1. No category

台灣第1c期攝護腺癌病患接受根除性
恥骨後攝護腺切除術之臨床研究
Clinical Study of Radical Retropubic
Prostatectomy in Taiwanese Patients with T1c
Prostate Cancer
歐宴泉 M.D, Ph.D
台中榮總 泌尿科 攝護腺疾病防治中心
大林慈濟醫院 大愛2F 第一會議室
7:30-8:30 Dec. 6 , 2005
台中榮總 「整合性攝護腺病
防治中心」簡介
1.
2.
3.
4.
5.
6.
7.
8.
前言
攝護腺疾病
攝護腺癌之國內、外現況
本院近年來之成果
成立本中心之必要性
業務分組
SWOT分析
本中心目標
一、 前言
• 攝護腺疾病是全球性的公共衛生及醫
療問題
• 台灣民眾重視醫療、人口老化、生活
飲食西化
台灣老年人口比率
65歲以上老年人口比率(%)
7.1
7.4
7.6
7.9
8.1
8.3
8.4
8.6
8.8
9
9.2
9.5
10
9
8
7
6
4
3
2
1
年
度 82
0
83 84 85 86 87 88 89 90 91 92 93
(%)
5
65歲以上老年人口比率(%)
二、攝護腺疾病
1. 慢性攝護腺炎
2. 攝護腺肥大合併下泌尿道
症候群
3. 攝護腺癌
慢性攝護腺炎
1. 發生於20-49歲及>70歲，病因不明
2. 症狀：疼痛（會陰、睪丸、龜頭、 恥骨上）、頻尿、
3.
4.
夜尿、影響生活品質
病人遊走各醫院
需長期服藥，治療方式五花八門，但效果均不佳，國
內、外均無標準療法
另類療法:中藥、中藥湯、膏藥、針
灸……….
Clinical stage of prostatitis as defined by the
NIH-CPCRN
Categories
Hallmark Symptoms
Traditional treatment
Category 1 – Acute bacterial
Pain
Antibiotics, urinary
drainage
Category 2 – Chronic bacterial
Pain, recurrent UTI
Antibiotics
Category 3 – Chronic
Prostatitis/Chronic pelvic
pain (CP/CPPS)
Discomfort and pain in pelvic
region for 3 or more months,
impact on voiding, sexual
function, and QOL
Anitibiotics, αadrenergic agents, 5αreductase inhibitors,
NSAIDs and COX-2
inhibitors
Category 3A – Inflammatory
Presence of white blood cells Pentosan polysulfate
Category 3B –Noninflammatory
No white blood cells
Physical therapy
Prostatic massage
Category 4 – Asymptomatic
No symptoms
No intervention
Clinical: Presence of Moderate to
Severe Symptoms (IPSS >7)
Asia
60
總有一天
會等到你
Patients (%)
USA
44
40
40
20
Australia
49
50
30
China
56
36
33 33
31
29
27
26
24
37
36
31
30
15
Canada
36
Holland
27
France
14
8
10
0
50-59
60-69
70-79
Age (years)
Oishi et al. 4th Int Cons BPH, 1997.
三、攝護腺癌之國內、外現況
台灣地區食物攝取成份改變
3500
每日 攝 取量 (大卡 )
3000
Total Calori Intake
2500
2000
Carbohydrate
1500
Fat
1000
500
0
1965
Protein
1970
1975
1980
1985
Year
1990
1995
2000
行政院農委會, 2003
Changes of Dietary Components
USA
1984
Calorie (Kcal)
Protein (g)
Fat (g)
CHO (g)
Taiwan
1994
1987
South Korea
1997
1985
1995
Japan
1985
1995
3,400
3,800
2,807
3,129
2,687
2,991
2,088
2,042
102
110
89
101
87
98
79
82
162
159
97
131
52
80
57
60
401
491
386
373
…
…
298
280
Directorate-General of Budget,
Accounting and Statistics, Executive Yuan, ROC
1982
1983
1984
1985
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
Incidence (per 100,000)
Age-Standardized Incidence in Taiwan
34
32
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
0
30
16.3
(n=2,012)
Year
Department of Health, ROC
台灣地區攝護腺癌死亡人數及粗死亡率
750
800
6.54
693
死亡數
700
6
6.07
死亡率%(每十萬人)
635
5.59
600
4.78
500
463
4.82
4.2
4
3.39
3
3.37
300
269
223
2.24
200
2.5
223
2
2.19
1
100
0
0
1991
1992
1993
1994
1995
1996
1997
Ye a r
1998
1999
2000
2001
2002
每
十
萬
人
﹂
371
366
5
4.97
粗
死
亡
率
﹁
561
540
531
申
報
400
人
數
7
四 、 本院近年來之成果
近五年台中榮總泌尿科經直腸
攝護腺超音波切片數目
385
400
385
378
373
351
350
300
250
數
量
229
超音波
超音波切
攝護腺癌
200
143
150
27%
95
121
23% 108
90
21%
82
100
25%
95
95
50
0
民89年
民90年
民91年
年度
民92年
民93年
21%
78
附件一
The Diagnosed New Case of Prostate Cancer in Taichung-VGH
台中榮民總醫院每年申報攝護腺癌數目
140
120
100
80
60
40
20
0
No. case
83
Year84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
23
34
18
32
44
66
48
55
56
84
70
87
101
73
86
100
18
2000 2001 200
133 115
12
0
恩主公
北醫
聖馬爾定
萬芳
羅東博愛
高醫
台中仁愛
慈濟
新光
2000
高榮
三總
國泰
500
成大
馬偕
中國
彰基
和信
奇美
高雄長庚
中榮
台大
林口長庚
北榮
Case No.
