Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5-year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III-IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III-IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow-up in the years after diagnosis, thus avoiding patients' discrimination.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>95%), Cure Prevalence (women who will not die of cancer), and Already Cured (living longer than Time to Cure). In 2018, 0.4% (121,704) of Italian women were alive after corpus uteri cancer, 0.2% (52,551) after cervical, and 0.2% (52,153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (Cure Prevalence). Women with gynaecological cancers have a residual excess risk of death <5% after 5 years since diagnosis. The Cure Fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time To Cure was ≤10 years for women with gynaecological cancers aged <55 years. 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were Already Cured. These results will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

The risk-based breast screening (RIBBS) study protocol: a personalized screening model for young women.

The optimal mammography screening strategy for women aged 45-49 years is a matter of debate. We present the RIBBS study protocol, a quasi-experimental, prospective, population-based study comparing a risk- and breast density-stratified screening model (interventional cohort) with annual digital mammography (DM) screening (observational control cohort) in a real-world setting. The interventional cohort consists of 10,269 women aged 45 years enrolled between 2020 and 2021 from two provinces of the Veneto Region (northen Italy). At baseline, participants underwent two-view digital breast tomosynthesis (DBT) and completed the Tyrer-Cuzick risk prediction model. Volumetric breast density (VBD) was calculated from DBT and the lifetime risk (LTR) was estimated by including VBD among the risk factors. Based on VBD and LTR, women were classified into five subgroups with specific screening protocols for subsequent screening rounds: (1) LTR ≤ 17% and nondense breast: biennial DBT; (2) LTR ≤ 17% and dense breast: biennial DBT and ultrasound; (3) LTR 17-30% or LTR > 30% without family history of BC, and nondense breast: annual DBT; (4) LTR 17-30% or > 30% without family history of BC, and dense breast: annual DBT and ultrasound; and (5) LTR > 30% and family history of BC: annual DBT and breast MRI. The interventional cohort is still ongoing. An observational, nonequivalent control cohort of 43,000 women aged 45 years participating in an annual DM screening programme was recruited in three provinces of the neighbouring Emilia-Romagna Region. Cumulative incidence rates of advanced BC at three, five, and ten years between the two cohorts will be compared, adjusting for the incidence difference at baseline.Trial registration This study is registered on Clinicaltrials.gov (NCT05675085).

Patient presentation, skin biopsy utilization and cutaneous malignant melanoma incidence and mortality in northern Italy: Trends and correlations.

BACKGROUND: The global increase in incidence of cutaneous malignant melanoma (CMM) occurring in the past decades has been partly attributed to increased diagnostic scrutiny of early lesions, with a potential phenomenon of overdiagnosis. The reported positive linear relation between skin biopsy rate and incidence of early CMM is compatible with this hypothesis. OBJECTIVES: We explored the ecological association between the trends in annual dermatologic office visit rates, skin biopsy rates, incidence rates of in situ and invasive CMM by tumour thickness category, and CMM mortality rates in the Emilia-Romagna Region (northern Italy). METHODS: Four cancer registries covering a population of 2,696,000 provided CMM incidence data for the years 2003-2017. Dermatologic office visit rates and skin biopsy rates were calculated using the Regional outpatient care database. All rates were age-standardized. Trends were described with the estimated average annual per cent change (EAAPC). Correlations were tested with the Spearman correlation coefficient. RESULTS: Incidence increased significantly. The increase was steeper for in situ CMM (EAAPC: men, 10.2; women, 6.9) followed by CMM <0.8 mm thick (9.1; 5.2), but the rates grew significantly for most subgroups of CMMs ≥0.8 mm thick. Mortality decreased significantly among women (-2.3) and non-significantly among men. For dermatologic office visit rate and skin biopsy rate the EAAPC were, respectively, 1.7 and 1.8 for men and 1.2 and 0.9 for women. Annual dermatologic office visit rate correlated with skin biopsy rate in both sexes. However, the proportion of skin biopsies out of dermatologic office visits was constant across the years (range: men, 0.182-0.216; women, 0.157-0.191). CONCLUSIONS: In Italy, the increasing CMM incidence trend is, at least in part, genuine. Overdiagnosis-if any-is due to an increased patient presentation at dermatologic offices and not to a lower dermatologic threshold to perform biopsy.

