Basic/Clinical Science

Topical Treatment of Bowens

Disease with 5-Fluorouracil

DOI: 10.1007/s10227-002-0158-6
J Cutan Med Surg 2003; 101105

Howard Bargman1 and Jacqueline Hochman2

Abstract
Background: Bowens disease is a common skin cancer. There are many different
therapeutic approaches to treatment. Topical 5-Fluorouracil (5-FU) cream has been
used for many years and there are many published papers attesting to its effectiveness.
However, no papers have presented long-term followup results with biopsy confirmation
of cure.
Objectives: The purpose of this article is to present the long-term findings following
the use of this cream in the treatment of Bowens disease.
Methods: Twenty-four patients with 26 biopsy-confirmed lesions of Bowens disease
were treated with topical 5-Fluorouracil cream and were followed for periods of up to
10 years. Posttreatment biopsies were performed in most cases.
Results: Two of the 26 lesions treated topically recurred at some point. The rest were
apparently cured.
Conclusion: The results presented in this article confirm that treatment of Bowens
disease with topical 5-Fluorouracil cream is safe and effective treatment.

Sommaire
Antecedents: La maladie de Bowen est un cancer de la peau frequent. Le traitement de
cette maladie peut emprunter differentes approches. La cre`me topique 5-Fluorouracil a
ete utilisee des annees durant, avec de nombreux articles publies attestant de son efficacite. Cependant, il ny a eu aucune publication presentant des resultats de suivi a` long
terme et une de biopsie confirmant la guerison.
Objectifs: Lobjectif de cet article est de presenter des resultats a` long terme de lusage
prolonge de cette cre`me dans le traitement de la maladie de Bowen.
Methodes: Vingt-quatre patients presentant 26 biopsies de lesions confirmees de la
maladie de Bowen etaient traites a` la cre`me topique 5-Fluorouracil et suivis durant des
periodes allant jusqua` dix ans. Des biopsies post-traitement etaient pratiquees dans la
plupart des cas.
Resultats: Il y a eu recurrence de 2 des 26 lesions traitees a` la cre`me topique. Le reste
des lesions etaient apparemment gueries.
Conclusion: Les resultats presentes dans cet article confirment que le traitement de la
maladie de Bowen a` la cre`me topique 5-Fluorouracil est efficace et sur.

n situ squamous cell carcinoma, well known as Bowens

disease (BD), was first described in 1912 by Professor
John T. Bowen of Boston. This form of skin cancer tends

1
Division of Dermatology, Sunnybrook and Womens Health Sciences
Centre, University of Toronto, Toronto, Ontario, Canada
2
House Staff, St. Michaels Hospital, Toronto, Ontario, Canada
Online publication: 27 November 2002
Correspondence to: Howard Bargman, 2927 Lawrence Avenue East, Scarborough, Ontario MlP 2S8, Canada, E-mail: hbargman@globalserve.net

to be persistent and progressive with a small potential for

invasion of about 35%.1 The main treatment options for
BD include excision, curettage, and desiccation; cryotherapy; radiotherapy; photodynamic therapy; laser;2 and
topical 5-FU.3,4 Hyperthermic treatment of Bowens
disease has recently been described5 and partial spontaneous regression has been noted.6 While no option has
proven to be superior in all clinical situations, advantages
and disadvantages of various treatment modalities have
been proposed. According to the guidelines for man-

101

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Journal of Cutaneous Medicine and Surgery

