rubrica

Screening

  • Paolo Giorgi Rossi1

  1. ASPLazio, Roma
Paolo Giorgi Rossi -

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Ricerca bibliografica periodo 15 ottobre 2010 – 17 gennaio 2011

Per leggere le caratteristiche di questa ROUTINE di ricerca clicca qui

Commento: Di 26 pubblicazioni individuate, 10 studi e una lettera erano relativi allo screening inteso come intervento di prevenzione attraverso la diagnosi precoce della popolazione. Sono emersi studi su tutti gli ambiti di screening oncologico più dibattuti, ma non sono stati individuati studi su screening non oncologici. In particolare due studi riguardano i programmi di screening del colon retto, il primo riporta una valutazione di effectiveness, analizzando la sensibilità di sei programmi basati sull’esame del sangue occulto in Veneto, mentre il secondo tenta una valutazione d’impatto misurando la diminuzione dell’incidenza del cancro del colon retto in Toscana e ipotizzando una relazione causale con l’avvio dei programmi di screening. Altri due studi riguardano lo screening mammografico, uno sull’uso dell’ecografia nei seni densi e il suo impatto sull’incidenza di cancri intervallo, il secondo sull’effetto dell’arbitrato nei casi di referti discordanti nella lettura delle mammografie. Anche per lo screening del cervicoracinoma sono usciti due lavori: il primo sull’uso del test HPV come test di triage delle lesioni di basso grado, il secondo un trial sull’uso dell’auto-prelievo per aumentare la compliance ai programmi organizzati. Due studi anche per lo screening del polmone: il primo è un’analisi dei casi trovati nel braccio d’intervento e in quello di controllo del trial DANTE, il secondo una re-analisi dei dati del trial della Mayo Clinic in cui si ipotizza un effetto di autoselezione dei partecipanti al braccio d’intervento come possibile causa della peggiore mortalità osservata. Infine è stato trovato uno studio sullo screening spontaneo con il PSA per lo screening della prostata e uno sullo screening per le mutazioni dei geni BRCA1 e 2 in pazienti con familiarità per cancro della mammella e dell’ovaio.

Di ogni articolo è disponibile l'abstract. Per visualizzarlo basta cliccare sul titolo.

1. Infante M, Chiesa G, Solomon D, Morenghi E, Passera E, Lutman FR, Bottoni E, Cariboni U, Errico V, Voulaz E, Ferraroli G, Testori A, Inzirillo F, Chiarenza M,Roncalli M, Cavuto S, Chiti A, Alloisio M, Ravasi G; for the DANTE Study Group. Surgical Procedures in the DANTE Trial, A Randomized Study of Lung Cancer Early Detection with Spiral Computed Tomography: Comparative Analysis in the Screening and Control Arm. J Thorac Oncol. 2010 Dec 21. [Epub ahead of print]
*Thoracic Surgery Department, IRCCS Istituto Clinico Humanitas, Rozzano (Milano); †Thoracic Surgery Department, Humanitas-Gavazzeni, Bergamo; ‡Biostatistics Unit, IRCCS Istituto Clinico Humanitas, Rozzano (Milano); §Radiology Department, IRCCS Istituto Clinico Humanitas, Rozzano (Milano); ∥Medical Oncology Department, Humanitas-Catania Oncology Centre; ¶Pathology Department, IRCCS Istituto Clinico Humanitas, Rozzano (Milano); #Italian Association for the Fight against Cancer,Milano; and **Nuclear Medicine Department, IRCCS Istituto Clinico Humanitas, Rozzano (Milano), Italy.
Abstract
BACKGROUND: The patient population derived from lung cancer screening programs with low-dose spiral computed tomography (LDCT) is different from the general population accessing thoracic surgical services.
METHODS: Retrospective review of all surgical cases in the DANTE trial, a randomized study of lung cancer screening with LDCT. Patient characteristics, workup, procedures, resections for benign disease, complications, tumor features, and final outcomes have been analyzed in the LDCT and in the control arm.
RESULTS: In the LDCT arm, 77 suspicious lesions were surgically managed in 72 patients. A benign lesion was diagnosed in 17 cases (22%). Major video-assisted thoracoscopic surgery resection was carried out in five lung cancer cases (7%) and segmentectomy in 11 (19%). Complete resection was achieved in 93%, and stage I rate was 73%. Two patients had a local recurrence after open lobectomy, and three had a resectable new primary. In the control group, 28 patients underwent 31 surgical procedures, in five cases (16%) for benign lesions. No major video-assisted thoracoscopic surgery resections were carried out. Resectability rate was 88%, and stage I rate was 52%. Five patients had a local recurrence and two had a second primary.
CONCLUSIONS: Surgery for benign lesions is a relevant issue in screening-derived patients. Local control may be achieved by minimally invasive techniques or segmentectomy; however, developing the necessary skills requires an effort by the surgical team. Long-term survivors have a noticeable chance of developing second primary cancers or resectable recurrences and may benefit from a second resection.

