Incidence of second primary cancers in three Italian population-based cancer registries.

This is the first population-based study carried out in a southern European region to evaluate the risk of a cohort of cancer patients for developing further cancers. The Tuscany Tumour Registry, the Ragusa Cancer Registry and the Cancer Registry of Romagna, three of the 14 population-based cancer registries active in Italy, were involved in the present study. Overall, 19,252 incident cases of cancer of the female breast, and of the colon, rectum, lung and stomach were followed-up for 48 358.3 person-years. Only second metachronous cancers were considered. Controlateral breast cancers were analysed separately. Multiple primaries (MPs) were defined according to the IACR-IACR rules. The observed (O) numbers of MPs were compared with those expected (E) from age-, sex- and registry-specific incidence rates. Overall, 463 MPs were diagnosed (O/E = 0.87, P < 0.001). The O/E ratios for cancers of the colon (O/E = 0.66), rectum (O/E = 0.72) and all sites combined (O/E = 0.78) in males were significantly lower than expected. The deficit of observed MPs was significant during the first period (2-12 months) and increased over time. Patients over 65 years of age had a significant lower risk of MP, whereas young cancer patients had significantly higher risks for all cancers and for female breast cancer. Male lung cancer patients had a significantly reduced O/E ratio for stomach cancer (O/E = 0.21). Rectal cancer patients had reduced risks of developing stomach cancer and tumours of all sites combined and a 3-fold increased risk of kidney cancers. Colon cancer patients had an overall reduction in risk of MPs, but female colon cancer patients had a significantly increased risk for tumours of the ovary and small intestine; no significant results were found for primary stomach cancers. Female breast cancer patients had a significantly increased risk of rectal cancer (O/E = 1.97), and when synchronous and bilateral breast cancers were considered, significant overall increases in risk were seen for all cancer sites (O/E = 1.6) and for rectal (O/E = 2), and especially for breast cancers (O/E = 3). The cohort analysed had a lower risk of developing further independent tumours than the general population. Several artefacts may have biased these results: the exclusion of synchronous cancers greatly reduced the overall MP risk, and the age-related differences may have been due to reduced medical surveillance and diagnostic aggressiveness. We have confirmed the increased risk for kidney cancers in rectal cancer patients and the association between cancers of the colon and ovary. The significantly increased risk for rectal cancer in female breast cancer patients is probably due to hormonal and dietary factors. For female breast cancer patients, controlateral breast cancer represented the highest risk. The increased risk of cancer of the small intestine in patients with colon cancer may be due to overdiagnosis within increased medical surveillance.

Estimation and projections of colorectal cancer trends in Italy.

BACKGROUND: Occurrence of and prognosis for tumours of the colon and rectum are thought to be changing rapidly due to simultaneous changes in risk factor prevalence, early diagnosis and treatment. In this paper time trends of morbidity, survival and mortality for colorectal cancer during the period 1970-1990 are estimated and analysed. METHODS: Mortality trends were obtained from official death certificates. Relative survival rates were computed from population-based cancer registries. Incidence and prevalence rates were estimated from mortality and survival data. RESULTS: Incidence rates were increasing during the period considered, with a lower rate of increase for the youngest birth cohorts. Relative survival rates of both colon and rectum cancers were higher for women, and for younger age groups, and were positively associated with period of diagnosis. No significant survival difference among the cancer registries used was found. A total of about 155,000 prevalent cases, 40% of which had been diagnosed > or = 7 years before, were estimated in the Italian population for the year 1990. Mortality rates were slightly increasing for men and stable for women. Projections of colorectal cancer trends to the year 2000 indicate major expected rises in both incidence and prevalence. CONCLUSION: Colorectal cancer represents a problem of growing impact for health services in Italy. This conclusion can probably be extended to many developed countries.

Cancer Incidence and Mortality in the Elderly: Profile of the Italian Problem.

In Italy, 28% of all deaths are due to cancer. Of the 15% of the population that is 65 years or older, 65% of cancer deaths occur in men and 69.5% in women. The proportional mortality and incidence of cancer in Italy varies with increasing age. All patients over 65 years are found to be at increased risk for intestinal cancers. In older men, the proportion of lung and urinary tract cancers decreases, while prostate, intestinal and gastric cancers increases. Prostate cancer predominates in men over 85 years and intestinal and gastric cancers are relatively more common than lung cancer. In women over age 74, intestinal cancer is most common. Breast, genital and lung cancers decrease rapidly with age, while stomach, liver, gallbladder and pancreatic cancers increase with age. The ratio of incidence to mortality for all cancers studied is shown to equalize with increased age, the probable result of lower hospitalization rates and less adequate cancer therapy for the elderly.

