Med.or.jp

Prostatic Diseases
Therapies for Prostate Cancer and
Treatment Selection

Professor and Chairman, Department of Urology,Tohoku University Graduate School of Medicine Abstract:
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.

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