Most Patients with Colorectal Tumors at Young Age Do Not Visit a Cancer Genetics Clinic

Abstract

PurposeThis study examined the referral process for genetic counseling at a cancer genetics clinic in patients with colorectal cancer
and to search for determinants of variation in this referral process.

MethodsPatients who were recently diagnosed with colorectal cancer at a young age or multiple cancers associated with Lynch syndrome,
hereditary nonpolyposis colorectal cancer, (N = 119) were selected from PALGA, the nationwide network and registry of histopathology
and cytopathology in the Netherlands. In a retrospective analysis, we examined whether these patients visited a cancer genetics
clinic and identified determinants for referral to such a clinic. Factors of patients, professional practice, and hospital
setting were explored with logistic regression modeling.

ResultsThirty-six (30 percent) patients visited a cancer genetics clinic. Seventy percent of patients whom the surgeon referred to
a cancer genetics clinic decided to visit such a clinic. Analysis of determinants showed that patients with whom the surgeon
discussed referral and that were treated in a teaching hospital were more likely to visit a cancer genetics clinic.

ConclusionThe referral process is not optimally carried out. To deliver optimal care for patients suspected of hereditary colorectal
cancer, this process must be improved with interventions focusing on patient referral by surgeons and raising awareness in
nonteaching hospitals.

Full text

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ORIGINAL
CONTRIBUTION
Most Patients with Colorectal Tumors
at Young Age Do Not Visit a Cancer
Genetics Clinic
Lucia I. H. Overbeek, M.Sc.1,2?Nicoline Hoogerbrugge, M.D., Ph.D.1,3?
JoannesH.J.M.vanKrieken,M.D.,Ph.D.4?FokkoM.Nagengast,M.D.,Ph.D.5?
Theo J. M. Ruers, M.D., Ph.D.6?Marjolijn J. L. Ligtenberg, Ph.D.1,4?
Rosella P. M. G. Hermens, Ph.D.2& On behalf of the MIPA Study Group
1 Department of Human Genetics, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
2 Center for Quality of Care Research, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
3 Department of Medical Oncology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
4 Department of Pathology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
5 Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
6 Department of Surgery, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands
PURPOSE: This study examined the referral process for
genetic counseling at a cancer genetics clinic in patients
with colorectal cancer and to search for determinants of
variation in this referral process.
METHODS: Patients who were recently diagnosed with
colorectal cancer at a young age or multiple cancers
associated with Lynch syndrome, hereditary nonpolyposis
colorectal cancer, (N=119) were selected from PALGA,
the nationwide network and registry of histopathology
and cytopathology in the Netherlands. In a retrospective
analysis, we examined whether these patients visited a
cancer genetics clinic and identified determinants for
referral to such a clinic. Factors of patients, professional
practice, and hospital setting were explored with logistic
regression modeling.
RESULTS: Thirty-six (30 percent) patients visited a cancer
genetics clinic. Seventy percent of patients whom the
surgeon referred to a cancer genetics clinic decided to visit
such a clinic. Analysis of determinants showed that
patients with whom the surgeon discussed referral and
that were treated in a teaching hospital were more likely
to visit a cancer genetics clinic.
CONCLUSION: The referral process is not optimally carried
out. To deliver optimal care for patients suspected of
hereditary colorectal cancer, this process must be im-
proved with interventions focusing on patient referral by
surgeons and raising awareness in nonteaching hospitals.
KEY WORDS: Colorectal neoplasms; Hereditary
nonpolyposis; Genetic counseling; Quality of health care;
Referral and consultation.
INTRODUCTION
Colorectalcancer(CRC)isthesecondleadingcauseofdeath
from cancer in Western society. Up to 10 percent of adults
have a first degree relative with CRC,1which increases their
risk of developing CRC. The relative risk to develop CRC in
families with multiple first-degree relatives is 4 to 6.2
The most common type of hereditary CRC is Lynch
syndrome defined as a germline mutation in one of the
DNA mismatch repair genes and formerly known as
hereditary nonpolyposis colorectal cancer, which is an
autosomal dominant disease. Lynch syndrome is charac-
terized by early onset CRC and by multiple episodes of
CRCs.3In addition, extracolonic cancers occur including
carcinomas of the endometrial, ovaries, small bowel,
stomach, sebaceous gland, biliary tract, and upper urinary
tract. Although Lynch syndrome accounts for about 1 to 3
percentofCRCs,4–7itiscrucialtoidentifyLynchsyndrome
because surveillance reduces morbidity and mortality by 65
percent over 15 years in unaffected relatives and reduces
the risk of recurrence of CRC in patients.8Optimal care for
patients at high risk of Lynch syndrome or another
hereditary CRC includes referral by clinicians to genetic
counseling at a cancer genetics clinic.