Descriptive epidemiology of stomach cancer in Ragusa, Sicily, 1981-1988.

An epidemiologic study was carried out on 475 incident cases of gastric cancer registered by the Ragusa Cancer Registry (Sicily) between 1981 and 1988. Distribution by sex, age, subsite, year of incidence, and survival was investigated. A reduction of incidence and mortality between 1981-84 and 1985-88 was observed in both sexes, and was more evident in males than in females. Survival was not significantly different for cancers of the various subsites.

Survival of patients with cancer of the stomach, colon and rectum, lung and breast in Ragusa, Sicily.

Survival of 1747 patients with cancer of the stomach, colon/rectum, lung and female breast was investigated on incident cases registered by the Ragusa Cancer Registry, covering the Province of Ragusa (275,000 inhabitants) between 1981 and 1986. Cases known from the death certificate only were excluded. Date of death was obtained by a linkage with death certificates issued for Ragusa residents. Living status was assessed directly at the Registrar's Office. Analysis was performed also by sex, age group and presence of histologic verification. Relative survival at 5 years of Ragusa cancer cases was of the same order of magnitude as that observed in the U.S.A. (1980) and in Switzerland (1970-1980). However, the slight differences observed were mostly in favor of the Swiss and American patients. Sex did not significantly influence survival, but younger patients survived longer than older ones. Lack of histologic verification was associated with poor survival.

Comparability issues within the ITACARE data base.

AIMS AND BACKGROUND: The aim of the study was to describe the extent of variability among Italian cancer registries in data managing practices that may affect differences in incidence and possibly in survival estimates. METHODS: a self-administered questionnaire was sent to each participating registry. The definitions of the diseases, of the start point and of the end point of survival computation were investigated. Moreover, information on the proportion of histologic confirmation, of ill-defined sites and of DCO (death certificate only) was also considered. RESULTS: There were some differences in cancer registration techniques among Italian cancer registries. As regards disease definition, the most relevant problems arose for urinary bladder. Skin melanoma should also be considered with some caution, due to variability among registries in coding in situ cases. For the CNS and meninges, the proportion of cases that could be differently considered was so limited that no effect on survival is expected. For female breast, colorectum and cervix uteri, the effect of early diagnosis services (which are active only in some areas) may lead to better survival estimates. The variability in incidence date definition was high among registries and sites, but its effect on survival was very limited. There was a wide variability in the proportion of DCOs and of DCIs (initially known from death certificate), which should be considered in survival comparisons. All the registries stated that they carried out an active follow-up of their patients. CONCLUSIONS: In general, quality standards of the registries are good and allow comparability of survival data. The variability of rules adopted by Italian registries may affect geographic survival differences only in a limited number of cancer sites, so that results should be interpreted with caution.

Agreement estimate among three Italian cancer registries in the coding of multiple primary cancers.

AIMS: The aim of the study was to compare agreement on the coding of multiple primary cancers (MPs) between three italian cancer registries, the Ragusa Cancer Registry (RCR), the Cancer Registry of Romagna (RTRo), and the Tuscany Tumor Registry (RTT), that adhere to different rules for accepting MPs and to study whether coding according to common International rules (IARC-IACR) increased comparability. METHODS: One hundred cases were randomly extracted from the archives of each registry from those recorded as having more than one cancer. For each of the 300 patients, the number of independent cancers was attributed independently by one coder from each registry. The coders coded the series twice: once following the local registry rules and once according to the IARC-IACR rules. The agreement was estimated by couples of coders by means of Cohen's kappa statistics. RESULTS: The agreement on MP status between coders using local rules and definitions was good between the RTT and RCR (kappa = 0.77) and very good between the RTRo and RCR (kappa = 0.81) and the RTT and RTRo (kappa = 0.96). Exclusion of 23 expected discordant cases increased the agreement. The agreement reached with the use of the IARC-IACR rules was very good (RTRo vs RCR, 0.95; RTT vs RTR, 0.94; RTT vs RTRo, 0.95). CONCLUSIONS: The comparison among the RTT, RTRo and RCR confirmed that the number of tumors considered MPs may be modified depending on the rules adopted. There were minor differences between the RTT and the RTRo since their rules were very similar. Most differences in agreement were with the RCR since its classification was conceptually different from the other two. The result on agreement with IARC-IACR rules is encouraging from the point of view of conducting a cooperative study among different registries on the incidence of MPs.

