Japanese Journal of Clinical Oncology Advance Access originally published online on August 12, 2006
Japanese Journal of Clinical Oncology 2006 36(10):649-654; doi:10.1093/jjco/hyl079
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© 2006 Foundation for Promotion of Cancer Research
Postoperative Radiotherapy for Patients with Prostate Cancer in Japan; Changing Trends in National Practice between 1996–98 and 1999–2001: Patterns of Care Study for Prostate Cancer
1 Department of Radiology, National Kyushu Cancer Center, Fukuoka, 2 Department of Clinical Radiology, Kyushu University, Fukuoka, 3 Department of Radiology, University of the Ryukyus, Okinawa, Nakagami-gun, 4 Department of Radiology, Yamanashi University, Chuo, Yamanashi, 5 Department of Medical Physics and Engineering, Nakagami-gun, Osaka University, Osaka and 6 Department of Radiological Technology, School of Health Sciences, Fujita Health University, Toyoakei, Aichi, Japan
For reprints and all correspondence: Tomonari Sasaki, Department of Radiology, National Kyushu Cancer Center, Notame 3-1-1, Minami-ku, Fukuoka 811-1395, Japan. E-mail: tsasaki{at}nk-cc.go.jp
Received April 14, 2006; accepted June 21, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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Objective: To evaluate the changing trends of standards and practices for postoperative radiotherapy (RT) for patients with prostate cancer in Japan.
Methods: The Japanese Patterns of Care Study (PCS) conducted a national survey in 84 institutions from 1996 to1998 (PCS96-98) and 76 institutions from 1999 to 2001 (PCS99-01). Detailed information relevant to RT was collected on a total of 169 patients (64 from 1996 to1998 and 105 from 1999 to 2001) with prostate cancer who had undergone radical prostatectomy.
Results: The fraction of clinical T3–4 tumours before prostatectomy decreased from 63% in the period 1996–98 to 26% in the period 1999–2001 (P = 0.0004). The pre-RT prostate-specific antigen level was significantly lower in 1999–2001 than in 1996–98 (P = 0.0002). We did not find a significant difference in the percentage of patients who received pelvic irradiation in the time periods between PCS96-98 and PCS99-01 (P = 0.18). Although the median radiation doses of 60 Gy were not changed between the surveys, various doses (from 20 to 74.6 Gy) were delivered to the prostatic bed. In the 1999–2001 survey, 73 of 105 patients received a median dose of 56 Gy in an adjuvant setting, while the other 32 received a median dose of 60 Gy in a salvage setting (P = 0.0015).
Conclusion: These data suggest that consensus has not been reached on the practice and management of postoperative RT for patients with prostate cancer in Japan.
Key Words: postoperative radiotherapy • prostate cancer • Patterns of Care Study
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INTRODUCTION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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The Patterns of Care Study (PCS), which was developed in the United States by the American College of Radiology and has been administered by them for over 25 years, was introduced to Japan to evaluate the current status of radiotherapy (RT) and to improve the quality of radiation oncology (1–3). The PCS in the United States has disclosed the evidences that elementary techniques contribute to improvement of outcome; for example: multiple fields' technique, dose escalation and higher energy beam selection >6 MV for prostate cancer (3). The Japanese PCS Working Group of Prostate Cancer conducted the first nationwide process survey of patients with prostate cancer who received RT between 1996 and 1998 (PCS96-98). Subsequently, a second PCS of patients treated with RT between 1999 and 2001 was conducted (PCS99-01). Nakamura et al. (4,5) presented the preliminary results of these surveys for RT in patients with prostate cancer in Japan. We present here the final analysis of PCS96-98 and PCS99-01 in order to reveal the status of national practices for postoperative RT for prostate cancer and the changing trends seen between 1996–98 and 1999–2001.
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SUBJECTS AND METHODS |
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The standard methods used in data collection for a national process survey have been described previously in detail (1,3). In brief, the PCS survey utilized a stratified two-stage cluster sampling design. An external audit team of radiation oncologists who were recruited from academic institutions surveyed 84 institutes from 1996 to 1998 and 76 institutes from 1999 to 2001, respectively (2). PCS96-98 and PCS99-01 stratified these institutions into either academic (university hospital or cancer centre) or non-academic institutions (other hospitals) according to a facility master list created by the Japanese Society of Therapeutic Radiation Oncology in 1997 and 2001, respectively. The following patient criteria were used in the process survey: (i) the patients had adenocarcinoma of the prostate without distant metastases; (ii) the patients were treated with RT during the period 1996–98 and 1999–2001; (iii) the patients had neither been diagnosed with any other malignancy nor treated with RT previously (4).
