© 2004 Foundation for Promotion of Cancer Research
Characteristics of Patients with Prostate Cancer Who Have Initially been Treated by Hormone Therapy in Japan: J-CaP Surveillance
1 Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, 2 Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, 3 Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, 4 Department of Urology, The University of Tokushima School of Medicine, Tokushima, 5 Department of Urology, Faculty of Medicine, The University of Tokyo, Tokyo, 6 Department of Urology, Sapporo Medical University, School of Medicine, Sapporo, 7 Department of Urology, University of Kyushu, Fukuoka, 8 Department of Urology, Nara Medical School, Kashihara, Nara, 9 Department of Urology, Keio University School of Medicine, Tokyo and 10 Department of Urology, Gunma University School of Medicine, Maebashi, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Objective: Hormone therapy for prostate cancer has empirically prevailed in Japan. We planned to evaluate the trends and outcome of hormone therapy for establishing an adequate guideline.
Methods: Patients with prostate cancer who were initially treated by hormone therapy were registered through the J-CaP registration system. This report summarizes the background factors.
Results: From January 2001 to October 2003, 17 872 patients were registered from 395 institutes throughout Japan. The background factors of 17 312 patients were analyzed. The 17 872 patients were estimated as composing more than half of newly diagnosed prostate cancer patients in Japan. Of these, 22.9, 35.1, 32.9 and 8.6% belonged to T1, T2, T3 and T4, respectively. For the purposes of hormone therapy, 77.5% was primary hormone therapy. Neoadjuvant setting and adjuvant setting were 18.1 and 4.3%, respectively. About 60% of the hormone therapy was combined hormone therapy with LH-RHa plus anti-androgens.
Conclusion: Irrespective of patients’ age, TNM, stage of illness, or histological background, the majority of prostate cancer patients in Japan are receiving hormone therapy. It is necessary to evaluate whether this trend is merely a continuation of past experience of Japanese urologists or if there is a difference in the profile of effect and side-effect in the case of Japanese patients compared to therapy given in Westerners.
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INTRODUCTION |
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In prostate cancer treatment, hormone therapy has been used in Europe and North America mainly to provide temporary relief for advanced cancers. However, the CaPSURE report (1), released in 2003, indicates that there is a rapid increase in the use of hormone therapy on localized cancer in the United States, which suggests a drastic change in the role of hormone therapy. Meanwhile, in Japan, hormone therapy has been used over many years in a considerable number of patients with localized or locally advanced prostate cancer. In recent years, while clinical trial data (2,3) indicating its usefulness have been accumulating, the outcomes have yet to be accurately analyzed. As typically seen in the early prostate cancer (EPC) studies of recent years in Europe and North America (4), clinical trials are being reported that point to the effectiveness of hormone therapy in localized cancer (5,6). Against this backdrop, in 2001 the Japan Study Group of Prostate Cancer (J-CaP Study Group) was inaugurated with financial support from the Japan Kidney Foundation. This project has been authorized by the Japan Urological Association. The purposes of this study group were to gather information about the hormone therapy administered to Japanese prostate cancer patients living in Japan and to analyze the outcomes of treatment in order to create a guideline for optimal hormone therapy. This report summarizes the background factors of patients receiving hormone therapy across most of Japan.
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PATIENTS AND METHODS |
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The rules for the J-CaP study group are summarized in the Appendix.
Eligible Institutions
Eligible institutions are Japanese urological institutions endorsing the purpose of this study that are able to obtain the approval of their own ethics committees (or IRB). Institutions that have not yet established their own ethics committee (or IRB) but can be vetted instead by an affiliated institution or can obtain approval from the person responsible for the institution are also included. As a rule, in each eligible institution, all cases of patients newly starting hormone therapy for prostate cancer in and after January 2001 will be regarded as subjects of the study.
Period of Research
Registration will commence when approval is obtained from the J-CaP Study Group. The term of case registration is for 3 years and the follow-up period is for 2 years.
