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Keywords:

  • epidemiology;
  • Japanese;
  • prostate neoplasm;
  • registration;
  • survival

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

Objectives:  In 2001, the Cancer Registration Committee of the Japanese Urological Association initiated a data collection of prostate cancer patients into a computer-based database. The aim of the present study is to report the clinical and pathological characteristics and outcomes of prostate cancer patients diagnosed in 2004 in Japan.

Methods:  Overall, 11 385 patients from 239 institutions were registered into the database. After excluding 1105 patients because of insufficient data, duplication or insufficient follow up, 10 280 patients were eligible for the analysis. Most of them (10 198, 99.2%) were Japanese and 1195 (11.6%) had metastatic disease at the time of diagnosis. The mean and median follow up was 53.2 months and 61.5 months, respectively.

Results:  The 5-year overall and prostate cancer-specific survival rate was 89.7% and 94.8%, respectively. The 5-year prostate cancer-specific survival rate of M0 and M1 disease was 98.4% and 61.1%, respectively. For 8424 cases of organ-confined or regional disease, Japanese urologists used as the initial treatment hormone ablation therapy alone (3360, 39.9%), radical prostatectomy (3140, 38.1%), radiation therapy (1530, 18.2%) and watchful waiting (394, 4.7%) including active surveillance or palliative observation.

Conclusions:  This is the first large population report of survival data in Japanese prostate cancer patients. In Japan, the disease population, survival period with metastatic disease and ratio of patients having hormone ablation therapy differ from those in Western countries.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

In the 1990s, prostate-specific antigen (PSA) testing became widespread in Japan, as in the USA and Europe. The incidence of prostate cancer in Japan also appears to be rising. There is no doubt that PSA screening contributes to earlier diagnosis of prostate cancer. Whether earlier detection of the prostate cancer in Japanese men helps reduce prostate cancer-specific mortality is unknown as a result of the lack of detailed information about Japanese prostate cancer patients.

In 2001, the Japanese Urological Association (JUA) initiated a study to estimate the etiology, diagnosis, initial treatment, pathological findings and final outcomes of prostate cancer using computer-based registration of prostate cancer patients from institutions all over Japan. In 2005, we published the initial report on the registered 4529 prostate cancer patients diagnosed in 20001 and the estimated etiology, diagnosis and initial planned treatment were analyzed. In 2010, detailed information including the main treatment modality used, adjuvant therapies used and survival of prostate cancer patients diagnosed in 2004 was collected to assess the current situation of prostate cancer in Japan.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

Patients and treatments

In 2010, data on patients diagnosed with prostate cancer in 2004 were collected, along with 5-year survival data and radical prostatectomy pathology results. Incidental cancer found within specimens removed during radical cystoprostatectomy for bladder cancer and transitional cell carcinoma of the prostate concomitant with bladder cancer were excluded from this registry. In all, 11 385 patients were registered from 239 institutions. Excluded from the analysis were 37 duplications (only one record was removed and the patient remained in the registry), six patients because of insufficient data and 1062 patients with less than 180 days of follow up, leaving 10 280 patients included in the analysis.

Variables

Pathological staging was based on the fifth edition of the TNM classification and the third edition of the General Rule for Clinical and Pathological Studies on Prostate Cancer (2001).2 For the PSA analysis, only cases measured with the Tandem-R kit PSA assay (n = 4567, 44.4%) were included to avoid statistical scatter. The definition of PSA failure was determined based on the clinician's judgement.

Survival data were analyzed according to the main treatment modality and the M stage. The initial main treatment modalities used were categorized into four groups: hormone ablation therapy alone (Hx), radical prostatectomy (RP) with or without neoadjuvant hormone treatment (NHT), radiation therapy (Rx) with or without NHT and watchful waiting (W/W) including active surveillance or palliative observation irrespective of the intent. Characteristics and outcomes from the four treatment groups were analyzed separately.

Analysis of progression-free survival was not possible as a result of difficulties in timing recurrence correctly. In some RP cases, adjuvant therapy was initiated just after the operation on the basis of the pathological findings. In addition, there were substantial differences in how post-Rx PSA failure was defined. For these reasons, the exact timing of recurrence was not able to be determined for a sizable number of patients, whom we consequently described as having “stable disease.” Therefore, we had no other choice but to focus on the mortality rate, overall survival (OS) and prostate cancer-specific survival (PCSS).

