Vincenzo De Lisi

Estimate of overdiagnosis of breast cancer due to mammography after adjustment for lead time. A service screening study in Italy

IntroductionExcess of incidence rates is the expected consequence of service screening. The aim of this paper is to estimate the quota attributable to overdiagnosis in the breast cancer screening programmes in Northern and Central Italy.MethodsAll patients with breast cancer diagnosed between 50 and 74 years who were resident in screening areas in the six years before and five years after the start of the screening programme were included. We calculated a corrected-for-lead-time number of observed cases for each calendar year. The number of observed incident cases was reduced by the number of screen-detected cases in that year and incremented by the estimated number of screen-detected cases that would have arisen clinically in that year.ResultsIn total we included 13,519 and 13,999 breast cancer cases diagnosed in the pre-screening and screening years, respectively. In total, the excess ratio of observed to predicted in situ and invasive cases was 36.2%. After correction for lead time the excess ratio was 4.6% (95% confidence interval 2 to 7%) and for invasive cases only it was 3.2% (95% confidence interval 1 to 6%).ConclusionThe remaining excess of cancers after individual correction for lead time was lower than 5%.

Cancer incidence in people with AIDS in Italy

People with HIV/AIDS (PWHA) have increased risk of some cancers. The introduction of highly active antiretroviral therapies (HAART) has improved their life expectancy, exposing them to the combined consequences of aging and of a prolonged exposure to cancer risk factors. The aim of this study was to estimate incidence rates (IR) in PWHA in Italy, before and after the introduction of HAART, after adjusting for sex and age through direct standardization. An anonymous record linkage between Italian AIDS Registry (21,951 cases) and Cancer Registries (17.3 million, 30% of Italian population) was performed. In PWHA, crude IR, sex‐ and age‐standardized IR and age‐specific IR were estimated. The standardized IR for Kaposi sarcoma and non‐Hodgkin lymphoma greatly declined in the HAART period. Although the crude IR for all non‐AIDS‐defining cancers increased in the HAART period, standardized IR did not significantly differ in the 2 periods (352 and 379/100,000, respectively). Increases were seen only for cancer of the liver (IR ratio = 4.6, 95% CI: 1.3–17.0) and lung (IR ratio = 1.8, 95% CI: 1.0–3.2). Age‐specific IRs for liver and lung cancers, however, largely overlapped in the 2 periods pointing to the strong influence of the shift in the age distribution of PWHA on the observed upward trends. In conclusion, standardized IRs for non‐AIDS‐defining cancers have not risen in the HAART period, even if crude IRs of these cancers increased. This scenario calls, however, for the intensification of cancer‐prevention strategies, notably smoking cessation and screening programs, in middle‐aged HIV‐patients.

Incidence of AIDS-defining cancers after AIDS diagnosis among people with AIDS in Italy, 1986-1998

A record linkage was carried out between the Italian National Registry of AIDS and 19 cancer registries. The aim was to evaluate the 1986 through 1998 trends in incidence rate (IR) of AIDS-defining cancers (ADCs) among persons with AIDS (PWA) in Italy overall and according to various characteristics. A steady decrease in IRs was found for Kaposi sarcoma (KS) in men between 1986–1992 (2.5 per 100 person-years [py]) and 1997–1998 (1.0 per 100 py). Conversely, the first decrease in IRs of KS in women (from 0.9 to 0.6 per 100 py) and of non-Hodgkin lymphoma in both genders (from 1.7 to 0.7 per 100 py) was seen between 1993–1996 and 1997–1998, thus pointing to a favorable impact of highly active antiretroviral therapies. The decline was consistent across different age and HIV transmission groups, but it was more marked in PWA with a CD4 count >50 cells/&mgr;L than in PWA with more severe immune suppression. As a proportion of AIDS cases, invasive cervical cancer increased from 1.5% in 1993–1996 to 2.4% in 1997–1998, but IRs after AIDS could not be evaluated. On account of the marked decline of KS in men in 1997–1998, the overall burden of ADCs in Italy became similar in both genders.

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.