Applying competing risks analysis to recurrences of primary breast cancer.

INTRODUCTION: in time-to-event analysis, competing risks are observed when a subject is at risk of multiple types of events. A competing risk is an event that prevents the event of interest from happening or modifies its chance to occur. OBJECTIVES: the purposes of this article are to provide an overview of competing risks analysis and to illustrate its application to the follow-up of breast cancer patients in order to estimate the risk of disease recurrence. DESIGN: cohort study. SETTING AND PARTICIPANTS: population-based random sample of patients with stage I-III primary female breast cancer diagnosed in 2000-2013, aged 15 years or older, resident in the Forlì health care district (northern Italy), treated surgically and with available information regarding disease laterality. MAIN OUTCOME MEASURES: subhazard ratio, hazard ratio and cumulative incidence function for loco-regional recurrences and distant metastasis during 10 years of follow-up. METHODS: breast cancer recurrences were evaluated taking into account death from any cause and occurrence of a second primary breast cancer as competing risks. Recent developments in competing risks methodology were used. The results obtained were compared with those from the Cox regression model, in which the competing risks were not accounted for. CONCLUSIONS: estimating the risk of recurrence without accounting for the competing risks resulted in a divergence of the hazard/subhazard functions. Competing risks analysis is preferable when the statistical assumption of independence of end-points may be violated.

How a faecal immunochemical test screening programme changes annual colorectal cancer incidence rates: an Italian intention-to-screen study.

BACKGROUND: This study aimed to evaluate the effectiveness of a biennial faecal immunochemical test (FIT) screening programme in reducing annual colorectal cancer (CRC) incidence in its dynamic target population. METHODS: The target population included over 1,000,000 persons aged 50-69 living in a region of northern Italy. The average annual response rate to invitation was 51.4%. Each observed annual age-standardised (Europe) rate per 100,000 persons between 2005, the year of introduction of the programme, and 2016 was compared with each expected annual rate as estimated with age-period-cohort (men) and age-period (women) models. RESULTS: For both sexes, the rates observed in 1997-2004 and those expected in 2005-2016 were stable. Observed rates increased in 2005, peaked in 2006 (the first full year of screening), dropped significantly below the expected level in 2009, and continued to decrease until 2013 (the eighth full year), after which no further significant changes occurred. In the pooled years 2013-2016, the observed incidence rate per 100,000 persons was 102.2 [95% CI: 97.4, 107.1] for men, 75.6 [95% CI: 71.6, 79.7] for women and 88.4 [95% CI: 85.3, 91.5] for both sexes combined, with an observed:expected incidence rate ratio of 0.68 [95% CI: 0.65, 0.71], 0.79 [95% CI: 0.76, 0.82] and 0.72 [95% CI: 0.66, 0.81], respectively. DISCUSSION: The study provided multiple consistent proofs of a causal relationship between the introduction of screening and a stable 28% decrease in annual CRC incidence after eight years.

Effects of Attendance to an Organized Fecal Immunochemical Test Screening Program on the Risk of Colorectal Cancer: An Observational Cohort Study.