Variations in the survival of adult cancer patients in Italy.

AIMS: As part of the ITACARE project, the present study analyzed and compared population-based data on the survival of adult cancer patients in Italy, according to sex, age, period of diagnosis and geographical area. METHODS: Nine Italian population-based cancer registries provided data on all their cancer patients (total 90,431 cases) followed for at least 5 years and diagnosed during the period 1978-1989. About 10% of the Italian population is covered by these registries. The data was analyzed by means of a multivariate model. RESULTS: The major findings were that there was a general improvement in 5-year relative survival over the study period (from 33% to 39%) and that there were significant differences in survival between different areas of the country, particularly for cancer sites which respond well to treatment. In general, the area covered by the Ragusa (Sicily) registry was characterized by significantly worse survival than other registry populations. Other important findings were that for all malignant cancer sites 5-year relative survival decreased with age from 50% for the youngest age class (15-44 years) to 27% for the oldest age class (75+ years) and that women have a better prognosis for most cancer sites (overall 5-year relative survival in women 48% vs 32% in men). CONCLUSIONS: The significant regional differences in survival may reflect unequal provision of care, particularly between northern-central Italy and the south. The reasons for the general survival improvement with time are not completely understood, whereas the marked overall sex difference is related to the fact that the commonest cancer in women (breast cancer) is eminently more treatable than the commonest malignancy in men (lung cancer). The unfavorable trend with increasing age may be due to increasing difficulty in applying complete therapy protocols as general health declines, sometimes in relation to an advanced cancer stage at diagnosis.

Reproducibility of histopathologic diagnosis and classification of non-melanocytic skin cancer: a panel exercise in the framework of the multicenter southern European study HELIOS.

AIMS AND BACKGROUND: The reproducibility of histologic diagnoses, and in particular of the distinction between basal and squamous cell forms, has been evaluated in the framework of a multicenter case-control study (in Italy, France, Spain and Switzerland) aimed to assess the causes of non-melanocytic skin cancers. METHODS: A panel composed of 10 pathologists from the collaborating centers was appointed. A total of 1,774 slides of routine diagnoses were blindly reviewed by a second panelist; discordant diagnoses underwent a third examination. Controversial and interesting cases were discussed during general sessions. RESULTS: The results showed a high degree of concordance (99.5%), with a Cohen's kappa of 0.85 (95% CI, 0.77-0.94) in the assessment of malignancy of lesions. The concordance in the distinction between large morphologic groups, basal cell carcinoma and squamous cell carcinoma was also high (Cohen's kappa = 0.85; 95% CI, 0.82-0.89). The assessment of histologic subtypes, degree of invasion and differentiation showed a lower degree of concordance, presumably as a consequence of a weaker consistency in the relevant classifications. CONCLUSIONS: The reproducibility study has therefore validated the epidemiologic study and in particular allowed to correct some misclassifications that could have lessened the analysis of the case-control study. In general, because of its characteristics (number of pathologists and variety of their origins, the large number of cases examined, blind examination of histologic slides), the conclusions of the study may show a certain degree of generalization, at least with regard to the countries represented. Routine histologic diagnoses of cutaneous carcinoma showed a high degree of reliability with reference to the assessment of malignancy and the distinction between basal and squamous cell carcinoma morphotypes.

[Survival for digestive system tumors: Italian population-based data and international comparisons]. / La sopravvivenza per tumore dell'apparato digerente: dati italiani su base di popolazione e confronti internazionali.

Survival for malignant tumour of the upper digestive tract, oesophagus, stomach and pancreas are analysed from the data of 5042 cases observed during the period 1976-1985 by the Italian cancer registries (CRs) of Varese, Latina, Ragusa and Florence. Three-year relative survival rates were 42% for patients with tumours of the upper digestive tract and 7% for those tumour of the oesophagus. Five-year relative survival for patients with stomach cancer was 20%. A worse prognosis was found for cases from the Latina and Ragusa CRs. One-year relative survival for patients with pancreatitic cancer was 17%. Younger age, histologic confirmation, period of diagnosis (for upper tract, stomach and pancreatitic cancers), and female gender (for tumours of the upper tract) resulted as positively associated to survival.

[Survival for tumors of the colon and the rectum in Italy]. / Sopravvivenza per tumori del colon e del retto in Italia.

