Urologic Oncology: Seminars and Original Investigations 23 (2005) 383–385
Lycopene as a chemopreventive agent in the treatment of high-grade
prostate intraepithelial neoplasia
Nayan Kumar Mohanty, M.S., M.Ch.(URO)*, Sunita Saxena, M.D.(PATH),
Uday Pratap Singh, M.S., Neeraj K. Goyal, M.S., Rajender Prakash Arora, M.S.Department of Urology, V.M. Medical College & Safdarjang Hospital, New Delhi, India
Received 5 May 2004; received in revised form 9 May 2005; accepted 10 May 2005AbstractObjective:
Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention.
High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown de?nite
results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing
prostate cancer from developing in this vulnerable group of patients.Materials and Methods:
A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day
for one year, and the other was periodically followed up. Total follow-up was one year.Results:
Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an
inverse relationship between lycopene and prostate-speci?c antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for
a longer period without any adverse reaction.Conclusion:
Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance.
© 2005 Elsevier Inc. All rights reserved.Keywords:
Lycopene; High grade prostate intraepithelial neoplasia; Prostate cancer1. Introduction
this process by pharmacologic agents gave birth to the
concept of chemoprevention. The concept of primary che-
Coined in the mid 1970s by Dr. Michael B. Sporn, the
moprevention for prostate cancer gained momentum in the
term chemoprevention is de?ned as the pharmacologic in-
1990s because of the disease high prevalence, slowly pro-
tervention with a natural or synthetic compound to reverse
gressive nature, and long latency [2– 4]. The ideal therapeu-
or suppress carcinogenesis in its early or premalignant
tic intervention would arrest disease progression during the
stages so as to prevent the development of invasive cancer
latency period and decrease the incidence of clinical dis-
. Recent advances in epidemiology and a better under-
ease. The success of chemoprevention depends on several
standing of molecular biology supported by clinical re-
search have prompted chemoprevention to the forefront of
? Treatment given to an otherwise healthy but a high-
this new approach for cancer control. The complex process
risk individual in whom prostate cancer develops.
of carcinogenesis can evolve over decades, from the ?rst
? Those therapeutic agents given must offer low-to-no
mutagenic initiation through multiple stages before ?nally
toxicity with a simple dose regime for better patient
ending in invasive cancer. During this process, a number of
molecular and cellular alterations affected by several exog-
? The ef?cacy of these agents should be beyond doubt.
enous and endogenous factors either enhance or retard the
? Motivate patients to use these agents all their lives .
process of carcinogenesis. Sporn’s proposal of reversing
Because research has shown that diet plays a great role in
the development of prostate cancer, many researchers have
* Corresponding author. Tel.: ?91-11-24676704; fax: ?91-11-
suggested that fat, soya, green tea, lycopene, selenium,
email@example.com (N.K. Mohanty).
vitamins, and retinoids are among others as modi?ers of
1078-1439/05/$ – see front matter © 2005 Elsevier Inc. All rights reserved.
384N.K. Mohanty et al. / Urologic Oncology: Seminars and Original Investigations 23 (2005) 383–385
prostate cancer risk. Data suggest that 13% of prostate
cancer cases may be preventable by reducing saturated fat
Serum PSA and serum lycopene
intake . Lycopene, a red carotenoid pigment, is found
Mean serum lycopene
abundantly in various fruits like guava, pink grapefruit,
watermelon, and tomato. With its potent antioxidant activ-
Study group A (20 patients)
ity, lycopene may protect cellular components from reactive
oxygen radical species. Epidemiologic data show that lyco-
pene consumption is associated with a decreased risk as
Control group B (20 patients)
well as a possible reduction in prostate cancer growth .
