The impact of overdiagnosis on thyroid cancer epidemic in Italy,1998-2012.

AIMS: In Italy, incidence rates of thyroid cancer (TC) are among the highest worldwide with substantial intracountry heterogeneity. The aim of the study was to examine time trends of TC incidence in Italy and to estimate the proportion of TC cases potentially attributable to overdiagnosis. METHODS: Data on TC cases reported to Italian cancer registries during 1998-2012 aged <85 years were included. Age-standardised incidence rates (ASR) were computed by sex, period, and histology. TC overdiagnosis was estimated by sex, period, age, and Italian region. RESULTS: In Italy between 1998-2002 and 2008-2012, TC ASR increased of 74% in women (from 16.2 to 28.2/100,000) and of 90% in men (from 5.3 to 10.1/100,000). ASR increases were nearly exclusively due to papillary TC (+91% in women, +120% in men). In both sexes, more than three-fold differences emerged between regions with highest and lowest ASR. Among TC cases diagnosed in 1998-2012 in Italy, we estimated that overdiagnosis accounted for 75% of cases in women and 63% in men and increased over the study period leading to overdiagnosis of 79% in women and 67% in men in 2008-2012. Notably, overdiagnosis was over 80% among women aged <55 years, and substantial variations were documented across Italian regions, in both genders. CONCLUSION(S): Incidence rates of TC are steadily increasing in Italy and largely due to overdiagnosis. These findings call for an update of thyroid gland examination practices in the asymptomatic general population, at national and regional levels.

Characteristics of people living in Italy after a cancer diagnosis in 2010 and projections to 2020.

BACKGROUND: Estimates of cancer prevalence are widely based on limited duration, often including patients living after a cancer diagnosis made in the previous 5 years and less frequently on complete prevalence (i.e., including all patients regardless of the time elapsed since diagnosis). This study aims to provide estimates of complete cancer prevalence in Italy by sex, age, and time since diagnosis for all cancers combined, and for selected cancer types. Projections were made up to 2020, overall and by time since diagnosis. METHODS: Data were from 27 Italian population-based cancer registries, covering 32% of the Italian population, able to provide at least 7 years of registration as of December 2009 and follow-up of vital status as of December 2013. The data were used to compute the limited-duration prevalence, in order to estimate the complete prevalence by means of the COMPREV software. RESULTS: In 2010, 2,637,975 persons were estimated to live in Italy after a cancer diagnosis, 1.2 million men and 1.4 million women, or 4.6% of the Italian population. A quarter of male prevalent cases had prostate cancer (n = 305,044), while 42% of prevalent women had breast cancer (n = 604,841). More than 1.5 million people (2.7% of Italians) were alive since 5 or more years after diagnosis and 20% since ≥15 years. It is projected that, in 2020 in Italy, there will be 3.6 million prevalent cancer cases (+ 37% vs 2010). The largest 10-year increases are foreseen for prostate (+ 85%) and for thyroid cancers (+ 79%), and for long-term survivors diagnosed since 20 or more years (+ 45%). Among the population aged ≥75 years, 22% will have had a previous cancer diagnosis. CONCLUSIONS: The number of persons living after a cancer diagnosis is estimated to rise of approximately 3% per year in Italy. The availability of detailed estimates and projections of the complete prevalence are intended to help the implementation of guidelines aimed to enhance the long-term follow-up of cancer survivors and to contribute their rehabilitation needs.

[Cardiovascular diseases and cancer incidence in general population: results from MATISS cohort]. / Incidenza di malattie cardiovascolari maggiori e tumori nella coorte longitudinale del Progetto MATISS in persone con differente profilo di rischio cardiovascolare.

