Carcinoma prostate is the most common cancer in men. Yet there are unresolved issues. It was thought that serum PSA levels would be diagnostic for this particular cancer. However, it has now been proven beyond doubt that it can be raised in many other conditions.

1. CarcinomaofProstate

2. Review Article
Carcinoma of prostate
Ajit Saxena*
Senior Consultant Urologist & Andrologist, Indraprastha Apollo Hospitals, Sarita Vihar, Delhi, India
a r t i c l e i n f o
Article history:
Received 15 January 2013
Accepted 17 January 2013
Available online 23 January 2013
Keywords:
Prostate cancer
Prostate biopsy
Pipeline drugs
Robot
a b s t r a c t
Carcinoma prostate is the most common cancer in men. Yet there are unresolved issues. It
was thought that serum PSA levels would be diagnostic for this particular cancer. However,
it has now been proven beyond doubt that it can be raised in many other conditions. The
search for an ideal marker is still on. Ultrasound-guided biopsies have made it possible to
detect early prostatic cancer. However, controversy exists as regards the number of bi-
opsies and period of repeat biopsy. The variation of Gleason score from center to center is
another diagnostic dilemma. Lot of advances have been made in the treatment of prostatic
cancer. While use of robots has simplified surgery to a large extent, newer chemo-
therapeutic agents have been successful in mitigating the misery due to the cancer. Trials
are on to develop vaccines and genetic manipulation to control the cancer.
Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
1. Introduction
Cancer is never good. But if I was asked to choose one then I
would choose cancer of the prostate gland. They are com-
paratively easy to diagnose. Even if picked up in the late
stages, good treatments are available but let us start from the
beginning. Cancer of the prostate is rare before 50 years of age.
It is one of the most killer diseases once the age advances.
Indeed, globally prostate cancer is number two killer.10,11
Sadly, in India most of the cases that come to urologist are
in an advanced stage of the disease. The advent of serum PSA
(prostate specific antigen) has resulted in early pick up of
disease.
Symptoms of Ca. Prostate are usually late. Thus patient
may be asymptomatic as regards the cancer but may present
with lower urinary tract symptoms. Many a times, the cancer
is diagnosed by histopathology of the tissue sent following
TURP. In late stages the patient may present with bony pains
and be treated as such by an orthopedic surgeon. Rarely
a person may present with deranged liver function and/or
enlarged lymph nodes in the abdomen.11
2. PSA and screening
One of the most useful tools in the early diagnosis of Ca.
Prostate is the measurement of serum PSA levels. Initially, this
biomarker was thought to be specific for the cancer of prostate
i.e. it was thought that PSA is only raised in the cancer of
prostate. We now know that PSA can also be raised in various
other conditions like inflammation of the prostate glands,
large size of the gland, prior instrumentation in the area etc. In
order to eliminate these false positive reports, other parame-
ters of PSA have been investigated. Hence the advent of free
PSA, PSA density, PSA velocity. There is no international
consensus regarding the other tests like USG. The important
point to understand is that the PSA reading alone does not
signify or rule out Ca. Prostate.16
Clinical experience has
shown that the diagnosis of Ca. Prostate is based on history,
* X-9, Sec-12, Noida 201301, India. Tel.: þ91 011 26925858, 26925801; fax: þ91 11 26823629.
E-mail address: ajitsaxena@hotmail.com.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 6 4 e6 6
0976-0016/$ e see front matter Copyright ª 2013, Indraprastha Medical Corporation Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.apme.2013.01.012