The first and most important part of the referral pro-
cess is the identification of patients suspected of hereditary
CRC by the treating physician. After the identification of
such patients, the next step is discussion of referral to
genetic counseling at a cancer genetics clinic by the treating
physician. The last part of the referral process is the
patients’ decisions to visit such a clinic.
Theextent thatthereferral process occurs isunknown.
The identification of patients with hereditary CRC is not
optimalyet.Forexample,theBethesda guidelines9describe
This work was supported by ZonMw, the Netherlands Organization for
Health Research and Development.
Addressofcorrespondence:R.P.M.G.Hermens,Ph.D.,CenterforQuality
of Care Research 114, Radboud University Nijmegen Medical Centre,
P.O. Box 9101, 6500 HB Nijmegen, Netherlands. E-mail: R.Hermens@
kwazo.umcn.nl
DOI: 10.1007/s10350-008-9345-x?VOLUME 51: 1249–1254 (2008)?©THE AUTHOR(S) 2008?PUBLISHED ONLINE: 7 JUNE 2008
1249

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which patients merit microsatellite instability analysis and
are widely used by genetic counselors; however, these
guidelines are not wellknown by clinicians outside genetics
departments.10,11When identification of such patients is
difficult, referral is possibly not discussed with all patients
that are considered to benefit from genetic counseling.
Regarding the decision of the patient to visit a cancer
genetics clinic, one study demonstrates that 26 percent of
patients, who are invited by letter, visit a cancer genetics
clinic;12this percentage is unknown in recently diagnosed
patients with whom referral is provided by their own
treating physician.
Accordingly, data on the referral process to genetic
counseling at a cancer genetics clinic is a first step to
improve the care for patients suspected of hereditary
CRC. Subgroups of hospitals, professionals, or patients in
which the referral process is not optimally carried out
may exist; hence, these subgroups need special attention
to improve the referral process. Therefore, identification
of determinants of the referral process at hospital,
professional, and patient level is useful.
The aim of this study was to examine actual care
regarding the referral process to genetic counseling at a
cancer genetics clinic in the Netherlands.
METHODS AND MATERIALS
Study Population
An observational study was performed to assess actual care
and determinants ofvariation in carefor patients suspected
of hereditary CRC. The study comprised 17 nonuniversity
hospitals in the Netherlands. Patients were selected by
PALGA, the nationwide network and registry of histopa-
thology and cytopathology in the Netherlands. A search
was performed to select consecutive patients, who com-
plied with the four selection criteria. The first three
selection criteria were chosen because they represent the
revised Bethesda guidelines that are independent of family
history or of the exact tumor type.13The last criterion was
added because these patients are at high risk of developing
CRC at a young age. The selection criteria were: (1) CRC
below the age of 50 years, or (2) second CRC below the age
of 70 years, or (3) CRC and extracolonic cancer associated
with Lynch syndrome below the age of 70 years, or (4) a
colorectal adenoma with high-grade dysplasia below the
age of 40 years. The patients were diagnosed between April
and December 2004. The study was performed according
to the rules of the Committee on Research Involving
Human Subjects, Region Arnhem-Nijmegen.
Data Collection
Referral Process to a Cancer Genetics Clinic. The referral
process consists of three parts: the identification of patients,
the referral by the treating physician, and the decision of the
patient. We analyzed the referral process as a whole and as
the patient decision. The referral process was considered
optimally carried out when the patient actually visited a
cancer genetics clinic for genetic counseling. In the
Netherlands, cancer genetics clinics are associated with
university medical centers. Some nonuniversity hospitals
have outpatient clinics for genetic counseling. To examine
the rate of patients that visited a cancer genetics clinic, these
clinics were asked to check whether the patients selected by
PALGA had visited.