OBJECTIVES: to assess the incidence of fatal and non-fatal major cardiovascular diseases and cancers in people with different cardiovascular risk profile of a longitudinal cohort. DESIGN: longitudinal study carried out in a large sample of general population, with a median follow-up of 17.7 years. SETTING AND PARTICIPANTS: MATISS longitudinal cohort, 7,491 men and women aged 20-75 years, free of cancer or cardiovascular diseases at baseline. Two cardiovascular risk groups (low-intermediate cardiovascular risk and high cardiovascular risk) and two educational levels (low level: primary school; middle/high level: middle/high school, university) have been considered. MAIN OUTCOME MEASURES: for both cancer and cardiovascular events the standardized incidence rates have been calculated, taking into account the cardiovascular risk profile and the educational level. RESULTS: people with a high-risk profile have higher incidence of major cardiovascular diseases and cancers. Furthermore, incidence rates are higher in people with lower educational level, except for cardiovascular diseases in men. CONCLUSIONS: this study shows that, in the considered population, cancer incidence rates are higher than cardiovascular diseases rates; moreover, cancer incidence is higher in people with high-risk cardiovascular profile. The increase of prevalence of favourable risk profile in the general population could represent effective community strategies for prevention of cardiovascular diseases and cancer. Major attention should be dedicated towards people at lower socioeconomical level.

Prostate cancer changes in clinical presentation and treatments in two decades: an Italian population-based study.

INTRODUCTION: The incidence of prostate cancer is on the rise in many industrialised countries, including Italy, most likely because of the spread of PSA testing. In Italy, prostate cancer mortality has been dropping since 2000, but it is difficult to understand whether PSA testing is the main reason, considering the role of treatment in prognosis. The objectives of this study were: (1) to describe Italian trends of prostate cancer risk categories and corresponding changes in treatment patterns and (2) to interpret changes in survival over time. METHODS: We made a retrospective observational study using population-based cancer registries. We examined two periods, 1996-1999 and 2005-2007, analysing the distribution of patients among risk groups and treatment changes in those intervals. We estimated 7- and 15-year relative survival with the cohort approach, Ederer II method. We analysed 4635 cases. RESULTS: There was downward risk migration from the first to the second period. In patients younger than 75 years, there was an increase in radical prostatectomy but not radiotherapy; patients older than 75 years rarely had treatment with radical intent. We noted an improvement of prostate cancer survival in the high-risk group. CONCLUSION: These findings raise several questions: the possible overtreatment of low-risk patients undergoing radical treatment; the utility of more aggressive treatment for elderly patients with high-risk disease; and the importance of a multidisciplinary clinical approach to ensure multiple and alternative treatment options. The increase in survival, with the decrease in mortality, suggests an effect of radical treatments on prognosis.

Screening for colorectal cancer in Italy: 2011-2012 survey.

We utilised the IMPATTO study's archives to describe the 2000-2008 colorectal cancer (CRC) incidence rate trends in Italy, once screening programmes based on the faecal immunochemical test were implemented in different areas. Data on CRCs diagnosed in Italy from 2000 to 2008 in subjects aged 40-79 years were collected by 23 cancer registries. Incidence rate trends were evaluated as a whole and by macro-area (North-Centre and South-Islands), presence of a screening programme, sex, ten-year age class, anatomic site, stage at diagnosis, and pattern of diagnosis (screen-detected, non-screen-detected). The annual percent change (APC) of incidence rate trends, with 95% confidence intervals (95%CI), were computed. The study included 46,857 CRCs diagnosed in subjects aged 40-79 years, of which 2,806 were screen-detected. The incidence rates in the North-Centre were higher than in the South and on the Islands. During the study period, screening programmes had been implemented only in the North-Centre and had a significant effect on incidence rates, with an initial sharp increase in incidence, followed by a decrease that started in the 3rd-4th years of screening. These incidence rate trends were exclusively due to modifications in the rates of stage I cases. After screening programmes started, incidence increased in all anatomic sites, particularly in the distal colon. The differential figures introduced by the implementation of screening programmes warrant a continuous surveillance of CRC incidence and mortality trends to monitor the impact of screening at a national level.

Changes in cervical cancer incidence following the introduction of organized screening in Italy.