In population based from four Italian cancer registries (Varese, Modena, Latina, Ragusa), five-years relative survival was 34% for colon cancer patients (no. = 1864) and 28% from rectum cancer patients (no. = 1117). However, rectum cancer patients showed higher survival rates in the first year of follow-up, which is possibly due to earlier diagnosis for sites more accessible to clinical examination. For colorectal cancer, age was an important prognostic factor, both in univariate and in multivariate analysis, adjusting for competitive mortality, sex, geographical area and year of diagnosis. In the same multivariate analysis, the prognosis was better for women, significantly for colon cancer and the excess death risk was reduced by 25-30% from 1978-79 to 1984-85. No significant differences were found among different geographical areas, possibly because of the low number of patients from some of the participating cancer registries.

[Analysis of the quality of death certificates for neoplasms in the province of Ragusa]. / Analisi della qualità dei certificati di morte per neoplasia in provincia di Ragusa.

The reliability of the death certificates issued in Ragusa for 379 of the 909 cancer patients registered in 1986 by the Ragusa Cancer Registry, who had died within 31 october 1988, was investigated. Data were available for 365 cases deceased. A consistent proportion (32.8%) of disagreements between diagnosis of the Registry and cause of death reported on death certificate was observed, concerning errors of the second and third digit of ICD-9 (21.9%) and for lack of mention of cancer in the death certificate. The main causes of the loss of information were the issuing of the certificate by a M.D. of the permanent medical ward and not by the family doctor, and the lack of the document released by the hospital upon discharge of the patient, usually containing indication on diagnosis and treatment.

Net survival: comparison between relative and cause-specific survival estimates.

This paper presents a comparison between cause-specific survival and relative survival calculated according to the Hakulinen method. The data are from the Tuscany Cancer Registry and we analysed the following cancer sites: stomach, colon, rectum, cervix and corpus uteri, female breast and skin melanoma. When cause-specific survival was calculated including among the deceased only those subjects whose death certificate reported strictly the same neoplasm as cause of death (three digits ICD-9), very good agreement between the two methods was found for stomach, lung, and skin melanoma and a good agreement was found for female breast. For cancer of the colon and rectum, in order to obtain similar estimates, deaths coded as caused by cancer in other sites of the large bowel and partially the not specified intestine had to be included. For cancer of the cervix and corpus uteri, in order to obtain similar estimates, but with cause-specific remaining higher than the relative estimates, deaths coded as not specified uteri cancer had to be included. In conclusion, cause-specific survival may be used also with overall mortality data, providing the death causes by cancers most susceptible to misclassification are to be included. However, using cause-specific survival creates some difficulties in comparative studies due to the different reliability of mortality data and to the different criteria used to identify the main cause of death.

[Estimate of the proportion of skin tumors attributable to sun exposure in 3 Italian populations]. / Stima della proporzione di tumori cutanei attribuibili all'esposizione solare in tre popolazioni Italiane.

Translation of recommendations on skin cancer prevention formulated by many national and international institutions into efficient steps requires measuring the potential impact in terms of preventable cases. This study analyses the proportion of skin cancers attributable to sun exposure in Turin, Trento and Ragusa. Estimates have been reached by applying the risk models calculated from the case-control study on melanoma in Turin and the Helios multi-centric study on skin carcinomas. The proportion of cases attributable to sun exposure has been subsequently calculated by correcting for the different proportion of skin characteristics among the populations taken into consideration. Attributable risks so calculated show medium to high values for melanoma in Turin (38%) and Trento (29%), while values are lower in Ragusa (17%). As for basal-cell carcinoma, attributable risk values are slightly inferior to those of melanoma. The risk of squamous-cell carcinoma attributable to sun exposure during outdoor work is the highest in Ragusa, with a value of 25%. Taking an annual incidence rate for melanoma of 9 cases per 100,000 inhabitants, and a preventive intervention with 50% of effectiveness, preventable cases should be 2 cases per 100,000 each year. This figure compared with 8 preventable cases of cervix cancer, in a similar population suggests an extremely cautious attitude in taking on programmes aiming to change life styles.

Coding criteria of bladder cancer: effects on estimating survival.