Furthermore, we examined the patient decision to visit
a cancer genetics clinic. A subgroup of patients with whom
the surgeon discussed referral to genetic counseling as docu-
mented in the surgical record comprised this analysis group.
Determinants for the Referral Process. Determinants at
thepatient,professional,andhospitallevelthatcouldexplain
the variation in the referral process were collected as follows:
1) Patient characteristics included age, sex, the criterion of
inclusion,presenceofcancerin the family, and survival.
Survivalwasmeasureduntilthe end of2006.These data
came along with the selection of patients by PALGA,
except for presence of cancer in the family and survival.
Family history was determined by surgical record
search, and the survival status was checked in the
hospital administration system. Presence of cancer in
the family was defined as any cancer, because we
considered taking a family history of any cancer as
awareness of potential genetic cause of cancer.
2) Professional performance characteristics included de-
scription of family history and referral to a cancer
genetics clinic obtained from surgical record search.
When a family history was described, the source noted
whether the surgeon described it or another clinician.
For example, if a family history was obtained from a
letter from an oncologist, a general internal specialist,
or a general practitioner, this was captured.
3) Hospital characteristics included size, teaching status,
and presence of an outpatient clinic for genetic
counseling and were captured by interviewing sur-
geons and were obtained from hospital websites.
Two independent researchers performed the surgical
recordsearch. Double surgicalrecordsearch wascarried out
in 9 out of 17 hospitals, and the agreement between these
researchers was substantial for ‘cancer in the family’ and
‘family history described’ (kappa=0.75 and 0.67, respec-
tively) and almost perfect for ‘registration that referral to a
cancer genetic clinic was discussed with patient’ (kappa=
0.81). Data sheets were made anonymous after surgical
record search, and data were entered into a database.
Statistical Analysis. Descriptive statistics described the
referral process for genetic counseling at a cancer genetics
clinic. Patient, professional, and hospital determinants were
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analyzed for ‘patients that visited a cancer genetics clinic’ and
‘patientsthatdidnotvisitacancergeneticsclinic’.Correlation
betweendeterminantswaschecked.Ifacorrelationcoefficient
greaterthan 0.4 wasdetected between two determinants, only
one determinant was tested. Multilevel analysis showed that
the rate of patients that visited a cancer genetics clinic did not
vary significantlybetween hospitals(ICC=0). Forthisreason,
a logistic regression model without correction for clustering
was used to assess determinants for the referral process. The
rate of patients that visited a cancer genetics clinic formed the
dependent variable, and the possible determinants formed
the independent variables. The percentage of variation that
the independent variables could explain was calculated using
Nagelkerke R2. Odds ratios (OR) were calculated to describe
associationsbetweenthedeterminantsandtherateofpatients
that visited a cancer genetics clinic. An OR greater than 1
meant a positive association. Two-sided P values of <0.05
were considered as statistically significant. Analyses were
performed with the SAS system for Windows Version 8.2.
(SAS Institute, Cary, North Carolina).
RESULTS
Referral Process to a Cancer Genetics Clinic
The study population selected by PALGA consisted of 119
patients: 62 males and 57 females. The mean age was
45.4 years (range: 26–69). Most patients (n=99) had CRC
below the age of 50 years (Table 1).
Of 119 patients, 36 patients (30 percent) visited a
cancer genetics clinic. Surgical records of 100 of 119
patients were available for review (33 records for patients
that visited a cancer genetics clinic and 67 records for
patients who did not visit respectively.
Familyhistorywasdescribed somewhereinthesurgical
recordof 88percent ofpatients (n=29)that visited a cancer
genetics clinic and 64 percent of patients (n=43) that did
not visit a cancer genetics clinic. A family history of cancer
was present somewhere in the surgical record of 61 percent
of patients (n=20) who visited a cancer genetics clinic and
of 34 percent of patients (n=23) who did not visit. The
surgeon had described the family history in 51 percent of
patients (n=17) who visited a cancer genetics clinic and in
28 percent of patients (n=19) that did not visit. The
surgeon discussed referral to genetic counseling at a cancer
genetics clinic with 48 percent of patients (n=16) that
visitedacancergeneticsclinicandwith10percentofpatients
(n=7) that did not visit a cancer genetics clinic (Table 1).
