Relative survival in elderly European cancer patients: evidence for health care inequalities

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1 Critical Reviews in Oncology/Hematology 35 (2000) Relative survival in elderly European cancer patients: evidence for health care inequalities M. Vercelli a,b,c *, R. Capocaccia d, A. Quaglia a, C. Casella b, A. Puppo b, J.W.W. Coebergh e, EUROCARE Working Group 1 a Department of Clinical & Experimental Oncology, Uni ersity of Genoa (UNIGE), Genoa, Italy b Sezione Registro Tumori, Istituto Nazionale Ricerca sul Cancro, Largo Rosanna Benzi, 10, I Genoa, Italy c GIOGer (Italian Group of Geriatrics Oncology), Genoa, Italy d Laboratory of Epidemiology & Biostatistics, National Institue of Health, Rome, Italy e Eindho en Cancer Registry, Eindho en, The Netherlands Accepted 10 May 2000 Contents 1. Introduction Patients and methods Results Differences in cancer survival by age group All tumours combined Breast and prostate tumours Gastrointestinal tumours Respiratory tumours Melanoma of skin Gynaecological tumours Urinary tumours Non-Hodgkin s lymphomas Differences in cancer survival by geographic area All tumours combined Breast and prostate tumours Gastrointestinal tumours Lung and bladder tumours in men Gynaecological tumours Differences in cancer survival between the elderly and the younger adults Discussion Reviewers Acknowledgements Appendix A * Corresponding author. Tel.: ; fax: address: vercelli@hp380.ist.unige.it (M. Vercelli). 1 The EUROCARE Working Group for this study is listed in Appendix A /00/$ - see front matter 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S (00)

2 162 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) References Biography Abstract This paper examines the survival of elderly European cancer patients, on the basis of the EUROCARE II results. Using Hakulinen and Abeywickrama s method, the relative survival rates at 1 and 5 years from diagnosis were computed by sex and quinquennial age group for the elderly (65 99 years old). Age-standardised rates for the whole elderly group were also calculated. The analysis covered: all malignancies combined, stomach, colon, rectum, pancreas, lung, melanoma, bladder, kidney and non-hodgkin s lymphomas for both sexes; prostate and larynx for men; and breast, ovary, uterine cervix and corpus for women. Data relating to cancer patients came from 44 population-based cancer registries in 16 European countries. The relative risks of death (RRs) of older patients (65 99) with respect to middle-aged adults (55 64) were computed by sex and country, for all malignancies only. The most prominent finding was the decrease in survival rates with increasing age for almost all cancer sites. The age-curves of survival rates at 1 year from diagnosis usually had a steeper slope than those at 5 years, particularly in women. This suggests that disease stage at presentation plays an important role in determining survival, particularly in the elderly. Thus, all factors which influence timing diagnosis in the elderly and cause a delay in tumour detection, such as psycho-social factors, access to care, co-morbidities and other clinical features affecting performance status, are very important predictors of prognosis. Very large geographic variations in relative survival rates were found among European countries. The ordering of countries was similar for almost all cancer sites. Western and Central Europe generally had the best survival, followed by Northern countries and by Southern ones (the latter with survival around the European average: 39% in men, 47% in women). The UK had survival rates unexpectedly lower than rates of nearest nations, often below the European average. Eastern countries usually had the lowest rates. In the very elderly patients (over 85 years), an apparent rise in the survival rates was noted, particularly at 5 years from diagnosis and in men. This too good survival is unlikely to be due to real better prognosis, but rather to a selection bias. Countries with this unusual rise are also those registering a high proportion of DCO cases (those cases retrieved by death certificate only) (around 10%) or DCO unavailable. Another natural bias has also to be taken into account: in elderly patients with a very bad prognosis, who are often suffering from other serious co-morbid conditions, cancer diagnoses could be under-notified and not reach at all the data sources commonly monitored by cancer registries Elsevier Science Ireland Ltd. All rights reserved. Keywords: Relative survival rates; Elderly patients; Neoplasm; Europe 1. Introduction The EUROCARE Programme is a long term project aimed at studying cancer patients survival in European countries; the first phase, EUROCARE I, whose results were published in 1995 [1], estimated survival rates of about patients newly diagnosed over the time period and followed-up at least for 5 years, examining data from 33 Cancer Registries and 12 European countries; one of the main findings was an important difference in survival across geographic areas. The subsequent phase, EUROCARE II, was undertaken with the purpose to update survival rates to 1989, with availability of data on cancer patients coming from a larger number of registries and participating countries, 45 and 16, respectively [2,3]. The other more specific aims were to evaluate recent survival time trends and to explain differences emerged among populations and in time. Since the first EUROCARE publication an important difference in survival between elderly and younger patients was noted for all the most common cancer sites [4]. For this reason it was decided to devote a specific paper to elderly cancer survival and its features [5], the special issue containing EUROCARE II study results [6]. Demographic, social and clinical reasons account for such interest. European population reached very high ageing levels, with a life expectancy of 87 and 83 years, respectively, in girls and boys born now; it is foreseen a further increase of persons aged 60 or more years, at least up to 2050, and a consequent rise of cancer burden, age being a major risk factor for this disease [7,8]. Unfortunately, European governments have to face a reduction of available resources for social policies; therefore, a careful health planning to satisfy the growing care demand of this population group is needed. In addition to these public health problems, it has to be noted that the deal of clinical issues affecting elderly cancer patients sometimes makes it difficult to apply diagnostic and therapeutic standardised protocols [9 12]. Moreover, the problem to adopt treatment with curative intent often is largely due to co-morbid conditions other than cancer and physiological impairment. In the aforementioned publication [5], within the framework of EUROCARE II programme, interest was focused on survival differences between elderly and