agement of BD,4 most of the treatment modalities have

good success rates with good or fair evidence to support
their use. However, in addition to effectiveness, it is
important to consider the cost, skill, and time required as
well as the availability of the method and the cosmetic
result. Nonsurgical methods may be preferable for many
reasons: (1) less technical expertise needed, (2) cosmetic
result often superior, (3) patient prefers less aggressive
treatment or cannot withstand surgery, e.g., aged or infirm, (4) indistinct lesion boundaries, (5) lesions in
anatomically difficult sites for surgery, i.e., ear,7
nose, penis, digit, (6) multiple lesions. 5-FU, in particular, has the advantage of availability, ease of application,
and little time, equipment, and technical expertise
required.4
Topical 5-FU was first used in the early 1960s as
experimental treatment for various skin lesions.810 In
1962, Klein et al.8 reported injecting 5-FU directly into
keratoacanthomas. The following year, Dillaha et al.9
described the selective effect of topical 5-FU on actinic
keratoses with minimal effect on surrounding normal
skin. Several studies have since been published supporting the usefulness of 5-FU in the treatment of BD.3,1115
The selective effect of 5-FU on various skin lesions
was initially thought to be due to direct cytotoxicity to
affected cells. However, it is now thought that delayed
hypersensitivity reaction plays a major role with 5-FU
acting as an immunogen.14,16
While 5-FU is currently an established treatment
option for BD, there is no consensus on the optimal
treatment duration and few studies have confirmed the
effectiveness of 5-FU with posttreatment biopsies. Dillaha et al.9 arbitrarily treated patients with topical 5-FU
for 4 weeks, twice daily. In an attempt to decrease recurrence rates, 5-FU has been combined with other
therapies including cryosurgery,7 iontophoresis,13 occlusion, and dinitrochlorobenzene.14 However, in 1979,
Sturm3 found that 5-FU alone for a longer treatment
duration of about 9 weeks was sufficient to decrease recurrences to 8%.
The purpose of this article is to report on the use of 5FU on 26 lesions in 24 patients with histologically proven
noninvasive BD and its effectiveness after an intended
treatment time of 9 weeks, measured by posttreatment
biopsy.

Method
Consecutive patients with histologically proven BD were
informed about the established treatments for this skin
cancer, including excision, curettage, and desiccation,
and were offered topical 5-FU as an alternative therapy.
The potential side effects of 5-FU were explained, including local irritation, redness, crusting, and ulceration
that can persist beyond the time of cream application, and
the potential for treatment failure. Study participants
were instructed to rub a 5% 5-FU cream into their Bo-

Volume 7 Number 2 March 2003

wens lesions twice a day for 9 weeks. For recurrences, a

repeat course of 5-FU was employed. At some time after
the lesions were healed, biopsies were taken in the majority of cases.

Results
From 1989 to 2001, 24 patients with histologically
proven noninvasive BD were treated with topical 5-FU
for an intended duration of 9 weeks, applied twice daily
(see Table I). Two of these patients had two Bowens
lesions in different locations, diagnosed at separate times,
and were treated each time with 5-FU. The study population included 11 females and 13 males with an average
age of 70 years. Lesion sites included those easily amenable to surgery and those with more difficult anatomic
sites such as the penis, finger, posterior ear, shin, neck,
zygoma, and cheek. Most lesions had been present for
several months to a year at the time of diagnosis. Two of
the 26 cases (5 and 17) lacked sufficient follow-up to
determine the outcome.
The length of the first treatment course for 13/26
cases was 8 weeks or longer. For 8 of the remaining
lesions, the regimen was discontinued at 6 weeks or
earlier when there was excessive local irritation or there
appeared to be significant clearance. In one case, there
was evidence of noncompliance and the total duration of
treatment was unknown (case 8). The average treatment
time was 7.7 weeks.
Posttreatment biopsies were done on 18 of the 26
lesion sites. Seventeen of the 18 histological specimens
showed evidence of resolution. Of the eight cases that
lacked posttreatment biopsies, six appeared to be clear
clinically and two lacked sufficient followup (cases 5 and
17). Clinical results ranged from complete restoration of
normal skin to redness and scarring to a discharging
leg lesion that was ultimately excised and clear of BD
(case 1).
One case (case 3) resolved clinically only for a brief
period of weeks and, after the first course of treatment, it
was retreated three times for 6, 8, and 10 weeks, respectively, with eventual clinical resolution. Clinical relapse was evident approximately 4 years later; this was
confirmed with repeat biopsy that once again showed the
presence of BD. 5-FU was restarted in March 2000 and
carried on for 10 weeks, and, as of February 2001, there
was no evidence of recurrence.
Case 24 had BD of the right ear. In November 1999,
he started treatment with 5-FU which he continued for
approximately 8.5 weeks. A followup biopsy taken in June
2000 was free of BD. In July 2000, the area was clinically
clear of BD, but in October 2000 a biopsy was taken
because of possible recurrence and this confirmed BD.
He restarted 5-FU for 9 weeks. Followup biopsy was
performed in late January 2001 and showed simply scar
and chronic inflammation. When last seen in July 2001,
the area was clear. This patient has had long-standing

Age
at Dx

73
77
68
67
71
73
77
79
65
68
71
55
67
68
76
48
85
86
76
77
63
67
72
57

70
69

Case
No.

