ARTICLE
Auteur(s) : Athanassios Kyrgidis1,
Konstantinos Vahtsevanos1, Thrasivoulos George
TZELLOS2, Persa Xirou3, Kyriaki
Kitikidou4, Konstantinos Antoniades5,
Christos C Zouboulis6, Stefanos
Triaridis7
1Department of Maxillofacial Surgery, Theagenio
Cancer Hospital, Thessaloniki, Greece
2Department of Pharmacology, School
of Medicine, Aristotle University of Thessaloniki,
Thessaloniki, Greece
3Department of Histopathology, Theagenio Cancer
Hospital, Thessaloniki, Greece
4Department of Forestry and Management
of the Environment and Natural Resources, Laboratory
of Forest Biometry, Dimokritos University of Thrace,
Orestias, Greece
5Department of Oral and Maxillofacial Surgery,
School of Dentistry, Aristotle University
of Thessaloniki, Thessaloniki, Greece
6Departments of Dermatology, Venereology,
Allergology and Immunology, Dessau Medical Center, Dessau,
Germany
71st Department of Otolaryngology, School
of Medicine, Aristotle University of Thessaloniki,
Thessaloniki, Greece
accepté le 6 Decembre 2009
Basal cell carcinoma (BCC) is the commonest malignancy in humans
[1]. BCC accounts for nearly 25% of all cancers in the human body
and for almost 75% of skin malignancies. The head and neck region
is the most common skin location of BCC development; up to 85% of
basal cell carcinomas develop in the head and neck region [1-3].
There is an urgent need for more research, since the incidence of
BCC is steadily increasing [4-7] and the number of
immuno-compromised patients, who exhibit a higher risk, is also
rising [8]. This increment is age standardized and is not
considered to be an effect of the ageing population in developed
countries [9]. In a previous review we underlined the need for
targeted studies to identify demographic, clinical and histological
predictors for second primary and/or recurrent BCC [10]. The
present study aimed to identify predictors of recurrence and second
primary tumour development in a cohort of subjects who were
surgically treated for BCC during a 12 year period in our
institution.
Materials and methods
The study was performed at Theagenio Cancer Hospital, which is the
tertiary cancer referral hospital for the region of Northern
Greece. Residents from all the prefectures of northern Greece as
well as from a part of central Greece are referred mainly via
expert practitioner referral, especially from district general
hospitals. The cohort sample consisted of one thousand and
sixty-two consecutive patients with 1,480 BCC treated by
surgery between May 1995 and December 2006.
Subjects’ data were retrospectively collected from 1995 to
September 2002 and prospectively collected from
October 2002 to December 2006. According to the
treatment protocol [11] follow-up was set on a 3, 6, and
12 month basis for the first year and on an annual basis ever
after. Detailed description of clinical appearance of the excision
area as well as prompt recording of any new skin lesions is
routinely documented in patients’ clinical records before surgery
and at the follow-up visits. The records of all adult patients who
underwent surgical excision for head and neck skin lesions were
collected for data analysis. All operations were performed by two
experienced surgeons or by residents under their supervision.
All patients with primary BCC were included in the study.
Patients referred for treatment of recurrent tumours were excluded,
where recurrent tumours were defined as those tumours which were in
contact with the scar of the previous surgical excision of skin
malignancy. Patients with a follow-up shorter than one year were
excluded from the current study. For the purpose of the current
study, the first BCC diagnosed and treated was considered as the
first primary tumour of the patients, irrespective of their
previous history of BCC; this is because the antecedent history of
BCC is frequently not reliable [12]. Consequently, the history of
previous BCC variable in the present study refers to the history of
previous BCC diagnosed in our institution, within the follow up
period.
Data collected and analyzed included patient age and gender,
anatomical site, size, clinical classification and histological
type of tumour, surgical excision margins and rate of recurrence.