3 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) younger adults, taking into account the whole Europe as a pool. Published results highlighted a prognosis disadvantage of the elderly and relative risks of death remarkably higher than in younger subjects, for several cancer sites, in particular at 1 year from diagnosis and for women. The purpose of this paper is to review prognosis of elderly European cancer patients, paying particular attention to differences in survival among countries, as already done for all patients and each tumour site in the special issue of EUROCARE II study [6]. In particular, the differences among quinquennial age groups within elderly age group by sex, cancer site and country, together with the relative risk of death of elderly patients (65 99 years) in comparison with those aged years for all malignancies combined will be described. 2. Patients and methods Survival data on European cancer patients, diagnosed in the period , were collected from 44 population-based cancer registries of 16 countries and provided to EUROCARE II programme. In this context, out of were elderly patients (65 99 years old). Characteristics of each registry and of national registration coverage are reported in a special issue containing EUROCARE II study results [2]. Quality of incidence data and the percentage of population over the age of 65 years in each country are shown in Table 1a, taken from the aforementioned publication [5]; Table 1b lists the per cent distribution of the more represented cancer sites by sex and country for the age group, in order to explain better the geographic differences in survival rates for all malignancies combined. Table 1a Data quality for the elderly (65 years or more) in EUROCARE II countries ( ) a Country Cases aged 65 years % aged 65 years No. Mean age (years) % of all cases %MV b % Lost to % DCO % Autopsies follow-up Men Women Men Women Europe c Northern Europe Iceland Finland Sweden* Denmark UK Scotland England Western and Central Europe The NA 0 Netherlands* Germany* Austria* Switzerland* France* NA 0 Southern Europe Italy* Spain* Eastern Europe Slovenia Slovakia Poland* Estonia a Taken from Vercelli M, et al., Eur J Cancer 1998;34(14): b MV, microscopical verification; DCO, death certificate only; NA, not available. c Includes DCO and autopsy cases (these were excluded from the survival analysis). * 20% of the national population covered. 1.4