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24

25
26

L leg
R 2nd finger

L medial leg
R lateral shin
R large finger
R wrist (dorsum)
L posterior ear
L cheek
Chest
Chest
R neck
L neck
R medial ankle
R middle finger
R ant shoulder
R wrist
L neck
L 3rd finger
L zygoma
L shin
R popliteal fossa
L calf
R forearm
L&R wrist
Glans penis
R ear

Site

Years
1

1
0.5
Years
5
0.6
1.5
>1
0.5
1
0.5
1015
0.5
0.2
Years
Decades
0.5
Months
Unknown
1.5
Months
>1
Unknown
1
1

Duration of
lesion prior to
presentation (yr)

TABLE I

5.3

6.6
17.8
56.9
50.6

13.0
9.5
4.2
7.9

20.5

5.0

6.2
2.4

7.9

77.3
79.3
7.5
15.4

Duration of
pathologic
F/U (mo)
Clear
Scar
(+) BD
No BD

Mild dysplasia
No BD, scar
No BD, scar
No BD, scar

No BD

Scar

Scar
Inflammation and patchy fibrosis

Scar

Scar
Solar elastosis
Scar
1. No evidence of malignancy
2. Recurrence
Scar

F/U biopsy
result
Clinical result
Discharging sore lesion
Slightly hypopigmented scar
Recurrence 3. Healing nicely
Faint indistinct erythema
Looks better
Clear
Small white scar
Clear, site not visible
Atrophic white scar
Healed with scar
Faint erythema
Clear, site not visible
Clear, erythema and scarring
Clear, site not visible
Thin white scar

Site still friable

Barely visible scar
Barely visible scar
Clear
White atrophic patch
Whitish scars
Clear
1. Clear
2. Recurrence
Erythema and atrophic scarring
Minimal white scar

Twenty-six cases of Bowens disease treated with 5-fluorouracil

19.0
204.4

69.3
62.4
68.9
50.6
2.4
32.5
50.1
64.5
35.4
72.0
20.5
143.4
5.0
114.5
13.0
1.5
3.0
39.5
28.4
9.7
77.3
81.3
137.6
30.2

Duration
of clinical
F/U (mo)

9.6
10

6
5.5
9
6.5
3.3
8
9
Unknown
6
7
6
8
9
7
8
7.3
8.4
6
10
6
7.7
8
12.6
8.6

5-FU R
time (wk)

H. Bargman and J. Hochman

Bowens Disease

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Journal of Cutaneous Medicine and Surgery

lymphoma for many years and receives chemotherapy off

and on as required.
The average duration of pathological and clinical
followup was 21.8 months and 55.2 months, respectively.
These calculations used a timeframe of 4 weeks/month.
Clinical followup was the time from initial biopsy to the
last clinical visit.