A method to estimate mortality trends when death certificates are imprecisely coded: An application to cervical cancer in Italy

Systematic analysis of mortality trends of cervix and corpus uteri cancers is difficult in Italy, as in many other countries, because of the poor specification of uterine cancer subsites in official death statistics. The aim of this article is to propose a method for the analysis of uterine cancers mortality based on high quality incidence and prevalence data from population‐based cancer registries. The method assumes that the excess mortality of cancer patients, compared to death rates expected in the general population, is attributable to the specific cancer. The method is applied to estimate mortality trends for cancers of cervix, corpus and uterus as whole, during the period 1987–1999, in an area covered by 8 Italian cancer registries. Official mortality rates for the 2 subsites were about 60% lower than excess mortality rates, due to the very high proportion of deaths attributed to not specified subsite. Age adjusted cervical cancer excess mortality rates decreased from 3.7 to 2.7 × 100,000 women. Excess mortality for corpus uteri cancer remained approximately stable between 3 and 3.3 × 100,000 women in the period 1990–1999. The results support the efficacy of organized screening in reducing cervical cancer mortality. The same method can be used to assess mortality rates for every cancer entity identifiable in cancer registries data, not otherwise available from official death records.

Changes in the Incidence of Thyroid Cancer Between 1991 and 2005 in Italy: A Geographical Analysis

BACKGROUND The incidence of thyroid cancer (TC) has been increasing over the last 30 years in several countries, with some of the worldwide highest TC incidence rates (IRs) reported in Italy. The objectives of this study were to evaluate by histological subtypes the geographical heterogeneity of the incidence of TC in Italy and to analyze recent time trends for papillary thyroid carcinoma (PTC) in different cancer registries (CRs). METHODS The study included cases of TC (<85 years of age) reported to 25 Italian CRs between 1991 and 2005. Age-standardized IRs were computed for all histological subtypes of TC according to CRs. Estimated annual percent change and joinpoint regression analysis were used for analysis of PTC. RESULTS In women, IRs of PTC ranged between 3.5/100,000 in Latina and 8.5/100,000 in Sassari for the period 1991-1995 (a 2.4-fold difference) and between 7.3/100,000 in Alto Adige and 37.5/100,000 in Ferrara for 2001-2005 (a 5.1-fold difference). In men, IRs ranged between 0.7/100,000 in Latina and 3.4/100,000 in Sassari for the period 1991-1995 (a 4.9-fold difference) and between 2.0/100,000 (Alto Adige, Trento) and 10.6/100,000 in Ferrara for 2001-2005 (a 5.3-fold difference). In both sexes, IRs significantly higher than the pooled estimates emerged for the most recent period in the majority of CRs located within the Po River plain and in Latina, but they were lower in the Alpine belt. For women, CRs reported higher IRs than pool estimates showed, between 1991 to 2005, a significantly more marked annual percent change (+12%) than other CRs (+7%). For men the corresponding estimates were +11% and +8%. CONCLUSIONS The distribution of PTC does not lend support to a role of environmental radiation exposure due to the Chernobyl fallout, iodine deficiency, or (volcanic) soils. Between 1991 and 2005, wide geographic variations in the incidence of PTC and heterogeneous upward trends emerged, suggesting that the heterogeneity was a relatively recent phenomenon; this appeared to be mainly explained by variations, at a local level, in medical surveillance.

The risk of developing a second, different, cancer among 14 560 survivors of malignant cutaneous melanoma: a study by AIRTUM (the Italian Network of Cancer Registries).

The aim of this study was to provide further quantitative data on the risk of second nonmelanoma cancers in patients with cutaneous malignant melanoma (CMM). A cohort of 14 560 population-based patients from the Italian Network of Cancer Registries incident during 1985–2002 were included and followed up for further incident cases and vital status. Standardized incidence ratios (SIR) were used to compare the number of observed second cancers with expected cancers. In a total of 69 581 person-years, 1020 second cancers were registered, of which 804.6 were expected (SIR=1.27; 95% confidence interval 1.19–1.35). The risk was similar for males and females, (SIR=1.27 and 1.26, respectively). The risk was slightly higher among younger (<60 years; SIR=1.44) than older (60+ years; SIR=1.19) patients. The overall risk in the period after CMM diagnosis did not change significantly (SIR=1.34 during the first 5 years and 1.12 afterwards). No differences in the overall risk were evident in different years of diagnosis, for different melanoma morphology types or for different geographical areas within Italy. Statistically significantly increased risks were found for nonmelanoma skin cancers [observed number (n)=362, SIR=3.12], for bone (n=5, SIR=6.08) and for kidney cancers (n=39, SIR=1.95) and lower than expected risks were found for liver (SIR=0.46) and lung cancers (SIR=0.71). We confirm that CMM patients are at high risk for nonmelanoma skin cancers. The reasons for the increased risk of kidney and bone cancers are not yet clear.