4 Table 1b Proportions of observed cases by site, country and sex for the elderly (65 years or more) ( EUROCARE II) 164 Men Stomach Colon Rectum Pancreas Women Lung Prostate Bladder Stomach Colon Rectum Pancreas Lung Breast Northern Europe Iceland Cases % Finland Cases % Sweden Cases % Denmark Cases % UK Scotland Cases % England Cases % Western and Central Europe The Netherlands Cases % Germany Cases % Austria Cases % Switzerland Cases % France Cases % Southern Europe Italy Cases % Spain Cases % Eastern Europe Slovenia Cases % Slovakia Cases % Poland Cases % Estonia Cases % M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000)

5 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Sweden presented the highest proportion of patients 65 years or more, with 15% of men and 20% women compared with 11 and 16% for the pooled European population. DCO (death certificate only) and autopsy cases were excluded from analysis of survival, but they represent very important indexes to interpret geographical survival differences. Elevated DCO proportions (more than 5%) were evident in Eastern countries (except Estonia), Austria, Germany, England and Spain, whilst very low percentages were characteristic of Nordic countries. Different methods among registries in collecting DCO cases must be seriously considered as determinant of possible bias that, particularly for oldest age groups, could affect survival rates [13]. The low percentages of lost cases indicate good follow-up procedures even in elderly population, while variation in microscopic verification seemed to be related to DCO percentages. Hakulinen and Abeywickrama s method was used in order to calculate the age-standardised relative survival rates at 1 and 5 years from diagnosis [14]. For countries where the registration coverage was not complete, the national estimates were calculated as a function of the covariates sex, age and registry area by means of a multiple regression model [15]. These estimates were computed by weighting of the sex, age- and registry-specific expected relative survival values. Differences between older (65 99 years) and younger patients (55 64 years) of both sexes were estimated by relative risks (RRs) of excess death attributable to cancers in each country, computing the ratio of relative survival rates logarithms. 3. Results 3.1. Differences in cancer sur i al by age group Fig. 1(a e) show, by graphs and tables, the relative survival rates and the observed cases at 1 and 5 years from diagnosis, registered by sex in the elderly age groups (65 69, 70 74, 75 79, 80 84, and years of age), for the pool of all EUROCARE II countries. Fig. 1(a) shows all malignancies combined, breast and prostate cancers, Fig. 1(b) stomach, colon, and rectum, Fig. 1(c) pancreas, lung and larynx cancers (the latter for men only), Fig. 1(d) melanoma, uterine cervix and Fig. 1. Relative survival rates (%) by sex and age in pooled EUROCARE II countries.

6 166 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Fig. 1. (Continued) corpus and ovary cancers, Fig. 1(e) non-hodgkin s lymphomas, bladder and kidney cancers All tumours combined For all malignancies (Fig. 1(a)) survival rates decreased particularly at 1 year from 60 to 51 and from 70 to 51, in men and women, respectively. On the contrary, at 5 years there were less differences for elderly age groups: in men values were stable around 39, with an unexpected increase to 44 in the oldest patients above 85 years; in women values diminished across age groups from 52 to Breast and prostate tumours Breast cancer (Fig. 1(a)) showed a rather good prognosis also in elderly women, survival rates being quite stable up to 79 years, both at 1 and 5 years from diagnosis (93 90 and 73 71, respectively); then, a higher decrease occurred in the last age groups. Also for prostate cancer (Fig. 1(a)), rates were relatively high up to 74 years (88 at 1 year, around 60 at 5 years), after this age values decreased regularly, in particular, at 1 year Gastrointestinal tumours Stomach cancer (Fig. 1(b)), despite a very poor prognosis, showed a remarkable decrease, constant until the last age group (from 25 to 12 at 5 years) for women, and until 84 years (from 20 to 13 at 5 years) for men, who registered an unusual rise in the age group over 85 years (22 at 5 years). Colon and rectum cancers (Fig. 1(b)) displayed similar descending patterns and absolute levels (a little better for colon). No major differences were noted between sexes: the decrease was higher for 1 year survival (from values around 70 to 45) and lower at 5 years (from values around to values between for the age group). It has to be noted the unexpected rise of survival rates in men s last age group. Survival of pancreatic cancer (Fig. 1(c)) was characterised by lowest values in both sexes, already in the first age group considered Respiratory tumours The prognosis of lung cancer (Fig. 1(c)) was very poor in both sexes and for each age group. The decreasing trends were very similar at 1 and 5 years.