附件二
各醫院攝護腺癌申報數
600
2001
400
300
200
100
(資料來源: 2005 衛生署癌症登記報告)
附件三 Annual cases of radical prostatectomy in TCVGH
台中榮民總醫院每年根除性攝護腺癌切除術病例數
50
40
30
20
10
0
Year 84
No. case
2
85-87
88
89
90
91
92
93
94
95
96
97
98
99
0
2
5
3
10
5
16
17
19
20
30
29
32
2000 2001 2002 2003 2004
44
44
49
45
43
附件四 泌尿外科近五年來攝護腺相關論文發表十六篇（SCI:11篇）
1. (SCI: 0.822)Chi-Rei Yang, Yen-Chuan Ou, Hao-Chung Ho, Yu-Lin Kao, Chen-Li Cheng, Jung-
2.
3.
4.
5.
6.
7.
8.
Ta Chen, Lai-Ping Chen and William l. Ho. Unsuspected prostate carcinoma and prostatic
intraepithelial neoplasm in Taiwanese patients undergoing cystoprostatectomy. Molecular
Urology 1999, Vol. 3, No. 1, p33-39.
Hao-Chung Ho, Chi-Rei Yang, Yen-Chuan Ou, Chen-Li Cheng, Yu-Lin Kao, Chia-Hsiang Lin,
Chung-Kuang Su, Kun-Yuan Chiu. Orthotopic neobladder (Studer pouch) after radical
cystoprostatectomy: Experience in Taichung Veterans General Hospital. J UROL ROC Vol.11
No.3, Sep. 2000, p114-1119.
(SCI: 2.461)Chaeyong Jung, Yen-Chuan Ou, Fan Yeung, Henry F. Frierson Jr., Chinghai Kao.
Osteocalcin is incompletely spliced in non-osseous tissues. Gene 271 (2001) 143-150.
(SCI: 0.691)Yen-Chuan Ou, Jung-Ta Chen, Chi-Rie Yang, Chen-Li Cheng, Hao-Chung Ho, YuLin Kao, Jiunn-Liang Ko, and Yih-Shou Hsieh. Preoperative prediction of extracapsular tumor
extension at radical retropubic prostatectomy in Taiwanese patients with T1c prostate cancer. Jpn
J Clin Oncol 2002; 32(5)172-176.
(SCI: 0.691)Yen-Chuan Ou, Jung-Ta Chen, Chi-Rie Yang, Chen-Li Cheng, Hao-Chung Ho,
Jiunn-Liang Ko and Yih-Shou Hsieh. Predicting prostate specific antigen failure after radical
retropubic prostatectomy for T1c prostate cancer. Jpn J Clin Oncol 2002; 32(12) 536-542.
(SCI: 1.447) Chi-Rei Yang, Yen-Chuan Ou, Yu-Ye Horng and Hong-Shen Lee. The Variation
of Percent Free Prostate-Specific Antigen Determined by Two Different Assays. Anticancer
Research 23: 707-712 (2003).
Weng-Ming Chen, Chi-Rei Yang, Yen-Chuan Ou, Chen-Li Cheng, Yu-Lin Kao, Hao-Chung Ho,
Chung-Kwang Su, Kun-Yuan Chiu, Jung-Ta Chen. Clinical Outcome of Patients with Stage T1a
Prostate Cancer. J Chin Med Assoc 2003;66: 236-240.
