Ⅵ Prostatic Diseases Therapies for Prostate Cancer and Treatment Selection Professor and Chairman, Department of Urology,Tohoku University Graduate School of MedicineAbstract:
The number of patients with prostate cancer has been increasing
rapidly as a result of the widespread use of prostate specific antigen (PSA) screen-ing and the aging of society. In Japan, prostate cancer is now recording the highestrate of increase in prevalence amongst all types of cancer. Localized prostatecancer can be managed using various treatment options such as surgery, radio-therapy, and watchful waiting, and each of these therapies has further options. Solong as patient selection is performed properly, the outcomes of these therapiesare comparable. However, wide variations are seen in the effects of various ther-apies on complications and QOL. In addition, we must consider the fact thatprostate cancer needs follow-up care for a relatively long period after treatment. Therefore, in choosing treatment options, we should consider not only the effectsof treatment, such as survival, but also the changes in QOL after treatment. It isimportant to support patients through the provision of information concerning QOL,so that they can understand the treatment from a broader perspective. Key words:
This article outlines the treatment options
Introduction
for prostate cancer, in particular early-stage
The number of patients with prostate cancer
cancer, showing a dramatic rate of increase in
is increasing rapidly as a result of the wide-
spread use of screening with prostate specificantigen (PSA), an effective tumor marker, and
Treatment Decision Processes with
as a result of the aging of society. In the Japa-
Patient Participation
nese population, prostate cancer is now record-ing the highest rate of increase in prevalence
Recent emphasis in the processes of cancer
diagnosis and treatment has been placed on the
This article is a revised English version of a paper originally published inthe Journal of the Japan Medical Association (Vol. 130, No. 2, 2003, pages 246–250). The Japanese text is a transcript of a lecture originally aired on April 25, 2003, by the Nihon ShortwaveBroadcasting Co., Ltd., in its regular program “Special Course in Medicine”.
importance of patient participation in treat-
ment decisions, predicated on the provision of
medical information covering all aspects of the
disease. In the case of prostate cancer, we can
use this approach as discussed below.
After a definite diagnosis is made based on
biopsy, the patient is told he has cancer, and
receives information on prostate cancer in
general. He receives an explanation concern-
ing the need for staging examinations and a
patients obtain information via the Internet. In
(Detected incidentally by histopathological examination)
our hospital, we not only provide patients witha written explanation, but also recommendthem to access the Japanese version (http://www.ccijapan.com) of Physician Data Query
(PDQ®) maintained by the National Cancer
Institute (NCI) in the U.S. to provide cancerinformation for patients.
information on his condition, including clinical
staging, malignancy (Gleason score), and PSA.
A detailed explanation is given concerning
treatment options and their benefits and risks.
A nomogram for estimating pathological stag-ing from the above clinical parameters has
been developed and introduced in clinicalpractice.1)
The patient chooses the optimal treatment
for himself, based on comprehensive consider-
prostatic hyperplasia is classified as stage A in
ation of the information. During this process,
the former and stage T1 in the latter. This clas-
physicians should evaluate the medical appro-
sification is specific to prostate cancer (Fig. 1).
priateness of the patient’s choice and provide
cancers that are non-palpable on digital rectal
With these processes in mind, the following
examination are detected by needle biopsy
sections review therapies for early-stage pros-
tate cancer and treatment selection.
PSA. These cancers are collectively classified asB0 or T1c. Currently, many of the cancersdetected by PSA screening and subjected to
Clinical Staging of Prostate Cancer
curative treatment are classified as T1c, and
This section discusses important points re-
these cancers represent a considerable part of
garding early-stage cancer as defined by clinical
staging. Japanese Classification of Prostate
Palpable cancers localized within the pros-
Cancer and the TNM classification are illus-
tate are classified as stage B or T2 (Fig. 2). Of
trated. Conventionally, a cancer detected in the
these, many of the cases with palpable cancer in
histopathological specimens from surgery for
both lobes of the prostate (T2b) are considered
Treatment strategies for prostate cancer by stage
to have histopathological extracapsular exten-
treatment. If the disease is well-differentiated
sion. If palpation or imaging diagnosis demon-
minute cancer in elderly patients, watchful
strates extracapsular extension or seminal vesi-
waiting can be a good option for T1c cancer.
cle infiltration, the cancer is diagnosed as T3.
