 3. The percentage relative survivalwith histologically confirmed prostaticcancer by a, age group (dark green <60years old; light green, 60–69; dark red,70–79; light red >80); b, tumour grade(dark green, well diCerentiated; light green,moderately diCerentiated; light red, poorly/undiCerentiated; dark green, unknown);and c, metastases (green, no/unknown, red,present) for the 6573 patients for whomsurvival data are available.

death in 55% of cases, and as other cause or conditionDiscussion

(1c or 2a) in 25%. In 20% of patients known to haveprostatic cancer, the diagnosis did not appear on the This is a historical, descriptive study from which useful

information has been obtained, some expected and somecertificate.


790 M. MURPHY et al.

not. Although NYCRIS is responsible for the registration rather than the direct eCect of the treatment. Forexample, the improved survival seen in those treatedof all cancers in the Northern and Yorkshire region, to

collect useful and relevant data there has to be communi- surgically was probably as a result of the inclusion ofthose having TURP for outlet symptoms, who werecation between registry staC and clinicians. This com-

munication will inevitably improve the quality of the incidentally found to have prostatic cancer (data notshown). The aim of treatment is dictated largely by thedata collected; since this study, the data definitions have

changed. patient’s age. Patients with localized prostatic cancerwould have been oCered a choice between radiotherapyThere has been a real increase in the incidence of

prostatic cancer in this series, which is paralleled by an or hormonal manipulation (either immediate ordeferred). Radiotherapy was rarely used to treat localizedincrease in mortality from prostatic cancer and an

increase in the proportion of patients with metastases at prostatic cancer, except for patients < 65 years old,although data to confirm this were not available. On thethe time of presentation (Figs 1 and 2). These findings

contradict previous reports showing no correlation other hand, those who were known to have symptomaticmetastases would invariably have received hormonalbetween the incidence of prostatic cancer and mortality

[8]. Other recent studies have shown an increased manipulation after diagnosis. Those with progressive oradvanced prostatic cancer had treatment which wasincidence of localized prostatic cancer, but have failed to

show a similar increase in metastatic disease [9]. designed to provide symptomatic control. Of men in thisseries, 5% were < 60 years old and many in this groupInevitably the diagnosis of prostatic cancer would have

increased during the decade as a result of greater aware- undoubtedly died prematurely as a result of prostaticcancer; 27% were 60–69 years old, and with earlierness, improved diagnostic techniques and factors such

as increased reporting of small foci of cancer in pathology diagnosis and definitive therapy, some may have livedlonger. Most patients in this series were 70–79 yearsspecimens. However, the present study pre-dates the use

of PSA testing in Yorkshire. The changes seen remained old, while the average life expectancy in Yorkshire was72 years. It is unlikely that their prostatic cancer wouldafter adjusting for changes in the male population. The

stability of the mortality/incidence ratio suggests consist- have significantly aCected life expectancy or quality oflife, especially because a large proportion of men in thisent registration practices in the region during the study.

In combination, these factors suggest that the changes cohort would also have had significant coexistingmorbidity.in the epidemiology of prostatic cancer in Yorkshire

are real. The calculation of relative survival enables groups ofpatients of diCerent ages to be compared, allowing forThe lack of histological verification in this elderly

cohort and the very few patients with documented bone diCerences in the underlying expected mortality due toother causes. In this study, as in others, the percentagemetastases reflected the low level of investigation of these

patients and the primary intention to treat them sympto- relative survival curves for diCerent age groups weresimilar (Fig. 3) [12]. This supports the belief that survivalmatically. Indeed, just 8% of patients were known to be

free of bone metastases in this series, whereas in 71% of prostatic cancer is similar in diCerent age groups [13].However, if prostatic cancer is diagnosed when younger,the metastatic status was not documented. With careful

staging investigations up to a half of patients with there is a greater likelihood that the disease will aCectsurvival simply because of a greater life expectancy forprostatic cancer have metastases [10], but in series

similar to the present, there were many fewer patients that individual [14]. Mortality data from prostatic cancerin Yorkshire are roughly equivalent to those in otherwith metastases [11]. Increasing use of radioisotope bone