The aim of this study is to evaluate the consistency between routine methods for coding urinary bladder tumours in eight Italian cancer registries and the European Network of cancer registries (ENCR) criteria. Furthermore, it aims to evaluating the impact of the discordance on survival data. Eight cancer registries took part in the study: Ferrara, Florence, Macerata, Ragusa, Romagna, Sassari, Turin and Varese. The first 100 cases of neoplasm of the urinary bladder incident in the years 1993-1994 were identified from the files of each registry. The original pathology reports were made available. A working group considered eligible to the study 699 cases of microscopically confirmed transitional carcinoma (ICD-O morphology code 812-813). Using the ENCR criteria, each of these was classified according to morphology code (8120 vs. 8130) and behaviour (1/ uncertain, /2 non-invasive, 3/ invasive). Information of tumour behaviour was classified as follows: (i) present, when expressly stated in the original report, (ii) deducible, when not expressly stated but suggested by the pathologist's description, and (iii) absent, when impossible to determine on the basis of the original pathology report. The working group classification of tumour behaviour and the classification of the registry of origin were compared. There was a full concordance in the case of complete agreement on the morphology code, and partial concordance when only the invasive or non-invasive behaviour code was agreed upon. As much as 92.5% cases were microscopically confirmed. Tumour behaviour was expressly stated in the original report of 69.2% cases, not stated but suggested by the pathologist's description in 21.2% cases, and impossible to determine in 9.6%. Agreement between the panel and the registry of origin was complete in 71.2% cases and partial in 12.3% while there was a complete discordance in 16.5% cases. The panel interpreted as non-invasive 111 cases coded as invasive by the registry of origin. Conversely, it was estimated that 24% cases included in incidence data were non-invasive. This article discusses the impact of misclassification on survival data.

[Methodological issues and first results of a record linkage between AIDS and Cancer Registries in Italy]. / Incrocio tra i Registri Tumori italiani e il Registro nazionale AIDS: aspetti metodologici e primi risultati.Cancer and AIDS Registry Linkage Study.

We report herein, the first results of a record linkage between the Italian AIDS Registry and 13 population-based Cancer Registries (about 8-million population in 1991). An anonymous linkage process was carried out on about 339,000 cancer notifications and 6,067 AIDS ones reported between 1982 and 1994. Out of 243 Kaposi's sarcomas (KS) below age 50 years recorded at either type of registry, 90 (37%) were reported as such by both. Sixty-eight percent of individuals with KS at Cancer Registries could be identified at the AIDS Registry. Sixty-two percent of individuals with KS and 65% of individuals reported as having non-Hodgkin's lymphoma (NHL) at RAIDS could be also found at Cancer Registries. Among 6,067 persons with AIDS 15-69 years old, observed and expected numbers of cancer and age-standardised incidence ratios (SIR) on a total of 25,759 person-years were computed. Significantly increased SIR was found for Hodgkin's disease (8.9; 95% CI: 4.4-16.0), invasive carcinoma of the cervix uteri (15.5; 95% CI: 4.0-40.1), and non-melanomatous skin cancer (3.0, 95%, CI: 1.3-5.9). As in previous studies, KS and NHL were greatly increased (SIR = 1,300 and 59, respectively). The risk for all cancer types, after exclusion of KS and NHL, was approximately twice the risk of the general population. An increased SIR of Hodgkin's disease in persons with AIDS is thus confirmed, though many-fold smaller than for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. These data indicate the potential of AIDS and Cancer Registries for improving cancer assessment in individuals with HIV/AIDS and elucidating the role of immune system on cancer onset.

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case-case-control study.

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma.

A case-control study on lip cancer risk factors in Ragusa (Sicily).

Incidence rates of lip cancer in males in Ragusa (Sicily) are amongst the highest in Europe [age-standardized rate (world) for 1980-82: 7.5 per 100,000]. A case-control study was conducted on 53 male cases and 106 controls matched for sex, age (+/- 2 1/2 years), residence and hospital from which cases had been drawn. Individual interviews were carried out for the evaluation of ethnic, environmental, pathologic and occupational risk factors. Lip cancer was significantly associated with: fair, brown, or red hair (relative odds = 2.3), blue eyes (r.o. = 5.3), fair skin (r.o. = 8.0), sensitivity to sunburns (r.o. = 4.1), working outdoors (r.o. = 4.9), coexistence of non-specific lesions of exposed body parts (r.o. = 12,2), low socioeconomic status (r.o. = 15.8), farming (r.o. = 2.6) and working in greenhouses (r.o. = 12.0). Recall of recurrent Herpes labialis was not significantly associated; also association with tobacco smoking was not significant after adjustment for socioeconomic status. Risk increased exponentially with the number of ethnic characteristics of northern European populations.