Japanese Journal of Clinical Oncology Advance Access originally published online on January 17, 2006
Japanese Journal of Clinical Oncology 2006 36(1):40-45; doi:10.1093/jjco/hyi216
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2006 Foundation for Promotion of Cancer Research
Radical External Beam Radiotherapy for Prostate Cancer in Japan: Results of the 1999–2001 Patterns of Care Process Survey
1 Department of Radiology, University of the Ryukyus, Okinawa, 2 Department of Clinical Radiology, Kyushu University, Fukuoka, 3 Department of Radiology, Yamanashi University, Nakatama-gun, Yamanashi, 4 Department of Radiology, Kyoto Prefectural University, Kyoto, 5 Department of Medical Physics and Engineering, Osaka University, Osaka, Japan and 6 Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
For reprints and all correspondence: Kazuhiko Ogawa, Department of Radiation Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox 7, Boston, MA 02114, USA. E-mail: kogawa{at}med.u-ryukyu.ac.jp
Received September 27, 2005; accepted November 16, 2005
 |
Abstract |
|---|
 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
Background: The Patterns of Care Study evaluated standards of practice for patients with clinically localized prostate cancer treated with radiotherapy in Japan. This study examined the influence of institutional stratification on care for patients receiving radical external beam radiotherapy.
Methods: A national survey of 66 institutions was conducted using two-stage cluster sampling, and detailed information was accumulated on 283 patients who received radiotherapy between 1999 and 2001.
Results: In A (academic) and B (non-academic) institutions, more than 80% of patients had intermediate or unfavorable risk disease. Although there were no significant differences in disease characteristics between A and B institutions, institutional stratification significantly affected radiotherapy practice patterns, such as the use of a CT-based treatment planning (A1: 91.5%, B: 77.1%; P = 0.0007) and the use of conformal therapy (A: 56.4%, B: 24.1%; P < 0.0001). CT-based treatment planning and conformal therapy significantly influenced total radiation dose (P < 0.0001 for each). Hormonal therapy was commonly used in both A and B institutions (A: 89.0%, B: 90.7%). Many patients with a favorable prognosis (A: 62.5%, B: 91.7%) received hormonal therapy, and most patients with unfavorable risk disease (A: 93.6%, B: 91.6%) also received hormonal therapy.
Conclusion: During the period 1999–2001, the majority of prostate cancer patients treated in Japan with radical external beam radiotherapy had advanced diseases. Institutional stratification significantly affected radiotherapy practice patterns, with the notable exception that radiotherapy was commonly combined with hormonal therapy regardless of the institutional stratification and individual risk.
Key Words: patterns of care study • prostatic carcinoma • type of institution • radiation therapy • hormone therapy
|
INTRODUCTION |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
The Patterns of Care Study (PCS) national survey is a retrospective study designed to establish national practice processes for selected malignancies over a specific time period (1–3). In addition to documenting practice process, the PCS is important for the development and spread of national guidelines for cancer treatment. PCS results should help to promote a high-quality care process in Japan and complement the role of clinical trials (1,4).
To improve the quality of radiation oncology, PCS was imported to Japan from the United States (5,6). The Japanese PCS Working Group of Prostate Cancer started a nationwide process survey for patients who underwent radiotherapy between 1996 and 1998 (7,8). Subsequently, a second PCS of Japanese patients treated between 1999 and 2001 was conducted. We have previously reported the preliminary results of the second PCS for radical external beam radiotherapy for prostate cancer patients (9–11).
In Japan, the number of deaths due to prostate cancer has been on a steep increase especially in elderly patients. The proportion of prostate cancer deaths among total cancer deaths also showed an increase from 0.9% in 1960 to 4.2% in 2000 (12). Since entering the prostate-specific antigen (PSA) era, clinicians are detecting earlier stage disease, and the rates of successful treatment for early-stage patients are increasing in Japan (13). Moreover, radiotherapy has become much more common because a significant amount of new treatment planning technology and methodology has become available. Therefore, optimal management of radiotherapy for prostate cancer patients has become a major concern in Japan. However, we have not been able to properly evaluate national practice processes owing to limited information. In July 2002, PCS audits for prostate cancer patients treated between 1999 and 2001 began, and data were collected for 283 patients who received radical external beam radiotherapy. In the current study, we have analyzed results of radical external beam radiotherapy for clinically localized prostate cancer and focused on how institutional stratification influences the patient characteristics, disease characteristics and patterns of radiotherapy in Japan.