Survival in adult Italian cancer patients, 1978-1989

Aims To present a systematic analysis of population-based cancer patient survival in Italy. Methods Population-based survival data have been made available from 10 Italian cancer registries within the ITACARE project. Data, collected and validated using a common protocol, included over 100,000 patients with cancer diagnosed between 1978 and 1989. Multivariate weighted analysis was used to provide relative survival estimates attributable to Italy at national level. Results Results are presented, according to a systematic frame, as the main object of the ITACARE study, involving crude and relative survival figures for adult Italian cancer patients, by age, sex, period of diagnosis and registry area. An estimate with reference to Italy as a whole is also presented by cancer site and for all malignant neoplasms combined. Age-standardized relative survival figures are presented to allow comparisons between Italian registries and also to give a basis for international comparisons with countries involved in the EUROCARE study. Conclusions For the fist time, population-based survival of cancer patients is made available in Italy on a large scale analysis of data from all the Italian cancer registries in a combined action. Estimates of cancer patient survival at a national level in Italy allow proper international comparisons with European countries and give elements of evaluation and discussion on the performance of the Italian health care system.

Non‐Hodgkin lymphoma among young adults with and without AIDS in Italy

To compare the presentation and prognosis of non‐Hodgkin lymphoma (NHL) in people with AIDS (PWA) and in the general Italian population, a record linkage study was carried out. The fraction of NHLs attributable to HIV/AIDS was also estimated. Information from the National AIDS Registry (RAIDS) was linked with records from 13 cancer registries (CR), covering about 15% of the Italian population. During the period 1985–94, among PWA ages 15–49, 136 NHLs were identified (8% of all NHLs) and were compared with 1,481 concurrent incident NHL cases of the same age group among non‐PWA. Percentages above 13% of all NHLs were registered in the northern areas of Genoa and Varese, i.e., the most heavily affected by the AIDS epidemic. Between 1 year prior to and 3.5 years after AIDS diagnosis, PWA showed an overall standardised incidence ratio (SIR) for NHL of 302. SIR was particularly high (394) within 3 months after AIDS diagnosis and subsequently declined to 170. SIR was somewhat higher in females (428) than in males (280) but similar among intravenous‐drug users (299) and other HIV‐transmission groups (309). High‐grade NHL, particularly immunoblastic and Burkitts lymphoma, were twice as frequent among PWA than non‐PWA. Conversely, low‐grade NHL were less frequent. Except for the high proportion of brain localisation, no clear difference emerged in the pattern of NHL presentation site in PWA compared with non‐PWA. At variance with NHL in the general population, among PWA histological grade had little impact on survival, which overall appeared to be very poor (2‐year survival: 10%; 95% confidence interval: 3%–17%). Our present linkage of RAIDS and CRs represents an efficient tool for the surveillance of trends in incidence and survival of NHL among PWA in Italy.

Stage-specific incidence of breast cancer before the beginning of organized screening programs in Italy

Objective: To measure stage-specific geographic and time variability of breast cancer in seven Italian areas before the onset of organized screening programs. Methods: All invasive cancers (8689 cases) arising in women aged 40–79 years during the pre-screening period 1985–1997, were considered. Multiple Poisson regression analysis was performed. Results: About 39% of the cases were classified as “early,” 52% as “advanced,” and 9% as “unspecified” stage. Age-adjusted incidence rates showed a significant geographic variation for early but not for advanced cancers (range: 58–103 cases/100,000 and 104–125 cases/100,000, respectively). The result was confirmed in the multiple regression analysis after adjustment for year of diagnosis and age. Early breast cancer risk adjusted for age and registry showed a significant increase over time (+ 3.9% per year for all ages, and + 6.2% per year for age category 50–79). In contrast, a decreasing time trend was observed for advanced cancer of 3 cm or over in women aged less than 60. Conclusions: In our study, early breast cancer incidence varied both by geographic area and time before the commencement of screening. The differences in early-stage incidence may well be related to differences in availability of “spontaneous” mammography. Late-stage incidence decreased over time in younger women and for very advanced cases, but not in the older ones, nor for cancers less than 3 cm. Early detection outside organized screening was only partially efficient in reducing advanced breast cancer incidence. The trend of incidence of advanced disease, as previously proposed, is confirmed to be a valid early indicator of effectiveness of screening.