7 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Fig. 1. (Continued) On the contrary, for larynx cancer in men (Fig. 1(c)) the prognosis was good also in the elderly, relative survival rates varying from 86 to 72 and from 63 to 58, at 1 and 5 years, respectively Melanoma of skin Melanoma (Fig. 1(d)) displayed the best prognosis observed in the elderly. The survival at 1 year was very similar in both sexes and showed only a slight decrease with age; the 5 years survival pattern was different, showing a great gap in absolute values between sexes and a deeper fall up to 84 years (from 65 to 51 and from 76 to 64 in men and women, respectively). After this age, rates rose up in both sexes unexpectedly Gynaecological tumours Uterine cervix and corpus cancers (Fig. 1(d)) presented a striking descending trend with increasing age, both at 1 and 5 years (from 53 to 24 and 74 to 31 at 5 years, for cervix and corpus, respectively). Ovarian cancer (Fig. 1(d)) presented a sharp fall of rates at 1 year, while 5 years rates varied only slightly Urinary tumours Survival of urinary tract cancers was characterised by a particular ratio between sexes: for almost all cancer sites, women had always better prognosis than men, but this was not true for bladder whose survival, at 1 and 5 years from diagnosis, was higher in men. Survival of kidney cancer did not show any advantage by sex. 5 years relative survival was better for bladder cancer than for kidney (Fig. 1(e)), the latter showing a sharper decrease with age for both sexes (from 48 to 24 in men and from 50 to 21 in women) Non-Hodgkin s lymphomas Finally, a bad prognosis was evident also for non- Hodgkin s lymphomas (Fig. 1(e)) in old patients: decrease of survival at 1 and 5 years with increasing age was higher for women, experiencing a better prognosis than men up to 74 years; after this age men exceeded women (33 vs. 24 at 5 years from diagnosis for age group).

8 168 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Fig. 1. (Continued) 3.2. Differences in cancer sur i al by geographic area In Tables 2a, 2b, 2c, 2d, 2e and 2f observed cases and relative survival rates at 5 years since diagnosis were shown by sex, country and elderly age groups. The selected cancer sites were all malignancies (Table 2a), prostate and breast (Table 2b), stomach (Table 2c), colon (Table 2d), lung and bladder only for men (Table 2e, uterine cervix and corpus (Table 2f) All tumours combined For all malignancies combined (Table 2a) relative survival rates of European countries varied in the elderly (the whole group of 65 years and more) within a rather narrow range, between 31 and 48 in men, 41 and 56 in women, with the exception of all Eastern countries and Scotland, largely below the average values of Europe (39 in men and 47 in women). These results for all cancers are only partially informative on the real cancer survival in the examined countries because influenced by the differences in site distribution by country, showed in Table 1b. Differences observed between Northern countries were small, Sweden showing the best survival, Finland the worst, particularly for oldest women, whilst in the UK larger variations were noted in both sexes between England and Scotland (38 versus 24 in men, 45 versus 30 in women). Western and Central Europe presented, in general, the best survival rates, exception made for The Netherlands, showing values below European average, especially in men. Southern countries presented survival rates very similar to Europe, Spain slightly over and Italy slightly below the average European values. The rather low overall relative survival rates for Finland within Northern Europe, for Scotland compared to England and for the Netherlands with respect to the nearest countries are partially explained by the higher percentage of cancers with a bad prognosis, such as stomach and lung tumours (Table 1b). The pattern described was often characteristic also of each considered cancer site, even if some interesting exceptions resulted from a careful analysis.