3. digital examination, trans-rectal ultrasound and PSA. If any
two parameters are positive then we proceed on to an ultra-
sound-guided prostatic biopsy. Only when the HPE shows
cancerous cells, the patient is labelled as a case of Ca. Prostate.
3. Investigations
Most of the centers have graduated from blind biopsy to ul-
trasound-guided one. The biggest advantage of TRUS biopsy is
that everything is under vision and even small nodules can be
targeted for biopsy. There is still no consensus on the number
of cores of the prostatic tissue to be taken at the time of bi-
opsy. Most of the centers feel that 8e10 cores should provide
representative sample from all lobes of the prostate.12,13
3.1. Histopathological grading
Gleason scoring is now universally accepted as being of
prognostic value. It is based on the nuclear pattern of the
prostatic cells. There are major and minor criteria. The clinical
implication of Gleason scoring is that a score of 7 or less have
better prognosis than if it is 8 or above. However, this scoring
is largely dependent on the experience of the histopathologist,
which may vary from center to center.12,13
4. Treatment
From the treatment point of view, it is best to divide as the
cancer e an early and advanced. An early case of cancer would
be an organ confined disease. Where as an advanced case of
tumor could be locally advanced as when tumor breaches the
prostatic capsule. It may extend up to the lateral pelvic wall.
The tumor can spread to the bones and involvement of the
lymph nodes occurs in the late stages of the disease.14,15
Most
of our patients belong to this late category. Hence the prostate
screening with serum PSA is relevant in our country.
4.1. Treatment of early Ca. Prostate
Currently there are three options available for early treatment
i.e. watchful waiting, radical surgery and radical radiotherapy.
4.1.1. Watchful waiting
There is a school of thought if a patient has short life expec-
tancy and co-morbid condition, then the treatment may be
more harmful than the disease itself. It is based on assump-
tion, that Ca. Prostate is a slow growing process.
Radical surgery has by far given the best results. There has
been much advancement in the technique employed to
remove the gland. Only a few years ago, open radical prosta-
tectomy was gold standard. This was replaced by the laparo-
scopic surgery and now we have the robot assisted radical
prostatectomy. The advantages of robotic technique are the
ease with which one can reach the depth of the male pelvis,
precise movements, less tissue damage and therefore faster
recovery. There is hardly any blood loss during the procedure.
Since the vision is magnified, more complete job particularly
at the apex of the prostate can be done.
4.1.2. Radical radiotherapy
Newer machines have made possible to target prostate glands
specifically without harming the bladder and the rectum. IGRT
and IMRT are two such procedures to eradicate the gland.
Implantation of radiation needles is done by a procedure
called bracy therapy. Although good results can be obtained,
radiotherapy is reserved for cases who are unfit for surgery for
any reason.
4.2. Medical therapy
It is for the advanced cases of prostate cancer. Hormonal
therapy is the standard first line treatment for advanced
prostate cancer. The normal prostate depends upon number of
hormones for its growth. The main hormone is testosterone is
produced primarily in the testes. Some of the androgen is also
produced by the adrenal cortex. The basis of hormonal therapy
lies in the fact that the circulating androgen stimulates un-
controlled growth of the gland i.e. Cancer. Thus if these hor-
mones can be countered, the cancer process can be reversed.
This is done by orchidectomy to limit testicular androgen
release along with Bicalutamide to counter the extra testicular
hormonal release. Orchidectomy can be surgical or medical. At
present medical prostatectomy is achieved by giving LHRH
agonists by inhibiting the pituitaryegonadal axis. It has the
same effect as surgically removed testis. There are many LHRH
analogs available in the market and these injections are to be
repeatedevery 1e6 months depending upon the type of agonist
used. In contrast, surgical removal of testes is a one time
treatment but is not reversible. Hormonal therapy forms the
first line treatment of advanced Ca. Prostate. However, it has
been estimated that the effect lasts on an average for 20
months following which the serum PSA starts rising thus sig-
nifying the resurgence of prostate cancer cells. This condition
is now called castrate-resistant prostate cancer.1,2
4.3. Chemotherapy
Many drugs are now available such as Ketoconazole which is
an antifungal agent. Although it can effectively lower testos-
terone level, it has to be given in high doses. This results in
significant toxicity. Lower doses are being evaluated in com-
bination with steroids.
4.3.1. Dutasteride
This inhibits the conversion of testosterone to its active form
dihydrotestosterone. However, its efficacy needs to be scien-
tifically evaluated.
4.3.2. Docetaxel
It is another chemotherapeutic agent used in CRPC cases.7
New treatment strategies have been developed in recent
years with good results. Some of which are abiraterone acetate.
This is a potent, selective irreversible inhibitor of enzyme
CYP17 targeting the both intracrine androgens. In a study
involving 21 patients, significant decline was seen in PSA along
with radiologic regression and improved pain control.5,8,9
MDV-3100 and BMS-641988 are novel antiandrogens, pre-
clinical developments.4
a p o l l o m e d i c i n e 1 0 ( 2 0 1 3 ) 6 4 e6 6 65

4. 4.4. Immunologic approach
It is well known that immune system can be stimulated by
antibody or T cell mediation to selectively kill tumor cells.
Studies are under way to deliver the T cells at the prostate
level so that they can recognise and kill the tumor cells.17,18
Gene therapy; it involves transfer of recombinant DNA into
human cells and its expression on those cells for therapeutic
response. This “repair gene” is transferred via the blood
stream to the prostatic cells using live attenuated viruses.3,6
Studies are being done to use a plant virus for this purpose
since these are nonantigenic.
This is just a beginning. There are many more newer mo-
dalities being tested which brings me to my opening state-
ment e cancer is never good. With so much research going
into the treatment of prostatic cancer its only a matter of time
before prostate cancer is conquered.
5. Conclusion
The last word on prostate cancer is yet to be written. Early
diagnosis of prostate cancer is possible with screening pro-
gramme. Several new molecules are in the pipeline which
may control the cancer much better than the current mole-
cules. It is possible that through gene therapy we may actually
see a cure of prostate cancer in our lifetime.
Conflicts of interest
The author has none to declare.
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