Breve commento a cura di Paolo Giorgi Rossi
I risultati del trial DANTE mostrano chiaramente come la pratica della diagnosi precoce spesso apra nuove problematiche per clinici ed epidemiologi: ben il 22% delle lesioni polmonari gestite chirurgicamente nel braccio d’intervento è risultato benigno, un carico di sovra-trattamento che deve essere attentamente considerato nella valutazione del rapporto fra benefici e danni indotti da un eventuale screening.

2. D'Ambrosio GG, Campo S, Cancian M, Pecchioli S, Mazzaglia G. Opportunistic prostate-specific antigen screening in Italy: 6 years of monitoring from the Italian general practice database. Eur J Cancer Prev. 2010 Nov;19(6):413-6.
SIMG Società Italiana di Medicina Generale-Italian College of General Practitioners, Firenze, Italy. d.ambrosio.gaetano@simg.it
Abstract
The practice of prostate-specific antigen (PSA) screening has been increasing in Italy despite uncertain scientific evidence and contrary recommendations from most scientific societies. In 2002, a survey of PSA screening diffusion among general practices was performed, looking for screening frequency and age pattern of screened individuals. The objective of this study was to assess whether the features of PSA screening did change after 6 years in the same considered setting. Using the data obtained from 500 Italian general practitioners providing information to the Health Search/CSD Patient database, we selected, for the study purpose 351,091 male individuals. We assumed PSA prescriptions performed during 2005-2008 in individuals without prostate cancer, or benign prostate disease, or urological symptoms history to have a screening purpose. Screening frequency was analyzed in the overall series, by year and by patient's age. Exposure to PSA screening (at least on PSA test in the considered period) of males aged over 50 years raised from 31.4% (confidence interval 95% 31.08-31.70%) during 2002 to 46.4% (confidence interval 95% 46.19-46.68%) during 2008. The highest yearly exposure to PSA screening (55%) and the highest frequency of repeat testing was observed in the 70-79 age range. PSA screening practice has continued to increase in Italy and is often performed in elderly people without any scientific rationale.

Breve commento a cura di Paolo Giorgi Rossi
È la Società Italiana di Medicina Generale stessa che ci dà un quadro piuttosto preoccupante di come e quanto venga prescritto il test del PSA per lo screening del carcinoma prostatico nella popolazione maschile sana. Le conclusioni degli autori sono dure e dimostrano un raro esempio di assunzione di responsabilità da parte di una società scientifica: “PSA (…) in Italy and is often performed in elderly people without any scientific rationale”