The initial diagnosis of BCC was based on clinical assessment,
while a pre-treatment biopsy was available on referral or performed
before total surgery in only a few cases. Medical consultation was
performed with every patient before surgery. Most excisions were
performed under local anaesthesia without sedation, while general
anaesthesia was used for larger tumours. A team of four expert
dermatopathologists was responsible for the histological
examination, which was confirmed to be BCC in all cases.
Institutional board approval was waived due to the observational
design of the present study.
Variables introduced in the current study were sex
(male/female), age, year of surgical treatment, follow-up duration,
population of place of residency (PPOR), occupational insurance
classification (agricultural, public servants, private sector
employees, private sector free professionals), anatomical location
of the lesion, side (left/right), clinical presentation [13] and
histology type [13, 14], in accordance with previously published
studies, tumour size dimensions, excision margins (negative, close,
positive), negative margin excised, recurrence (yes/no). Tumour
size, histology type, and excision margins were obtained from
histology reports. High-risk histology BCC includes superficial
(ICD-O code 8091/3) [15], infiltrative/morphoeic (ICD-O code
8092/3) [15] and micronodular (ICD-O code 8090/3) [15] subtypes and
has been described before [14]. Close excision margins are rarely
reported in the literature. In this field, pathologists usually
classify tumour specimens in which peripheral and deep margin
negative clearance is recorded to be less than 1 mm at least
once, on any side of the tumour [14]. In contrast, the terms
“negative” and “positive” excision margins are self explanatory.
Sex, age, year of treatment, PPOR, and occupational classification
were obtained from the patients’ administrative hospital records.
Site of the lesion, side, clinical presentation and recurrence were
obtained from patient's medical records. We used the occupational
insurance health system [16], which is widely applied in Greece as
it allows for the characterization of unemployed individuals within
a specific population group. Most variables were used as
independent cohort exposures, while second primary tumour and
recurrence were used as dependent outcome variables. An expert
independent investigator collected data from administration,
medical and histology records and filled in the database. Selection
bias was minimized by including all verified cases treated for the
past 12 years in the study. Differential misclassification and
informational bias was not possible due to the definite
pathological diagnosis and detailed record maintenance. Selection
bias for relative risk (RR) approximations was addressed via
matching.
Statistical methods
All variables were checked for normal distribution via the
Kolmogorov-Smirnov test for Normality. Pearson's r correlation
coefficient and Phi coefficient were used for scale and dichotomous
variable correlations, respectively. Pearson's Chi Square test was
used for different exposure group comparisons. Relative risks and
corresponding 95% confidence intervals (95% CI) were approximated
by odds ratios (OR) through conditional univariate and multivariate
logistic regression. Both manual and automated fitting procedures
were used. Automated model selection proved more parsimonious.
Survival analysis was conducted with the life-table analysis. Cox's
proportional hazards regression model was used to assess the
effects of covariates on the length of the interval. Hazard rates
were calculated for each of the first eleven follow-up years. Alpha
level was set at 0.05 while an alpha level of 0.10 was
used as cut off for variable removal in the automated model
selection for multivariate regression. Logistic regression models
were determined to account for outcome better than would be
expected by chance (p < 0.001 for both) via the Wald test
and the chi-square likelihood ratio test. Goodness of fit was
examined by adjusted R square (R2). Tests for
interactions were automatically commenced by the statistical
package through the fitting procedure. All p values were derived
from two-sided statistical tests. Significance and logistic
regression model calculations were made with the SPSS
16.0 package (Statistical Package for Social Sciences, SPSS
Inc., Chicago, Ill.).
Results
Demographics
One thousand and sixty two patients with a total of
1,480 tumours met the inclusion criteria. The male to female
ratio was 1.4:1, and the average age of the patients on first
examination was 70.1 ± 11.1 years. The youngest patient was
15-years-old and the oldest 97-years-old. The majority of patients
were in their eighth (38.0%), seventh (27%) and ninth (17%) decades
of life. As expected, BCC was not found to be common before
50 years of age (5%). Age, when statistically analyzed, was
not found to be a predictor of recurrence (Pearson's Chi square, p
= 0.086).