|
PATIENTS AND METHODS |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
The 1999–2001 Japanese PCS consisted of an extramural audit survey of 66 institutions using stratified two-stage cluster sampling. Data were collected for 528 patients with prostate cancer who received radiotherapy. The PCS group developed an original data format in collaboration with the American College of Radiology (ACR, Philadelphia, PA). The following patient eligibility criteria were used: prostatic adenocarcinoma without evidence of distant metastasis; radiotherapy between 1999 and 2001 with no prior radiotherapy; and no concurrent or prior diagnosis of another malignancy. Patients who had prior prostatectomy and patients with hormone-refractory cancer were also excluded for this analysis. The PCS surveyors were 20 radiation oncologists from academic institutions. For each institution surveyed, one radiation oncologist visited and surveyed data by reviewing patients' charts. In order to validate data quality, the PCS utilized an Internet mailing list including all the surveyors. On-site real time checks and adjustments of the data input were available to each surveyor and to the PCS committee.
Using the 1999 facilities master list (14), the 1999–2001 PCS stratified institutions as follows: A1, academic institutions (university hospital or cancer center) with 
430 patients yearly; A2, academic institutions with <430 patients; B1, non-academic institutions (other hospitals) with 130 patients yearly; and B2, non-academic institutions with <130 patients. Among the 528 patients identified, 283 patients who received radical external beam radiotherapy were selected for analysis, and results for these patients are reported.
Regarding risk, the 1999 US PCS identified the following as adverse features: PSA > 10 ng/ml; Gleason combined score > 6; and T stage 3. On the basis of this, the US PCS categorized patients into the following risk groups: favorable—zero adverse features; intermediate—one adverse feature; unfavorable—two or more adverse features (15). Because data for the Gleason combined score were missing for 47% (132/283) of our study patients, we substituted tumor differentiation for the Gleason combined score as one of the adverse features. Thus, the set of adverse features for Japanese patients consisted of the following: PSA > 10 ng/ml; poorly-differentiated disease; and T stage 3. Japanese patients were then categorized into the following risk groups: favorable—zero adverse features; intermediate—one adverse feature; unfavorable—two or more adverse features.
Statistical analyses were performed using the Statistical Analysis System at the PCS data center at Osaka University (16). Statistical significance was tested using the 
2-test and the Student's t-test. A P-value < 0.05 was considered statistically significant.
|
RESULTS |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
PATIENT AND DISEASE CHARACTERISTICS
Patient and disease characteristics are shown in Table 1, stratified by institution type (academic versus non-academic). No significant differences in disease characteristics were observed, including pretreatment PSA level, tumor differentiation, Gleason combined score and T stage. In both A (academic) and B (non-academic) institutions, more than 80% of patients had intermediate or unfavorable risk diseases. Major reasons for selecting radiotherapy included patient preference, advanced or high-risk disease, medical contraindication and old age.
|
TREATMENT CHARACTERISTICS
Institutional and therapy characteristics are shown in Table 2. Not unexpectedly, institutional type was closely related to radiation oncology infrastructure (e.g. equipment and personnel), which in turn significantly affected radiotherapy practice patterns, such as beam energy
10 MV (A: 86.4%, B: 59.6%; P < 0.0001), usage of portal films or electric portal images (A: 90.1%, B: 55.1%; P < 0.0001), all fields treatment for each day (A: 86.7%, B: 61.0%; P < 0.0001), usage of a CT-based treatment planning (A: 91.5%, B: 77.1%; P = 0.0007) and use of conformal therapy (A: 56.4%, B: 24.1%; P < 0.0001). Use of CT-based treatment planning and conformal radiotherapy significantly influenced total radiation dose (Figs 1 and 2; P < 0.0001 for each). The only patients who received total radiation doses 70 Gy were patients who had CT-based treatment planning. Significantly, more patients who had conformal therapy (compared with those who did not have conformal radiotherapy) received total radiation doses 70 Gy. Portal films or electronic portal images were used for 90.1% in A institutions and 55.1% in B institutions (P < 0.0001). All fields were treated each day for 86.7% in A institutions and 55.1% in B institutions (P < 0.0001). Pelvic irradiation (clinical target volume is prostate gland, seminal vesicle and pelvic lymph nodes) was used in 26.2% of patients in A institutions and 42.4% of patients in B institutions (P = 0.0087). The median number of full-time equivalent (FTE) radiation oncologists was 2.4 in A institutions but only 0.4 in B1 institutions (P < 0.0001).
|
|
|
Hormonal therapy was commonly used before, during and after radiotherapy for a mean duration of 1.4 ± 1.0 years (A: 89.0%, B: 90.7%). Luteinizing hormone-releasing hormone (LH-RH) agonists and antiandrogens were frequently used as hormonal agents. In contrast, the use of chemotherapy was uncommon (A: 7.9%, B: 3.6%).