Discussion
The compelling evidence supporting the use of 5-FU in
the treatment of BD prompted the use of this agent in a
community practice as an alternative to standard treatments including excision, curettage, and desiccation.
In the literature, there is a lack of histological data
confirming the effectiveness of various treatments for
BD. This study uses both clinical followup and biopsy
results to determine the endpoint of clearance. Posttreatment biopsies were done on 18 of the 26 lesion sites
and only two showed residual BD, both when clinical
suspicion arose. Of those that were histologically clear,
only one presented uncertainty on visual inspection (a
discharging lesion) and one recurred. Seven out of eight
cases that were just assessed visually looked clear with no
report of recurrence following treatment. One of these
eight cases (case 17) involved a patient, now deceased,
with a friable lesion site when last seen. Of the eight cases
without histological evaluation, two healed so completely
that an appropriate biopsy site could not be delineated,
one involved a site that was over the shin and was too
depressed to biopsy, and two were lost to follow-up.
Overall, the clinical results were very good. In the majority of cases, there was either complete restoration of
normal skin or redness and/or scarring.
The plan to treat Bowens lesions with 5-FU for 9
weeks was based on Sturms3 finding that the recurrence
rate was significantly reduced to 8% with a longer median treatment time of 9 weeks. Earlier studies involving
34-week regimens resulted in higher recurrence rates.
Major factors thought to contribute to the recurrence of
BD are follicular involvement and indistinct margins.
Longer treatment times may be needed in some cases to
eradicate follicular foci.
About half of our patients did not complete 89 weeks
of treatment for reasons that included excessive irritation
and early clinical resolution. A third of the patients discontinued 5-FU after approximately 6 weeks of use. The
decision to stop treatment early was usually a mutual one
made between the physician and the patient. In only one
case (case 8), noncompliance appeared to be a factor.
Recurrences occurred in only two cases, one after 6 weeks
(case 3) and one after 8.6 weeks of initial treatment with
5-FU (case 24). In the former case (case 3), multiple
treatment courses were required for complete resolution.
In the latter case (case 24), repeat treatment has apparently eradicated the BD. While 34-week regimens have
not shown favorable results in previous studies, 6 weeks

Volume 7 Number 2 March 2003

of 5-FU applied twice daily may be sufficient to clear BD

in some patients. Perhaps clinical judgment has an important role to play in determining the appropriate
treatment duration for the individual patient.
In many patients, 5-FU caused mild discomfort with
local irritation, redness, and crusting that resolved shortly
after cessation of treatment. For some, steroid creams
and antibiotic ointments were prescribed to ameliorate
the reactions. In three cases (2, 18, and 20), treatment
time was cut short by 33.5 weeks due to excessive local
irritation. However, the lesions were shown to be clear of
BD by histological and/or clinical examination.
In an attempt to shorten treatment time and/or decrease recurrence rates, 5-FU has been combined with
other topical agents as well as adjunctive techniques to
enhance skin penetration. Occlusion with plastic film has
been shown to increase the intensity of response and
shorten therapy time.3 However, there may be more
discomfort with this method thus outweighing its benefits. In addition, a longer course may be necessary for
follicular penetration. In 1979, Heising7 found the
combination of cryosurgery and topical 5-FU useful in
one case of BD of the ear. Strange et al.17 used topical
tretinoin to enhance penetration of 5-FU. More recently,
Welch et al.13 employed iontophoresis to facilitate 5-FU
delivery to deeper areas of involvement. The shorter
treatment time of 4 weeks with 8 sessions was effective
for 25 out of 26 patients, but the need for biweekly visits
presented significant inconvenience. Another treatment,
intralesional interferon (IFN) alpha-2b, has been shown
to produce similar clinical results to topical 5% 5-FU
cream in the treatment of BD and may produce more
dermal inflammation. However, its use is limited by its
cost and inconvenience to the patient.18
The question of masking invasive cancer with the use
of topical 5-FU has been raised in The Schoch Letter.19
Two cases have been described in which metastatic
squamous cell carcinoma was newly diagnosed within
weeks of treating actinic keratoses with topical 5-FU.19
According to Sturm, who considers topical 5-FU to be
both highly effective and safe, these events must be very
rare or unrelated to the use of 5-FU.20

Conclusion
The move toward more conservative treatment of skin
cancer is consistent with the shifting approach to cancer
treatment in general. Just as conservative treatment is
preferable to radical surgery in certain cases of breast
cancer, topical treatment of BD can be as effective if not
better than surgical methods. Moreover, the superior
cosmetic results, low cost, ease of application, and
availability make topical 5-FU a very good option in the
treatment of BD. Topical 5-FU is especially valuable for
cases involving multiple Bowens lesions, anatomically
difficult sites for surgery, and patients who cannot withstand surgery. A 9-week treatment plan is likely appro-

H. Bargman and J. Hochman

Bowens Disease

priate to keep recurrence rates low but modifications

should be made based on individual responses. Posttreatment biopsies are not necessary in all cases but may
be used in practice when the visible result is unclear or
treatment is stopped prematurely.

References
1. Kao GF. Carcinoma arising in Bowens disease. Arch Dermatol
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4. Cox NH, Eedy DJ, Morton CA. Guidelines for management of
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105

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