Patients’ occupational insurance status was analyzed (table 1). Compared to the Greek population (table 1), there are significantly more
patients with agricultural occupational insurance in our cohort
(Pearson's Chi square, p < 0.001, table
1) [16]. Patients who developed a second primary BCC
differed from those who did not, regarding their occupational
insurance status (Pearson's Chi square, p = 0.006, table 1). More specifically, patients with private
sector occupational insurance demonstrated a 45% reduced risk for
developing second primary BCC compared to patients with
agricultural occupational insurance (OR 0.55, 95% CI: 0.39-0.77, p
= 0.001).
Table 1 Age, Gender, Occupational insurance, High-risk
histology, Positive margins and close margins descriptives of 1,062
patients treated for basal cell carcinoma (BCC) at the Department
of Maxillofacial Surgery, Theagenio Cancer Hospital
|
Descriptive measure
|
Patients with a single BCC
|
Patients with a single BCC which reoccurred
|
Patients with multiple BCC
|
Patients with multiple BCC who experienced recurrence
|
Pearson's Chi-square, Pc
|
|
Patient Count
|
814
|
18
|
196
|
25
|
< 0.001
|
|
Mean age (years ± SD)
|
70.0 ± 11.5
|
63.6 ± 8.9
|
71.1 ± 9.9
|
72.2 ± 8.4
|
0.88
|
|
Mean follow up (years ± SD)
|
3.9 ± 1.6
|
4.1 ± 1.5
|
4.7 ± 2.1
|
5.4 ± 2.1
|
0.90
|
|
Males (%)
|
56.9
|
66.7
|
64.1
|
56.0
|
0.71
|
|
Occupational insurance statusa
|
Agricultural (%)
|
26.1a
|
40.5
|
50
|
49.2
|
72.0
|
0.006b
|
|
Private Sector Employees (%)
|
51.7a
|
39.6
|
33.3
|
28.5
|
20.0
|
|
Private Sector Free Professionals (%)
|
17.5a
|
10.4
|
11.1
|
13.0
|
4.0
|
|
Public Servants (%)
|
4.6a
|
9.4
|
5.6
|
9.3
|
4.0
|
|
“High-risk” Histology (%)
|
80.3
|
88.9
|
83.3
|
96.0
|
0.65
|
|
Positive Margins (patient count)
|
39
|
1
|
5
|
6
|
<0.001
|
|
Close Margins (patient count)
|
40
|
0
|
6
|
0
|
<0.001
|
Incidence
For incidence trend analysis, only patients enrolled until
2001 were selected because a plastic surgery department
started operating in the year 2002 in the Hospital. These
patients were not included in this cohort study due to different
treatment and follow-up protocols; therefore, the incidence trend
estimation could only be unbiased for the years 1995-2001. The
incidence evaluation demonstrated an increase in our sample of BCC
patients between 1995 and 2001. Interestingly, the incidence
is increasing in younger patients. We used a dichotomous variable
to isolate younger patients. The two groups (≤ 55 years, >
55-year-old) were sex matched (Pearson's Chi square, p = 0.337).
The odds ratio for patients younger than 56 years old newly
diagnosed with BCC increased 20% per each year from 1995 to
2001 (OR 1.2, 95% CI: 1.05-1.38, p = 0.009).
Follow-up period
Patients were followed for an average of 4.0 ± 1.8 (range
1-12) years, summing for a total of 4,302 patient-years.
Clinical presentation
The smallest tumour size recorded in the present study was
0.07 cm2 and the largest 104.5 cm2.
127 tumours were smaller than, or equal to, 10 × 10 mm in
size. 681 tumours were larger than 10 × 10 mm but smaller
than or equal to 20 × 20 mm in size. 431 were larger than
20 × 20 mm in size but smaller than 30 × 30 mm in size.
