Japanese Journal of Clinical Oncology 33:527-532 (2003)
© 2003 Foundation for Promotion of Cancer Research
Trends in the Practice of Radiotherapy for Localized Prostate Cancer in Japan: a Preliminary Patterns of Care Study Report
1 Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 2 Department of Radiology, University of the Ryukyu School of Medicine, Naha, 3 Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita, Osaka, 4 Department of Radiation Therapy, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka and 5 Department of Radiation Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Background: This is the first study to examine the characteristics and changes of the patterns of radiotherapy for prostate cancer in Japan.
Methods: The Japanese Patterns of Care Study (PCS) conducted a random survey of 84 institutions nationwide. Detailed information was collected on prostate cancer patients without distant metastases, who received radiotherapy during 1996–1998 and 1999–2001.
Results: The patients were divided into three groups: The Fresh Group (n = 338) was treated with radical radiotherapy with photon beams; the Surgery Group (n = 115) was treated after prostatectomy; and the Hormone-Refractory Group (n = 117) was treated after progression from hormonal therapy. In the Fresh Group, there was a decline in the fraction of patients with T3-4 tumors, from 65.2% in 1996–1998 to 43.9% in 1999–2001. In 1999–2001, a higher median dose of 69 Gy was irradiated as compared to 65 Gy in 1996–1998. In particular, the fraction of the patients treated with doses 
70 Gy increased from 16.4% to 46.3%. In the Surgery Group, the percentage of clinical T3-4 tumors before prostatectomy decreased from 71.4% in 1996–1998 to 16.2% in 1999–2001. The median radiation dose of 60 Gy did not change, but the 1999–2001 results showed a decrease in the use of doses <60 Gy. In the Hormone-Refractory Group, the median dose increased from 60 Gy in 1996–1998 to 67 Gy in 1999–2001.
Conclusion: These data suggest that radiation doses for prostate cancer in Japan have increased dramatically within a short period of time.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Incidence rates, pathological features, clinical manifestation, and the management of prostate cancer vary around the world. In Japan, the mortality rates for prostate cancer are low, but have been increasing rapidly with a rapidly aging population (1). Hormonal therapy was commonly utilized in Japan, partly because a considerable number of prostate cancer patients had advanced diseases or poorly differentiated tumors (2). However, since the introduction of a prostate-specific antigen (PSA) for the screening of prostate cancer (3), it has become possible to detect early stage prostate cancer in Japanese patients. In addition, radical radiation therapy has been better accepted as an option for the curative treatment of prostate cancer (4). Therefore, the characteristics and the patterns of treatment of prostate cancer are rapidly changing in Japan.
In 1998, the Japanese Patterns of Care Study (PCS) started investigating the national practice process for the treatment of cancer patients (5). The records of prostate cancer patients treated with radiotherapy during 1996–1998 and 1999–2001 were surveyed. The purpose of this preliminary study is to examine the characteristics of and the changes in the patterns of radiotherapy for prostate cancer in Japan, by comparing the results of the 1996–1998 and 1999–2001 PCS surveys.
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PATIENTS AND METHODS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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From 1998 to 2002, extramural audits were performed at 84 institutions randomly selected from stratified master lists of radiation therapy facilities across Japan. Radiation therapy facilities were divided into four strata (A1, A2, B1, B2) according to their characteristics (i.e. academic or nonacademic and the number of patients treated with radiation per year) (5–7). The following eligibility criteria were used in the process survey: (a) The patients had adenocarcinoma of the prostate without distant metastases; (b) the patients were treated with radiotherapy during 1996–1998 and 1999–2001; (c) the patients had neither been diagnosed with any other malignancy nor been treated with radiotherapy previously, although patients may have had a radical prostatectomy or hormonal therapy prior to radiotherapy. In the 1996–1998 survey, 160 patients were examined in 17 A1 institutions (university hospital/cancer center treating
300 patients/year), 76 patients in 14 A2 institutions (university hospital/cancer center treating <300 patients/year), 59 patients in 13 B1 institutions (other institutions treating 120 patients/year) and 16 patients in six B2 institutions (other institutions treating <120 patients/year). In the 1999–2001 survey, 156 patients were examined in 19 A1 institutions (university hospital/cancer center treating 430 patients/year) and 128 patients in 15 B1 institutions (other institutions treating 130 patients/year), and a further survey in A2 (university hospital/cancer center treating <430 patients/year) and B2 institutions (other institutions treating <130 patients/year) is in progress. In this report, a total of 595 patients were divided into three groups: The Fresh Group (n = 338) was treated with radical radiotherapy with photon beams; the Surgery Group (n = 115) was treated after prostatectomy; and the Hormone-Refractory Group (n = 117) was treated after progression from hormonal therapy (Table 1). The remaining patients, who were treated with high-dose-rate brachytherapy or proton beams, were excluded from this report. For statistical analysis, the differences between the proportions were tested by the chi-squared test. A P value <0.05 was considered to indicate a statistically significant difference.