BACKGROUND & AIMS: This cohort study compared colorectal cancer (CRC) incidence and mortality between people who participated in an Italian regional biennial fecal immunochemical test (FIT) screening program and people who did not. METHODS: The program started in 2005. The target population included over 1,000,000 people aged 50 to 69 years. The FIT was a one-sample OC-Sensor (Eiken Chemical Co, Tokyo, Japan) (cutoff, ≥20 µg hemoglobin/g feces). The average annual response rate to invitation was 51.4%. The records of people invited up to June 2016 were extracted from the screening data warehouse. Attenders were subjects who responded to the first 2 invitations or to the single invitation sent them before they became ineligible. Non-attenders were subjects who did not respond to any of these invitations. The records were linked with the regional CRC registry. People registered up to December 2016 were identified. Self-selection-adjusted incidence rate ratios (IRRs) and incidence-based CRC mortality rate ratios (MRRs) for attenders to non-attenders, with 95% confidence intervals (CIs), were calculated. RESULTS: The cohort generated 2,622,131 man-years and 2,887,845 woman-years at risk with 4490 and 3309 CRC cases, respectively. The cohort of attenders was associated with an IRR of 0.65 (95% CI, 0.61-0.69) for men, 0.75 (95% CI, 0.70-0.80) for women and 0.69 (95% CI, 0.66-0.72) for both sexes combined. The self-selection-adjusted IRR was 0.67 (95% CI, 0.62-0.72) for men and 0.79 (95% CI, 0.72-0.88) for women. The IRR for stage I, II, III, and IV CRC was 1.35 (95% CI, 1.20-1.50), 0.61 (95% CI, 0.53-0.69), 0.60 (95% CI, 0.53-0.68) and 0.28 (95% CI, 0.24-0.32) for men and 1.64 (95% CI, 1.43-1.89), 0.60 (95% CI, 0.52-0.69), 0.73 (95% CI, 0.63-0.85) and 0.35 (95% CI, 0.30-0.42) for women. The overall incidence-based CRC MRR was 0.32 (95% CI, 0.28-0.37) for men, 0.40 (95% CI, 0.34-0.47) for women and 0.35 (95% CI, 0.31-0.39) for both sexes combined. The adjusted MRR was 0.35 (95% CI, 0.29-0.41) for men and 0.46 (95% CI, 0.37-0.58) for women. CONCLUSIONS: Attendance to a FIT screening program is associated with a CRC incidence reduction of 33% among men and 21% among women, and a CRC mortality reduction of 65% and 54%, respectively.

The relative contribution of the decreasing trend in tumour thickness to the 2010s increase in net survival from cutaneous malignant melanoma in Italy: a population-based investigation.

BACKGROUND: The long-term increase in survival from cutaneous malignant melanoma (CMM) is generally attributed to the decreasing trend in tumour thickness, the single most important prognostic factor. OBJECTIVES: To determine the relative contribution of decreased tumour thickness to the favourable trend in survival from CMM in Italy. METHODS: Eleven local cancer registries covering a population of 8 056 608 (13.4% of the Italian population in 2010) provided records for people with primary CMM registered between 2003 and 2017. Age-standardized 5-year net survival was calculated. Multivariate analysis of 5-year net survival was undertaken by calculating the relative excess risk (RER) of death. The relative contribution of the decrease in tumour thickness to the RER of death was evaluated using a forward stepwise flexible parametric survival model including the available prognostic factors. RESULTS: Over the study period, tumour thickness was inversely associated with 5-year net survival and multivariate RER in both sexes. The median thickness was 0.90 mm in 2003-2007, 0.85 mm in 2008-2012 and 0.75 mm in 2013-2017 among male patients, and 0.78 mm, 0.77 mm and 0.68 mm among female patients, respectively. The 5-year net survival was 86.8%, 89.2% and 93.2% in male patients, and 91.4%, 92.0% and 93.4% in female patients, respectively. In 2013-2017, male patients exhibited the same survival as female patients despite having thicker lesions. For them, the increasing survival trend was more pronounced with increasing thickness, and the inclusion of thickness in the forward stepwise model made the RER in 2013-2017 vs. 2003-2007 increase from 0.64 [95% confidence interval (CI) 0.51-0.80] to 0.70 (95% CI 0.57-0.86). This indicates that the thickness trend accounted for less than 20% of the survival increase. For female patients, the results were not significant but, with multiple imputation of missing thickness values, the RER rose from 0.74 (95% CI 0.58-0.93) to 0.82 (95% CI 0.66-1.02) in 2013-2017. CONCLUSIONS: For male patients in particular, decrease in tumour thickness accounted for a small part of the improvement in survival observed in 2013-2017. The introduction of targeted therapies and immune checkpoint inhibitors in 2013 is most likely to account for the remaining improvement.