181 tumours were larger than 30 × 30 mm. Tumour size was
not found to be associated with PPOR (Pearson's Chi square, p =
0.068).
Tumours developed in 46.3% on the left side, in 51.9% on the
right side and in 1.8% solely at the middle line. Head and neck BCC
occurred most commonly on the foramen (12.0%) and the cheek (11.6%)
followed by the suborbital area (9.5%) and the nasal bridge (9.2%).
No significant correlation was found between tumour site and
recurrence (Pearson's Chi square, p = 0.788).
Histology
Extent of negative margin excised in our cohort ranged from
2 to 15 mm (mean 6 ± 4) according to the size and
presentation of the tumours [17]. Close excision margins appear to
result more often when wider margins are taken (mean 9 vs
6 mm, Student's t, p = 0.003) while positive margins do not
(mean 6.2 vs 5.3 mm, Student's t, p = 0.364). On
histological examination, excision margins were confirmed to be
negative in 1316 (90.8%) cases, positive in 72 (5.0%)
cases and close in 61 (4.1%) cases. Four out of five tumours
(81.6%) were histologically classified as high-risk [13, 18].
High-risk histology was associated with increased risk for
recurrence (OR 3.47, 95% CI: 1.07-11.25, p = 0.038). This result
was statistically significant and clearly demonstrated that a
tumour classified as high-risk has a 3-fold risk for recurrence.
Predictors of second primary tumour
839 patients had a single tumour, while 223 (21%)
patients either presented with multiple primary lesions or
experienced a second primary BCC within the follow-up period (range
2-12 lesions), which was treated with a second surgical
excision. Previous studies reported similar data, [19, 20] however,
due to the longer follow-up period, we hereby report up to
12 primary tumours excised in 2 of our patients.
Univariate analysis showed a 25% increased risk for developing
another BCC per every single year of follow up (OR 1.25, 95% CI:
1.17-1.34, p < 0.001).
PPOR was associated with risk for second primary tumour
(Pearson's Chi square, p = 0.006). More to the point, univariate
analysis showed that patients living in villages with less than
5,000 residents had a 2-fold risk for presenting with multiple
BCC (OR 1.91, 95% CI: 1.33-2.76, p = 0.001).
Life table analysis of second primary tumours occurring during
the follow-up period is presented in table
2. The median free of second primary tumour time was
7 years.
Multivariate analysis with a Cox proportional hazards model,
including as covariates sex, age group, and PPOR showed as
significant risk factors for development of second primary tumour:
age between 70-79, (OR 2.97, 95% CI: 1.26-7.00, p = 0.13, logit =
age < 49) and PPOR < 5,000 residents (OR 1.66, 95%CI:
1.20-2.31, p = 0.003, logit = PPOR > 100,000).
Table 2 Risk of a second basal cell skin carcinoma
(BCC) in 1,062 patients of the Department of Maxillofacial Surgery,
Theagenio Cancer Hospital: Survival analysis by the life-table
method
|
Follow-up intervalsa start time
(years)
|
Number of patients entering interval
|
Number of patients withdrawing during interval
|
Number of second primary BCC
|
Hazard Rate
|
|
0
|
1,062
|
0
|
0
|
0.00
|
|
1
|
1,062
|
0
|
9
|
0.01
|
|
2
|
1,053
|
231
|
27
|
0.03
|
|
3
|
795
|
149
|
22
|
0.03
|
|
4
|
624
|
131
|
40
|
0.07
|
|
5
|
453
|
249
|
71
|
0.24
|
|
6
|
133
|
40
|
14
|
0.13
|
|
7
|
79
|
15
|
17
|
0.27
|
|
8
|
47
|
8
|
7
|
0.18
|
|
9
|
32
|
9
|
8
|
0.34
|
|
10
|
15
|
3
|
4
|
0.35
|
|
11
|
8
|
4
|
3
|
0.67
|
|
12
|
1
|
0
|
1
|
0.00
|
Predictors of recurrence
Regarding recurrence and excision margins, we found significant
correlation neither between close excision margins and BCC
recurrence nor between negative excision margins and recurrence.