OBJECTIVE: To quantify the impact of organized cervical screening programs (OCSPs) on the incidence of invasive cervical cancer (ICC), comparing rates before and after activation of OCSPs. METHODS: This population-based investigation, using individual data from cancer registries and OCSPs, included 3557 women diagnosed with ICC at age 25-74years in 1995-2008. The year of full-activation of each OCSP was defined as the year when at least 40% of target women had been invited. Incidence rate ratios (IRRs) with 95% confidence intervals (95% CIs) were calculated as the ratios between age-standardized incidence rates observed in periods after full-activation of OCSPs vs those observed in the preceding quinquennium. RESULTS: ICC incidence rates diminished with time since OCSPs full-activation: after 6-8years, the IRR was 0.75 (95% CI: 0.67-0.85). The reduction was higher for stages IB-IV (IRR=0.68, 95% CI: 0.58-0.80), squamous cell ICCs (IRR=0.74, 95% CI: 0.64-0.84), and particularly evident among women aged 45-74years. Conversely, incidence rates of micro-invasive (stage IA) ICCs increased, though not significantly, among women aged 25-44years (IRR=1.34, 95% CI: 0.91-1.96). Following full-activation of OCSPs, micro-invasive ICCs were mainly and increasingly diagnosed within OCSPs (up to 72%). CONCLUSION(S): Within few years from activation, organized screening positively impacted the already low ICC incidence in Italy and favored down-staging.

Estimates of cancer burden in Lazio.

AIMS AND BACKGROUND: Since 1983 a population-based cancer registry has been operating in Lazio which provides incidence and survival data and covers the entire Latina province, amounting to 10% of the regional population. The aim of this paper is to provide estimates of the incidence, mortality and prevalence for seven major cancers in the Lazio region for the period 1970-2015. METHODS: The estimates were obtained by applying the MIAMOD method, a statistical back-calculation approach to derive incidence and prevalence figures starting from mortality and relative survival data. Survival was modeled on the basis of published data from the Italian cancer registries. RESULTS: In 2012 the most frequent cancer sites were breast, colon-rectum and prostate with 5,529, 5,315 and 4,759 new diagnosed cases, respectively. The cancers with increasing incidence trends were breast cancer, lung cancer and skin melanoma in women, and prostate cancer, colorectal cancer and melanoma in men. The incidence rates of uterine cervix and stomach cancer decreased. The male lung cancer rates increased, reaching a peak in the late 1980s, and then decreased. Prevalence increased for all the considered cancers except cervix cancer. In 2012 breast, colorectal and prostate cancer had the highest prevalence, with 68,239, 36,617 and 33,934 prevalent cases, respectively. In the final period of the study the mortality declined for all cancers except female lung cancer. In 2012, the highest mortality rates were estimated for lung cancer in both men and women, with 89 and 40 deaths per 100,000, respectively. CONCLUSION: These estimates give a useful description of the present and future cancer patterns in the Lazio region. Incidence, mortality and prevalence projections provide new information for health resource planning. Furthermore, they point to the need to reinforce the organized screening programs, especially for breast and colorectal cancer.

Estimated glomerular filtration rate, all-cause mortality and cardiovascular diseases incidence in a low risk population: the MATISS study.

BACKGROUND: Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far. DESIGN: Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD. METHODS: Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula. RESULTS: At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73 m(2) and more than 70% had a 10-year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (<90 and ≥109 mL/min/1.73 m(2), respectively) were associated to an increased risk for both all-cause mortality (hazard ratio 1.6, 95% confidence interval 1.2-2.1 and 4.3, 1.6-11.7, respectively) and incident CVD (1.6, 1.0-2.4 and 7.0, 2.2-22.9, respectively), even if adjusted for classical risk factors. CONCLUSIONS: These findings strongly suggest that in an elderly, general population at low risk of CVD and low prevalence of reduced renal filtration, even a modest eGFR reduction is related to all-cause mortality and CVD incidence, underlying the potential benefit to this population of considering eGFR for their risk prediction.

Clinical characteristics and plasma lipids in subjects with familial combined hypolipidemia: a pooled analysis.