Method
Data under the following headings for each registered case will be relayed to the secretariat server over the Internet: date of birth, family history, date of PSA reading, PSA value, PSA kit name, testosterone value, biopsy date, Gleason score, histological grade, clinical stage, case history, details of hormone therapy, whether or not there has been progress observation, whether or not surgery was carried out, date of surgery, operative procedure, whether or not radiotherapy is being conducted, irradiation method, irradiation date, progress. TNM classification used was the 5th edition (7). Histological grade and other criteria were adopted in accordance with the Japanese Urological Association/Japan Society of Pathology 3rd Edition of General Rules for Clinical and Pathological Studies on Prostate Cancer (8).
Follow-up Method
The registered cases, as a rule, are to be updated once every 3 months with regard to test data, change in treatment and progress data. The secretariat immediately contacts institutions not updating information, requesting data input. The secretariat forwards input forms for data addition, and confirms registered cases as of that date as necessary. Additionally, assistance can be given on adding test data and entering changes in treatment and progress data.
This report concerns patient background factors, tumor factors and treatment details of registered cases between 2001 and October 2003.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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Participating Institutions
By October 2003, 395 institutions throughout Japan had registered, acquiring IDs and passwords. Eleven institutions of the 395 later withdrew registration. Fig. 1 gives an overview of the year of registration and type of institution. The number of university hospitals registering was 76 (60.2% of university hospitals in Japan); in detail, 35 national university hospitals (83.3%) have been included.
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Number of Registered Patients
As shown in Fig. 2, 17 872 patients were registered by October 2003. This survey investigated patients who were first diagnosed with prostate cancer at the registered institutions during this period. Respectively, 7952 and 8195 new patients were reported in 2001 and 2002 by 246 and 216 institutions. Of these new patients, 5969 and 6064 were newly administered hormone therapy, and 5646 and 5651 were registered with J-CaP. In summary, it is shown that 75% of new patients were given hormone therapy in some form and 70% registered with J-CaP.
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Patient Background Factors
Of the 17 872 registered patients at the time of data compilation, data were collected from 17 312 patients. 529 cases without any record of hormone therapy commencement date were excluded, as were 31 cases whose therapy was reported as commencing in 2000. Family history, age at diagnosis and PSA value at diagnosis are given in Table 1.
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Tumor Background Factors
A summary of Gleason score, histological grade, TNM classification and clinical stage (TNM) is given in Table 2.
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Hormone Therapy
As to the reason for hormone therapy, primary application of hormone therapy was the most prevalent, comprising 77.5% of the total, followed by 18.1% neoadjuvant and 4.3% adjuvant (Table 3).
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Table 3 also indicates an overview of the types of hormone therapy. The combined use of LH-RHa + anti-androgen drug is the largest, comprising 60%. Anti-androgen monotherapy was 7.1% and LH-RHa monotherapy was 12.8%.
Table 4 shows the relations between the purpose of hormone therapy and T category, clinical stage, Gleason score and age. A notable feature is that in all categories, primary use of hormone therapy was the most common.
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Table 5 shows the relations between the type of hormone therapy and T category, clinical stage, Gleason score and age. In all categories and ages, combined androgen blockade (CAB) was used in the main. In Table 6, details are given of the main treatment methods when hormone therapy was administered as neoadjuvant, as well as the details of main treatment methods when used as adjuvant.
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Compliance of Survey Data
Omission of data entry among registered data included 0.2% of patients for whom PSA values were not recorded. Meanwhile, omission of histological grade accounted for 7.8% and omission of clinical stage 6.1%. As for Gleason score, 23% of registered cases in 2001 had no entry, but in 2002 this had decreased to 11.9% and by 2003, to 6.5%. This is thought to be because in the First Edition of the Japanese Urological Association and Japan Society of Pathology’s General Rules for Clinical and Pathological Studies on Prostate Cancer, Gleason score entry was not compulsory. Only in the Second Edition did Gleason score become required.