The PCS96-98 and PCS99-01 surveys in Japan contain detailed information on a total of 835 patients with prostate cancer treated with RT during the respective survey periods (PCS96-98: 307 patients, PCS99-01: 528 patients). A total of 169 patients who received RT after radical prostatectomy (RP) were selected for this analysis (PCS96-98: 64 patients; PCS99-01: 105 patients). In addition to the analysis of changing trends in national practice between PCS96-98 and PCS99-01, the type of RT used (adjuvant or salvage setting) was revealed in the 1999–2001 survey. Seventy-three of the 105 patients were treated with adjuvant RT and the other 32 received salvage RT.
For statistical analysis, the differences between the proportions were tested by the 
2-test. A P-value < 0.05 was considered statistically significant difference.
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RESULTS |
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Patients and disease characteristics in the PCS96-98 and PCS99-01 surveys are shown in Table 1. Proportion of non-academic to academic hospitals was significantly different between the two surveys (PCS96-98 and PCS99-01) (P = 0.004). We found a significantly lower fraction of patients with clinical T3–4 tumours (26%: P = 0.0004) and with positive surgical margins (56%: P = 0.042) between 1999 and 2001 than between 1996 and 1998 (T3–4: 63%, positive surgical margins: 78%). Although the distribution of the pre-treatment prostate-specific antigen (PSA) level was not different between the 1996–98 and 1999–2001 surveys (P = 0.44), the distribution of the pre-RT PSA level was significantly different between the surveys (P = 0.0002). In the 1999–2001 survey, 71% of the patients received RT at a <1 ng/ml level of PSA compared with 28% in the 1996–98 survey.
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The treatment characteristics are shown in Table 2. The use of
10 MV was significantly decreased in the PCS99-01 (73%) group compared with the PCS96-98 (92%) (P = 0.0059) one. The frequency of conformal therapy was also significantly lower in the PCS99-01 (23%) than in the PCS96-98 (65%) (P < 0.0001). The percentage of pelvic irradiation was not significantly different between the two survey periods (1996–98: 52%, 1999–2001: 41%) (P = 0.18). The distribution of radiation doses is shown in Fig. 1. The median radiation doses during 1996–98 and 1999–2001 did not change (60 Gy).
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Although the percentage of patients who received hormonal therapy was not different between the surveys (1996–98: 83% versus 1999–2001: 72%) (P = 0.18), a lower number of patients were treated with chemotherapy in the 1999–2001 survey (8%) than in the 1996–98 survey (27%) (P = 0.0045).
Table 3 shows the comparison of patient characteristics and the treatment process according to the type of RT administered (adjuvant versus salvage setting) in the PCS99-01. The fraction of patients with a pre-RT PSA < 0.4 ng/ml in the adjuvant setting was significantly higher than that in the salvage setting, and the percentage of patients with a positive surgical margin in the adjuvant setting was higher than that in the salvage setting. The fraction of patients who received pelvic irradiation was significantly higher in the adjuvant setting than in the salvage setting (P < 0.0001). The distribution of the total dose to the prostatic bed is shown in Fig. 2. We observed a significant difference in median doses to the prostatic fossa between the adjuvant (56 Gy) and salvage settings (60 Gy) (P = 0.0015). However, more than half of patients in the salvage setting received total doses of <64 Gy.
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DISCUSSION |
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TOPAbstractINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONReferences |
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PATIENTS' CHARACTERISTICS
In this analysis, we revealed changes in the practice of postoperative RT for patients with prostate cancer in Japan. The fraction of patients with T3–4 tumours was significantly decreased from the PCS96-98 survey to the PCS99-01 one. This result might indicate that high-risk patients with clinical T3–4 tumours tend not to be subjected to RP. However, Ogawa et al. (6,7) documented that significantly earlier T-stages (T1–2) were found between 1999 and 2001 than between 1996 and 1998 in their analysis of the patients who received radical RT for prostate cancer. These results may indicate the recent expansion of the indications for RT in patients with prostate cancer in Japan.
The pre-RT PSA level was significantly lower in the PCS99-01 patients than in the PCS96-98 ones. This might be a reflection of the accumulating evidence that lower pre-RT PSA is associated with success in the treatment of patients with PSA failure after prostatectomy (8,9). However, in the 1996–98 survey, we did not identify whether each patient received RT in the adjuvant or salvage setting because of the lack of data. The fraction of patients who received adjuvant RT as opposed to salvage RT might differ between the surveys.