Statistical methods

For statistical analysis, Student's t-test was used for analysis of intergroup differences in means and the χ2-test was used for intergroup comparisons. Survival data was analyzed by the Kaplan–Meier method.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

Overall data

The registered patients' characteristics including age, PSA, Gleason score and TNM classification were summarized according to the main initial treatment modality (see Table S1, supporting information). In the 10 280 patients, the number of the patients treated by Hx, RP, Rx and W/W was 4934 (49.8%), 3212 (31.5%), 1605 (10.4%) and 485 (4.7%), respectively. The 44 patients were treated by other modalities. There were statistically significant differences among patients in different treatment groups. Patients treated with RP were the youngest (median age 68.0 years), with patients treated with Hx on average approximately 8.5 years older (median age 76.0 years). Overall, median PSA at diagnosis was 13.0 ng/mL, but the median PSA within the W/W group was 7.3 ng/mL, which was the lowest. Median Gleason score was 7 among Hx, RP and Rx groups, and 6 in W/W patients. Approximately 50–60% of each group was staged as T1c or T2 disease. In contrast, 11.5% of patients presented with metastatic disease at the time of diagnosis.

The 5-year OS and PCSS of all 10 280 patients was 98.7% and 94.8%, respectively. Figure 1 shows the Kaplan–Meier curves according to M stage. Bony disease (M1b) comprised the majority of M1 patients. The 5-year OS and PCSS was 61.8% and 66.7%, respectively. In M1 disease, there was a significant correlation between survival and Gleason score (P < 0.001).

image

Figure 1. Kaplan–Meier curves of (a) overall survival and (b) prostate cancer-specific survival according to M stage (n = 10 280).

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T1-4N0M0 prostate cancer

There were 8424 patients with T1-4N0M0 prostate cancer. The distribution and proportion of clinical T (cT) stage and age by treatment group are shown in Figure 2. Interestingly, in Japan more than 30% of patients received Hx as the main treatment modality across all cT stages. Even for cT1 or cT2 disease, RP, Hx and Rx were carried out in approximately 50%, 30% and 20% of the cases, respectively. The age distribution differed dramatically across treatment groups. For patients less than 75 years-of-age, RP was widely used. Rx was carried out at similar rates (approximately 20%) in patients up to 80 years-of-age. Hx was the major treatment in patients over 80 years-of-age.

image

Figure 2. Age distribution by main treatment modality in patients with T1-4N0M0 prostate cancer (n = 8424). (a) Totals and numbers of patients who underwent each treatment modality. (b) Percentages of each treatment by age. Hx, hormone ablation therapy; RP, radical prostatectomy; Rx, radiation therapy; W/W, watchful waiting.

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OS and PCSS in T1-4N0M0 disease by treatment group were shown to be 97.6% and 99.6% in RP, 95.6% and 98.5% in Rx, 96.4% and 99.7% in W/W and 88.9% and 97.7% in Hx. Five-year PCSS for patients without metastatic disease was excellent (98.4%).

Distribution of age and PSA in patients with T1-4N0M0 prostate cancer according to treatment was shown in Figure S1. Figure S2 shows cT distribution and the main treatment adopted in these patients. Figure S3 shows overall and prostate cancer-specific survival by main treatment adopted in these patients.

Radical prostatectomy

RP was carried out in 3212 patients (see Table S2, supporting information). Overall, 96.2% of RP patients had radical prostatectomy through the retropubic approach, and 89% had an open procedure. Concerning neurovascular bundle preservation, 70.4% of the patients received RP without nerve preservation. Lymph node dissection was carried out in 91% of the patients with mainly limited obturator lymph node dissection (71.6%).