3. Costa S, Venturoli S, Mennini FS, Marcellusi A, Pesaresi M, Leo E, Falasca A, Marra E, Cricca M, Santini D, Zerbini M, Pelusi G. Population-based frequency assessment of HPV-induced lesions in patients with borderline Pap tests in the Emilia-Romagna Region: the PATER study. Curr Med Res Opin. 2011 Jan 12. [Epub ahead of print]
Department of Gynaecology and Obstetrics, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Abstract
Background: The PATER study assessed the frequency of high-risk (HR) and low-risk (LR) human papillomavirus (HPV) in HPV-induced lesions in patients with borderline cytology.
Methods
: This retrospective observational cohort study was designed to evaluate ASCUS patients detected through a local cervical cancer screening programme and referred to the Department of Gynaecology and Obstetrics at the S. Orsola-Malpighi University Hospital in Bologna, in the period between January 2000 and December 2007.
Results
: In 1047 patients aged 38.4±9.6 years (range 23-65 years), 34.8% (n=364) was positive for HR- or LR-HPV DNA. The mean age of women with HPV infection was significantly lower compared with the negative group (36.8±9.4 versus 39.3±9.6 years; p<0.001). Overall, 357 (34.1%) women had cervical lesions: 279 (26.6%) had CIN1, 18 (1.7%) CIN2, and 60 (5.7%) CIN3+. HR-HPV genotype was detected in 83.3%, and 91.5% of patients with CIN2 and CIN3+ respectively. Among the 124 CIN1 HPV-positive women, 8.9% harboured LR-HPV genotypes, 80.6% HR-HPV and 10.5% a combination of HR- and LR-HPV. HPV-6 and 11 accounted for 19.4% of all HPV-positive CIN1 lesions.
Conclusion: Our study suggest that: in ASCUS patients over 40 years there is a low risk of positivity for HPV infection; the HPV DNA testing in patients with CIN3+ and a mean age close to 40 years is highly sensitive (98.3%) and acceptably specific (75.5%); the frequency of LR-HPV (alone or in combination with HR) in ASCUS cytology is not negligible. A tetravalent-based HPV vaccination alongside the screening programme would provide considerable clinical, organizational, and economic benefits.
4. Corsetti V, Houssami N, Ghirardi M, Ferrari A, Speziani M, Bellarosa S, Remida G,Gasparotti C, Galligioni E, Ciatto S. Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: Interval breast cancers at 1year follow-up. Eur J Cancer. 2011 Jan 4. [Epub ahead of print]
Ambulatori Raphael, Calcinato (BS), Italy.
Abstract
Surveillance of interval cancers (IC) provides a measure of breast screening efficacy. Increased breast density is a predictor of breast cancer risk and of the risk of IC in screening. Improving screening sensitivity in women with dense breasts, through adjunct ultrasound (US), may potentially reduce IC; however this has not been proven. We report on first-year IC in a retrospective cohort of 8865 women who had 19,728 screening examinations (2001-2006): women with non-dense (D1-D2) breasts received mammography (M) screening, and women with dense (D3-D4) breasts also received ultrasound. Data linkage with both hospital discharge records and cancer registry databases was used to identify IC. Underlying cancer rates (cancers observed within 1-year from screening) were 6.3/1000 screens in the D1-D2 group and 8.3/1000 screens in the D3-D4 group. Cancer detection rate (CDR) was 5.98/1000 in all screening examinations; in D3-D4 breasts ultrasound had an additional CDR of 4.4/1000 screens. There were 21 first-year IC, an overall interval cancer rate (ICR) of 1.07/1000 negative screens: 0.95/1000 in women <50years and 1.16/1000 screens in women >50years. ICR by breast density were 1.0/1000 negative screens in D1-D2, and 1.1/1000 negative screens in D3-D4. Interval cancers were early stage (in situ or small invasive) cancers, almost all were node-negative. Screening sensitivity was 83.5% for mammography alone in D1-D2 breasts relative to 86.7% for mammography with ultrasound in D3-D4 breasts. Our study shows that including ultrasound as adjunct screening in women with D3-D4 breasts brings the IC rate to similar levels as IC in non-dense breasts -this suggests that additional cancer detection by ultrasound is likely to improve screening benefit in dense breasts, and supports the implementation of a randomised trial of adjunct ultrasound in women with increased breast tissue density.
5. Zorzi M, Fedato C, Grazzini G, Stocco FC, Banovich F, Bortoli A, Cazzola L, Montaguti A, Moretto T, Zappa M, Vettorazzi M. High sensitivity of five colorectal screening programmes with faecal immunochemical test in the Veneto Region, Italy. Gut. 2010 Dec 30. [Epub ahead of print]
Istituto Oncologico Veneto IOV IRCCS, Padua, Italy.
Abstract
Objective Although guaiac-based faecal occult blood test screening has been shown to be effective in reducing colorectal cancer (CRC) mortality, it has been criticised mostly for its low sensitivity. Italian CRC screening programmes are based on immunochemical tests (iFOBT). We collected and analysed the interval cancers (ICs) found by five screening programmes to estimate their sensitivity.
Methods ICs were identified in subjects who had a negative result in a screening examination from 2002 to 2007 (N=267 789); data were linked with 2002-2008 hospital discharge records (HDR). Analysis was based on the follow up of 468 306 person-years. The proportional incidence-based sensitivity was estimated overall and by sex, age class, time since last negative iFOBT result, anatomical site,and history of screening (first or subsequent test).
Results Overall, 126 ICs were identified, compared to 572 expected cancers. The proportional incidences were 15.3% and 31.0% in the first and the second interval-years, respectively, with an overall episode sensitivity of 78.0% (95% CI: 73.8 to 81.6). Sensitivity was higher for males than females (80.1% vs 74.8%); no differences were observed by age, anatomical site or between programmes. The test sensitivity of iFOBT was 82.1% (95% CI 78.1% to 85.3%).
Conclusions iFOBT-based screening programmes showed a high performance in terms of sensitivity as estimated through the IC rates. The screening schedule utilised in our programmes (single iFOBT, positivity threshold of 100&emsp14;ng Hb/ml of sample solution, inter-screening interval of 2&emsp14;years) shows low rates of missed cancers that are diagnosed during the interval. HDR are a convenient and reliable source of data for IC studies.