Follow-up Data
For approximately 92% of the registered cases in 2001 and 75% of the registered cases in 2002, the input of follow-up data was confirmed at least once. The period (median) from the start of hormone therapy to the latest follow-up data entry was 406 days (between 0 and 964) for 2001-registered cases and 189 (between 0 and 615) for 2002-registered cases.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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In Japan, the General Rules for Clinical and Pathological Studies on Prostate Cancer issued by the Japanese Urological Association and Japan Society of Pathology were first published in 1985 (9) and this set of rules has been widely used ever since. The document gives a guideline on diagnosis and a detailed description of rules associated with making entries on patient background, tumor background and treatment method. Most of the papers presented at such meetings, such as the academic conference of the Urological Association, follow these rules and their diffusion rate is extremely high. The J-CaP survey basically followed the rules, and the accuracy of TNM diagnoses and clinical stage diagnoses is considered to be high. The Japanese Urological Association started a prostate cancer registration system from 2001, in accordance with these rules. However, this system is a registration of all prostate cancers. Therefore, when, for example, focusing on hormone therapy, we cannot necessarily expect satisfactory outcome data.
The morbidity of prostate cancer in Japan has been remarkably lower than in Europe and North America (10). Furthermore, due to anxieties about radiotherapy and the slowness of the introduction of technical expertise in radical prostatectomy, in many cases surgical castration or estrogen administration has been conducted across the board (11). However, in recent years Japan has seen an overwhelming increase in morbidity and mortality from prostate cancer (10). Compounding this, the influx of information about prostate and surgical techniques from Europe and North America has led to a rapidly growing debate on the method of treatment. Naturally, the trend towards newer treatment is beginning with reference to European (12) and North American guidelines (13) and the trend is set to continue.
At present, with financial assistance from the Ministry of Health, Labor and Welfare, the Japanese Urological Association is working on the drafting of a prostate cancer treatment guideline at the earliest possible date. What is of concern here is that, in addition to the circumstances previously mentioned, there have been very few clinical trials with strong evidence carried out in this country. This causes a desperate lack in clinical data specific to Japan, which is essential to establish such a guideline. Hormone therapy in Japan, which has been administered only empirically, should be re-examined correctly to determine what outcome it is actually providing for the patients. Otherwise, it is likely that Japan’s treatment guideline will become a reproduction of those of Europe and North America. Ethnic and philosophical differences, religious background, differences in perceptions about sex, and economic background—these diverse factors must be taken into account in the drafting of the most appropriate guideline for a country. The general attitude toward hormone therapy in Japan is similar to other East Asian countries (14). The recent treatment and clinical trial findings on hormone therapy in Europe and North America aimed at achieving long-term stable results indicate that we should examine the outcome of hormone therapy not only in Japan but throughout the world (4–6). The CaPSURE data reported in 2003 (1) consists of the analyses of 3439 cases, showing that the proportion of primary hormone treatment on localized prostate cancer rose dramatically from 4.6% in 1989 to 14.2% in 2001 and pointed firmly to the need to review the existing guidelines.
The institutions registered with J-CaP cover 60.2% of all university hospitals. According to Japan Cancer Statistics 2003, the number of patients newly diagnosed with prostate cancer in 1998 was 15 814 (15). In view of the proportion of J-CaP registered patients obtained in the survey of new patient numbers mentioned earlier, ~50% of new prostate cancer patients were treated by hormone therapy and registered with J-CaP. J-CaP had requested reports on the number of newly diagnosed prostate cancer patients in the registered institutions. Out of 358 institutions, 246 had responded as of 2001. Based on this report, 7952 patients were newly diagnosed with prostate cancer in those 246 institutions. Of these, 5969 patients (75.1%) were treated by hormone therapy in some form. Among those patients, 5646 (71%) were registered with J-CaP. In other words, 94.6% of the patients who had initiated a hormone therapy in 2001 were registered with J-CaP. This figure is almost the same in 2002. This illustrates the breadth of significance of this study. Patient background factors and PSA values at diagnosis would not represent the general trend because of the bias that patients registered for this study are receiving hormone therapy for the first time. However, we should make a special note of the low frequency of familial prostate cancer.