The percentages of patients with favorable, intermediate and unfavorable tumors were 15.2%, 37.0% and 47.9%, respectively. The percentages of patients with favorable, intermediate and unfavorable tumors treated with hormonal therapy were 72.2%, 93.1% and 92.0%, respectively. The use of hormonal therapy did not significantly differ between A and B institutions (Fig. 3, P = 0.12). Many patients with a favorable prognosis (A: 62.5%, B: 91.7%, P = 0.0655) received hormonal therapy, and most patients with unfavorable risk (A: 93.6%, B: 91.6%) also received hormonal therapy.
|
10 (2) not poorly differentiation (3) T stage < 3. |
DISCUSSION |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
The 1999–2001 PCS revealed that more than 80% of Japanese patients treated with radical external beam radiotherapy had intermediate or unfavorable risk diseases, and that institutional type did not significantly affect disease characteristics, such as pretreatment PSA levels, Gleason combined score and T stage. In the current study, the higher rate of missing data in Gleason combined score was observed. During the period between 1999 and 2001, many Japanese physicians may consider the Gleason combined score less important for prostate cancer treatment.
The current study also demonstrated significant variations in radiotherapy practice patterns according to the type of institution, specifically in the beam energies utilized and in the use of a CT-based treatment planning and conformal therapy. These practice differences indicate that the quality of radiotherapy was significantly higher in academic institutions than in non-academic institutions. The lower rate of pelvic irradiation in academic institutions than in non-academic institutions may also reflect the more frequent use of CT-based treatment planning and conformal therapy in academic institutions. Similarly, two other Japanese PCS studies of esophageal cancer and cervical cancer have also identified significant differences in treatment patterns between academic and non-academic institutions (5,6).
Practice processes in non-academic institutions in Japan were closely related to structural immaturity, especially in terms of equipment and personnel. Concerning treatment equipment and radiotherapy technique, lower rates of beam energy 10 MV, usage of portal films or electric portal images, and all fields treatment for each day were observed in non-academic institutions. Moreover, in non-academic institutions, only 77.1% of patients received CT-based treatment planning and 24.1% of patients received conformal therapy, compared with 91.5% and 56.4%, respectively, in academic institutions. The use of CT-based treatment planning and conformal radiotherapy significantly influenced total radiation dose. In the United States, the overall quality of radiotherapy for prostate cancer has been improving for years and has been higher than that in Japan: 95% of US patients received CT-based treatment planning and 80% received conformal therapy in the 1999 US PCS (15,17–20). On the other hand, radiotherapy for prostate cancer was still developing in Japan during the period when this national survey was conducted. Therefore, in order to provide high-quality radiotherapy in Japan, facilities need appropriate treatment planning capabilities. Modern radiotherapy requires CT-based treatment planning or conformal therapy to improve target dose distribution while reducing normal tissue dose (21).
The 1999–2001 PCS survey also revealed that the median number of FTE radiation oncologists employed by non-academic institutions to manage their many patients was lower than the median number employed by academic institutions (A: 2.4, B: 0.4, P < 0.0001). At the same time, the number of patients treated with radiotherapy has continually increased in every institutional type, with an overall increase of 140% over the past 10 years (22). These trends call for increasing the number of FTE radiation oncologists on duty especially in non-academic institutions.
The current study demonstrated the almost routine administration of hormonal therapy (A institutions: 89.0%, B institutions: 90.7%) to Japanese patients treated between 1999 and 2001. Moreover, the percentage of favorable risk patients receiving hormonal therapy remains high in Japan despite the results of several US studies indicating that radical radiotherapy alone can control disease in favorable risk patients. Pollack et al. (23) indicated that a total dose of 70 Gy was sufficient to control disease with a pretreatment PSA level <10 ng/mL. Hanks et al. (24) found that patients with pretreatment PSA < 10 ng/ml did not benefit from dose escalation >70 Gy. Therefore, the primary non-surgical treatment practice for US patients with favorable risk disease is radical external beam radiotherapy without hormonal therapy unlike the practice we identified in Japan. One major reason for the frequent use of hormonal therapy in Japan may be the high rate of health insurance coverage for Japanese people (25). However, in line with current treatment practice in the United States, we propose that radical external beam radiotherapy alone should also be the treatment of choice for favorable risk patients in Japan.