Angiopoietin-like 3 (ANGPTL3) regulates lipoprotein metabolism by modulating extracellular lipases. Loss-of function mutations in ANGPTL3 gene cause familial combined hypolipidemia (FHBL2). The mode of inheritance and hepatic and vascular consequences of FHBL2 have not been fully elucidated. To get further insights on these aspects, we reevaluated the clinical and the biochemical characteristics of all reported cases of FHBL2. One hundred fifteen FHBL2 individuals carrying 13 different mutations in the ANGPTL3 gene (14 homozygotes, 8 compound heterozygotes, and 93 heterozygotes) and 402 controls were considered. Carriers of two mutant alleles had undetectable plasma levels of ANGPTL3 protein, whereas heterozygotes showed a reduction ranging from 34% to 88%, according to genotype. Compared with controls, homozygotes as well as heterozygotes showed a significant reduction of all plasma lipoproteins, while no difference in lipoprotein(a) [Lp(a)] levels was detected between groups. The prevalence of fatty liver was not different in FHBL2 subjects compared with controls. Notably, diabetes mellitus and cardiovascular disease were absent among homozygotes. FHBL2 trait is inherited in a codominant manner, and the lipid-lowering effect of two ANGPTL3 mutant alleles was more than four times larger than that of one mutant allele. No changes in Lp(a) were detected in FHBL2. Furthermore, our analysis confirmed that FHBL2 is not associated with adverse clinical sequelae. The possibility that FHBL2 confers lower risk of diabetes and cardiovascular disease warrants more detailed investigation.

Screening patterns within organized programs and survival of Italian women with invasive cervical cancer.

OBJECTIVES: To evaluate screening patterns within organized cervical screening programs (OCSPs) and survival of women with invasive cervical cancer (ICC). METHODS: A population-based study was conducted in Italian areas covered by cancer registries and OCSPs. The study included all women aged 25-65 years diagnosed with ICC between 1995 and 2008, and their screening histories within OCSPs were retrieved. Hazard ratios (HR) of death and 95% confidence intervals (CI) were computed according to screening pattern, using Cox models adjusted for age, ICC stage, and major confounders. RESULTS: Among 3268 women with ICC, 20% were never-invited to OCSP, 36% were never-compliant with OCSP's invitation, 33% were compliant and had a screen-detected ICC within OCSP (i.e., after a positive cytology), and 11% were compliant but had a non-screen-detected ICC. Screen-detected ICCs were more frequently micro-invasive (42%) compared to non-screen-detected ones (14%). Compared to women with screen-detected ICC, the adjusted HRs of death were 1.9 (95% CI 1.5-2.4) for those never-invited, 2.0 (95% CI 1.6-2.5) for never-compliant, and 1.7 (95% CI 1.3-2.4) for compliant women having non-screen-detected ICC. CONCLUSION: Prolonged survival, beyond down-staging, of women with ICC detected within OCSPs in Italy, further calls for improvements of OCSPs' invitational coverage and participation.

Increased incidence of thyroid cancer in Latina, Italy: a possible role of detection of subclinical disease.

OBJECTIVE: To describe the thyroid cancer incidence trends and geographical patterns in the Latina Province of Lazio, Italy using the population-based cancer registry. METHODS: We extracted from the Latina cancer registry all cases of thyroid cancer from 1997 to 2006. Cases were classified according to morphological type and diameter. Data for diagnostic procedures for Latina Province residents from 2001 to 2006 were extracted from the regional outpatient procedures information system. RESULTS: A total of 982 cases were diagnosed, for a standardized incidence of 8.3 and of 27.9 per 100,000 in males (n, 220) and in females (n, 762), respectively. The annual percent change (APC) was +16.7% (95% CI +7.2, +27.2) and +10.5% (95% CI +6.5, +14.6) in males and females, respectively. The increase was mostly due to papillary (n, 759) and small (≤20 mm) cancers (n, 617), with no difference by age (<45 years; n, 431). The APC of neck ultrasound performed was +8.7% (95% CI +0.1, +18.1) and +9.0% (95% CI +1.1, +17.4) and that of biopsy/cytology was +17.0% (95% CI +13.0, +21.3) and +16.6% (95% CI +6.2, +28.1) in men and women, respectively. The geographic pattern of biopsy/cytology was similar to that of cancer incidence but not to that of neck ultrasound. CONCLUSIONS: In Latina, the increase in thyroid cancer incidence was more rapid than in the rest of Italy, particularly for types with a good prognosis. While tumor size and histotype suggest an increase in detection instead of an increase in disease occurrence, data on diagnostic procedure reimbursements cannot provide an explanation.