The outcomes of 3200 RP patients according to NHT duration are summarized (see Table S3, supporting information). Because of uncertain NHT status, 12 patients were excluded. In the RP with NHT group (n = 1164), most pathological parameters including node metastasis (pN) and surgical margin status (ew) were better than in those patients without NHT (n = 2045; P < 0.001), except for seminal vesicle invasion (sv). However, the survival status of RP with NHT group did not differ from the RP without NHT group. The disease-free rate and prostate cancer death rate in the RP group within this observation period of approximately 5 years was approximately 70–75% and less than 1%, respectively.

Hormonal therapy alone

In this registration series, 4934 patients were treated with Hx alone (see Table S4, supporting information). In these patients, 3582 patients (72.6%) had non-metastatic disease (M0) and 1061 patients (21.5%) had bony metastasis (M1b). The combination of luteinizing hormone-releasing hormone (LH-RH) analogs with non-steroidal anti-androgen drugs were used in the majority of the Hx patients (67.4%). In M0 disease, 25% of patients received monotherapy with LH-RH analogs or surgical castration, and 67.4% patients were treated with maximum androgen blockade (MAB). Estrogen or estramustine phosphate therapy as the initial Hx was rare for M0 disease. For M1b disease, 82% of patients received MAB and 14.4% of patients received estrogen or estramustine phosphate as the initial treatment. The 5-year PCSS in patients with M0 disease was 93.3% and in M1b patients, it was 71.2%. In M0 patients, 8.4% of the patients died of other causes, which seemed to be higher when compared with patients treated with other modalities.

Curative radiation for prostate cancer

Rx as a radical treatment was used for 1554 patients. There were 28 patients who received particle radiotherapy and 27 patients were treated by uncertain modality. Excluding these patients, the characteristics of the 1499 patients are summarized (see Table S5, supporting information). Radiation therapy was classified as external beam radiation therapy with Liniac (EBRT; n = 1241), brachytherapy (BT; n = 210) or a combination (BT + EBRT; n = 48). Median age in EBRT was 72.9 years and median PSA was 15.0 ng/mL. In contrast, that in BT was 70.0 years and median PSA was 7.30 ng/mL. When compared with EBRT patients, BT patients were younger and had lower PSA, Gleason scores and earlier stage disease. The median PSA level in patients who received EBRT was 15.0 ng/mL, higher than in RP patients. In 1241 EBRT patients, 88.6% received radiation to the prostate only and the median dose in EBRT was 70 Gy. No cancer deaths were observed in patients who received BT and BT + EBRT. In the EBRT group, 5-year PCSS was 98.3% (see Table S6, supporting information).

Watchful waiting

In this registry, W/W included active surveillance, deferred treatment and palliative observation. At the time of registration, 72.4% of patients were maintained on watchful waiting. In the W/W group, 0.62% of the patients died of prostate cancer. The incidence was similar to that in the RP patients (see Table S7, supporting information).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

The present report is the first large-scale study of the characteristics and survival of prostate cancer patients in Japan based on multi-institutional registry data. The estimated number of newly diagnosed prostate cancer patients in Japan in 2005 was 42 997.3 This registry seems to cover approximately one-quarter of newly diagnosed prostate cancer in Japan. With regard to prostate cancer incidence and mortality, ethnic differences between American or European and Asian men are well known. Understanding the actual situation of Japanese prostate cancer patients is indispensable to addressing many clinical issues regarding prostate cancer treatment.

The incidence of metastatic prostate cancer at the initial registration was 11.6% in the present study. In the USA, 6.5% were distant stage according to the report from the 1990–2000 database of the Surveillance, Epidemiology and End Results (SEER) Program4, suggesting the incidence of metastatic disease is higher in Japan than in the USA. However, the incidence was 21.3% from the Japanese registration data in 2000.1 Compared with the data from 2000, the ratio of distant disease in 2004 was reduced by half. However, the number of the distant diseases in 2000 (n = 964) was almost the same as that in 2004 (n = 1195).

In the report derived from the 1973–2000 database of the SEER Program4, 5- and 10-year PCSS were approximately 99% and 95%, respectively. Two-thirds of patients were diagnosed with well or moderately differentiated localized or regional prostate cancer. Among these patients, 5- and 10-year PCSS were approximately 100%. In the present study, 5-year PCSS was 94.8%, which resembles the SEER data from 1995. The PCSS of localized or regional prostate cancer was 98.4%, similar to the SEER data. Five-year PCSS of patients with bony metastasis in Japan was 66.7%, which was better than the 27–37% 5-year PCSS in the USA4. The reason why Japanese patients with bony metastasis showed a longer survival period than American patients is uncertain.