Six of 17 hospitals had an outpatient clinic for genetic
counseling. Forty-two percent of patients (n=15) who
visited a cancer genetics clinic and 27 percent of patients
(n=22) who did not visit were treated in a hospital with
an outpatient clinic for genetic counseling.
Patient Decision to Visit a Cancer Genetics Clinic
We examined the last part of the referral process, i.e., the
decision of a patient to visit a cancer genetics clinic among
the 23 patients with whom their surgeon discussed referral
to genetic counseling at a cancer genetics clinic. Of these
patients, 16 of 23 (70 percent) visited a cancer genetics
clinic. Within this subgroup of patients, 81 percent of the
patients (n=13) that visited and 43 percent of patients (n=
3)whodid notvisita cancergeneticsclinicwere treatedin a
teaching hospital (Table 2). Thirty-one percent of the
patientsthatvisited(n=5)and14percentofpatients(n=1)
that did not visit a cancer genetics clinic were treated in a
hospital with an outpatient clinic for genetic counseling.
Table 1. Determinants for colorectal cancer patients visiting a cancer genetics clinic
DeterminantVisited (N=36) N (%) Did not visit (N=83) N (%) Total (N=119) N (%)
Patient
Sex, male
CRC below age 50a
Second CRC below age 70
CRC and extracolonic cancer below age 70b
Colorectal adenoma with high dysplasia, below age 40
Cancer in familyd
Survivalc
Professionald
Documented family history
Documentation by surgeon of family history
Referral discussion
Hospital
< 600 beds
600–800 beds
> 800 beds
Teaching hospital
Presence of outpatient genetics counseling clinic
21 (58)
30 (83)
4 (11)
2 (6)
0 (0)
20 (61)
30 (83)
41 (49)
69 (83)
4 (5)
5 (6)
5 (6)
23 (34)
72 (87)
62 (52)
99 (83)
8 (7)
7 (6)
5 (4)
43 (43)
102 (86)
29 (88)
17 (51)
16 (48)
43 (64)
19 (28)
7 (10)
72 (72)
36 (36)
23 (23)
6 (17)
17 (47)
13 (36)
33 (92)
15 (42)
27 (33)
25 (30)
31 (37)
68 (82)
22 (27)
33 (28)
42 (35)
44 (37)
101 (85)
37 (31)
aCRC, colorectal cancer?bExtracolonic cancers: cancers associated with Lynch syndrome including carcinomas of the endometrial, ovaries, small bowel, stomach, sebaceous gland,
biliary tract, and upper urinary tract.?cSurvival was measured until the end of 2006.?dDeterminants measured by surgical record search, 100/119 surgical records were available: 33
of patients were referred and 67 of patients were not referred to genetic counseling respectively.
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Determinants for the Referral Process
We analyzed for the presence of subgroups of hospitals,
professionals, or patients in which the referral process was
not optimally carried out. Because the determinants “family
historydescribed,”“familyhistorydescribedbythesurgeon,”
and “cancer in the family” were correlated, we chose to put
“family history described” as determinant into the logistic
regression model. Logistic regression analysis showed that
the referral process was associated with “registration that
referral was discussed” OR, 15.4; 95 percent CI, 4.1–58.3 and
“teaching hospital” OR, 8.8; 95 percent CI 1.6–48.6. These
characteristics accounted for 31 percent of the variance.
Because of the small number of patients (n=23) with
whom the surgeon discussed referral to a cancer genetics
clinic, logistic regression was unable to be performed in
this subgroup. Therefore, factors that determine the
referral process in this subgroup of patients could not be
explored. However, univariate analysis showed an associ-
ation between the referral process and hospital character-
istics including size, teaching status, and presence of an
outpatient clinic for genetic counseling.