Five-year annual incidence and clinico-molecular features of breast cancer after the last negative screening mammography at age 68-69.

OBJECTIVE: The European Commission Initiative on Breast Cancer recommendation for triennial screening of women aged 70-74 is based on very weak evidence. A cohort of Italian women who had their last biennial screening mammography at age 68-69 was followed up for 5 years, assumed to represent the interval to another hypothetical screening mammography, in order to determine the annual proportional incidence of interval breast cancer. METHODS: The cohort included 118,370 women. They had their last mammography between 1997 and 2008. Incident breast cancers were identified by record-linking the cohort with the regional breast cancer registry. The expected incidence in the age range 65-74 was estimated with an age-period-cohort model. The number of interval cancers was divided by the expected number to obtain their proportional incidence. RESULTS: Overall, there were 298,658 woman-years at risk with 371 interval cancers versus 988.8 expected. In the first, second, third, fourth, and fifth interval year, the proportional incidence was 0.09 (95% confidence interval, 0.06-0.13), 0.32 (0.25-0.39), 0.60 (0.49-0.73), 0.75 (0.60-0.92), and 0.81 (0.60-1.07), respectively. Between the second and the fifth year, tumour stage and molecular subtype did not change significantly. CONCLUSION: Though not supported by these findings, the proposal of triennial screening for women aged 70-74 merits further research, because the 95% confidence interval of the third-year proportional incidence of interval cancer included 0.50-the maximum limit considered acceptable for women aged 50-69. KEY POINTS: • The third-year incidence of breast cancer relative to the expected one was 0.60 (95% confidence interval, 0.49-0.73). • Between the second and the fifth year, tumour stage and molecular subtype did not change significantly (p >0.10). • The proposal of a 3-year screening interval at age 70-74 merits further evaluation.

[Update of survival of cancer patients in Italy: geographical comparisons and focus on patients with cancers targeted by screening programmes, childhood cancers, and smoking-associated cancers]. / Aggiornamento della sopravvivenza dei pazienti con tumore in Italia: confronti geografici e focus su pazienti con tumori oggetto di screening, pediatrici e associati al fumo.

OBJECTIVES: to update the Italian estimates of survival for patients with a paediatric cancer, tobacco smoke-associated cancers, and cancers targeted by screening; to assess geographical differences. DESIGN: population-based descriptive study. SETTING AND PARTICIPANTS: incident cancer cases diagnosed in 2010-2014, with follow-up to 2018, from 17 Italian cancer registries (covering 31% of the national population; 43% of the population residing in the North-Centre of the country and 8% of the population living in the South and Islands). MAIN OUTCOME MEASURES: age-standardized 5-year net survival (NS) by cancer site or type, sex, age, and geographical area. RESULTS: NS of patients aged ≥15 years with breast, prostate, colorectal, and lung cancers was higher in the North-Centre than in the South and Islands. The overall survival of people diagnosed with cancer in childhood (0-14 years) was 84.3%, with similar values among the geographical macro-areas and between males and females. Women with breast cancer within the current target age of the screening programmes and those in the younger age groups (45-49 years) show similar survival values; the same is true for women with colorectal cancer. In both cases, survival decreased in the age groups after the age of cessation of screening programmes. Survival of patients with tobacco smoke-associated cancers varies according to cancer site (from 11.1% for patients with pancreatic cancer to 79.7% for those with bladder cancer). For most cancer sites, women have higher survival than men. CONCLUSIONS: for adults, a geographical survival gap persists. The results may contribute to the debate on extending the target age for screening programmes and to support initiatives to encourage tobacco smoking cessation even after cancer diagnosis. For patients who receive a cancer diagnosis in childhood, survival similar to highest values internationally.

Mid-term trends and recent birth-cohort-dependent changes in incidence rates of cutaneous malignant melanoma in Italy.

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe.

Results of Compliant Participation in Five Rounds of Fecal Immunochemical Test Screening for Colorectal Cancer.

BACKGROUND & AIMS: We investigated the magnitude and temporal patterns of the decreasing trend in main performance measures of fecal immunochemical test (FIT) screening for colorectal cancer (CRC) observed in second and subsequent rounds. METHODS: We followed up 494,187 participants from the first round of a regional biennial FIT screening program in Italy (cut-off value for positivity, 20 µg hemoglobin/g feces) for 5 total rounds (2005-2016). At each round, only compliant participants were eligible. Performance measures from the first, third, fourth, and fifth rounds were compared with those from the second round (the first incidence round) using rate ratios from multivariate Poisson regression models and relative risk ratios from multinomial logistic regression models. RESULTS: Between the second and the third rounds, a significant 20% to 30% decrease was found in the proportion of men with a positive FIT result (from 5.2% to 4.3%) and in detection rates of advanced adenoma (from 13.4 to 10.2 per 1000), CRC (from 1.7 to 1.4 per 1000), and advanced neoplasia (from 15.1 to 11.6 per 1000). Positive predictive values (PPVs) decreased by 10% or less between the second and third rounds. Detection rates and PPVs for adenoma stabilized by the fourth and fifth rounds. The PPVs for advanced adenoma, CRC, and advanced neoplasia decreased slightly in men and women by the fourth and fifth rounds. The detection rate of proximal colon cancer stabilized after the second round, whereas the detection rate of distal colon cancer decreased until the fourth round in men (from 0.7 to 0.3 per 1000), and the fifth round in women. CONCLUSIONS: These findings support the notion that FIT screening prevents progression of a subset of advanced adenomas. Screening intensity could be modulated based on results from previous rounds, with a risk-based strategy.

Incidence trends of vulvar squamous cell carcinoma in Italy from 1990 to 2015.

OBJECTIVE: The incidence of vulvar squamous cell carcinoma has increased for decades in most Western countries - a trend virtually restricted to women aged <50 or 60 years. In southern Europe, conversely, the trends have been insufficiently studied. This article reports a study from Italy. METHOD: Thirty-eight local cancer registries, currently covering 15,274,070 women, equivalent to 49.2% of the Italian national female population, participated. Invasive cancers registered between 1990 and 2015 with an International Classification of Diseases for Oncology, 3rd revision, topography code C51 and morphology codes compatible with vulvar squamous cell carcinoma (n = 6294) were eligible. Incidence trends were analysed using joinpoint regression models, with calculation of the estimated annual percent change (EAPC), and age-period-cohort models. RESULTS: Total incidence showed a regular and significant decreasing trend (EAPC, -0.96; 95% confidence interval (CI), -1.43 to -0.48). This was entirely accounted for by women aged ≥60 years (EAPC, -1.34; 95% CI, -1.86 to -0.81). For younger women, the EAPC between 1990 and 2012 was 1.20 (95% CI, 0.34 to 2.06) with a non-significant acceleration thereafter. This pattern did not vary substantially in a sensitivity analysis for the effect of geographic area and duration of the registry. The age-period-cohort analysis revealed a risk decrease in cohorts born between 1905 and 1940 and a new increase in cohorts born since 1945. CONCLUSIONS: The decreasing trend observed among older women and the resulting decrease in total rate are at variance with reports from most Western countries. Age-period-cohort analysis confirmed a decreasing trend for earliest birth cohorts and an opposite one for recent ones.

Estimating the impact of an organised screening programme on cervical cancer incidence: A 26-year study from northern Italy.

The impact of the organised cervical cancer (CC) screening programmes implemented in Europe since the 1990s has been insufficiently evaluated. We investigated the changes in CC incidence following the introduction of a screening programme in the Emilia-Romagna Region (northern Italy). The study period was 1988-2013. The programme, targeting women aged 25-64 years (1,219,000 in 2018), started in 1998. The annual incidence rates that would be expected in 1998-2013 in the absence of screening were estimated, first, by analysing the annual rates in 1988-1997 with a log-linear model and, second, by analysing the annual rates in 1988-2013 with an age-period model in which the period effect was enforced to be linear. Cervical adenocarcinoma incidence trend over the entire period was used to validate both estimates. Observed annual rates were compared to the two series of expected ones with the incidence rate ratio (IRR). Incidence remained stable during 1988-1997, peaked in 1998 and then decreased until 2007, when it stabilised. The two series of expected rates were virtually coincident and their trends roughly paralleled the stable adenocarcinoma incidence trend. After 2007, the median IRR was 0.60 (95% confidence interval, 0.45-0.81) based on the log-linear model and 0.58 (95% confidence interval, 0.34-0.97) based on the age-period model. Thirty-six to seventy-five CC cases were prevented annually for an average annual frequency of 6.5 per 100,000 women in the target population. In summary, consistent circumstantial evidences were obtained that the organised screening programme brought about a 40% reduction in annual CC incidence after 10 years.

Annual mammography at age 45-49 years and biennial mammography at age 50-69 years: comparing performance measures in an organised screening setting.

OBJECTIVE: To compare the results of 5 years of annual mammography screening at age 45-49 with the results of 5 years of biennial screening at age 50-54 and 55-69. METHODS: In an Italian screening programme, data from 1,465,335 mammograms were analysed. Recall rates, invasive assessment rates, surgical biopsy (including excisional biopsy and definitive surgical treatment) rates, and cancer detection rates were calculated for the first screen (first) and, cumulatively, for the second and subsequent screens (second+). RESULTS: The rate ratios between younger women and the two groups of older ones were (in parentheses, original figures per 1000 mammograms if not otherwise specified): recall rate: first 1.11 (103.6 vs. 93.5) and 1.11 (vs. 93.2), second+ 2.10 (208.9 vs. 99.7) and 2.77 (vs. 75.5); invasive assessment rate: first 0.94 (23.0 vs. 24.5) and 0.94 (vs. 24.6), second+ 1.63 (35.8 vs. 22.0) and 1.56 (vs. 23.0); surgical biopsy rate: first 0.68 (5.9 vs. 8.6) and 0.45 (vs. 13.2), second+ 1.35 (11.5 vs. 8.5) and 0.88 (vs. 13.0); total detection rate: first 0.63 (4.3 vs. 6.7) and 0.37 (vs. 11.7), second+ 1.30 (8.9 vs. 6.8) and 0.74 (vs. 12.0); total positive predictive value of surgical biopsy: first 0.93 (72.8% vs. 78.0%) and 0.82 (vs. 88.9%), second+ 0.96 (77.2% vs. 80.5%) and 0.83 (vs. 92.7%). CONCLUSION: Younger women experienced two to threefold higher cumulative recall rates at second+ screens and limited differences in surgical biopsy rate. Albeit encouraging, these results must be completed with further investigation, especially on interval cancer incidence. KEY POINTS: • At repeated screens, cumulative recall rate was two- to threefold higher for younger women. • Differences in cumulative surgical referral and surgical biopsy rates were moderate. • Differences in positive predictive value of surgical biopsy were particularly small.

Early Gastric Cancer: Clinical Behavior and Treatment Options. Results of an Italian Multicenter Study on Behalf of the Italian Gastric Cancer Research Group (GIRCG).

BACKGROUND: Early gastric cancer (EGC) generally has a good prognosis. However, the current definition of EGC includes various subgroups of patients with different pathological characteristics and different prognoses, some of whom have aggressive disease with a biological behavior similar to that of advanced carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 1,074 patients with EGC who had undergone surgery between 1982 and 2009. The cumulative incidence function of cancer-specific mortality and competing mortality were estimated using the Fine and Gray method. RESULTS: The median follow-up period was 193 months (range 1-324). Five hundred and sixty-two (52.3%) patients died, 96 (8.9%) from EGC. The 5-, 10-, and 15-year cumulative incidence rates for mortality of all causes were 20.5% (95% confidence interval [CI] 18.0-22.9), 37.1% (95% CI 34.7-40.7), and 52.6% (95% CI 49.1-56.0), respectively; for cancer-specific mortality, 6.0% (95% CI 4.5-7.6), 9.9% (95% CI 7.9-11.9), and 11.1% (95% CI 8.8-13.3), respectively; and for mortality of other causes, 14.4% (95% CI 12.1-16.6), 27.2% (95% CI 24.2-30.2), and 41.5% (95% CI 38.1-43.3), respectively. A significant increase in the risk of cancer-specific mortality was observed for lesions >2 cm (adjusted hazard ratio [HR] = 1.44, 95% CI 1.07-1.94), Pen A-type disease (adjusted HR = 1.73, 95% CI 1.15-2.61), and node-positive cancers (adjusted HR = 2.28, 95% CI 1.61-3.21). CONCLUSION: Patients with EGC with tumors >2 cm, Pen A-type disease according to Kodama, or lymph node metastases show a poorer prognosis and an increased risk of cancer-specific mortality. IMPLICATIONS FOR PRACTICE: Early gastric cancer generally has a good prognosis, and some patients can be treated radically by endoscopic resection. However, the current definition of early gastric cancer includes subgroups of patients with an aggressive disease. In particular, patients with lymph node metastases and Pen A-type tumors according to Kodama's classification need a more invasive treatment, such as subtotal or total gastrectomy with an extended D2 lymphadenectomy, plus eventual adjuvant chemotherapy.

Extension of the target age range of mammography screening programme and governance of mammography practice in the Emilia-Romagna Region (Northern Italy). / Estensione dell'età-bersaglio del programma di screening mammografico e governo della pratica mammografica in Emilia-Romagna.

"OBJECTIVES: to evaluate the effectiveness of the regional law No.1035 enacted in 2009 by the local government of the Emilia- Romagna Region (Northern Italy) with the purpose of revising the rules of access to breast-care services. The law dictated the extension of the organised mammography screening programme to women aged 45-49 and 70-74 years in order to decrease their spontaneous screening rates and, thus, the waiting times for the access to diagnostic mammography by women of all ages. DESIGN: study of time trends (joinpoint regression analysis and before/ after analysis) in annual percent mammography rates and in waiting times for access to clinical radiology facilities (2006-2014) among resident women. The information was taken from the regional Department of Health. SETTING: public and accredited private radiology facilities. MAIN OUTCOME MEASURES: age-specific and waiting-time-specific (months) percent rates of organised screening mammography, spontaneous screening mammography, and diagnostic mammography. RESULTS: following the regional law No.1035, screening rates among women aged 45-49 and 70-74 years reached levels comparable to those attained by women aged 50-69 years. Spontaneous screening rates dropped and waiting times for spontaneous screening mammography (women aged 40-44 years) were cut. For diagnostic mammography, the rates remained stable, except for a decrease among women aged 35-39 and 45-49 years, and waiting times decreased in a constant manner over the study period. CONCLUSIONS: the above-mentioned law met most of its goals. Comprehensive programmes regulating mammography practice at the population level can be effective."

Patterns and determinants of receipt of follow-up mammography and/or clinical examination in a cohort of Italian breast cancer survivors.

Information regarding the use of mammography by breast cancer survivors is limited. This study aimed at evaluating the compliance to surveillance mammography and/or clinical breast examination and the associated factors among patients living in northern Italy. A cancer registry-based cohort of 1304 patients living in the Health Care District of Forlì was followed up for 10 years. Eighty percent of patients had a mammogram and/or clinical breast examination during the first year after treatment. The proportion decreased to 67 % at 10 years of follow-up. Three demographic characteristics were independently associated with lower odds of having an annual mammogram and/or clinical breast examination: age at diagnosis [odds ratio (OR) 0.51, 95 % confidence interval (CI) 0.41-0.63 for patients aged 65-74 years; and OR 0.14, 95 % CI 0.11-0.18, for patients ≥75 years versus patients aged <64 year]; socio-economic status (OR 0.81, 95 % CI 0.65-1.00, for deprived patients versus patients of the reference class); and hospital travel time greater than 30 min (OR 0.44, 95 % CI 0.29-0.68 versus ≤15 min). With respect to clinical and disease characteristics, lower odds were observed for patients treated with mastectomy (OR 0.79, 95 % CI 0.65-0.97), for patients diagnosed with in situ breast cancer (OR 0.68, 95 % CI 0.46-0.99) as well as with stage II + breast cancer (OR 0.77, 95 % CI 0.63-0.94), and for patients with ≥3 Elixhauser comorbidities (OR 0.43, 95 % CI 0.26-0.71). Adherence to follow-up declined over time. Knowledge of associated factors may assist in improving access to care for breast cancer survivors.

Problems, solutions, and perspectives in the evaluation of interval cancers in Italian mammography screening programmes: a position paper from the Italian group for mammography screening (GISMa).

In this position paper, a self-convened team of experts from the Italian Group for Mammography Screening (Gruppo italiano screening mammografico, GISMa) pointed out the problems that increasingly hamper the feasibility and validity of the estimate of the proportional incidence of interval breast cancer (IBC) in Italy, suggested potential solutions and an agenda for research, and proposed that the question of the sensitivity of mammography be viewed in a larger perspective, with a greater attention to radiological review activities and breast radiology quality assurance programmes. The main problems are as follows: the coverage of cancer registration is incomplete; the robustness of using the pre-screening incidence rates as underlying rates decreases with time since the start of screening; the intermediate mammograms performed for early detection purposes may cause an overrepresentation of IBCs; the classification of many borderline screening histories is prone to subjectivity; and, finally, the composition of cohorts of women with negative screening results is uncertain, because several mammography reports are neither clearly negative nor clearly positive, and because of the limitations and instability of the electronic mammography records. Several possibilities can be considered to cope with these issues: standard methods for using the hospital discharge records in the identification of IBCs should be established; for the calculation of regional estimates of the underlying incidence, a suitable mathematical model should be identified; the definition of IBC according to the 2008 GISMa guidelines needs to be updated, especially with respect to in situ cancers and to invasive cancers with borderline screening histories; a closer adherence to standard screening protocols, with a simplified patient management, would make it easier to objectively identify IBCs; alternative methods for estimating the sensitivity of mammography should be taken into consideration; and, finally, analysis could be restricted to the absolute incidence rate of IBC, which would make comparison of the risk between neighbouring populations possible. Epidemiologists must extend their attention to the prevention of the risk of IBC and the implementation of breast radiology quality assurance practices. Epidemiologists and radiologists can share common objectives: it is necessary to promote the idea that the availability of a registry-based series of IBCs is not a prerequisite for their radiological review; radiological review of breast cancers greater than 20mm in size detected at second and subsequent screens, that are potential substitutes for IBCs, needs radiological and epidemiological validation studies; the advent of digital mammography brings about the possibility to create libraries of mammograms accessible online, which enables the conduct of large studies of the diagnostic variability of radiologists; and, finally, epidemiologists and radiologists have the responsibility to monitor the effects that a loss of cumulative professional experience in screening centres, due to the imminent retirement of a substantial proportion of healthcare workforce, could cause on their performance.