9 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Fig. 1. (Continued) Breast and prostate tumours Breast cancer (Table 2b), registered the highest survival values in Northern countries (81 67), followed by Western and Central Europe (80 62), Southern countries (76 70), UK (63 61) and Eastern countries (62 54). Prostate cancer (Table 2b) showed the aforementioned pattern with the highest values in Western and Central Europe (73 55), followed by Northern countries (65 42), Southern Europe (55 48), UK (48 44) and, lastly, Eastern countries (59 36), important exceptions being represented by low values of Denmark (42) and Italy (48) and high values of Slovakia (59) Gastrointestinal tumours As regards digestive tract cancers, namely stomach (Table 2c) and colon (Table 2d) a very high variability across countries was noted: also excluding extreme values, that is the highest and the lowest survival rates, colon survival ranged from 30 (Slovenia) to 55 (Austria) in men and from 35 (Slovenia and Estonia) to 54 (Sweden) in women. Also stomach cancer, notwithstanding a very poor prognosis, presented values which differed more than 2-fold across European countries: ranging from 9 (England and Scotland) to 23 (Spain) in men and from 9 (Scotland) to 28 (Spain) in women. For both sites and sexes the best survival rates were registered in Western and Central countries with values often over European average, followed by Northern countries; Eastern Europe and, unexpectedly, the UK showed lowest values. Interesting exceptions were represented by Denmark and Southern countries; Denmark had survival rates lower than nearest countries and often below the European average values. Italy and Spain, showing usually rates around the average, presented better prognoses for stomach tumour, particularly in women Lung and bladder tumours in men Lung cancer (Table 2e) showed a very bad prognosis in all European countries with values between 11 and 4. Bladder cancer (Table 2e) presented one of the largest variability and, even considering the second highest and the second lowest value, survival rates of Finland were almost two times higher than those of Poland (66 versus 35). Geographic distribution pattern

10 Table 2a Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) 170 All malignant neoplasms Men Age groups (years) Women Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000)

11 Table 2b Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) Prostate Men Age groups (years) Breast Women Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000)

12 172 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) of survival was similar to the one described for all malignancies, with some interesting exceptions: Switzerland, which usually showed high rates, surprisingly registered only 48, a value largely below European average; on the contrary, Slovakia presented rates too high (56) in respect with its geographic area. The UK survival rates for bladder were better than for other cancer sites (58 for Scotland and 62 for England), very close, indeed, to European values Gynaecological tumours As far as gynaecological cancers are concerned (Table 2f), it must be noted that it has a geographic variability less pronounced than for other tumours; in particular, also excluding the lowest and highest values, all countries were within a range of 57 and 42 for uterine cervix and of 76 and 58 for corpus uteri. Indeed, survival rates of breast, uterine cervix and corpus cancers in Eastern countries were more similar to other countries than rates of the other sites. Table 2c Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) Stomach Men Age groups (years) Women Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates

13 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Table 2d Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) Colon Men Women Age groups (years) Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates Uterine cervix and corpus cancers displayed the highest values in Western and Central Europe, followed by Northern and Southern countries; lower values characterised UK and Eastern countries Differences in cancer sur i al between the elderly and the younger adults In Fig. 2 death relative risks at 5 years from diagnosis, for patients aged years vs. the years one, are displayed for all malignancies combined, by country and sex. This representation for all cancers is obviously confounded by the different site distribution by country; however, it is informative from a public health point of view, representing features common to a large number of patients and to National Health Systems, especially if these results are interpreted considering also the different proportions. For all malignancies appeared that only old women experienced a relative risk of death higher than younger

14 Table 2e Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) 174 Lung Men Age groups (years) Bladder Men Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000)

15 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) patients (RRs between 1.2 and 1.6), while in men no large differences were evident (RRs ranging between 0.8 and 1.2 close to European value). The prognostic disadvantage of elderly patients was more pronounced taking into account survival rates at 1 year from diagnosis: in this case also older men had relative death risks higher than younger patients (data not shown). 4. Discussion A preceding paper, dealing with relative survival in European elderly cancer patients [5], presented and discussed survival data paying special attention to differences between older (65 99 years) and younger patients (55 64 years); in order to develop this analysis survival rates were estimated for Europe, considered as Table 2f Observed cases and relative survival rates (%) at 5 years by country and age group for the elderly ( EUROCARE II) Women Uterine cervix Uterine corpus Age groups (years) Europe Cases Rates Northern Europe Iceland Cases Rates Finland Cases Rates Sweden Cases Rates Denmark Cases Rates UK Scotland Cases Rates England Cases Rates Western and Central Europe The Netherlands Cases Rates Germany Cases Rates Austria Cases Rates Switzerland Cases Rates France Cases Rates Southern Europe Italy Cases Rates Spain Cases Rates Eastern Europe Slovenia Cases Rates Slovakia Cases Rates Poland Cases Rates Estonia Cases Rates

