Il razionale dello
screening del cancro del
colon-retto
Prof. Dario Sorrentino
Cattedra di Gastroenterologia
Università di Udine
Caratteristiche fondamentali dello screening
per neoplasia nella popolazione generale
1. Malattia frequente
2. Preceduta da una lesione preneoplastica
asportabile in modo curativo
3. Che insorge su organo/tessuto “accessibile”
Chair of Gastroenterology, University of Udine
Caratteristiche fondamentali dello screening
per neoplasia nella popolazione generale
1. Malattia frequente
2. Preceduta da una lesione preneoplastica
asportabile in modo curativo
3. Che insorge su organo/tessuto “accessibile”
Chair of Gastroenterology, University of Udine
PESO SOCIO-ECONOMICO DEL CANCRO DEL COLON
• Rischio di malattia 6%
• Rischio di morte 3%
ITALIA
USA
Chair of Gastroenterology, University of Udine
30.000 nuovi casi per anno
15.000 morti per anno
152.000 nuovi casi per anno
57.000 morti per anno
CRC: incidence and mortality worldwide
Cases
ASR
Mortality
19.11
37.30
9.91
254816
152178
102640
14.44
25.37
7.8
237595
149470
88121
Males
World
498754
More developed countries 318694
Less developed countries 180059
(51%)
(48%)
(56%)
Females
World
445963
More developed countries 291897
Less developed countries 154064
Chair of Gastroenterology, University of Udine
(53%)
(51%)
(57%)
In Europe, in the 2000’s:
CRC cases: 304687 Lung cancer cases: 301090
Increasing incidence since 1970
Unchanged mortality since 1985
In US:
Decreasing incidence since 1985
Decreasing mortality since 1974
Chair of Gastroenterology, University of Udine
CRC incidence
(x100000/year)
2004: males
Chair of Gastroenterology, University of Udine
Caratteristiche fondamentali dello screening
per neoplasia nella popolazione generale
1. Malattia frequente
2. Preceduta da una lesione preneoplastica
asportabile in modo curativo
3. Che insorge su organo/tessuto “accessibile”
Chair of Gastroenterology, University of Udine
TRE TIPI DI CANCRO DEL COLON-RETTO
1. SPORADICO
2. CHE INSORGE SU IBD
3. EREDITARIO
Chair of Gastroenterology, University of Udine
Il cancro sporadico origina dal polipo
adenomatoso
Chair of Gastroenterology, University of Udine
STORIA NATURALE SEQUENZA
ADENOMA-CARCINOMA
Chair of Gastroenterology, University of Udine
STORIA NATURALE SEQUENZA
ADENOMA-CARCINOMA
COME LA
CONOSCIAMO?
Chair of Gastroenterology, University of Udine
Epidemiologia della poliposi e del cancro del colon
Sleisenger & Fordtran 1986
Chair of Gastroenterology, University of Udine
2006; 355:1912
Fu K, Sano Y
Chair of Gastroenterology, University of Udine
EVENTI DELLA CARCINOGENESI
COLORETTALE
MODELLO DI VOGELSTEIN
Chair of Gastroenterology, University of Udine
Identification of tumorigenic breast cancer cells
Al Hajji et al PNAS 2003;100 3983
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
Maintenance of normal stem cell: Wnt pathway
Adenomatous polyposis coli:
tumor suppressor gene mutated
in:
•FAP syndrome AND
•Vast majority of sporadic colon
adenomas and adenocarcinomas
Chair of Gastroenterology, University of Udine
Beachy et al NATURE VOL Nature
432 182006
NOVEMBER 2004
Wnt pathway in colorectal cancer
Accumulation of β-catenin in adenoma inside a villus of the small intestine
and in a small aberrant crypt focus in the colon of a min (multiple intestinal
neoplasia – APC mutant) mouse.
Chair of Gastroenterology, University of Udine
Science
Radtke 2005
and Clevers
SCIENCE 25 MARCH 2005
Caratteristiche fondamentali dello screening
per neoplasia nella popolazione generale
1. Malattia frequente
2. Preceduta da una lesione preneoplastica
asportabile in modo curativo
3. Che insorge su organo/tessuto “accessibile”
Chair of Gastroenterology, University of Udine
RESEZIONE ENDOSCOPICA
Courtesy Gastrolab
Chair of Gastroenterology, University of Udine
The National Polyp Study
Winawer SJ, Zauber AG, Ho MN, O’Brien MJ, Gottlieb LS, Sternberg SS,
Waye JD, Schapiro M, Bond JH, Panish JF, et al. National Polyp Study
Workgroup. Prevention of Colorectal cancer by colonoscopic polypectomy.
N Engl J Med 1993;329:1977-81.
•Winawer SJ, Zauber AG, O’Brien MJ, et al. The National Polyp Study
Workgroup: design, methods and characteristics of patients with
newly diagnosed polyps. Cancer 1992;70:1236-45.