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RESULTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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Changing Trends in the Practice of Radical Radiotherapy for Clinically Localized Prostate Cancer
The characteristics of the patients and disease treated with radical radiotherapy are shown in Table 2. There was a decline in the fraction of patients with T3-4 tumors, from 65.2% in 1996–1999 to 43.9% in 1999–2001. The percentages of well-differentiated tumors and N0 diseases increased in 1999–2001, while the pretreatment PSA levels were similar between the two surveys.
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The reasons for the choice of radiotherapy given to these patients are shown in Table 3. In the 1996–1998 survey, most patients were treated with radiotherapy because of the advanced stage of their tumors or due to old age. However, the percentage of the patients who received radiotherapy because of their preference increased dramatically in the 1999–2001 survey (P < 0.0001).
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A combination of radiation therapy and hormonal therapy was performed in 86.9% and 88.0% of the patients in the 1996–1998 and 1999–2001 surveys, respectively. Hormonal therapy was performed before, during and after radiation therapy in 79.2%, 75.3% and 75.4% of the patients in the 1996–1998 survey, respectively, and in 81.2%, 82.8% and 82.1% of the patients in the 1999–2001 survey, respectively. There were no significant differences in the use of hormonal therapy between the two surveys.
The distribution of radiation doses is shown in Fig. 1. The median dose to the prostate was 65 Gy and 69 Gy in the 1996–1998 and 1999–2001 surveys, respectively. The 1999–2001 PCS results showed a shift to higher doses and a decrease in the use of inadequate doses <60 Gy (P < 0.0001). In particular, the percentage of patients who received 70 Gy increased from 16.4% in the 1996–1998 survey to 46.3% in the 1999–2001 survey.
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In the 1996–1998 survey, a higher median dose was irradiated in A (65 Gy) than B (59.5 Gy) institutions, and conformal radiotherapy was utilized for more patients in A (65.6%) than B (0%) institutions. In the 1999–2001 survey, there was no difference in the median dose of 69 Gy between the two types of institutions, but the rate of utilization of conformal radiotherapy was still lower in B (15.6%) than in A (62.9%) institutions.
Changing Trends in the Practice of Radiotherapy after Prostatectomy
Patients and disease characteristics are shown in Table 4. There was a clear decline in the fraction of patients with clinical T3-4 tumors before prostatectomy, from 71.4% in 1996–1999 to 16.2% in 1999–2001. The percentage of positive surgical margins also decreased from 78.7% to 48.8% (P = 0.0053) (Table 5). Hormonal therapy was combined with radiotherapy in 90.6% and 67.3% of the patients in the 1996–1998 and 1999–2001 surveys, respectively (P = 0.003). Hormonal therapy was performed before, during and after radiation therapy in 86.9%, 62.7% and 64.9% of the patients in the 1996–1998 survey, respectively, and in 72.5%, 51.4% and 51.4% of the patients in the 1999–2001 survey, respectively. However, differences were not significant.
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Radiotherapy was started within 6 months, during 6–12 months and more than 12 months after prostatectomy in 63.0%, 6.2% and 30.8% of the patients in 1996–1998, respectively, and in 41.3%, 23.9% and 34.8% of the patients in 1999–2001, respectively (P = 0.012). Figure 2 shows the radiation doses to the surgical bed. The median radiation dose of 60 Gy did not change, but the 1999–2001 results showed a decrease in the use of doses <60 Gy.
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Radiotherapy for Localized Hormone-refractory Prostate Cancer
Patient and disease characteristics of hormone-refractory prostate cancer at the time of radiotherapy are shown in Table 6. Most patients had T3-4 diseases, and 20–30% had regional lymph node metastases.
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The distribution of radiation doses is shown in Fig. 3. The median dose to the prostate was 60 Gy and 67 Gy in the 1996–1998 and 1999–2001 surveys, respectively. The 1999–2001 PCS results showed a shift to higher doses. The median duration of hormonal therapy before radiotherapy was 17 months and 34 months in the 1996–1998 and 1999–2001 surveys, respectively.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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The present study revealed the characteristics of and changes in the patterns of radiotherapy for prostate cancer in Japan.