In contrast, a growing body of evidence suggests that radiotherapy with hormonal therapy is more effective than radiotherapy alone for high-risk patients. For instance, the results of various randomized trials by the Radiation Therapy Oncology Group (RTOG) and the European Organization for the Research and Treatment of Cancer (EORTC) demonstrated that combining radiotherapy with hormonal therapy was advantageous for high-risk patients with clinically localized prostate cancer (26,27). The 1999 US PCS reported that 79% of radiotherapy patients with unfavorable risk disease received hormonal therapy in the United States, reflecting the penetration and growing acceptance of clinical trial results demonstrating the efficacy of combination treatment approaches (15). In Japan, the 1999–2001 PCS also found that radiotherapy combined with hormonal therapy represents the standard care for patients with unfavorable risk disease, with over 90% of such patients receiving combination therapy. Based upon clinical study data and the US PCS data, radiotherapy combined with hormonal therapy for Japanese patients with unfavorable risk disease appears to be a reasonable practice.
In summary, our analysis of the 1999–2001 PCS data revealed that most prostate cancer patients treated in Japan with radical external beam radiotherapy have advanced diseases and that institutional type significantly influences radiotherapy practice patterns. Differences in practice patterns must not be disregarded when they can negatively influence outcome. The impact of these practice differences on outcome should be examined in a future study. The current study also demonstrated that radiotherapy was commonly combined with hormonal therapy regardless of institution type and disease risk group. Therefore, the optimal use of hormonal therapy also needs to be addressed in future studies.
|
Acknowledgments |
|---|
Supported by Grants-in-Aid for Cancer Research (Grant No. 14-6) from the Ministry of Health, Labor and Welfare of Japan. We thank all radiation oncologists who participated in this study. Their efforts to provide information to us make these surveys possible. We are grateful for the continuous thoughtful support we have received from the US PCS committee for 9 years.
|
References |
|---|
|
TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
|---|
1 Hanks GE, Coia LR, Curry J. Patterns of care studies: past, present and future. Semin Radiat Oncol 1997;7:97–100.[CrossRef][ISI][Medline]
2 Owen JB, Sedransk J, Pajak TF. National averages for process and outcome in radiation oncology: methodology of the patterns of care study. Semin Radiat Oncol 1997;7:101–7.[CrossRef][ISI][Medline]
3 Tanisada K, Teshima T, Ohno Y, Inoue T, Abe M, Ikeda H, et al. Patterns of care study quantitative evaluation of the quality of radiotherapy in Japan. Cancer 2002;95:164–71.[CrossRef][ISI][Medline]
4 Inoue T. Quality assurance of radiotherapy and its clinical assessment. Jpn J Clin Oncol 2002;32:497–505 .
5 Teshima T, Abe M, Ikeda H, Hanks GE, Owen JB, Yamada S, et al. Patterns of care study of radiation therapy for cervix cancer in Japan: the influence of the stratification of institution on the process. Jpn J Clin Oncol 1998;28:388–95.
6 Teshima T, Abe M, Ikeda H, Hanks GE, Owen JB, Hiraoka M, et al. Patterns of care study of radiation therapy for esophageal cancer in Japan: influence of the stratification on the process. Jpn J Clin Oncol 1998;28:308–13.
7 Nakamura K, Teshima T, Takahashi Y, Imai A, Koizumi M, Mitsuhashi N, et al. Radical radiotherapy for prostate cancer in Japan: a patterns of care study report. Jpn J Clin Oncol 2003;33:122–6.
8 Nakamura K, Teshima T, Takahashi Y, Imai A, Koizumi M, Mitsuhashi N, et al. Radiotherapy for localized hormone-refractory prostate cancer in Japan. Anticancer Res 2004;24:3141–5.[Medline]
9 Nakamura K, Ogawa K, Yamamoto Y, Sasaki T, Koizumi M, Teshima T, et al. Trends in the practice of radiotherapy for localized prostate cancer in Japan: a preliminary patterns of care study report. Jpn J Clin Oncol 2003;33:527–32.
10 Ogawa K, Nakamura K, Sasaki T, Yamamoto T, Koizumi M, Teshima T, et al. Radical external beam radiotherapy for prostate cancer in Japan: preliminary results of the 1999–2001 patterns of care process survey. Jpn J Clin Oncol 2004;34:29–36.
11 Ogawa K, Nakamura K, Sasaki T, Yamamoto T, Koizumi M, Inoue T, et al. Radical external beam radiotherapy for prostate cancer in Japan: preliminary results of the changing trends in the patterns of care process survey between 1996–1998 and 1999–2001. Jpn J Clin Oncol 2004;34:131–6.