DISCUSSION
Only one-third of the patients with recently diagnosed CRC
that meet criteria for referral to genetic counseling visited a
cancer genetics clinic. Seventy percent of patients with
whom the surgeon discusses referral to a cancer genetics
clinic decided to visit such a clinic. Patients with whom the
surgeon discussed referral to genetic counseling and that are
treated in a teaching hospital are more likely to visit a cancer
genetics clinic. Determinants could not be identified for
visiting a cancer genetics clinic in the subgroup of patients
whom receive discussion of referral by their surgeon. These
data show that the referral process to genetic counseling at a
cancer genetics clinic is not optimally carried out and needs
to be improved.
Identifying patients with hereditary CRC is crucial
because surveillance substantially reduces morbidity and
mortality.8Optimal care for patients suspected of heredi-
tary CRC includes referral to genetic counseling at a cancer
genetics clinic by the treating physician. Our percentage of
patients that visited a cancer genetics clinic is comparable
to results of a previous study where 26 percent of clinicians
recommended genetic counseling for patients with a family
history consistent with Lynch syndrome.10Another study
shows that 16 percent of patients are referred to genetic
counseling.11Their selection criteria are similar to ours,
but slightly more patients with multiple tumors were
included than patients with CRC below the age of 50 years.
In contrast, in our study almost all patients had CRC below
the age of 50 years.
Additionally, our study examined the existence of
subgroups of hospitals, professionals, or patients in which
the referral process is not optimally carried out. Patients
with whom the surgeon discusses referral to genetic
counseling and that are treated in a teaching hospital are
more likely to visit a cancer genetics clinic. Therefore, to
optimize the referral process, efforts should be concentrat-
ed on increasing referral discussions for genetic counseling
by treating physicians and in increasing awareness in
nonteaching hospitals. A reason not to discuss referral to
a cancer genetics clinic may be the presumption that
patients cannot deal with this message at a time that they
receive the diagnosis of cancer. However, most patients
find it highly acceptable to have the information about
Lynch syndrome at the time of diagnosis.14
In our study, seventy percent of patients with whom
the treating physician discussed referral to genetic counsel-
ing visited a cancer genetics clinic. Twenty-six percent of
patients invited by letter for an information session about
Lynch syndrome visited a cancer genetics clinic.12Our
study and previous work suggest referral by the treating
physician might be more effective than an invitation letter.
Table 2. Patient decision to visit a cancer genetics clinic after referral
DeterminantVisited (N=16) N (%) Did not visit (N=7) N (%) Total (N=23) N (%)
Patient
Sex, male
CRC below age 50a
Second CRC below age 70
Cancer in familyc
Survivalb
Professionalc
Documented family history
Documentation by surgeon of family history
Hospital
< 600 beds
600–800 beds
> 800 beds
Teaching Hospital
Presence of outpatient genetics counseling clinic
12 (75)
15 (94)
1 (6)
11 (69)
14 (88)
4 (57)
7 (100)
0 (0)
5 (71)
5 (71)
16 (70)
22 (96)
1 (4)
16 (70)
19 (83)
16 (100)
11 (69)
5 (71)
3 (43)
21 (91)
14 (61)
4 (25)
7 (44)
5 (31)
13 (81)
5 (31)
4 (57)
2 (29)
1 (14)
3 (43)
1 (14)
8 (35)
9 (39)
6 (26)
16 (70)
6 (26)
aCRC, colorectal cancer.?bSurvival was measured until the end of 2006.?cDeterminants measured by surgical record search.
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Thirty percent of patients with whom the treating
physician discussed referral did not visit a cancer genetics
clinic. Because of the small number of patients with whom
referral to a cancer genetics clinic was discussed, we were
not able to identify subgroups of patients that are more
likely to visit a cancer genetics clinic after discussion of
referral by their surgeon. However, in this subgroup of
patients, univariate analysis showed that patients are more
likely to visit a cancer genetics clinic when an outpatient
clinic for genetic counseling is present in their hospital.
These findings reflect the impact of both easy access to
genetic counseling and higher awareness of treating
physicians on the genetic counseling referral process.
Univariate analysis of a study that examined determinants
for access to reference care centers for patients with CRC
shows that distance plays a role in the access to care.15This
trends needs to be confirmed by multivariate analysis
among a larger number of patients.