Majority of the patients who received radical radiotherapy in Japan had a high-risk disease (7). However, there were increases in the fraction of patients with well-differentiated carcinomas, T1-2 tumors, and N0 diseases in the 1999–2001 survey, compared with the results in 1996–1998. Although there was no significant difference in PSA levels between the two survey periods, a downward shift in stage is expected to occur in Japan as has been observed in Western countries.
Radical radiation doses to the prostate showed a shift to higher doses in the 1999–2001 survey, but the doses used in Japan were slightly lower than those typically used in the United States. In the 1999 PCS for prostate cancer in the United States, the median dose to the prostate was 70.5 Gy (8). It is well known that radiation dose is a strong independent predictor of failure, and external beam radiation alone in modest doses of 60–65 Gy is insufficient to eradicate prostate tumors (9). However, if radiotherapy is combined with androgen ablation, which may have synergistic effects with radiotherapy (10), higher doses may not have a major impact on local control. In particular, if the majority of the high-risk patients have an element of a systemic disease, the combination of radiotherapy with systemic treatment such as long-term hormonal therapy is more effective than local treatment alone. Under conditions in which most patients have high-risk disease and radiotherapy is commonly combined with long-term hormonal therapy in Japan (7), adequate doses to the prostate should be carefully evaluated.
The percentage of patients who chose radiation therapy as their preferred treatment increased dramatically in the 1999–2001 survey compared to the 1996–1998 survey (55.8% versus 7.8%). This may be because patients have become more informed about radiotherapy as an available curative treatment option, and the general public has become more aware of the advantages of radiotherapy.
In the Fresh Group, no difference was observed in the median dose of 69 Gy between A and B institutions in the 1999–2001 survey. However, conformal radiotherapy was utilized for only 15.6% of the patients in B institutions, as compared to 62.9% in A institutions. It has been reported that increasing the radiation dose with conventional techniques is associated with an increased likelihood of long-term complications (11). The impact of this difference on the outcome should be determined by follow-up studies in the future.
The role of radiotherapy as an adjuvant or salvage therapy after prostatectomy remains controversial. Adjuvant radiotherapy can be combined with prostatectomy to improve the results in patients with tumors that extend beyond the prostate capsule. The potential advantage of immediate adjuvant radiotherapy is to treat residual tumors when the smallest possible volume, which is the most curable, is present. Petrovich et al. demonstrated that a median dose of 48 Gy in adjuvant radiotherapy reduced the risk of local recurrence in patients with pathological T3 prostate cancer (12). In contrast, doses >65 Gy are recommended for salvage radiotherapy in those patients with rising PSA levels after prostatectomy (13). Although we did not identify whether radiotherapy was performed as an adjuvant or salvage therapy in this report due to the lack of data, the efficacy of the median dose of 60 Gy in this study should be evaluated in the future.
The fraction of patients with clinical T3-4 tumors before prostatectomy decreased from 71.4% in the 1996–1999 survey to 16.2% in the 1999–2001 survey. It is becoming increasingly clear that the down-staging of patients with T3-4 tumors before prostatectomy does not offer any long-term benefit (14). Although the number of patients is small, the trends observed in our survey may be a reflection of the accumulating evidence regarding the indication of prostatectomy.
In Japan, a considerable number of patients have been treated with androgen ablation alone (15); however, androgen ablation is only palliative. Radiotherapy may be used to treat local progression with a curative intent or to release urinary obstructive symptoms as a palliative treatment. Although radiotherapy for hormone-refractory prostate cancer has an excellent local control rate, the prognosis of the patients is poor (16,17). The PCS in Japan, which surveyed a total of 595 patients with regionally localized prostate cancer, revealed that 115 patients (19.7%) received radiotherapy because the disease was hormone-refractory. Since only a small series of data exists on the efficacy of radiotherapy in the management of hormone-refractory prostate cancer (17), this PCS series may be the largest series in the world. Future analysis of the clinical outcomes in these surveys will provide a great deal of useful information.
In conclusion, the data in this study suggests that radiation doses for prostate cancer are increasing in Japan, although the percentage of hormonal management usage did not change significantly. Radiotherapy has been recognized as a curative treatment for prostate cancer in Japan. However, there are many unanswered questions concerning treatment strategies. In addition, patient characteristics in Japan are different from those in the Western countries (18). We should develop appropriate treatment strategies for prostate cancer, based on the social and racial background of patients in Japan.
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
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This study was supported by the Grant-in-Aid for Cancer Research (Nos 10–17 and 14–6) from the Ministry of Health, Labor and Welfare and a Grant from the Japan Society for the Promotion of Sciences. We thank all the radiation oncologists who participated in this study for their efforts in providing us with information that made these surveys possible.