None of the 46 patients histologically reported to have their
BCC excised with close margins developed recurrence. On the other
hand, there were 43 recurrent BCC in the remaining
1016 patients; that is a 4% recurrence rate, during the
follow-up. As expected, there was a significant correlation between
recurrence and positive excision margins (Phi = 0.11, p <
0.001). Hence, 7 out of 51 patients (13.7%)
histologically reported to have had their BCC excised with positive
margins had a recurrence, in contrast to 36 out of the
remaining 1011 (3.6%). There was a 4-fold increased risk for
recurrence when excision margins were positive (OR 4.31, 95% CI:
1.82-10.22, p = 0.001) (table 3).
Reccurence was not found to be correlated with tumor size
(Pearsons’ r = 0.15, p = 0.626) or negative margin excised (r =
0.19, p = 0.550).
PPOR was a potent predictor of recurrence (Pearson's Chi square,
p = 0.004). Subjects who reside in villages with less than
5,000 residents have a 5-fold risk of recurrence, while those
who live in agricultural towns with more than 20,000 residents
have a 4-fold risk of recurrence (table
3), when compared to urban populations. This result is
anticipated as one should consider the different proportions of
these populations in sun-exposed occupational activities. However,
there was no significant association between recurrence and
occupational insurance (Pearson's Chi square, p = 0.064).
There was a 21% increased risk for recurrence for each year a
patient was followed-up (OR 1.21, 95% CI: 1.06-1.37, p = 0.003)
(table 3).
Life table analysis of recurrent tumours along the follow up
years is presented in table 4. The
median free of recurrence time was 12 years.
Multivariate analysis with a Cox proportional hazards model,
including as covariates sex, age group, and PPOR, showed as
significant risk factors for recurrence: history of previous BCC
(OR 2.86, 95% CI: 1.54-5.34, p = 0.001), PPOR <
5,000 residents (OR 4.23, 95%CI: 1.61-11.13, p = 0.003, logit
= PPOR > 100,000) and PPOR > 20,000 residents (OR 3.92,
95%CI: 1.24-12.38, p = 0.020, logit = PPOR >100,000). It should
be noted that the hazard rates increase with the years, thus the
risk of a recurrent BCC remains high despite the number of years
passed (table 4). Due to the small
incidence of recurrent tumours (43 in 1480 excisions from
1062 patients), hazard is probably underestimated in the Cox
model [21].
The most potent predictors of recurrence concerning the tumour
itself were the presence of positive excision margins and the
high-risk (aggressive) histology type, and concerning the patient
were, PPOR, history of previous BCC and duration of the follow-up
period (table 3). Although no
significant correlations were found between the predictors studied,
adjusted OR are also presented (table
5).