For the same reason, the background to the tumor in this report would not represent the overall trend of prostate cancer in Japan. Nevertheless, considering the finding that an extremely large number of patients are receiving hormone therapy, we can safely say that they express the overall background factors of prostate cancer in Japan to a fairly high degree of accuracy.
The analysis of the purpose and types of hormone therapy shows that there is a distinctively different trend in Japan compared to Europe or North America. These are the first findings in Japan based on a large-scale organized survey. To summarize: (i) many patients are receiving hormone therapy irrespective of age, TNM, stage of illness or histological background; (ii) more than 70% of them are under primary hormone therapy; and (iii) roughly 60% undergo combined androgen blockade (CAB). Since no clear outcome investigation has yet been carried out, we should evaluate this present status of hormone therapy in Japan either as: (i) it is merely a continuation of past experience, and in the near future, it should be managed carefully by adopting European and American guidelines; or (ii) it is still difficult to judge whether the effect of hormone therapy for Japanese patients is different in the profile of effects and side-effects from that for Westerners. What is more, in T2 treatment no accurate randomized study has been conducted so far globally on whether surgical treatment and radiotherapy are truly more effective than hormone therapy. Therefore, on this point we must reserve any conclusions.
The NCI–PDQ (13) and EAU guidelines (12) attach virtually no significance to hormone therapy on T2 prostate cancer. As for T3, the emphasis is on its significance as neoadjuvant before radiotherapy and little importance is assigned to the sole application of hormone therapy. Even when there is metastasis, there is debate on whether immediate hormone therapy is appropriate and also on whether there is any point in CAB; however, no clear conclusions have been reached (16,17).
In such circumstances, there are two clinical trial results in Japan reported recently that are extremely interesting. The first (2) is the results of a randomized study on hormone therapy given to localized or locally advanced prostate cancer. This was a comparative trial of LH-RHa + chlormadinone acetate (CMA) versus LH-RHa alone on patients in whom radical prostectomy was not chosen as treatment for whatever reason. The results are interim, with an observation period less than 5 years. So far, progression-free survival is good for CAB. Even when both groups are put together, it has been determined that the same survival rate as the one expected for the population of that age group has been obtained. The other study (3) is a comparative trial of LH-RHa + bicalutamide versus LH-RHa + placebo administered for patients with locally advanced or metastatic prostate cancer. The observational period is again short, but in both PSA progression-free survival and time to PSA response, the CAB group was significantly better. Meanwhile, in a successive survey of QOL using FACT-P that was officially translated into Japanese (18), the CAB group showed a significantly better result (19). This is indicative of the perception that the effects of hormone therapy on QOL are different between Japanese and Western patients (20). Therefore, it is important to examine whether or not recent clinical trial results take into account ethnic differences in the broad sense, including the lifestyle and philosophical backgrounds of Japanese and Western people.
In future, in the treatment of prostate cancer in Japan, it is evident that the importance of hormone therapy should be investigated with specific focus on Japanese people. We await the further analysis of the outcome findings, which is the aim of the J-Cap Study.
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APPENDIX |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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J-CaP Home Page: Rules for Use
1. The J-CaP Home Page is to be created as an Internet server.
2. Use of the case database on the J-CaP Home Page is restricted to doctors who are joint researchers and the use of the database requires a user ID and password issued by means of prior registration.
3. Communication between the case database server and users is to be protected by encryption (SSL).
4. The names of institutions and patients (initials) displayed in the case database are to be encoded so that individual patients cannot be identified.
5. Information concerning joint researchers’ institutions and patient names (initials) will only be accessible to database administrators with a special ID and password and only at the designated location (administrative secretariat).
6. The ID and password of the above-mentioned administrators will be stored as strictly confidential and no record of them will be kept.
7. The disposal of case data and information concerning joint researcher institutions and patient names (initials) after the completion of the J-CaP Study Group’s research period will be determined at a later date by administrators.