Other cases are treated with curative therapiessuch as surgery and radiotherapy. Treatment Strategies According to Staging Treatment for Localized Prostate Cancer
T1 and T2 cancers localized within the pros-
tate are usually given curative treatment, such
The main treatment options are radical pros-
as radical prostatectomy and radiotherapy (Fig.
tatectomy, radiotherapy, and watchful waiting
3). In locally advanced T3 cancer, the effective-
(Table 1). Hormone therapy is not a curative
ness of surgery or radiotherapy alone is limited,
therapy; it should always be considered as a
and a combination with hormone therapy is
palliative treatment. Hormone therapy is often
selected for exacerbation after watchful wait-
Cases with metastasis are treated with hor-
ing and recurrence after curative treatment.
androgens, or castration. However, hormone
an important treatment option for suspected
therapy is palliative. After a period of response,
well-differentiated minute cancer and for
many cases develop into a condition of hor-
elderly patients. In this case, regular PSA tests
mone-resistant cancer. Few chemotherapy reg-
are essential. It may be said that watchful
imens are effective for prostate cancer. While
waiting is a viable treatment option owing to
some are effective, none has been reported to
the ability of simple PSA tests to predict dis-
contribute to the elongation of survival.
Minute T1 cancers are classified as T1a, and
most of these do not require treatment. Non-
also been remarkable. As for external irradia-
palpable cancers that are detected only by
tion, conventional rotation therapy and pen-
abnormal PSA levels, i.e., T1c cancers, include
dulum irradiation are being replaced by new
a wide spectrum of conditions from non-life-
methods, such as 3-D conformal radiation and
threatening minute cancer to locally advanced
intensity modulated radiation therapy (IMRT).
cancer. The treatment for T1c cancers, there-
In these methods, careful preplanning of the
fore, has many options, and it is important
field of irradiation to fit the shape of the pros-
for us to understand characteristics of each
tate enables high-dose irradiation to the organ
with the primary cancer while minimizing the
dose to surrounding organs. These methods
achieved an enhancement of anticancer effi-
cacy and a marked reduction of bladder and
Brachytherapy, which uses small radioactive
sources placed in the prostate, is gaining sup-
port recently. This treatment is being per-
formed as frequently as surgery in the U.S.
Brachytherapy was approved in Japan in 2003,
and its use as a low-invasive treatment is
Anatomy around the prostate (lateral view)
(Tobisu, K.: Cancer Surgery — Surgical Techniques Series,
As for surgery, radical prostatectomy is the
Urinary Cancers (Kakizoe, T. ed.). Medical View Co., Ltd.,
most widely used treatment for early-stage
prostate cancer.3) Operation methods haveimproved greatly in the last 10 years, and verystable outcomes are reported nowadays. In
Anatomical Features of the Prostate
view of the invasiveness of treatment and its
and Treatment Complications
contribution to survival, patients consideredfor surgery should have at least 10 years of
In discussing the characteristics of curative
therapies for prostate cancer, it is important tounderstand the anatomy of the prostate andsurrounding structures (Fig. 4). During surgery,
Types of Surgical Therapy
the prostate and the seminal vesicle are re-
moved as a mass, and the bladder is anas-
for radical prostatectomy, and each has various
tomosed to the urethra. The apical portion of
the prostate is in contact with the external ure-
thral sphincter. Along the posterior and lateral
most frequently, and this method is well estab-
aspects of the prostate run the rectum and the
lished. The perineal approach, as the name
cavernous nerves of the penis, the so-called
implies, does not involve surgical operation on
the lower abdomen, and thus is less surgically
As seen from the anatomic locations of these
invasive. The use of this method is also slowly
structures, curative therapies for prostate can-
cer must be viewed from 2 aspects: (1) com-
Laparoscopic radical prostatectomy is a newly
plete resection or disappearance of the pros-
developed method in which all procedures are
tate and (2) preservation of the important
performed using video assistance. Its advan-
function of surrounding structures. With the
tages are small surgical wounds and quick post-
increasing knowledge of pelvic anatomy, treat-
operative recovery. However, much is left for
ment techniques have been improved, and sur-
future evaluation with respect to complete
gery that spares the erection nerves is exten-
cancer elimination and functional recovery.
sively performed. The advance in preservation
Because laparoscopic radical prostatectomy
has not been covered by national health insur-
ance, patients who desire this surgery must
develops in the posterior-lateral aspect of the
prostate, i.e., in the vicinity of the erectionnerves. Because the complete cure of cancer is
Therapies for Localized Prostate Cancer and
Therapies for Early-Stage Prostate Cancer and
Urinary incontinence, sexual dysfunction (ED),
stenosis of vesicourethral anastomosis,general complications of surgery
with the passage of time after treatment. As a
the priority in surgery, the appropriateness
peculiarity of radiotherapy, rectal injury or
of nerve-sparing surgery must be determined
ED can develop late after treatment. Recent
carefully based on information such as pre-
development of 3-D conformal radiation and
intensity modulated radiation therapy has re-
For these anatomical reasons, each type of
duced the occurrence of these complications.
therapy for localized prostate cancer may cause
In contrast with the above 2 types of curative
characteristic complications (Table 2).