scans would inevitably have increased the identification regions of the UK but do not compare favourably withthose from other countries (Table 2). Overall 5-yearof metastatic disease during the latter part of the study

period. However, once again this would not appear to survival of those for whom histological confirmation wasnot available (12.7%) was similar to the survival ofexplain the extent of the changes seen. The proportion

of patients with metastatic disease was higher in the those who were known to have metastases in the groupwith histological confirmation (13.8%).younger groups, although the distribution of histological

tumour grades appeared to be similar (Table 1). This The diagnosis of prostatic cancer was often omittedon the death certificate, but its complete absence in 20%may be because younger patients were likely to undergo

more detailed staging investigations than the older men. of known cases was higher than expected. In isolation,such inaccuracies may give a false impression of vari-Indications for treatment were not recorded; the

impact of treatment on disease progression is therefore ations in the incidence of prostatic cancer. Of cases ofprostatic cancer notified to the Registry, #2% haveunknown in this cohort. In general, treatment was not

oCered with intent to cure and therefore survival in the death certificate details only, suggesting that by using asystem of notification from several sources (includingdiCerent treatment groups reflected patient selection



Table 2 International comparisons of 5-year survival with prostatic Detroit metropolitan area 1973–94. Cancer 1996; 78:cancer; from *[6] and † [10] 1260–6

5 Mettlin C, Jones GW, Murphy GP. Trends in prostatic careCountry 5-year survival in the United States 1874–1990; observations from the

patient care evaluation studies of the American College ofSweden (1983–87)* 62 Surgeons Commissions of Cancer. Cancer Abst 1993;Finland* 60 48: 83–91Norway* 55 6 Jensen OM, Parkin DM, Mc Lennan R, Muir CS, Skeet RG.Denmark* 38 Cancer Registration. Principles and Methods. Lyon: IARC,USA (SEER, 1979–86)† 73 1991Yorkshire (1981–90) 7 Chamberlain J, Melia J, Moss S, Brown J. Report prepared

all cases 44for the health technology assessment panel of the NHS

histological confirmation 49executive on the diagnosis, management, treatment andcost of prostate cancer in England and Wales. Br J Urol1997; 79: 1–32

8 Lu-Yao GL, Greenberg ER. Changes in prostate cancerrecords from radiotherapy and outpatient units), a high

incidence and treatment in USA. Lancet 1994; 343: 251–4standard of completeness is achieved. That 55% of 9 Newcomber LM, Stanford JL, Blumenstein BA, Bawer MK.patients had prostatic cancer listed as the main or Temporal trends in rates of prostatic cancer: decliningimmediate cause of death refutes the belief that patients incidence of advanced stage disease. 1974–94. J Uroldie with rather than from prostatic cancer. 1997; 158: 1427–30

10 Schroder FH. Current concepts in the management ofIn conclusion, prostatic cancer is the second common-prostatic cancer. Am J Clin Oncol 1988; 11: 1–5est cause of death from cancer in men. This survey of a

11 Harvei S, Tretli S, Langmark F. Cancer of the prostate inrelatively stable population confirms a real increase inNorway 1957–91 – A descriptive study. Eur J Cancerincidence in all age groups. It will be interesting to1996; 32A: 111–7determine the eCect that PSA testing has on incidence

12 Gronberg H, Damber J, Jonsson H, Lenner P. Patient agerates and the eCect that radical treatment has uponas a prognostic factor in prostate cancer. J Urol 1994;

mortality from prostatic cancer in the future.152: 892–5

13 Harrison GS. The prognosis of prostatic cancer in theyounger man. Br J Urol 1983; 55: 315–20Acknowledgements

14 Johannson J, Adami H, Andersson S, Bergstrom R,We thank the Northern and Yorkshire Cancer Registry Holmberg L, Krusemo UB. High 10-year survival rate in

patients with early, untreated prostatic cancer. JAMAand Information Service staC for collecting these data.1992; 267: 2191–6

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Changing trends in prostatic cancer