The main treatment used for non-metastatic prostate cancer patients in Japan was quite different from that in the USA. In the USA, approximately half of prostate cancer patients received surgery and more than one-third underwent Rx.5 In Japan, Hx comprised of 39.9% of the initial main treatment, even for non-metastatic prostate cancer. One of the reasons for the high rate of Hx might be the relatively advanced age at diagnosis. Another reason might be the high rate of health insurance coverage and indifference about erectile dysfunction. In the present study, the most frequent treatment for non-metastatic prostate cancer in patients less than 70-years-old was RP (62.5%). Essentially, for patients younger than 70-years-old, Japanese urologists might choose treatments in agreement with major guidelines published by the National Comprehensive Cancer Network and the European Association of Urology, among others.

Concerning the administration of Hx medications, MAB therapy was recommended for stage D2 prostate cancer.6 However, in Japan, 65% of patients with non-metastatic disease received MAB therapy and 25% of them received LH-RH analogs or surgical castration as monotherapy. The 5-year PCSS of non-metastatic prostate cancer patients in Japan showed excellent results, even in the W/W group. The OS of patients with Hx seemed to be lower than that with other modalities. The patients undergoing Hx are relatively older.

In the present series, detailed data on RP was analyzed. In 2004, open retropubic RP (89.6%) with obturator lymph node dissection (71.6%) was the most common procedure. Interestingly, just 20% of patients received nerve-sparing operations in Japan. In high-volume hospitals in the USA, most radical prostatectomy seems to be carried out using the nerve-sparing technique. For most Japanese men, there might be less concern about sexual function when compared with American men.

The pathological results were sorted by NHT duration, because they might be affected by NHT status. Similar to the data from many randomized controlled studies of NHT7,8 most pathological findings were improved by longer NHT, except for seminal sv and pN. However, there was no remarkable improvement in prognosis despite longer NHT as previously reported. However, these data came from non-randomized, non-historically controlled patients.

Additionally, the present study might be the largest population study of Rx in Japan. In past years, the trends and patterns of Rx in Japan were reported by the patterns of care study (PCS).9,10 The age, PSA, Gleason score and radiation dose in the EBRT group of the present study were similar to PCS data. The median PSA of 15.0 ng/mL in the EBRT patients was higher than that of the patients treated with RP. Japanese urologists seemed to select EBRT for treating localized advanced disease. The EBRT group in the registry had a disease-free rate of 58% and a stable disease rate of 22.7%. Recently, higher dose radiation has been recognized to contribute to better cancer control. In 2004, 11.0% of the patients received 72 Gy and 11.4% patients received 76 Gy EBRT. Nearly 50% of patients underwent 68 Gy EBRT. Recently, relatively high dose EBRT in combination with NHT was attempted using the intensity modulated radiotherapy technique.

In conclusion, this is the first report of survival data involving one-quarter of newly diagnosed prostate cancer patients in Japan. In Japan, the patient population, survival period with metastatic disease and the ratio of patients receiving Hx differ from Western countries. Also noteworthy is the reduction in the ratio of metastatic prostate cancer at diagnosis, which was 11.6% in 2004, approximately half the rate in 2000. However, the total number of newly diagnosed patients with metastatic prostate cancer in 2004 was almost same as that in 2000. In terms of localized (cT2 or earlier stage) prostate cancer, Hx was used as the main treatment in 36.7% of Japanese patients. The 5-year survival of patients with localized prostate cancer was excellent irrespective of the main treatment used. Five-year OS and PCSS of patients with M1b disease were superior to that in the USA.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