16 176 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Fig. 2. All malignant neoplasms: relative risk of death for European cancer patients aged years compared with those aged years by country ( EUROCARE II). a pool, and for the whole elderly age group (65 99 years). The present report examines more specifically two other aspects of elderly patients survival, considering first of all five smaller age classes within the whole elderly group (that is 65 69, 70 74, 75 84, years) with the purpose to highlight more detailed features of survival across different ages, and then focusing on each European country participating in the project. The first and most prominent finding was the decrease in survival rates with increasing age for almost all cancer sites; the lowering pattern changed specifically for each tumour site examined, even if it was possible to point out some general remarks common to all malignancies. Age-curves of survival rates at 1 year from diagnosis usually had a steeper slope than those at 5 years. This suggests that disease stage at presentation plays an important role in determining particularly elderly survival [4]. As a consequence, all factors which influence timing in diagnosis for the elderly and cause a delay in tumour detection, such as psycho-social factors, access to care, comorbidities and other clinical features affecting performance status, are very important predictors of prognosis [9,11,12,16 18]. Survival rates at 5 years in men did not decrease at all; probably, after a very high mortality of patients affected by advanced and unfavourable disease, elderly patients who received a curative treatment could experience survival rates similar to younger subjects. The relatively bad prognosis for all malignancies combined of Dutch men is probably caused by extremely high rates of tobacco related cancer in the elderly: in the 1950s 90% of all Dutch males smoked.