12 Yoshimi I, Mizuno S. Cancer Statistics Mortality trends of prostate cancer in Japan: 1960–2000. Jpn J Clin Oncol 2003;33:367.[Medline]
13 Ogawa K, Nakamura K, Onishi H, Sasaki T, Koizumi M, Shioyama Y, et al. Radical external beam radiotherapy for clinically localized prostate cancer in Japan: changing trends in the patterns of care process survey between 1996–1998 and 1999–2001. Anticancer Res 2005;25:3507–11.[ISI][Medline]
14 JASTRO Database Committee. Present status of radiotherapy in Japan- the regular structure survey in 1999. J Jpn Soc Ther Radiol Oncol 2001;13:227–35 (in Japanese).
15 Zelefsky MJ, Moughan J, Owen J, Zietman AL, Roach M 3rd, Hanks GE. Changing trends in national practice for external beam radiotherapy for clinically localized prostate cancer: 1999 patterns of care survey for prostate cancer. Int J Radiat Oncol Biol Phys 2004;59:1053–61.[Medline]
16 SAS Institute Japan, SAS System version 8 Introducing Guide. Tokyo, Japan 2000 (in Japanese).
17 Teshima T, Owen JB, Hanks GE, Sato S, Tsunemoto H, Inoue T. A comparison of the structure of radiation oncology in the United States and Japan. Int J Radiat Oncol Biol Phys 1996;34:235–42.[CrossRef][ISI][Medline]
18 Owen JB, Coia LR, Hanks GE. The structure of radiation oncology in the United States in 1994. Int J Radiat Oncol Biol Phys 1997;39:179–85.[ISI][Medline]
19 Gerber RL, Smith AR, Owen J, Hanlon A, Wallace M, Hanks G. Patterns of care survey results: treatment planning for carcinoma of the prostate. Int J Radiat Oncol Biol Phys 1995;33:803–8.[CrossRef][Medline]
20 Hanks GE, Teshima T, Pajak TF. 20 years of progress in radiation oncology: prostate cancer. Semin Radiat Oncol 1997;7:114–20.[CrossRef][Medline]
21 Sumi M, Ikeda H, Tokuuye K, Kagami Y, Murayama S, Tobisu K, et al. The external radiotherapy with three-dimensional conformal boost after the neoadjuvant androgen suppression for patients with advanced prostatic carcinoma. Int J Radiat Oncol Biol Phys 2000;48:519–28.[CrossRef][ISI][Medline]
22 Iami A, Teshima T, Ohno Y, Inoue T, Yamashita T, Mitsuhashi N, et al. The future demand for and structural problems of Japanese radiotherapy. Jpn J Clin Oncol 2001;31:135–41.
23 Pollack A, Zaggers GK, Smith LG, Lee J, von Eschenbach AC, Antolak JA, et al. Preliminary results of a randomized radiotherapy dose-escalation study comparing 70 Gy with 78 Gy for prostate cancer. J Clin Oncol 2000;23:3904–11.
24 Hanks GE, Schultheiss TE, Hanlon AL, Hunt M, Lee WR, Esptein BE, et al. Optimization of conformal radiation treatment of prostate cancer: report of a dose escalation study. Int J Radiat Oncol Biol Phys 1997;37:543–50.[CrossRef][ISI][Medline]
25 Takara K. The origins and development of public health in Japan. In: Detels R, McEwen J, Omenn GS, editors. Oxford Textbook of Public Health, 3rd edn. Vol. 1. The Scope of Public Health. New York: Oxford University Press 1997,55–77.
26 Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. New Engl J Med 1997;337:295–300.
27 Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, et al. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol 1997;15:1013–21.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Nakamura, Y. Shioyama, S. Tokumaru, N. Hayashi, N. Oya, Y. Hiraki, K. Kusuhara, T. Toita, H. Suefuji, N. Hayabuchi, et al. Variation of Clinical Target Volume Definition among Japanese Radiation Oncologists in External Beam Radiotherapy for Prostate Cancer Jpn. J. Clin. Oncol., April 1, 2008; 38(4): 275 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakamura, T. Mizowaki, H. Imada, K. Karasawa, T. Uno, H. Onishi, K. Nihei, S. Sasaki, M. Ogura, and T. Akimoto External-Beam Radiotherapy for Localized or Locally Advanced Prostate Cancer in Japan: A Multi-Institutional Outcome Analysis Jpn. J. Clin. Oncol., March 1, 2008; 38(3): 200 - 204. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||