These clinicopathological statistics are the results from a number of institutions in Japan (see Appendix I, supporting information). We are grateful for the cooperation of many Japanese urologists. This document was created by the Cancer Registration Committee of the Japanese Urological Association.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information
  • 1
    Cancer registration committee of the Japanese Urological Association: clinicopathological statistics on registered prostate cancer patients in Japan: 2000 report from Japanese Urological Association. Int. J. Urol. 2005; 12: 4661.
  • 2
    Japanese Urological Association and the Japanese Society of Pathology. General Rule for Clinical and Pathological Studies on Prostate Cancer. Kanehara, Tokyo, 2001.
  • 3
    CANCER STATISTIC IN JAPAN 2010, The Editorial Board of the cancer Statistics in Japan Foundation for Promotion of Cancer Research. 2010.
  • 4
    Brenner H, Arndt V. Long-term survival rates of patients with prostate cancer in the prostate-specific antigen screening era: population-based estimates for the year 2000 by period analysis. J. Clin. Oncol. 2005; 23: 4417.
  • 5
    Welch HG, Albertsen PC. Prostate cancer diagnosis and treatment after the introduction of prostate-specific antigen screening: 1986–2005. J. Natl Cancer Inst. 2009; 101: 13259.
  • 6
    Prostate Cancer Trialists' Collaborative Group. Maximum androgen blockade in advanced prostate cancer: an overview of the randomized trials. Lancet 2000; 355: 14918.
  • 7
    Soloway MS, Pareek K, Sharifi R et al.; the Lupron Depot Neoadjuvant Prostate Cancer Study Group. Neoadjuvant androgen ablation before radical prostatectomy in cT2bNxMo prostate cancer: 5-year results. J. Urol. 2002; 167: 11216.
  • 8
    Aus G, Abrahamsson PA, Ahlgren G et al. Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial. BJU Int. 2002; 90: 5616.
  • 9
    Ogawa K, Nakamura K, Sasaki T et al. Japanese Patterns of Care Study Working Subgroup of Prostate Cancer. Radical external beam radiotherapy for prostate cancer in Japan: differences in the patterns of care among Japan, Germany, and the United States. Radiat. Med. 2008; 26: 5762.
  • 10
    Nakamura K, Ogawa K, Sasaki T et al. Japanese Patterns of Care Study Working Subgroup of Prostate Cancer. Patterns of radiation treatment planning for localized prostate cancer in Japan: 2003–05 patterns of care study report. Jpn J. Clin. Oncol. 2009; 39: 8204.

Supporting Information

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. Conflict of interest
  9. References
  10. Supporting Information

Fig. S1 Distribution of age (A) and PSA (B) in patients with T1-4N0M0 prostate cancer (n = 8424) according to treatment. RP, radical prostatectomy; Rx, radiation therapy; Hx, hormone ablation therapy; W/W, watchful waiting.

Fig. S2 cT distribution and the main treatment adopted in patients with T1-4N0M0 prostate cancer (n = 8424). The graph A shows totals and numbers of patients who underwent each treatment modality. The graph B shows percentages of each treatment by clinical stage. RP, radical prostatectomy; Rx, radiation therapy; Hx, hormone ablation therapy; W/W, watchful waiting.

Fig. S3 Kaplan–Meier curves of overall survival (A) and prostate cancer-specific survival (B) by main treatment adopted in patients with T1-4N0M0 prostate cancer (n = 8224). RP, radical prostatectomy; Rx, radiation therapy; Hx, hormone ablation therapy; W/W, watchful waiting.

Table S1 Characteristics of the registered patients.

Table S2 Characteristics of 3212 radical prostatectomy patients.

Table S3 Outcome of 3200 radical prostatectomy cases with or without neoadjuvant hormonal therapy.

Table S4 Outcome of 4934 patients treated with hormone ablation therapy alone.

Table S5 Characteristics of patients treated with radiation therapy as the main treatment.

Table S6 Outcome of patients treated with radiation therapy as the main treatment.

Table S7 Outcome of 485 patients treated with watchful waiting.

Appendix I Statistics from various institutions in Japan.

FilenameFormatSizeDescription
IJU_2895_sm_FigS1.eps2818KSupporting info item
IJU_2895_sm_FigS2.eps378KSupporting info item
IJU_2895_sm_FigS3.eps1982KSupporting info item
IJU_2895_sm_Tables-Appendix.pdf69KSupporting info item

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