TREATMENT PROCESS
We observed significantly lower fractions of the use of 10 MV and conformal therapy in the PCS99-01 survey than in the PCS96-98 one. However, Ogawa et al. (6) documented that the changes in the use of 10 MV and conformal therapy for patients with primary prostate cancer were not significant between the PCS96-98 and PCS99-01 surveys. This discrepancy might have arisen from the significantly higher fraction of patients who had received postoperative RT in non-academic hospitals in the 1999–2001 survey than in the 1996–98 survey in our analysis (P = 0.004). Ogawa et al. (10) also documented in their other report that the institutional stratification significantly affected the patterns of RT, such as the beam energy and the administration of conformal therapy.
The most appropriate radiation dose in the post-prostatectomy setting is controversial, as indicated by the wide range of doses noted in previous reports (45–75 Gy) (11). The American Society for Therapeutic Radiation Oncology (ASTRO) consensus panel recommended doses of 64 Gy for patients with PSA failure after RP (12). On the other hand, Petrovich et al. (13) demonstrated that a median dose of 48 Gy in adjuvant RT reduced the risk of local recurrence in patients with pathological T3 prostate cancer. Our results also demonstrated that various doses were applied to the patients who had undergone RP, whether in the adjuvant or salvage setting.
Employing a conformal 3D planning system and promoting a dose escalation of >64 Gy may improve local control and biochemical relapse-free survival for patients with prostate cancer who receive postoperative RT alone (11,14). Ogawa et al. (7) showed that the radiation doses for patients with primary prostate cancer were higher in the PCS99-01 survey than in the PCS96-98 one, and discussed that the use of an increasing radiation dose might reflect the widespread dissemination of clinical trial results. However, our analysis revealed that the median dose for patients who received postoperative RT in Japan did not change from 1996–98 to 1999–2001. Furthermore, only half of the patients who were subjected to salvage RT in the PCS99-01 received doses of over or equal to 64 Gy, the dosage which was recommended by ASTRO (Fig. 2). Although previous reports of postoperative RT for patients with prostate cancer are rare in Japan, the next PCS may reveal the dissemination of evidence for dose escalation.
There have been no randomized trials to define the field sizes of postoperative irradiation for patients with prostate cancer, and no consensus about the best radiation therapy volume. Pelvic irradiation was performed in 40–50% of the patients, and no significant difference was found in the percentage of patients treated with pelvic irradiation between the PCS96-98 and PCS99-01 surveys. According to the previous analyses, the prostate and immediately adjacent tissues have been considered to be a reasonable clinical target volume in the adjuvant setting (15,16). However, some previous reports documented the significant benefits of pelvic irradiation for patients in a salvage setting, showing a trend towards better PSA control in those patients with adverse pathological features (including a positive surgical margin, etc.) (17,18). However, the PCS99-01 survey revealed that a higher fraction of the patients received pelvic irradiation in the adjuvant setting than in the salvage setting in Japan.
ADJUVANT VERSUS SALVAGE
The role of postoperative RT for prostate cancer has been controversial. The previous retrospective analyses showed improvement in the local control and disease-free survival of the patients with high-risk pathological features who received adjuvant RT compared with similar patients treated with RP alone (15,19,20). Recently, the first randomized study evaluating the benefits of postoperative RT in prostate cancer was reported by Bolla et al. (21), who documented a significant benefit of postoperative RT in the biochemical relapse-free survival rate and clinical locoregional failure rate in patients with high risk factors after RP by the analysis of a total of 1005 patients who were allocated to postoperative RT or observation. There is no data based on randomized trials favouring adjuvant over salvage RT. The fraction of patients in the adjuvant setting was higher than that in the salvage setting from among all patients who received postoperative RT in the PCS99-01 survey. However, this result may not reflect the actual trend towards postoperative RT in Japan, so further investigation into more cases is needed in the future.
CONCLUSIONS
Our results revealed national trends in the treatment of prostrate cancer and changes in the practice of postoperative RT for patients in Japan with this disease. The management and strategies (including radiation field and dosages) varied, and the role of postoperative RT for patients with prostate cancer remains controversial (adjuvant RT versus salvage RT). Further evidence needs to be accumulated on postoperative RT for patients with prostate cancer in order to establish appropriate treatment strategies. In addition, continuous nationwide surveys should be performed to evaluate the dissemination of the results that have been collected.
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Acknowledgments |
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This study was supported by Grants-in-Aid for Cancer Research (Grant Nos. 10-17 and 14-6) from the Ministry of Health, Labor and Welfare of Japan, the Japanese Foundation of Aging and Health, the Japan Society for the Promotion of Science and Japanese Cancer Research. The authors would like to thank all of the radiation oncologists who participated in this study; the information they gathered made these surveys possible. We are grateful for the 10 years of continuous, thoughtful support we have received from the U.S. PCS Committee.
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References |
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