Table 3 Predictors for recurrence of BCC in 1,062
patients of Department of Maxillofacial Surgery, Theagenio Cancer
Hospital, 1,480 basal cell carcinomas. Predictors concerning
tumours are in italic while predictors concerning patients are in
roman
|
Predictor
|
ORa
|
95% Confidence Intervalsa
|
P Valueb
|
|
Lower
|
Upper
|
|
Positive excision margins
|
4.31
|
1.82
|
10.22
|
p = 0.001
|
|
High-risk (aggressive) histology type
|
3.47
|
1.07
|
11.25
|
p = 0.038
|
|
PPOR village < 5,000 residents
|
5.03
|
1.90
|
13.33
|
p = 0.001
|
|
PPOR agricultural town > 20,000 residents
|
4.52
|
1.41
|
14.53
|
p = 0.011
|
|
History of previous BCC
|
2.27
|
1.25
|
4.11
|
P = 0.007
|
|
Every single year of follow up
|
1.21
|
1.06
|
1.37
|
p = 0.003
|
|
Every additional second primary tumour
|
1.38
|
1.18
|
1.60
|
p < 0.001
|
Table 4 Risk of a recurrent BCC in 1062 patients of the
Department of Maxillofacial Surgery, Theagenio Cancer Hospital:
Survival analysis by the life-table method
|
Follow-up intervala start time (years)
|
Number of patients entering interval
|
Number of patients withdrawing during interval
|
Number of recurrent BCC
|
Hazard rate
|
|
0
|
1,062
|
0
|
0
|
0.00
|
|
1
|
1,062
|
8
|
1
|
0.00
|
|
2
|
1,053
|
255
|
3
|
0.00
|
|
3
|
795
|
162
|
9
|
0.01
|
|
4
|
624
|
166
|
5
|
0.01
|
|
5
|
453
|
308
|
12
|
0.04
|
|
6
|
133
|
50
|
4
|
0.04
|
|
7
|
79
|
27
|
5
|
0.08
|
|
8
|
47
|
13
|
2
|
0.05
|
|
9
|
32
|
16
|
1
|
0.04
|
|
10
|
15
|
6
|
1
|
0.09
|
|
11
|
8
|
7
|
0
|
0.00
|
Table 5 Adjusted predictors for recurrence of BCC in
1062 patients of the Department of Maxillofacial Surgery, Theagenio
Cancer Hospital, 1480 basal cell carcinomas. Predictors concerning
tumour are in italic, predictors concerning patients are in roman
|
Conditional multivariate regression modelb
|
Predictor
|
Adjusted ORa
|
95% Confidence Intervalsa
|
P Valuec
|
|
lower
|
upper
|
|
1st Model, tumours
|
Positive excision margins
|
3.56
|
1.87
|
6.78
|
P < 0.001
|
|
High-risk (aggressive) histology type
|
2.06
|
1.02
|
4.17
|
p = 0.044
|
|
2nd Model, patients
|
PPOR village < 5,000 residents
|
4.32
|
1.61
|
11.61
|
P = 0.004
|
|
PPOR agricultural town > 20,000 residents
|
4.07
|
1.24
|
13.35
|
p = 0.021
|
|
History of previous BCC
|
4.32
|
2.25
|
8.31
|
p < 0.001
|
|
Every single year of follow up
|
1.14
|
1.01
|
1.30
|
p = 0.047
|
|
Every additional second primary tumourd
|
1.01
|
0.81
|
1.27
|
p = 0.908
|
Discussion
BCC is reported to be more common in males, with male to female
ratio ranging from 9:1 [22, 2] to a 1:1.1 [23] in recently
published works. The incidence of BCC seems to be increasing over
time [4-7]. In our study, an obvious increment was observed between
1995 and 2001. After 2002, available data from our hospital is
not comprehensive enough to allow further supporting of this
hypothesis. The overall literature reports a rising incidence in
younger patients [24-27], although there are studies which did not
find such an increase [28]. However, the cut-off age used varies
between different investigators. Since one cannot be confident that
the study population reflects the overall population of Northern
Greece, we conclude that the present study reveals a rising
incidence trend for the Greek population. Of note, Greece does not
have a cancer registry for BCC, thus detecting incidence trend as a
secondary outcome would be of value to practitioners.
Subjects with agricultural occupational insurance demonstrated a
higher incidence of BCC in our cohort, which might be attributed to
extended periods of UV exposure [29, 30]. Other UV exposed
professions reported by several researchers [31] to be at greater
risk for BCC development are outdoor workers in general, garage
workers and fishermen. Nonetheless, being from a smaller village
appears to be a significant risk factor for the recurrence of BCC.
This knowledge may influence preventive strategies as well as
health care access and utilization.