17 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) Also the large and consistent differences in survival for all cancers, existing within UK, with England having better survival than Scotland, are explained by a different distribution of cancers in the two countries; indeed Table 1b shows a different site distribution by geographic area: in the Netherlands and Scotland there were much higher proportions of the short survival tumours such as lung. A second general remark concerns differences by sex: in elderly women the fall of survival rates with age, both at 1 and 5 years, was more pronounced than in elderly men. This outcome, particularly evident in age-curves of survival for all malignancies, was influenced, above all, by the poor prognosis of gynaecological cancers in elderly women. The same sex-related differences were found in a similar population-based survival study of SEER programme, and explained in the light of a different stage distribution by sex [19]; however, psycho-social factors such as social isolation, reduced financial resources, educational level and cognitive status, have not to be forgotten when dealing with elderly women [20]. Very large geographic variations were registered among European countries in accordance to other reports dealing with survival rates in all patients and not specifically in the elderly [6,21]. Countries rank was similar for almost all cancer sites examined: Western and Central Europe had the highest values, often over the European average, followed by Northern countries and by Southern ones; these latter showed values around European average; Eastern countries usually had the lowest rates. As regards the UK survival rates always were lower than rates of nearest nations, and often lower than those of Europe. An editorial published in the British Medical Journal tried to explain the reasons for such a poor performance [22]. The author focused the attention on the quality of cancer care in Britain and suggested that a small number of medical oncologists and radiotherapists and a significantly lower use of chemotherapy than other European countries could be a possible cause [23]. As a consequence a large number of cancer patients is not referred to specialised cancer centres [24] and a wide variation of clinical outcomes has been reported in different hospitals. Considering the variability magnitude, cancers which showed very large differences in survival between countries were digestive tract tumours; the prognoses of these cancers are largely influenced by disease stage at presentation and by the possibility to apply surgical treatment with curative intent [25,26]. Variability could be determined by differences of health care facilities and, therefore, by difficulties of access to health care services causing a consequent delay in early detection; in some countries, it is also possible that opportunistic screening with occult blood test is more widespread and extended also to elderly people. Survival variability for prostate cancer is probably related to the different diffusion of relatively new diagnostic tests and therapeutic practices, such as transrectal ultrasonography (TRUS), echo-guided biopsy (EGB) and trans-urethral resection of prostate (TURP). This hypothesis is confirmed by the very good prognosis of Northern European patients, also of the elderly over 85 years: in Northern countries the very high incidence rates probably caused a greater awareness of this cancer and consequently a deeper attention for this disease; on the contrary, a near country like Denmark presented very low values, owing to the attitude of general practitioners not to adopt an intensive diagnostic approach towards incidental prostatic tumours [27]. Indeed, differences observed, ranging from 36 of Poland to 73 of Switzerland are largely due to the lead time bias and not to a real variation of prognosis [28]. Gynaecological cancers differed less among countries than other cancers because survival rates of Eastern nations were closer to those of other geographic areas, and because, for uterine cervix, rates of Finland, Sweden and Denmark were lower than usual. This may be explained by the fact, that screening activity for cervical cancer has eradicated early cancers with a favourable survival. Thus, the cancer burden in the Nordic countries will reflect those with really poor prognosis inasmuch they must be the more aggressive ones or those not picked up by screening methods in less advanced stages. Inter-country variations for bladder cancer in men were remarkable, but not fully reliable, due to a lack of standardisation in case collection, some cancer registries including also non invasive tumours: it is rather unusual to find so low survival rates for Switzerland, where indeed only invasive cancers are registered. It is noticeable that in oldest patients (over 85 years), for some cancer sites, namely all malignancies combined, melanoma and non-hodgkin s lymphomas in both sexes, prostate, stomach, colon in men and ovary in women, there was an unexpected rise of survival rates; such phenomenon, more evident at 5 years from diagnosis and in men, unlikely was due to a real better prognosis in this extreme age group, but more probably due to some biases. This too good prognosis of very old patients is not so surprising, if we consider the survival age-curves of each country: nations with this unusual rise are also those registering a high proportion of DCO cases (around 10%) or DCO unavailable, that is England, The Netherlands, Germany, Austria, France, Spain and Eastern countries except Estonia (Table 1a). Therefore the values for the last age group in those countries are influenced by a selection bias of patients with a better prognosis, due to a lack of retrieved cases deriving from DCI (cases Initially notified from Death Certificate) by follow-back. In addition to the problem of DCO, another natural bias has to be taken into account when we deal with