•Winawer SJ, Zauber AG, O’Brien MJ, et al. National Polyp study Workgroup:
randomized comparison of surveillance intervals after colonoscopic
removal of newly diagnosed adenomatous polyps. N. Engl J
Med 1993;328:901-6.
•Winawer SJ, Fletcher RH, Miller L, et al. Colorectal cancer screening:
clinical guidelines and rationale. Gastroenterology 1997;112:594-642.
•Winawer SJ, Fletcher RH, Rex D, et al. Colorectal cancer screening and
surveillance: clinical guidelines and rationaledupdate based on new
evidence. Gastroenterology 2003;124:544-60.
•Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy
surveillance and polypectomy: a consensus update by the U.S.
Multi-Society Task Force on colorectal cancer and the American
Cancer Society. Gastroenterology 2006;130:1872-85.
•Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonoscopy
surveillance and polypectomy: a consensus update by the U.S. MultiSociety Task Force on colorectal cancer and the American Cancer Society.
CA Cancer J Clin 2006;56:143-59.
>90% reduction
in CRC
Chair of Gastroenterology, University of Udine
Caratteristiche fondamentali dello screening
per neoplasia nella popolazione generale
1. Malattia frequente
2. Preceduta da una lesione preneoplastica
asportabile in modo curativo
3. Che insorge su organo/tessuto “accessibile”
Chair of Gastroenterology, University of Udine
La colonscopia ottica
Courtesy Gastrolab
Chair of Gastroenterology, University of Udine
Il razionale dello screening del
cancro del colon-retto
Quale screening?
Chair of Gastroenterology, University of Udine
Tests disponibili per lo screening CRC
1. SOF annuale
2. Sigmoidoscopia ogni 5 anni
3. SOF + sigmoidoscopia annualmente e ogni
5 anni
4. Colonoscopia ogni 10 anni
6. Nuove opzioni
Chair of Gastroenterology, University of Udine
TESTS FOR DIAGNOSIS OF CRC
Sensitivity of some screening tests for the detection of
colonic neoplasia.
Test
Any
advanced
neoplasia
Tubular
adenoma
>10mm
Villous
adenoma
Highgrade
dysplasia
Invasive
cancer
Fecal occultblood test
alone
23.9
17.5
24.4
28.6
50
Sigmoidoscopy 70.3
69.9
64.4
77.6
79.2
Fecal occultblood test plus
sigmoidoscopy
76.2
68.9
83.7
83.3
75.8
Colonoscopy gold standard
Chair of Gastroenterology, University of Udine
American Gastroenterological Association
Colorectal cancer screening and surveillance: Clinical
guidelines and rationale—Update based on new evidence
– Gastroenterology 2003; 124: 544
•Men and women at average risk should be offered screening with one of
several options beginning at age 50 years.
•The rationale for presenting multiple options is that no single test is of
unequivocal superiority and that giving patients a choice allows them to
apply personal preferences and may increase the likelihood that
screening will occur.
•The strategies are not equal with regard to evidence of effectiveness,
magnitude of effectiveness, risk, or up-front costs.
•Reviewing the rationale section for each screening test will provide
clinicians with information that they can use in presenting the relative
effectiveness of each test to patients.
Chair of Gastroenterology, University of Udine
AGA proposed algorithm for CRC screening
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
Recommended CRC screening tests in different countries
Chair of Gastroenterology, University of Udine
Il razionale dello screening del
cancro del colon-retto
In Italia?
Chair of Gastroenterology, University of Udine
Sorrentino D, Paduano R, Bernardis V, Piccolo A, Bartoli E.
Colorectal cancer screening in Italy: feasibility and cost-effectiveness in a model area.
Eur J Gastroenterol Hepatol. 1999 Jun;11(6):655-60.
OBJECTIVE: To evaluate the feasibility and cost-effectiveness of screening programmes for
colorectal cancer in Italy.
DESIGN; We compared five types of programmes: annual faecal occult blood testing,
sigmoidoscopy (every 5 years), faecal occult blood testing plus sigmoidoscopy (every 1 and
5 years), colonoscopy (every 10 years) (all in the age group 55-69 years, last examination at
70 years) and 'filter' colonoscopy. The latter had to be performed in persons at 50 years of
age and repeated every 10 years until the age of 70. Costs for the tests and colon cancer
care were paid by the Regional Health Office to the hospitals performing the
procedures/treatments.
SETTING: Data were applied to a small model area in northern Italy (Gemona, 80,000
inhabitants) with well-known demographic (age distribution) and epidemiological (colon
cancer incidence) features.