6. Zorzi M, Baracco S, Fedato C. Limited effect of summer warming on the sensitivity of colorectal cancer screening. Gut. 2010 Dec 29. [Epub ahead of print] Istituto Oncologico Veneto IOV IRCCS, Padua, Italy.

7. Giorgi Rossi P, Marsili LM, Camilloni L, Iossa A, Lattanzi A, Sani C, Di Pierro C, Grazzini G, Angeloni C, Capparucci P, Pellegrini A, Schiboni ML, Sperati A, Confortini M, Bellanova C, D'Addetta A, Mania E, Visioli CB, Sereno E, Carozzi F. The effect of self-sampled HPV testing on participation to cervical cancer screening in Italy: a randomised controlled trial (ISRCTN96071600). Br J Cancer. 2010 Dec 21. [Epub ahead of print]
Agency for Public Health, Lazio Region, Via di S Costanza 53, Rome 00198, Italy.
Abstract
Background:In Italy, cervical cancer screening programmes actively invite women aged 25-64 years. Programmes are hindered by low participation.
Methods:A sample of non-responder women aged 35-64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone,whereas a fourth group was directly sent the self-samplers home.
Results:Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82-1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45-0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10-1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24-2.30), but not in Abruzzo (N178,RR=0.95; 95% CI=0.61-1.50), a prevalently rural area.
Conclusions:Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered. British Journal of Cancer advance online publication, 21 December 2010; doi:10.1038/sj.bjc.6606040www.bjcancer.com.
8. Marchina E, Fontana MG, Speziani M, Salvi A, Ricca G, Di Lorenzo D, Gervasi M, Caimi L, Barlati S. BRCA1 and BRCA2 genetic test in high risk patients and families: counselling and management. Oncol Rep. 2010 Dec;24(6):1661-7.
Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology, University of Brescia, 25123 Brescia, Italy. marchina@med.unibs.it
Abstract
Hereditary breast cancer accounts for 5-10% of all cases of breast cancer and 10-15% of ovarian cancer and is characterised by dominant inheritance, early onset, the severity of the disease and bilaterality. About 30% of cases with hereditary breast and ovarian cancer have mutations in the BRCA1 and BRCA2 genes. Women with a mutation in the BRCA1 gene have a 80-90% lifetime risk of developing breast cancer, and 40-65% chance of developing ovarian cancer. Most studies carried out throughout the world indicate that the prevalence of BRCA1 and BRCA2 mutation is lower than originally suggested by early studies on large families with several affected members. Studies performed in Italy have reported different prevalence of BRCA1 and BRCA2 mutations, probably due to different selection criteria and to the variability of the techniques used. In this study, we performed a screening of BRCA1 and BRCA2 in families from northern Italy with familial recurrence of breast cancer or ovarian cancer in which the individual risk of patients of being carriers of BRCA1 and BRCA2 mutation was evaluated using BRCAPRO (CAGene) software. We enrolled 27 patients of 101 unrelated families selected when they fulfilled the inclusion criteria of the American Society of Clinical Oncology (ASCO). Specific risk evaluation, genetic test administration if needed, and discussion of the results were offered during multi-disciplinary genetic, surgical and psychological counselling. Seven probands (35%) found BRCA1/2 sequence variation carriers; no BRCA1 and BRCA2 mutations were detected in the remaining 13 probands. Two (15%) patients had BRCA1 mutations and 5 (25%) patients had BRCA2 mutations. In the latter case, BRCA2 delA 9158fs+29stop mutation in exon 22, never previously described and a new sequence variation (T703N) in exon 11 were identified.