High-grade prostate intraepithelial neoplasia (HGPIN) is
now identi?ed as a premalignant condition of prostate ma-
lignancy that is a well-established histological entity. Many
ceived 4 mg lycopene (Lyc-O-Mato, LycoRed Natural
benign prostatic adenomas that are surgically removed will
Products Industries, Ltd., Beer-Sheva, Israel) twice a day
show HGPIN in their histology. HGPIN has been graded as
for one year continuously and were followed for another
low (grade I) and high (grades II and III) histologically. If
year. None of the 20 patients in group B (control group)
identi?ed early and kept on chemoprevention, these patients
received any medication and were only followed for 2 years
with HGPIN can be prevented from the development of
occult prostate cancer in the future because it is the potential
The baseline serum lycopene, total PSA of both groups
precursor of ovoid prostate cancer. We undertook this study
was obtained before therapy. Both groups were followed for
to treat HGPIN with lycopene and follow-up for 2 years
2 years at 3 monthly intervals with serum lycopene and
with a control group in a randomized fashion to establish the
serum PSA, and DRE. Prostate biopsy was performed as
ef?cacy and safety of lycopene as a chemopreventive agent
and when indicated during follow-up. Normal serum PSA
level in our laboratory was 0 – 4 ng/dL (during our study),
and the serum lycopene level was 300 ng/dL. Both groups
were advised to continue their normal diet, but the control2. Materials and methods
group was advised to reduce its intake of tomato and melon.
A total of 230 patients undergoing transurethral resection3. Results
of the prostate for benign prostatic hyperplasia (BPH) was
reviewed for our study. After a thorough clinical examina-
The serum PSA level in the treated group A decreased
tion, all patients underwent uro?owmetry, digital rectal ex-
for a mean level of 6.07–3.5 ng/ml, while in the control
amination (DRE), total serum prostate-speci?c antigen
group B, it increased from a mean value of 6.55 to 8.06
(PSA), serum lycopene, transrectal ultrasonography, and
ng/ml. Similarly, the serum lycopene level was increased
prostate biopsy only in suspected patients. Of the 230 pa-
from the mean value of 360 to 680 ng/ml in group A but
tients, serum PSA was increased in 38 (?4 ng/ml), and
decreased from a mean value of 378 to 180 ng/ml in the
another 30 had an abnormal DRE. All 68 patients were
group B. During follow-up, 6 patients had increased PSA in
subjected to sextant prostate biopsy, of which 15 (11 with an
group A and 9 in group B. Subsequent prostate biopsy in
abnormal DRE and 4 with increased PSA) had malignancy
these patients with increased PSA showed 4 patients with
and were subsequently excluded from the study, leaving a
BPH and 2 with adenocarcinoma in study group A, while
total of 215 patients for evaluation in our study.
the totals were 3 with BPH and 6 with adenocarcinoma in
After being established as BPH clinically, all 215 pa-
the control group B.
tients underwent transurethral resection of the prostate as a
On follow-up DRE in patients in group A, suspicious
standard treatment for their features of prostatism. Tissue
nodules were felt in 2 (10%) who also had increased PSA,
was sent for histopathologic examination conducted by one
on whom biopsy was proved adenocarcinoma prostate. In
onco-pathologist for uniformity. Of the 215 patients, 160
patients in group B, follow-up DRE showed suspicious
had benign hyperplasia of prostate, 11 had low-grade pros-
nodule in 6 (30%) with increased PSA and subsequent
tate intraepithelial neoplasia (grade I) along with BPH, 40
biopsy proved adenocarcinoma. No adverse effects were
had HGPIN (grade II in 16 and grade III in 24 patients), and
observed in the lycopene therapy group. Our study clearly
another 4 had occult prostate malignancy along with HG-
P I N in their histopathology report, respectively ( Table 1).
There were 40 patients with HGPIN who were random-
? HGPIN is a precursor of ovoid prostate malignancy.
ized into 2 groups: group A (n ? 20) and group B (n ? 20).
? Lycopene can act as a chemopreventive agent in pre-
The patients in group A (ie, study group) had HGPIN, with
venting or delaying the development of malignancy in
grade II disease in 8 and HGPIN in 12, while the same
these high-risk patients.
number was included in the control group, group B for
? There exists an inverse relationship between serum
uniformity. All 20 patients in group A (study group) re-
PSA and serum lycopene level.
N.K. Mohanty et al. / Urologic Oncology: Seminars and Original Investigations 23 (2005) 383–385
? Being a vegetable carotenoid, lycopene is very safe for5. Conclusions
This initial small trial has shown that lycopene is an
effective chemopreventive agent in preventing HGPIN from4. Discussion
becoming prostate cancer. However, a larger clinical trial is
warranted to establish the potentiality of lycopene as a
Prostate cancer is an excellent model for chemopreven-
chemopreventive agent for the treatment of prostate cancer.
tion therapy because of its high prevalence, slowly progres-
sive malignancy, and long latency. There is an abundance of
literature available indicating that lycopene reduces the oc-References
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- Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia
- Materials and methods