RESULTS: All-inclusive 10-year costs per screenee and per death prevented (in US dollars)
were: 965 and 77,200 for faecal occult blood testing; 436 and 15,500 for sigmoidoscopy;
1521 and 35,000 for sigmoidoscopy plus faecal occult blood testing; 510 and 15,100 for
colonoscopy; 510 and 14,000 for 'filter' colonoscopy. With 'filter' colonoscopy the programme
required 870 colonoscopies per year, while with colonoscopy 13,700 colonoscopies were
needed at time zero.
CONCLUSIONS: In Italy, screening programmes based on sigmoidoscopy/colonoscopy are
more cost effective than those based on faecal occult blood testing. 'Filter' colonoscopy at
age 50 appears superior to the other types of endoscopy-based screening programmes
because it utilizes, at any point in time, a much smaller fraction of available resources.
Chair of Gastroenterology, University of Udine
COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA
RESULTS
Hospital use in different screening strategies
100
90
80
70
60
%
50
40
30
20
10
0
NO SCREENING
Chair of Gastroenterology, University of Udine
FOBT
SIG
FOBT+SIG COLONSCOPY
COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA
RESULTS
Costs per screenee per 10 years ( €)
2000
C
o
s 1000
t
s
0
FOBT
SIGM
FOBT+SIGM
COLONOSCOPY
FC50
Type of screening
Costs include administration of the test plus all the procedures requested by the result of the test itself
Chair of Gastroenterology, University of Udine
COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA
RESULTS
Costs per death prevented ( €)
80000
70000
60000
C 50000
o
s 40000
t
s 30000
20000
10000
0
FOBT
SIGM
FOBT+SIGM
COLONOSCOPY
FC50
Type of screening
Costs per death prevented: costs of a given screening program divided the number of lives saved by
that program
Chair of Gastroenterology, University of Udine
COLORECTAL CANCER SCREENING IN ITALY: FEASIBILITY AND COST-EFFECTIVENESS IN A MODEL AREA
FEASIBILITY
AGE GROUPS
MALES
FEMALES
TOTAL
50-54
2.865
2.495
5.360
55-69
6.443
7.225
13.668
70-74
1.605
2.667
4.272
50-W
13.303
17.611
30.914
75-W
2.390
5.224
7.614
00-W
38.682
41.015
79.697
55-64
4.480
4.751
9.231
51-60
5.366
4.993
10.359
50
460
412
872
60
450
440
890
•The screening plans based on sigmoidoscopy or on colonoscopy require 13700
procedures at time 0 and 18700 every 5 or 10 years.
•With "filter" colonoscopy the program requires 872 colonoscopies per year.
Chair of Gastroenterology, University of Udine
C. Hassan, A. Zullo, A. Laghi, I. Reitano, F. Taggi, P. Cerro, F. Iafrate, M. Giustini, S. Winn and S. Morini
Colon cancer prevention in Italy: Cost-effectiveness analysis with CT colonography and endoscopy
Dig Liver Dis. 2007;39:242-50
To compare the efficacy and cost-effectiveness of CTC screening in a simulated Italian
population with those of colonoscopy and flexible sigmoidoscopy (FS).
Methods
The cost-effectiveness of different screening strategies was compared using a Markov
process computer model, in which in a hypothetical population of 100 000 50 year-olds
were investigated by CTC, colonoscopy or FS every decade. Outcomes were projected
to the Italian national level.
Results
CRC incidence reduction was calculated at 40.9%, 38.2%, and 31.8% with colonoscopy,
CTC and FS, respectively. As compared to no screening, all screening programs were
shown to be cost-saving, allowing a saving of 11€, 17€, and 48€ per person with
colonoscopy, FS and CTC, respectively. FS appeared to be less cost-effective than
CTC, whilst colonoscopy appeared to be an expensive option as compared to CTC.
Undiscounted national expenditure was calculated to be €1042489512, €1093268285,
and €1198783428 for FS, CTC and colonoscopy, respectively, as compared to
€695818078 without screening.
Conclusion
CRC screening is cost-saving in Italy, irrespective of the technique applied. CTC
appeared to be more cost-effective than FS, and it may also become a valid alternative
to colonoscopy.
Chair of Gastroenterology, University of Udine
Il razionale dello screening del
cancro del colon-retto
Dove siamo in
Italia
Chair of Gastroenterology, University of Udine
N.of CRC
deaths.
Males, Italy
2009
???
Milestones:
Cervical K screening
Adenoma-K sequence known
First FOBT screening study
Debate over
CRC screening
First colonscopy
screening study
Chair of Gastroenterology, University of Udine
Minnesota study
Il razionale dello screening del
cancro del colon-retto
Altrove…
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
Chair of Gastroenterology, University of Udine
N.of CRC
deaths.
Males, US
Chair of Gastroenterology, University of Udine
Nei Paesi Occidentali
Benchè la compliance rimane un ostacolo
è difficile al giorno d’oggi giustificare
l’assenza di uno screening per CRC nella
popolazione generale.
Chair of Gastroenterology, University of Udine