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FOOTNOTES |
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+ For reprints and all correspondence: Hideyuki Akaza, Department of Urology, Faculty of Medicine, Institute of Clinical Medicine, University of Tsukuba, 1–1–1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. E-mail: akazah{at}md.tsukuba.ac.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONAPPENDIXREFERENCES |
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1 Cooperberg MR, Grossfeld GD, Lubeck DP, Carroll PR. National practice patterns and time trends in androgen ablation for localized prostate cancer. J Natl Cancer Inst 2003;95:930–1.
2 Akaza H, Homma Y, Okada K, Yokoyama M, Usami M, Hirao Y, et al. A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up. BJU Int 2003;91:33–6.[Medline]
3 Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, et al. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol 2004; in press.
4 See W, Iversen P, Wirth M, McLeod D, Garside L, Morris T. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer. Eur Urol 2003;44:512–7.[CrossRef][Web of Science][Medline]
5 Labrie F. Androgen blockade in prostate cancer in 2002: major benefits on survival in localized disease. Mol Cell Endocrinol 2002;198:77–87.[Medline]
6 Labrie F, Candas B, Gomez JL, Cusan L. Can combined androgen blockade provide long-term control or possible cure of localized prostate cancer? Urology 2002;60:115–9.[Web of Science][Medline]
7 UICC. TNM classification of the malignant tumors. 5th edition, edited by LH Sobin and Ch Wittekind 1997, Wiley-Liss, New York.
8 General rules for clinical and pathological studies on prostate cancer; 3rd edition. Kanehara Publication Inc, 2001. Japan Urological Association, Tokyo.
9 General rules for clinical and pathological studies on prostate cancer; 1st edition. Kanehara Publication Inc, 1985. Japan Urological Association, Tokyo.
10 Yoshimi I, Mizuno S. Mortality trends of prostate cancer in Japan: 1960–2000. Jpn J Clin Oncol 2003;33:367.[Medline]
11 Kumamoto Y, Tsukamoto T, Umehara T, Harada M, Shimazaki J, Fuse H, et al. Clinical studies on endocrine therapy of prostatic carcinoma (3): Histopathological features of prostatic carcinoma and its prognosis. Hinyokika Kiyo 1990;36:295–305.[Medline]
12 Aus G, Abbou CC, Pacik D, Schmid HP, van Poppel H, Wolff JM, Zattoni F; EAU Working Group on Oncological Urology. EAU guidelines on prostate cancer. Eur Urol 2001;40:97–101.[Web of Science][Medline]
13 NCI–PDQ, Prostate cancer treatment. http://www.nci.nih.gov/cancerinfo/pdq/treatment/prostate/healthprofessional/
14 Akaza H, Naito S, Cheng C, Kaisary A, Soebadi DM, Umbas R, et al. Asian trends in prostate cancer hormone therapy. Gan To Kagaku Ryoho 2002;29:1951–61.[Medline]
15 Cancer statistics in Japan 2003. Foundation for promotion of cancer research (FPCR). http://www.ncc.go.jp/jp/statistics/2003/
16 Klotz LH, Newman T. Does maximal androgen blockade (MAB) improve survival? A critical appraisal of the evidence. Can J Urol 1996;3:246–50.[Medline]
17 Patterson SG, Balducci L, Pow-Sang JM. Controversies surrounding androgen deprivation for prostate cancer. Cancer Control 2002;9:315–25.[Medline]
18 Hinotsu A, Niimi M, Akaza H, Miyanaga N, Takeshima H, Eremenco S, Cella D. Development of Japanese version of QOL questionnaire for bladder and prostate cancer patients using FACT-Bl and P: pilot study. Gan To Kagaku Ryoho 1999;26:657–66.[Medline]
19 Naito S, Tachibana M, Deguchi T, Namiki M, Hirao Y, Arai Y, et al. Addition of bicalutamide 80 mg to LHRH-agonist monotherapy in patients with advanced prostate cancer: impact on quality of life. J Clin Oncol 2004;23:4703.
20 Mendoza JB. The role of hormone therapy in the treatment of locally advanced prostate cancer—Regional perspectives Asia. Eur Urol 2004;45(Suppl 3):12–6.
Received February 26, 2004; accepted March 29, 2004
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