9. Caumo F, Brunelli S, Tosi E, Teggi S, Bovo C, Bonavina G, Ciatto S. On the role of arbitration of discordant double readings of screening mammography: experience from two Italian programmes. Radiol Med. 2010 Oct 27. [Epub ahead of print]
Centro di Prevenzione Senologica (CPS), P.O. Marzana, ULSS 20, Piazza L. Lambranzi, 1, 37142, Marzana, Verona, Italy.
Abstract
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 euros, whereas 216 spared assessment procedures would have cost 14,558.4-23,346 eruos.
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.
10. Dominioni L, Poli A, Mantovani W, Rotolo N, Imperatori A. Volunteer effect and compromised randomization in the Mayo Project of screening for lung cancer. Eur J Epidemiol. 2011 Jan;26(1):79-80. Epub 2010 Oct 23.
Center for Thoracic Surgery, University of Insubria, Ospedale di Circolo, Viale Borri 57, 21100, Varese, Italy, lorenzo.dominioni@uninsubria.it.
Abstract
It has been confirmed recently that the volunteer effect in lung cancer screening is characterized by higher lung cancer mortality risk in self-selected screening participants. The Mayo Lung Project, the most influential trial of screening for lung cancer ever completed, was conducted in nonvolunteer Mayo Clinic outpatients, with a peculiar study design that rendered the randomization vulnerable to the volunteer effect. Of all non volunteers randomized in the Mayo Lung Project, only those allocated in the screened group were asked consent to participate in the trial. The final Mayo Lung Project report stated that 655 randomized non volunteers refused screening and were excluded from the study, thus documenting violation of the rule that no selection should occur after randomization. The long-term follow-up of the Mayo Lung Project showed an enigmatic result which has never been explained: the lung cancer mortality was 13% higher in the screening intervention group than in the control group [4.4 (95% CI 3.9-4.9) vs. 3.9 (95% CI 3.5-4.4) per 1,000 person-years; P = 0.09]. Such overrepresented mortality is consistent with the volunteer effect and supports the concept that the Mayo Lung Project randomization was compromised by the post-randomization self-selection of participant nonvolunteers.
11. Crocetti E, Buzzoni C, Zappa M. Colorectal cancer incidence rates have decreased in central Italy. Eur J Cancer Prev. 2010 Nov;19(6):424-5.
Clinical and Descriptive Epidemiology Unit, Institute for Cancer Study and Prevention ISPO, Florence, Italy. e.crocetti@ispo.toscana.it
Abstract
We analyzed colorectal cancer incidence data from the Tuscany Cancer Registry, central Italy, for the period 1985-2005. We carried out a trend analysis through a Joinpoint regression analysis, and summarized trends as annual percent change (APC) of the standardized (European standard) rates. Colorectal incidence rates increased until 1996 (APC=+1.4, 95% CI: 0.8-1.9), then decreased significantly (APC=-1.1, 95% CI: -0.8 to -0.4). The change was detected as statistically significant in the age group of 54+ years. Among younger individuals, we observed an increasing incidence until 2003. In the same geographical area, a colorectal screening programme has been active from 1982; it was initially based on guaiac faecal occult blood testing (GFOBT) and on immunological testing (IFOBT) since the mid 1990s. The decline in colorectal cancer incidence since 1996, in the whole population and especially among individuals older than 54 years, may suggest the effect of FOBT screening in terms of precancerous polyps removal.