Tumour size in our cohort of patients is probably larger than
those reported by other authors [2]. This might be attributed to
late presentation of the patients to our department; a similar
trend of late presentation was previously reported for laryngeal
cancer patients in our region [32, 33]. Obviously, the late
presentation effect on tumour size only concerns the first
presentation of the patients to our department since the follow up
protocol eliminates delayed presentation once the patient is
enrolled.
For a better comparison among studies on recurrence rates,
life-table analysis (tables 2 and
4) has been reported to provide the best approximation of
the true recurrence rates [17, 34]. Recurrence rates are reported
to be similar between surgical and Mohs Micrographic Surgery (MMS)
techniques [35-39], while they appear to be higher in those
patients treated with radiotherapy [40]. We found that positive
margins pose a statistically significant four-fold risk for
recurrence. Other authors reported tumours with positive margins to
exhibit a higher recurrence rate (26%) than those with negative
margins (14%) over a 5-year follow-up period [37] but their results
were not statistically significant. One could argue that positive
margins are widely considered to lead to recurrence especially if
the follow up period is long enough. However, this argument has not
been supported by solid evidence such as that from our study.
Definition of the relevant risk for “recurrence” is important for
the decision of follow-up or a re-excision. Close excision margins
are not associated with recurrence, since none of the
46 tumours classified as such did recur. To the best of our
knowledge, this is the first study in the literature to provide
recurrence data for close excision margins for head and neck BCC.
This information may be of importance for practitioners and
dermatopathologists, since close margins are routinely stated in
histology reports.
We found a three-fold risk for recurrence with high-risk
histological type. Thus such patients should be monitored more
closely. To our knowledge, this is the earliest solid evidence
associating “high-risk” histology type of BCC with high-risk for
recurrence. Nevertheless, the clinical utility of “high-risk”
histology is diminished by the fact that approximately 4 out
of five tumours in this study were classified as high-risk. Still,
“high-risk” histology is widely reported [13, 18] and we believe
that our results are of importance to both pathologists and
surgeons.
223 of 1,062 patients developed at least one
additional BCC during the follow-up period. In a meta-analysis,
Marcil et al. reported a 3-year cumulative risk of 44% for the
development of a second primary tumour [41]. We estimated the
cumulative 3-year actual risk of a second primary tumour to be 14%
for the first three years, 39% for the following three years and
79% for the three year period between the seventh and the ninth
year of follow-up (table 2). In the
current study, we found that recurrence is more frequent in
patients with history of previous BCC. On the other hand, this
might be attributed to new BCC arising in the same area, rather
than true recurrences, since some of these patients demonstrated a
trend for multiple primaries.
In the literature, no agreement exists regarding the duration of
the follow-up period. Some authors reported that follow-up longer
than 3-4 years has limited benefit [41], while others
recommended a longer follow-up, stating that the actual risk for
the appearance of a second BCC or a recurrent BCC increases over
time [19]. Despite the mean follow up period of 4 years,
proportional hazards analysis, follow up range and the sample size
allow for calculating median time intervals for second primary and
recurrence. New evidence published herein supports the need for
longer follow-up periods for patients with BCC, especially those
exhibiting certain risk factors. Since we estimated the median time
to a second primary at seven years, we suggest that patients should
be followed on yearly basis for at least that long to detect second
primary tumours early. The proposed seven year follow up is also
anticipated to implement early diagnosis of subsequent
non-cutaneous malignancies [42].
Evidence from the present study suggests that patient follow up
after BCC excision should be scheduled based on the
dermatopathologist's evaluation. The strongest predictors for
recurrence found in this study are the positive excision margins
and high-risk histology type. The information of a higher incidence
in agricultural population could be of importance for primary care
planning. The results justify a longer follow up planning for
patients subjected to surgical excision for BCC, to detect
recurrence early; follow up duration could be subject to certain
demographic, clinical and pathological predictors. Additional
long-term studies are required for better understanding of the
prognostic significance of these predictors.
Acknowledgements
Financial support: none. Conflict of interest: none.
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