Ourstudyisunique,sinceitexamineddeterminantsfor
referral to and acceptance of genetic counseling for
hereditary CRC. A limitation is some of the determinants
were measured by surgical record search. For example, of
the patients that visited a cancer genetics clinic, 48 percent
had a notation in the surgical record that referral to genetic
counseling had been discussed. This method of data
collection does not monitor everything that is discussed
between patient and treating physician and potentially leads
to underestimation. However, to identify subgroups of
patients that are more likely to visit a cancer genetics clinic,
the difference between patients that visited and patients that
did not visit such a clinic was used. Underestimation likely
affects both groups equally. Moreover, the discussion of
referral to genetic counseling at a cancer genetics clinic
would likely to be registered in the surgical record. Another
possibility is that the oncologist or the family doctor dis-
cussed referral to a cancer genetics clinic. Again, we expect
that this rate does not differ between the two groups.
Therefore, we assume that our results reflect actual clinical
practice.
A 30 percent rate of uptake for genetic counseling
shows that there is room for improvement in the referral
process among patients who are considered to benefit from
genetic counseling. The identification of patients suspected
of hereditary CRC is the first and most important part of
the referral process. On the one hand, the Bethesda
guidelines, which describe which patients merit microsa-
tellite instability analysis, could be implemented among
cliniciansinvolvedinthecareofCRCpatients.Ontheother
hand, an alternative method to identify hereditary CRC
among patients with recently diagnosed CRC could be
implemented. In this new method clinical practice roles
havetobechanged.16Thepathologistinsteadofthetreating
physician is responsible for the identification of patients
suspected of hereditary CRC. The pathologist selects
patients for microsatellite instability analysis of a patient’s
tumor. Next, the treating physician discusses the result of
microsatellite instability analysis and referral to genetic
counseling with patients with a microsatellite instable
tumor. With this new method, at least twice as many
patients with Lynch syndrome were identified compared
with current practice.16In addition, fewer patients have to
be referred to genetic counseling because patients with a
microsatellite stable tumor without a family history of CRC
are not considered at risk for Lynch syndrome.
CONCLUSION
Most patients with CRC at young age or with multiple
cancers associated with Lynch syndrome do not visit a
cancer genetics clinic according to current guidelines. To
improve the referral process, improvement efforts should
focusondiscussionofreferralbysurgeonsandawarenessin
nonteaching hospitals. In addition implementation of
guidelines or a new method to detect hereditary CRC in
routine clinical practice is certainly needed.
ACKNOWLEDGMENTS
The authors thank PALGA, the nationwide network and
registry of histopathology and cytopathology in the
Netherlands for selecting patients; Reinier Akkermans
for statistical assistance. The authors thank the following
for checking referrals to genetic counseling: Department
of Human Genetics of University Hospital Maastricht,
Erasmus MC Rotterdam, University Medical Centre
Groningen, University Medical Centre Utrecht, and
Leiden University Medical Centre. For the availability of
surgical records: the Department of Pathology and Sur-
gery of Meander Medical Centre Amersfoort, St. Jansdal
Hospital Harderwijk, Alysis zorggroep Arnhem, Gelderse
Vallei Ede, HagaZiekenhuis The Hague, Albert Schweitzer
Hospital Dordrecht, Catharina Hospital Eindhoven,
Medisch Spectrum Twente Enschede, Twenteborg Hospital
Almelo, Elkerliek Hospital Helmond, Medical Centre
Leeuwarden, Canisius Wilhelmina Hospital Nijmegen,
Medical Centre Rijnmond Zuid Rotterdam, Jeroen Bosch
Hospital ‘s-Hertogenbosch, Hospital Bernhoven Veghel/
Oss, St Elisabeth HospitalTilburg, and TweestedenHospital
Tilburg.
The MIPA Study Group consists of the authors and E.
M. M. Adang, Ph.D., H. G. Brunner, M.D., Ph.D., B.
Gordijn, Ph.D., R. P. T. M. Grol, M.D., Ph.D., H. Hollema,
M.D., Ph.D., J. H. Kleibeuker, M.D., Ph.D., M. F. Niermeijer,
M.D., Ph.D., R. H. Sijmons, M.D., Ph.D.
Open Access This article is distributed under the terms
of the Creative Commons Attribution Noncommercial
License which permits any noncommercial use, distribu-
tion, and reproduction in any medium, provided the
original author(s) and source are credited.
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