This study was presented in part at the Japan/USA PCS Workshop, Tokyo, Japan, February 2003.
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FOOTNOTES |
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+ For reprints and all correspondence: Katsumasa Nakamura, Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Maidashi 3–1–1, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: nakam{at}radiol.med.kyushu-u.ac.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONACKNOWLEDGMENTSREFERENCES |
|---|
1 Hirao Y, Cho M. Statistical analysis of prostate cancer in Japan. Nippon Rinsho 2002;60:53–8 (in Japanese).
2 Kubota Y, Imai K, Yamanaka H. The correlation of stage and pathology of prostate cancer in Japan. Int J Urol 2000;7:139–44.[Medline]
3 Watanabe H. Mass screening program for prostatic cancer in Japan. Int J Clin Oncol 2001;6:66–73.[Medline]
4 Ikeda H, Kagami Y, Tokuue K, Sumi M. Results of a survey of current trends in radiotherapy for patients with the prostate cancer at 34 institutions in Japan. Hinyouki Geka 1999;12:1015–20 (in Japanese).
5 Inoue T. Quality assurance of radiotherapy and its clinical assessment. Jpn J Clin Oncol 2002;32:497–505.
6 Teshima T, Tanisada K, Ohno Y, Inoue T, Hiraoka M, Yamashita T, et al. Clinical quality assurance at institutions according to a patterns of care study. Japanese PCS Working Group. Gan To Kagaku Ryoho 2000;27:1201–7 (in Japanese).[Medline]
7 Nakamura K, Teshima T, Takahashi Y, Imai A, Koizumi M, Mitsuhashi N, et al. Radical radiation therapy for prostate cancer in Japan: a Patterns of Care Study Report. Jpn J Clin Oncol 2003;33:122–6.
8 Zelefsky MJ, Moughan J, Owen J, Zeitman A, Hanks GE. Changing trends in the national practice for external beam radiotherapy for clinically localized prostate cancer: the 1999 patterns of care survey for prostate cancer. Int J Radiat Oncol Biol Phys 2002;54:8–9 (abstract).
9 Pollack A, Zagars GK. External beam radiotherapy dose response of prostate cancer. Int J Radiat Oncol Biol Phys 1997;39:1011–8.[CrossRef][Medline]
10 Laverdiere J, Gomez JL, Cusan L, Suburu ER, Diamond P, Lemay M, et al. Beneficial effect of combination hormonal therapy administered prior and following external beam radiation therapy in localized prostate cancer. Int J Radiat Oncol Biol Phys 1997;37:247–52.[CrossRef][Medline]
11 Zelefsky MJ, Leibel SA, Kutcher GJ, Fuks Z. Three-dimensional conformal radiotherapy and dose escalation: where do we stand? Semin Radiat Oncol 1998;8:107–14.[CrossRef][Web of Science][Medline]
12 Petrovich Z, Lieskovsky G, Stein JP, Huberman M, Skinner DG. Comparison of surgery alone with surgery and adjuvant radiotherapy for pT3N0 prostate cancer. BJU Int 2002;89:604–11.[Medline]
13 Schild SE. Radiation therapy after prostatectomy: now or later? Semin Radiat Oncol 1998;8:132–9.[CrossRef][Web of Science][Medline]
14 Pollack A, Zagars GK. Androgen ablation in addition to radiation therapy for prostate cancer: is there true benefit? Semin Radiat Oncol 1998;8:95–106.[CrossRef][Web of Science][Medline]
15 Tanaka M, Murakami S, Suzuki N, Oikawa T, Kinsui H, Hamano S, et al. Trends of prostate cancer: comparison between 1986–90 and 1991–95 at Asahi General Hospital. Hinyokika Kiyo 1998;44:775–80 (in Japanese).[Medline]
16 Kraus PA, Lytton B, Weiss RM, Prosnitz LR. Radiation therapy for local palliative treatment of prostatic cancer. J Urol 1972;108:612–4.[Medline]
17 Lankford SP, Pollack A, Zagars GK. Radiotherapy for regionally localized hormone refractory prostate cancer. Int J Radiat Oncol Biol Phys 1995;33:907–12.[Medline]
18 Egawa S, Suyama K, Arai Y, Matsumoto K, Tsukayama C, Kuwao S, et al. A study of pretreatment nomograms to predict pathological stage and biochemical recurrence after radical prostatectomy for clinically resectable prostate cancer in Japanese men. Jpn J Clin Oncol 2001;31:74–81.
Received May 17, 2003; accepted September 9, 2003
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