18 178 M. Vercelli et al. / Critical Re iews in Oncology/Hematology 35 (2000) survival: in elderly patients with a very bad prognosis, who are often suffering from other serious co-morbid conditions, cancer diagnoses could be under-notified and not reach at all the data sources commonly monitored by cancer registries [11,12]. However, all data concerning older persons have to be considered with caution, since the quality of demographic, incidence and mortality data is less reliable [29]. The survival of the very elderly showed the largest geographic variations and some high survival rates should be considered with caution. On the contrary, low survival rates in Eastern European countries, where also younger patients experience a poor prognosis, are probably quite reliable in the light of the pattern of social and economic determinants influencing health care outcome [21,30]. Other ad hoc studies are warranted in order to examine more specifically the issues noted in this paper. Reviewers This article was kindly reviewed by Dr Lazzaro Repetto (IST-Istituto per la Ricerca sul Cancro, Oncologia Medica I, Largo Rosanna Benzi, 10, I Genoa, Italy), Dr Martine Extermann (H. Lee Moffitt Cancer Centre & Research Institute, Magnolia Street, Tampa, Fl 33612, USA) and Dr Desmond Yip (Department of Medical Oncology, Guy s Hospital, St. Thomas Street, London SE1 9RT, UK). Acknowledgements The EUROCARE study was financed through the BIOMED programme of the European Union and partially through the Europe Against Cancer programme 99/CAN/ The authors are grateful to the following Ligurian Cancer Registry personnel: Dr Stefano Parodi and Dr Maria Antonietta Orengo for the collaboration, Dr Arianna Desideri for the linguistic revision and Mrs Roberta Cogno for the technical assistance and typing. Appendix A The EUROCARE Working Group for this study is: Austria: W. Oberaigner Cancer Registry of Tyrol. Denmark: H. Storm (Danish Cancer Society). Estonia: T. Aareleid (Estonian Cancer Registry). Finland: T. Hakulinen (Finnish Cancer Registry). France: D. Pottier (Calvados Digestive Cancer Registry), J. Mace- Lesec h (Calvados General Cancer Registry), J. Faivre (Côte d Or Digestive Cancer Registry), G. Chaplain (Côte d Or Gynaecologic Cancer Registry), P.M. Carli (Côte d Or Malignant Haemopathies Registry), P. Arveux (Doubs Cancer Registry), J. Estève (International Agency for Research on Cancer), C. Exbrayat (Isère Cancer Registry), N. Raverdy (Somme Cancer Registry). Germany: H. Ziegler (Saarland Cancer Registry). Iceland: L. Tryggvadottir, H. Tulinius (Icelandic Cancer Registry). Italy: F. Berrino (Project Leader), P. Crosignani, G. Gatta, A. Micheli, M. Sant (Lombardy Cancer Registry), E. Conti (Latina Cancer Registry), M. Vercelli (Liguria Cancer Registry, NCI/UNIGE, Genova), M. Federico, L. Mangone (Modena Cancer Registry), M. Ponz de Leon (Modena Colorectal Cancer Registry), V. D e Lisi (Parma Cancer Registry), R. Zanetti (Piedmont Cancer Registry), L. Gafà, R. Tumino (Ragusa Cancer Registry), F. Falcini (Romagna Cancer Registry), A. Barchielli (Tuscan Cancer Registry), R. Capocaccia, G. De Angelis, F. Valente, A. Verdecchia (National Institute of Health, Rome). Poland: J. Pawlega, J. Rachtan (Cracow Cancer Registry), M. Bielska Lasota, Z. Wronkowski (Warsaw Cancer Registry). Slovakia: A. Obsitnikova, I. Plesko (National Cancer Registry of Slovakia). Slovenia: V. Pompe Kirn (Cancer Registry of Slovenia). Spain: I. Izarzugaza (Basque Country Cancer Registry), P. Viladiu (Girona Cancer Registry), C. Martinez-Garcia (Granada Cancer Registry), I. Garau (Mallorca Cancer Registry), E. Ardanaz, C. Moreno (Navarra Cancer Registry), J. Galceran (Tarragona Cancer Registry). Sweden: T. Möller (Southern Swedish Regional Tumour Registry). Switzerland: J. Torhorst (Basel Cancer Registry), C. Bouchardy, L. Raymond (Geneva Cancer Registry). The Netherlands: J.W.W. Coebergh (Eindhoven Cancer Registry), R.A.M. Damhuis (Rotterdam Cancer Registry). Scotland: A. Gould, R.J. Black (Scottish Cancer Registry). England: T.W. Davies, D. Stockton (East Anglian Cancer Registry), M.P. Coleman (London School of Hygiene and Tropical Medicine), E.M.I. Williams, J. Littler (Merseyside and Cheshire Cancer Registry), D. Forman (Northern and Yorkshire Cancer Registry and Information Service), M.J. Quinn (Office for National Statistics), M. Roche (Oxford Cancer Intelligence Unit), J. Smith (South and West Oxford Cancer Intelligence Unit), J. Bell (Thames Cancer Registry), G. Lawrence (West Midlands Cancer Intelligence Unit). References [1] Berrino F, Sant M, Verdecchia A, Capocaccia R, Hakulinen T, Estève J, editors. Survival of Cancer Patients in Europe. The EUROCARE Study. IARC Sci Pub No 132, Lyon, [2] Berrino F, Gatta G, Chessa E, Valente F, Capocaccia R. Introduction: the EUROCARE II study. In: Coebergh JWW, Sant M, Berrino F, Verdecchia A, editors. Survival of adult cancer patients in europe diagnosed from 1978 to 1989: the EUROCARE II Study (Special Issue), Eur J Cancer 1998;34: