Meta-analysis of agreement between MRI and pathologic breast tumour size after neoadjuvant chemotherapy.

BACKGROUND: Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of agreement. METHODS: A systematic literature search was undertaken. Mean differences (MDs) in tumour size between MRI or comparator tests and pathology were pooled by assuming a fixed effect. Limits of agreement (LOA) were estimated from a pooled variance by assuming equal variance of the differences across studies. RESULTS: Data were extracted from 19 studies (958 patients). The pooled MD between MRI and pathology from six studies was 0.1 cm (95% LOA: -4.2 to 4.4 cm). Similar overestimation for MRI (MD: 0.1 cm) and ultrasound (US) (MD: 0.1 cm) was observed, with comparable LOA (two studies). Overestimation was lower for MRI (MD: 0.1 cm) than mammography (MD: 0.4 cm; two studies). Overestimation by MRI (MD: 0.1 cm) was smaller than underestimation by clinical examination (MD: -0.3 cm). The LOA for mammography and clinical examination were wider than that for MRI. Percentage agreement between MRI and pathology was greater than that of comparator tests (six studies). The range of Pearson's/Spearman's correlations was wide (0.21-0.92; 16 studies). Inconsistencies between MDs, percentage agreement and correlations were common. CONCLUSION: Magnetic resonance imaging appears to slightly overestimate pathologic size, but measurement errors may be large enough to be clinically significant. Comparable performance by US was observed, but agreement with pathology was poorer for mammography and clinical examination. Percentage agreement can provide supplementary information to MDs and LOA, but Pearson's/Spearman's correlation does not provide evidence of agreement and should be avoided. Further comparisons of MRI and other tests using the recommended methods are warranted.

Application of breast tomosynthesis in screening: incremental effect on mammography acquisition and reading time.

OBJECTIVE: The aim of this study was to supplement the paucity of information available on logistical aspects of the application of three-dimensional (3D) mammography in breast screening. METHODS: We prospectively examined the effect on radiographers' and radiologists' workload of implementing 3D mammography in screening by comparing image acquisition time and screen-reading time for two-dimensional (2D) mammography with that of combined 2D+3D mammography. Radiologists' accuracy was also calculated. RESULTS: Average acquisition time (measured from start of first-view breast positioning to compression release at completion of last view) for seven radiographers, based on 20 screening examinations, was longer for 2D+3D (4 min 3 s; range 3 min 53 s-4 min 18 s) than 2D mammography (3 min 13 s; range 3 min 0 s-3 min 26 s; p<0.01). Average radiologists' reading time per screening examination (three radiologists reading case-mix of 100 screens: 10 cancers, 90 controls) was longer for 2D+3D (77 s; range 60-90 s) than for 2D mammography (33 s; range 25-46 s; p<0.01). 2D+3D screen-reading was associated with detection of more cancers and with substantially fewer recalls than 2D mammography alone. CONCLUSION: Relative to standard 2D mammography, combined 2D+3D mammography prolongs image acquisition time and screen-reading time (at initial implementation), and appears to be associated with improved screening accuracy. ADVANCES IN KNOWLEDGE: These findings provide relevant information to guide larger trials of integrated 3D mammography (2D+3D) and its potential implementation into screening practice.

Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI.

Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16-188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1-2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [k(ep)], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0-58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted.

Interobserver agreement in breast radiological density attribution according to BI-RADS quantitative classification.

PURPOSE: The authors sought to assess interobserver agreement in classifying mammography density according to quantitative Breast Imaging Reporting and Data System (BI-RADS) criteria. MATERIALS AND METHODS: Six expert mammography readers were tested on a set of 100 mammograms. Interobserver agreement was determined according to the kappa statistic, adjusting for chance agreement, on a four-category (D1 vs. D2 vs. D3 vs. D4) or two-category (D1-2 vs. D3-4) basis. Agreement with a panel of 12 readers who had been tested on the same set in a previous study was also assessed. RESULTS: The six readers showed good agreement when compared in pairs [agreement on a four-category basis was substantial (kappa=0.60-0.80) for 13 pairs and almost perfect (kappa>0.80) for two pairs); agreement on a two-category basis was substantial for 12 pairs and almost perfect for three pairs) or compared with the panel (on a four-category basis, agreement was substantial for five of six readers and almost perfect for one; on a two-category basis, agreement was substantial for all readers). CONCLUSIONS: In agreement with previous studies, visual classification of mammography density according to BI-RADS quantitative criteria was highly reproducible among readers; nevertheless, attribution to the "dense breast" (BI-RADS D3-4) category, which might be adopted as a determinant of different screening protocols (such as adjunct ultrasonography or yearly interval) varied among readers (range 6-15%). Controlled studies should be performed comparing visual with computer-density category attribution, the latter possibly being a better alternative due to its absolute reproducibility.

Proportional incidence and radiological review of large (T2+) breast cancers as surrogate indicators of screening programme performance.

OBJECTIVES: Surrogate measures of screening performance [e.g. interval cancer (IC) proportional incidence] allow timely monitoring of sensitivity and quality. This study explored measures using large (T2+) breast cancers as potential indicators of screening performance. METHODS: The proportional incidence of T2+ cancers (observed/expected cases) in a population-based screening programme (Trento, 2001-2009) was estimated. A parallel review of 'negative' preceding mammograms for screen-detected T2+ and for all ICs, using 'blinded' independent readings and case-mixes (54 T2+, 50 ICs, 170 controls) was also performed. RESULTS: T2+ cancers were observed in 168 screening participants: 48 at first screen, 67 at repeat screening and 53 ICs. The T2+ estimated proportional incidence was 68% (observed/expected = 168/247), corresponding to an estimated 32% reduction in the rate of T2+ cancers in screening participants relative to that expected without screening. Majority review classified 27.8% (15/54) of T2+ and 28% (14/50) of ICs as screening error (P = 0.84), with variable recall rates amongst radiologists (8.8-15.2%). CONCLUSIONS: T2+ review could be integrated as part of quality monitoring and potentially prove more feasible than IC review for some screening services. KEY POINTS: • Interval breast cancers, assumed as screening failures, are monitored to estimate screening performance • Large (T2+) cancers at screening may also represent failed prior screening detection • Analysis of T2+ lesions may be more feasible than assessing interval cancers • Analysis of T2+ cancers is a potential further measure of screening performance.

Analysis of proportional incidence and review of interval cancer cases observed within the mammography screening programme in Trento province, Italy.

PURPOSE: The aim of this study was to assess the performance of the mammography screening programme in Trento Province, Italy, by analysing the interval cancers (IC) observed from 2001 to 2008. MATERIAL AND METHODS: IC were identified by linking screening archives with local cancer registry and pathology archives as well as with hospital discharge records. Proportional incidence was determined according to breast cancers expected in the absence of screening, estimated on the basis of patients/year at risk and age-specific incidence. The review of screening mammograms preceding ICs was performed by an external (three radiologists) and an internal (five radiologists) panel and aimed at assessing the proportion of IC reviewed as screening errors. Results were compared with European Community (EC) recommended standards. RESULTS: IC proportional incidence was 15.90% for the first year (EC standard <30%) and 25.77% for the second year (EC standard <50%) of the interval. At external review, 18.4% of cases were reviewed as screening errors (identified by at least two of three reviewers), whereas at internal review (identified by at least three of five reviewers) it was 17.4% (EC standard <20%). No significant difference was observed between external and internal review (mean recall rate 8.3% vs. 9.0%; mean identification rate 19.7% vs 19.6%). CONCLUSIONS: The study confirms good performance of the mammography screening programme in Trento Province, Italy. Comparable results of external and internal reviews suggest that the latter, no doubt easier to be implemented, might be adopted as a routine procedure to assess this early efficacy indicator.

Benefits of double reading of screening mammograms: retrospective study on a consecutive series.

PURPOSE: The purpose of this study was to assess the performance of delayed second reading of screening mammograms when added to real-time reading plus immediate assessment. MATERIAL AND METHODS: The study setting was the mammography screening programme of an Italian Local Health Unit. Recall rate and cancer detection rate at first reading or informed second reading only were assessed in a cohort of 23,629 women aged 50-69 years screened during 2007-2008. Incremental recall rate, incremental cancer detection rate and incremental cost of second reading were determined. RESULTS: Recall rate was 13.0% at first and 2.7% at second reading (incremental recall rate +21.1%). Overall, recalls were more frequent in the younger decade and in the presence of denser breasts. Cancer detection rate was 7.06‰ (n=167) at first and 0.93‰ (n=22) at second reading (incremental cancer detection rate +13.1%). Compared with first reading, second reading detected more cancers depicted as isolated microcalcifications and distortions (40.9% vs. 16.2%, p=0.02) and at a lower stage (stage 0-I 81.8% vs. 69.5%, p=0.34). The cost of adding delayed second reading was + 3.65 per screened individual or 3,926.61 per incremental cancer detected. CONCLUSIONS: The study confirms the efficacy of second reading, even as an adjunct to real-time single reading plus immediate assessment. Incremental recall rate is acceptable in view of the incremental cancer detection rate, and both figures are within the range of literature reports on double-reading performance.

On the role of arbitration of discordant double readings of screening mammography: experience from two Italian programmes.

PURPOSE: The authors sought to assess the role of arbitration by a third reader of discordant double readings to reduce the rate of recalls to diagnostic assessment. MATERIALS AND METHODS: A consecutive series of 7,660 double readings of screening examinations were considered. Discordant recalls were arbitrated by an expert reader (negative/positive). Diagnostic assessment was performed irrespective of arbitration results, and its outcome was used as reference standard for the study purpose. Assuming that negative arbitration would deny recall, its impact was assessed in terms of reduced recall rate and reduced cancer detection rate. Cost analysis of introducing arbitration was performed according to these results. RESULTS: Recalls at double reading were 528 (6.8%), of which 230 (43.5%) were concordant and 298 (56.5%) were discordant. The latter underwent arbitration, which was negative in 216 (72.4%) and positive in 82 (27.6%) cases, respectively. Overall, 49 cancers were detected (6.39 ‰ screened, 9.2% recalled): 43 cancers were detected among concordant (5.6 ‰ screened, 18.6% concordant) and six among discordant recalls (0.7 ‰ screened, 2.0% discordant). Six cancers were observed among arbitrated cases: five (6%) in positive and one (4.6 ‰) in negative arbitrations. Negative arbitration would have spared 216 assessment procedures (2.8% absolute, 40.9% relative reduction of recall rate) while missing one cancer case (0.13 ‰ absolute, 2.0% relative reduction of cancer detection rate). Arbitration cost was 74 euro, whereas 216 spared assessment procedures would have cost 14,558.4-23,346 euro. CONCLUSIONS: Arbitration is a cost-effective procedure that could be employed as a first measure to counterbalance excess recall rate observed in a double-reading scenario.

Detection rates of cancer, high grade PIN and atypical lesions suspicious for cancer in the European Randomized Study of Screening for Prostate Cancer.

THE AIM OF THE STUDY: This article presents the incidence of prostate cancer, isolated high grade prostatic intraepithelial neoplasia (PIN) and atypical lesions suspicious for prostate cancer (LSPC) during subsequent screening rounds in the centres of five of the countries participating in the European Randomized Study of Screening for Prostate Cancer (ERSPC). The incidence and predictive value of high grade PIN and LSPC for prostate cancer in subsequent biopsy following these diagnoses were evaluated. PATIENTS AND METHODS: Study group consisted of 56,653 screened men in the ERSPC centres of Finland, Italy, Netherlands, Sweden and Switzerland, who underwent 3-7 screening rounds at 2-4 year interval. Data for prostate cancer were obtained from the ERSPC central database. Data for high grade PIN and LSPC were gathered from each ERSPC centre. Detection rates of subsequent prostate cancer in the first re-biopsy after these diagnoses were determined. RESULTS: The average cancer detection rate was 3.5%, 3.2% and 3.5% for the completed rounds 1, 2 and 3, respectively, in all five centres. Incidence of high grade PIN increased from 1.5% in the first round to 5.0% in the third round, varying among centres in the first round between 0.8% and 7.6%. The cancer detection rate in the first re-biopsy after the diagnosis of high grade PIN was 12.9%. Incidence of LSPC was 2.4%, 2.7%, 2.2% and 2.6% in the first, second, third and fourth round, respectively. The cancer detection rate at the first re-biopsy after the diagnosis of LSPC was in average 33.8%. CONCLUSIONS: Cancer detection rate was stable during the three screening rounds. The wide variation in frequency in particular of high grade PIN among the ERSPC centres suggests a considerable inter-observer variation. The average comparatively low detection rate of isolated high grade PIN in the first screening round may be screening-related, while its consistent increase during three screening rounds could be the consequence of a.o. previous screening and ageing of the population. The observed low risk of prostate cancer after isolated high grade PIN in this screening setting is in line with the current recommendation to abstain from early repeat biopsies after this diagnosis. The association of LSPC with high incidence of prostate cancer in re-biopsies confirms the need for early repeat biopsies and follow-up of these men. The low percentage of LSPC (<3% of biopsies) throughout all rounds is reassuring as it limits the biopsy burden in a screening setting.

Change of tumour characteristics and treatment over time in both arms of the European Randomized study of Screening for Prostate Cancer.

OBJECTIVE: To evaluate a change in tumour characteristics and applied treatments over time in the control arm of all centres of the European Randomized study of Screening for Prostate Cancer (ERSPC) and to compare this with similar data of the screening arm. METHODS: Between 1993 and 2003, 182,160 men, aged 50-74 years, were randomised to the screening arm (N=82,816) and the control arm (N=99,184). Men in the screening arm were offered Prostate Specific Antigen (PSA) testing every 4 years whilst men in the control arm received usual care. Tumour characteristics and treatment were evaluated in all men diagnosed with prostate cancer up to December 2006 or the third screening round. Data on the control arm were divided into 3 periods: 1994-1998, 1999-2002 and 2003-2006. RESULTS: Tumour characteristics were more favourable over time in both the control and the screening arm, with especially increasing proportions of T1C tumours with 29% in 1994-1998 versus 50% in 2003-2006 and 48% at the initial screening round versus 75% at the third screening round, respectively. Tumour characteristics observed in the last period of the control arm were comparable to tumour characteristics in the initial screening round. In the control arm, treatment changed over time with surgery as the most common treatment in the entire observed period, but almost doubling of expectant management and the combination of hormone therapy and radiotherapy over time. In the initial screening round, surgery was the most common treatment (42%), changing over time to expectant management as the most frequently applied treatment in the third screening round (33%). CONCLUSION: Tumour characteristics in the control arm became more favourable over time and show similarity with prostate cancer cases detected at the initial screening round. The most prominent change in treatment over time was an increase of application of expectant management in both arms of the ERSPC. These observations reflect an increasing rate of opportunistic testing over time in men randomised to the control arm.

B3 breast lesions determined by vacuum-assisted biopsy: how to reduce the frequency of benign excision biopsies.

PURPOSE: The aim of this study was to identify parameters allowing differentiation among the diverse group of B3 lesion at stereotactic vacuum-assisted biopsy (VAB) to identify patients with a low risk of cancer and who can therefore be referred for follow-up rather than surgery and thus reduce the number of unnecessary surgical procedures. MATERIALS AND METHODS: Among 608 VAB procedures performed for nonpalpable ultrasound (US)-occult mammographic abnormality, 102 cases of B3 were included in this study. Mammographic lesion type, lesion size, Breast Imaging Reporting and Data System (BIRADS) category, number of specimens per lesion and presence of atypia were retrospectively analysed. Results were compared with histological findings at surgery (53 cases) or mammographic findings during follow-up (49 cases). Statistical analysis was performed with univariate analysis (chi-square test), and statistical significance was set at p<0.05. RESULTS: The majority of cases were depicted as isolated microcalcifications (82.3%), were smaller than 10 mm (80.4%), had a low level of radiological suspicion (64.7%) and had 11 or more cores sampled (94.1%). Atypia at VAB was reported in 60 of 102 cases (58.8%). Carcinoma was found at excision in 5/60 (8%) B3 lesions with atypia and in no B3 lesions without atypia (p=0.146). Cancer at surgery was more frequent among cases of isolated microcalcifications (p=0.645), cases with high radiological suspicion (p=0.040) and those with a smaller number of cores sampled (borderline significant p=0.064). CONCLUSIONS: On the basis of our experience, the presence or absence of atypia in our series proved to be the reliable criterion to prompt or avoid surgery in cases with a VAB finding of B3 lesion. This criterion may therefore be adopted in practice to more accurately select patients for surgery.

"CADEAT": considerations on the use of CAD (computer-aided diagnosis) in mammography.

Computer-aided diagnosis (CAD) has been extensively reported to increase sensitivity by about 10% when added to a single reading while increasing recall rate by 12%, and its current use can be safely recommended in clinical practice. CAD has been suggested as a possible alternative to conventional double reading in screening. Uncontrolled comparison is consistent and suggests that CAD is comparable to double reading in incremental cancer detection rate (CAD +10.6%, double reading +9.1%) and possibly better in recall rate (CAD +12.5%, double reading +28.8%). However, controlled studies comparing single reading + CAD to conventional double reading are not consistent and on average suggest a lower cancer detection rate (-5.1%) and a lower recall rate (-9.8%) for CAD. Scientific evidence is not sufficient for a safe recommendation of single reading + CAD as a current alternative to conventional double reading.

Analysis of interval cancers observed in an Italian mammography screening programme (2000-2006).

PURPOSE: The purpose of this study was to assess the interval cancer (IC) proportional incidence and review IC cases observed in an Italian mammography screening programme during 2000-2006. MATERIALS AND METHODS: ICs were identified through linkage of a screening database with the local cancer registry and hospital discharge records to calculate proportional (observed/expected) incidence. Negatively reported mammograms preceding ICs underwent blind review (randomly mixed with negative controls in a 2:1 ratio) by three expert radiologists and classified according to European guidelines criteria (OC=occult, MS=minimal sign, SE=screening error) according to majority report. Proportional IC incidence and rate of reviewed IC classified as SE were compared with European guideline standards. RESULTS: Proportional IC incidence was 10.8% in the first and 40.0% in the second year of the interval (European standard=30% or 50%, respectively). Sensitivity estimate for the 2-year interval was 74.6%. ICs were reviewed as SE, MS or OC in 15.0%, 14.0% or 71.0% of cases, respectively. Corresponding review results for negative controls were 7.0%, 25.0% or 68.0%, respectively. Positive predictive value for IC was 51.7% for SE and 21.8% for MS reporting category, respectively (p=0.008). European standard (<20% reviewed as SE) was reached. CONCLUSIONS: The study shows that the sensitivity of the mammography programme was good, complying with European guideline recommendations. Assessment of IC-based early indicators of screening efficacy is feasible in a current screening programme and should become a routine procedure.

Early detection of breast cancer: overview of the evidence on computer-aided detection in mammography screening.

We review the evidence on computer-aided detection (CAD) as an adjunct to mammography interpretation, and discuss the complexity of its impact on decision-making and potential medico-legal aspects. CAD prompts the reader to review lesions on the mammogram and re-evaluate the decision on whether to recall CAD-prompted findings. Studies show that CAD can improve the sensitivity of a single reader, with an incremental cancer detection rate (from adding CAD to a single read) ranging between 1 and 19%. However, CAD will also substantially increase the recall rate (decrease the reader's specificity) causing additional recall in approximately 6-35% of women. Evidence indicates that CAD does not perform as well as double (human) reading in the context of organized breast screening where double reading is the standard of care. Although CAD can identify and prompt readers to missed cancers, the high number of false-positive prompts (1.5-4 false prompts per case) can have an adverse effect on clinical decision-making, and detracts from CAD's application in screening practice. Refinement in CAD algorithms, in combination with increasing implementation of digital mammography, may improve the potential use of CAD in mammography reading, but will require prospective evaluation.

Computer-assisted diagnosis (CAD) in mammography: comparison of diagnostic accuracy of a new algorithm (Cyclopus, Medicad) with two commercial systems.

PURPOSE: The study compares the diagnostic accuracy (correct identification of cancer) of a new computer-assisted diagnosis (CAD) system (Cyclopus) with two other commercial systems (R2 and CADx). MATERIALS AND METHODS: Cyclopus was tested on a set of 120 mammograms on which the two compared commercial systems had been previously tested. The set consisted of mammograms reported as negative, preceding 31 interval cancers reviewed as screening error or minimal sign, and of 89 verified negative controls randomly selected from the same screening database. RESULTS: Cyclopus sensitivity was 74.1% (R2=54.8%; CADx=41.9%) and was higher for interval cancers reviewed as screening error (90.9%; R2=54.5%; CADx=81.8%) compared with those reviewed as minimal sign (65.0%; R2=55.0%; CADx=20.0%). Specificity was 15.7% (R2=29.2%; CADx=17.9%). Overall accuracy was 30.8% (R2=35.8%; CADx=24.1%). The positive predictive value of a case with CAD marks [regions of interest (ROI)] was 23.4% (23/98; R2=16.0%; CADx=15.1%). Average ROI number per view among negative controls was 1.13 (R2=0.93; CADx=0.99). Cyclopus was more sensitive for masses compared with isolated microcalcifications (208 vs 62 ROI; R2=90 vs 213; CADx=192 vs 130). CONCLUSIONS: Compared with two other commercial systems, Cyclopus was more sensitive (R2 p=0.14; CADx p=0.02) and less specific (R2 p=0.02; CADx p=0.64).

Early detection of second breast cancers improves prognosis in breast cancer survivors.

BACKGROUND: The impact of early detection of second breast cancers in women who have survived a primary breast cancer is unknown. We examined the prognostic effect of detection of ipsilateral breast relapse (IBR) or contralateral breast cancer (CBC) in the asymptomatic relative to symptomatic phase. PATIENTS AND METHODS: Subjects were women with histology-verified second (invasive or in situ) breast cancer (N = 1044) in a breast centre in Florence (1980-2005). Symptom status, test, tumour stage, and outcomes data were obtained from clinical records and linkage with mortality registry. Disease-specific survival was measured from first cancer diagnosis to avoid lead-time bias. Sensitivity analysis was used to allow for length-time bias. RESULTS: Second cancers (IBR = 455; CBC = 589; median age 60 years) were diagnosed in 699 asymptomatic and 345 symptomatic women (67% versus 3%, P < 0.0001). Mammography was more sensitive than clinical examination (86% versus 57%, P < 0.0001); however, 13.8% of cases were only identified clinically. Asymptomatic cancers were smaller than symptomatic for both IBR (P < 0.001) and CBC (P < 0.001). Early-stage tumours were more frequent in asymptomatic (58.1%) than symptomatic (22.6%) women (P < 0.0001). Fewer women with asymptomatic than symptomatic CBC had node metastases (P = 0.0001). Hazard ratio (HR) for asymptomatic (relative to symptomatic) detection was 0.51 (0.32-0.80) for IBR, 0.53 (0.36-0.78) for CBC, and 0.53 (0.40-0.72) in all subjects (P < 0.0001). Length bias-adjusted HRs ranged from 0.53 to 0.73. CONCLUSION: Detection of second breast cancers in the asymptomatic phase leads to detection of early-stage cancer and improves relative survival by between 27% and 47%.

Immunochemical faecal occult blood test: number of samples and positivity cutoff. What is the best strategy for colorectal cancer screening?

Immunochemical faecal occult blood tests have shown a greater sensitivity than guaiac test in colorectal cancer screening, but optimal number of samples and cutoff have still to be defined. The aim of this multicentric study was to evaluate the performance of immunochemical-based screening strategies according to different positivity thresholds (80, 100, 120 ng ml(-1)) and single vs double sampling (one, at least one, or both positive samples) using 1-day sample with cutoff at 100 ng ml(-1) as the reference strategy. A total of 20 596 subjects aged 50-69 years were enrolled from Italian population-based screening programmes. Positivity rate was 4.5% for reference strategy and 8.0 and 2.0% for the most sensitive and the most specific strategy, respectively. Cancer detection rate of reference strategy was 2.8 per thousand, and ranged between 2.1 and 3.4 per thousand in other strategies; reference strategy detected 15.6 per thousand advanced adenomas (range=10.0-22.5 per thousand). The number needed to scope to find a cancer or an advanced adenoma was lower than 2 (1.5-1.7) for the most specific strategies, whereas it was 2.4-2.7, according to different thresholds, for the most sensitive ones. Different strategies seem to have a greater impact on adenomas rather than on cancer detection rate. The study provides information when deciding screening protocols and to adapt them to local resources.

PSA doubling time as a predictor of the outcome of random prostate biopsies prompted by isolated PSA elevation in subjects referred to an outpatient biopsy facility in a routine clinical scenario.

AIM: To assess the validity of PSA doubling time (PSADT) as a predictor of prostate sextant biopsy outcome in patients with PSA levels in the 4-10 ng/mL range. MATERIAL AND METHODS: A consecutive series of 355 sextant biopsies performed during 2001-2007 in subjects with negative digital rectal examination and transrectal ultrasonography was considered. Variables tested as possible predictors were age, total and free/total PSA value, PSA velocity and PSA doubling time. While PSA at time of biopsy and free/total PSA were determined with a standardized method undergoing strict quality control, previous PSA values used to assess velocity/doubling time came from other labs using different assays over widely varying intervals of time. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis. RESULTS: Apart from free/total PSA ratio, no other studied variable showed a statistically significant and independent association with biopsy outcome, either at univariate or multivariate analysis. No studied variable had a good performance as a biopsy indicator. Depending on the variable considered, 1.17 to 1.97 cancers would be missed to spare 10 benign biopsies. CONCLUSION: When based on PSA data determined with different assays over widely varying intervals and in the absence of an underlying protocol for PSA surveillance, PSA velocity and doubling time should never discount a biopsy prompted by total PSA elevation.