therapies, watchful waiting cannot cause any
direct complications. On the other hand, pro-
reported to cause postoperative urinary incon-
tinence, sexual dysfunction (erectile dysfunc-
cause a certain amount of psychological stress
tion; ED), stenosis of vesicourethral anastomo-
to the patient and a risk for stage progression
sis, and other specific complications, in addition
to wound infection and other general surgerycomplications. Thanks to the improvement in
Therapies for Early-Stage
methods of operation, urinary incontinence is
Prostate Cancer and QOL
rarely severe and disabling. It usually occurstransiently after surgery, and improves with the
compare the patient’s QOL after surgery and
Postoperative ED is inevitable when nerves
radiotherapy in the treatment for early-stage
are not preserved. With nerve-sparing surgery,
functional recovery can be expected to some
No difference is reported to occur between
extent. Recovery of sexual function can be
the effects of surgery and radiotherapy on gen-
expected even with unilateral nerve sparing
eral health-related QOL, including physical
procedures. When recovery of erection is in-
function, mental health, social life, and daily
sufficient, the use of Viagra® is likely to achieve
recovery of sexual function in more than half of
On the other hand, there are marked differ-
ences in disease-specific QOL directly related
Complications of radiotherapy typically in-
to prostate cancer treatment.5) With respect to
clude anorectal injury (diarrhea, bloody stools,
urinary continence, radiotherapy provides bet-
anal pain) and bladder dysfunction (increased
urinary frequency, miction pain, difficulty in
because surgery removes the prostate with
urinating) resulting from radiation exposure of
hyperplasia, it dramatically improves lower
adjacent organs. Many cases improve gradually
urinary tract symptoms such as difficulty in
urinating and increased urinary frequency.
Wide variations are seen in the effects of vari-
Radiotherapy often causes transient aggrava-
ous therapies on complications and QOL. In
tion of urination symptoms shortly after treat-
addition, we must consider the fact that pros-
ment, as a result of inflammation and other
tate cancer needs followup care for a relatively
effects of irradiation. With respect to sexual
function, surgery tends to result in poorer QOL
Therefore, in choosing treatment options, we
because of the risk for surgical damage to erec-
should consider not only treatment effects such
tion nerves. Since surgery has almost no effect
as survival but also the changes in QOL after
on the rectum, it provides better QOL related
treatment. It is important to support patients
to bowel function than radiotherapy.
through the provision of information concern-
As summarized above, the 2 representative
ing QOL, so that they can understand the treat-
methods of curative treatment provide charac-
teristic QOL outcomes after treatment. It isimportant that patients understand these dif-
REFERENCES
ferences. We also need to pay attention to thefact that this scheme on QOL may change with
Partin, A.W., Mangold, L.A., Lamm, D.M. et
progress after treatment. Finally, it should be
al.: Contemporary update of prostate cancer
noted that recent remarkable developments
staging nomograms (Partin Tables) for the
in both surgery and radiotherapy have been
new millennium. Urology 2001; 58: 843–848.
Non-palpable (T1c) prostate cancer — a new
reducing these differences in QOL outcome.
approach. Arai, Y. (planning & organization),Yoshida, O. (ed.), Urology View 1(2), Medical
Conclusion
Arai, Y., Egawa, S., Tobisu, K. et al.: Radical
This paper outlines the therapies for pros-
retropubic prostatectomy: Time trends, mor-
tate cancer and the process of treatment selec-
bidity and mortality in Japan. BJU Int 2000;
tion focusing particularly on localized prostate
cancer, which is often detected by PSA tests.
Arai, Y., Nakagawa, H. and Namiki, S.: ED
The treatment for localized prostate cancer has
and surgery for pelvic malignant tumors. TheJournal of Therapy 2003; 84 (11): 135–139. (in
many options, including surgery, radiotherapy,
and watchful waiting, and each of these ther-
Namiki, S., Tochigi, T., Arai, Y. et al.: Health
apies also includes many options. As long as
related quality of life after radical pros-
patient selection is performed properly, the
outcomes of these therapies are comparable.
prostate cancer Int J Urol 2003; 10: 643–650.
Chiropractic Cervical Adjustment Cervical adjustment, also known as neck manipulation, is a precise manual procedure applied to the joints of the neck. Cervical adjustment works to improve joint mobility in the neck, restoring range of motion, and reducing muscle hypertonicity thereby relieving pressure and tension.1 Patients typically notice a reduction of pain, soreness, stiffness and
COMPTE-RENDU SYNTHETIQUE DE LA SEANCE DU 8 novembre 2005 ETAIENT PRESENTS : • Membres de la Commission du génie biomoléculaire : M. FELLOUS, Président M. MESSEAN, Vice-Président Mme CASSE, M. CUGUEN, Mme DATTEE, MM. JACQUEMART, JESTIN, LUNEL, PASCAL, Mme RAVAIL-DELY, M. SERALINI. 1) Dossiers de demande mise sur le marché DOSSIER EFSA/GMO/UK/2005/11 relatif à la dema