[Cancer incidence and mortality in the cohort of residents close to the Italian nuclear power plants of Borgo Sabotino and Garigliano]. / Incidenza di tumori e mortalità nella coorte dei residenti in prossimità delle centrali nucleari italiane di Borgo Sabotino e del Garigliano.

INTRODUCTION: the potential health impacts due to the decommissioned Nuclear power plants (NPP) located in Borgo Sabotino and Garigliano in Central Italy (active from the early 1960s to the late 1980s) have raised several concerns. Brain, thyroid, breast and lung cancer and leukaemia have been associated with exposure to ionizing radiations, but the health effects of nuclear plants on the resident populations are controversial. OBJECTIVE: to evaluate whether living close to NPPs is associated with an increased risk of cancer incidence and mortality. METHODS: we defined a cohort of residents within 7 km from the NPPs during the period 1996-2002. Individual follow-up for vital status at 01.01.2007 was conducted using municipality data. Gender specific Standardized Incidence and Mortality Ratios, adjusted for age, were calculated (SIR and SMR) using the regional population as reference. Each participant's address was assigned to a distance from the NPP on the basis of a GIS. A relative risk (RR, CI95%), adjusted for age and socioeconomic status, was calculated in 3 bands of increasing radius from the plants: 0-2, 2-4, and 4-7 km (reference group), using a Poisson regression model. RESULTS: the cohort was of 39,775 people, 32%of whom lived near (0-4 km) the NPP. No differences in mortality was found when comparing the cohort with the regional population; among women living within 7 km from the NPP, we found thyroid cancer incidence higher than expected (SIR 1.53 CI95% 1.18-1.95). However, when the analysis was conducted on the basis of the distance from the NPP, we found a statistically significant increase in male mortality only for causes unrelated to radiation exposure (all causes, stomach cancer, and cardiovascular diseases). No mortality excess was observed among women living close to the NPPs. No statistically significant distance-related gradient was observed for cancer incidence both in men and women. CONCLUSIONS: living close to the NPP was not associated with mortality for causes related to radiation exposure. However, the results suggest to continue the epidemiological surveillance of the population.

Cancer prevalence in Italy: an analysis of geographic variability.

PURPOSE: Statistics on cancer prevalence are scanty. The objectives of this study were to describe the cancer prevalence in Italy and to explore determinants of geographic heterogeneity. METHODS: The study included data from 23 population-based cancer registries, including one-third of the Italian population. Five-year cancer prevalence was observed, and complete prevalence (i.e., all patients living after a cancer diagnosis) was estimated through sex-, age-, cancer site-, and observation period length-specific completeness indices by means of regression models. RESULTS: In 2006, 3.8 % of men and 4.6 % of women in Italy were alive after a cancer diagnosis, with a 5-year prevalence of 1.9 % and 1.7 % in men and women, respectively. A relevant geographic variability emerged for all major cancer sites. When compared to national pooled estimates, crude cancer prevalence proportions were 10 % higher in the north and 30 % lower in the south of Italy. However, these variations were consistently reduced after age adjustment and, in both sexes, largely overlapped those of incidence rates, with correlations >0.90 between variations of prevalence and incidence for all cancer sites and areas. CONCLUSIONS: Magnitude of the cancer prevalence and the geographic heterogeneity herein outlined in Italy will help in meeting the needs of specific population of survivor patients.

Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization.

CONTEXT: Familial combined hypolipidemia causes a global reduction of plasma lipoproteins. Its clinical correlates and metabolic implications have not been well defined. OBJECTIVE: The objective of the study was to investigate the genetic, clinical, and metabolic characteristics of a cohort of subjects with familial combined hypolipidemia. DESIGN: The design of the study included candidate gene screening and the comparison of the clinical and metabolic characteristics between carrier and noncarrier individuals. SETTING: The study was conducted in a general community. SUBJECTS: Participants in the study included individuals belonging to nine families with familial combined hypolipidemia identified in a small town (Campodimele) as well as from other 352 subjects living in the same community. MAIN OUTCOMES MEASURES: Serum concentrations of lipoproteins, Angiopoietin-like 3 (Angptl3) proteins, and noncholesterol sterols were measured. RESULTS: The ANGPTL3 S17X mutation was found in all probands, 20 affected family members, and 32 individuals of the community. Two additional frame shift mutations, FsE96del and FsS122, were also identified in two hypocholesterolemic individuals. Homozygotes for the ANGPTL3 S17X mutation had no circulating Angptl3 and a marked reduction of all plasma lipids (P < 0.001). Heterozygotes had 42% reduction in Angptl3 level compared with noncarriers (P < 0.0001) but a significant reduction of only total cholesterol and high-density lipoprotein cholesterol. No differences were observed in the plasma noncholesterol sterols between carriers and noncarriers. No association between familial combined hypolipidemia and the risk of hepatic or cardiovascular diseases were detected. CONCLUSIONS: Familial combined hypolipidemia segregates as a recessive trait so that apolipoprotein B- and apolipoprotein A-I-containing lipoproteins are comprehensively affected only by the total deficiency of Angptl3. Familial combined hypolipidemia does not perturb whole-body cholesterol homeostasis and is not associated with adverse clinical sequelae.

[Skin cancer risk factors in childhood: findings of a survey in an Italian area characterized by atypical migration]. / Infanzia e fattori di rischio per tumori della cute: risultati di un'indagine in un'area italiana oggetto di una migrazione atipica.

OBJECTIVE: to evaluate the association of different phenotypes with sun sensitivity factors, sun protection behavior and ethnicity in school-age children. DESIGN: cross sectional study in the framework of a survey of children using a self-administered questionnaire. SETTING AND PARTICIPANTS: 35412 children attending primary schools in the provinces of Latina and Rome, located in the Lazio region (Italy), in the 1998-2001 time period. MAIN OUTCOME MEASURES: Odds Ratios (ORs) and their relative 95% Confidence Intervals (95% CI) computed through univariate and multivariate logistic regression models. RESULTS: "FOTO positive" phenotype, a proxy variable of the fair phenotype, was directly and significantly associated with the tendency to sunburn (OR 4.64; 95% CI 4.39-4.89), the presence of freckles on the face (OR 1.65; 95% CI 1.55-1.77), of naevi on the left forearm (OR 1.18; 95% CI 1.12-1.25), the number of grandparents born in northern areas (OR 1.54; 95% CI 1.15-2.07, for four northern grandparents versus none), the residence in Latina Province (OR 1.13; 95% CI 1.07-1.20) and the use of sunscreens (OR 1.70; 95% CI 1.55-1.88). An inverse association was observed with the male sex (OR 0.91; 95% CI 0.86-0.96), the increase of school-class level (OR 0.66; 95% CI 0.61-0.72, for the highest versus the lowest school-class level) and the ability to tan (OR 0.38; 95% CI 0.34-0.42). CONCLUSION: These findings confirmed that fairness of phenotype is associated in children with other skin cancer risk factors as well as ethnicity and parents' sun protection behavior.

Validating regional Hospital Information System data through comparison with a local cancer register to identify interval cancers of a breast screening program.

The objective of this study was to evaluate the accuracy of the Hospital Information System (HIS) in monitoring the breast cancer incidence and interval cancers compared with the cancer registry (CR). The HIS data linked with CR and Mammographic Screening Information System data for breast cancer cases diagnosed in the period 1999-2003. The sensitivity and positive predictive value of the HIS data were calculated using the CR as a gold standard. One thousand two hundred and thirty-six breast cancers were registered by the CR and 1028 were reported in the HIS. The sensitivity rate was 83.2% and the positive predictive value was 83.0%; similar results were obtained in the screening target population (50-69 years old). Fifteen invasive breast cancers occurred among screened women identified by HIS (four interval cancers and 11 screen-detected), two were registered as in situ in the CR. The HIS seems to have the potential to identify interval breast cancers, but the low accuracy of information does not permit an exact measure of the incidence.

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.