(SCI: 1.447) Yen-Chuan Ou, Jung-Ta Chen, Chi-Rei Yang, Jiunn-Liang Ko, Yih-Shou Hsieh,
Chinghai Kao. Expression of osteocalcin in prostate cancer before and after hormonal therapy.
Anticancer Research 23: 3807-3812 (2003).
9. (SCI: 0.691) Yen-Chuan Ou, Jung-Ta Chen, Chen-Li Cheng, Hao-Chung Ho, Chi-Rei Yang.
Radical prostatectomy for prostate cancer petients with prostate-specific antigen > 20 ng/ml.
Jpn J Clin Oncol 2003; 33(11) 574-579.
10. (SCI: 2.456) Wen-Ming Chen, Chi-Rei Yang, Chen-Li Cheng, Yen-Chuan Ou. Novel
Technique to Facilitate Urethral Stump Exposure After Radical Retropubic Prostatectomy.
Urology 63: 1170-1171, 2004.
11. Yu-Lin Kao, Chi-Rei Yang, Cheng-Hshu Chen. Urinary exenteration on a renal transplant
recipient with multifocal urothelial cancers and prostatic adenocarcinoma. J Chin Med Assoc
2004;67:422-424.
12. Yun-Yuan Chiu, Chi-Rei Yang. Effects of Finasteride on Prostate Volume and ProstateSpecific Antigen. J Chin Med Assoc Vol. 67, No. 11, 1-4, 2004.
13. (SCI：1.347)Chi-Rei Yang, Chung-Knang Su, Kun-Yuan Chiu, Hao-Chung Ho, Yen-Chuan
Ou, Cheng-Li Cheng, and Huei Lee. Free/Total Prostate Specific Antigen Ratio for Prsotate
Cancer Detection: A Prospective Blind Study. Anticancer Research 25: xx-xx, 2005.
14. (SCI：0.667)Wen-Ming Chen, Chi-Rei Yang, Yen-Chuan Ou, Hao-Chung Ho, Chung-Kuang
Su and Kun-Yuan Chiu, Chen-Li Cheng. Combination Regimen in the Treatment of Chronic
Prostatitis. Archives of Andrology. xx-xx, 2005.
15. (SCI: 2.456)Twu CM, Ou YC, Yang CR, Cheng CL, Ho HC. Predicting risk factors for
inguinal hernia after radical retropubic prostatectomy Urology. 2005 Oct;66(4):814-8
16. 晚期攝護腺癌之第二線荷爾蒙治療：泌尿科創新及爭議性議題，九州圖書文物有限公司
2004年版P67-78.
附件五 近六年有關攝護腺之研究計劃 (11 件)
1.
2.
3.
4.
5.
6.
7
8.
9.
10.
11.
Finasteride & Doxazsin對攝護腺出血及勃起機制在
動物之研究(TCVGH-935001A)
良性及惡性人類攝護腺組織運用免疫化學及生物化
學偵測男性荷爾蒙、黃體素、雌激素感受器之研究
(TCVGH-935003A)
挫傷引起之脊髓外傷所誘發下泌尿道功能異常之評
估：神經滋養因子之研究(TCVGH-935005D)
賀昊中
930101-931231
陳文銘
930101-931231
程千里
930101-931231
鳥苷酸環化酶在注射環磷醯胺引發出血性膀胱炎上
所扮演角色之探討 (TCVGH-NGHU937605)
腹腔鏡輔助之攝護腺根除
(TCVGH 925002A)
雌性素受體β在攝護腺癌扮演促進生長角色之研究
(TCVGH 925003A)
Finasteride治療後的人體前列腺組織的5-α還原同位
脢 (TCVGH 915003A)
原發性膀胱頸阻塞的基因表現(TCVGH905002A)
程千里
930101-931231
裘坤元
920101~ 921231
陳文銘
920101~ 921231
高育琳
910101~ 911231
高育琳
900101~ 901231
藉血清中攝護腺特異抗原指數來區別台中及苗栗縣
居民之攝護腺癌之盛行率(TCVGH905003A)
攝護腺癌細胞死亡訊息及攔截受體之表現
（TCVGH-895001C）
骨鈣質在原發性及轉移性攝護腺癌之表現—轉移性
攝護腺癌之新靶子基因（TCVGH-895003A）
裘坤元
900101~ 901231
楊啟瑞
880701-890630
歐宴泉
880701-890630
附件六 近四年攝護腺疾病相關之臨床試驗（共七件）
編
號
研究計劃題目
國際
國內
贊助廠
商
主持
人
期間
1.
Terazopin treatment for benign prostate hyperplasia
國內
衛達藥廠 楊啟瑞
歐宴泉
91/0293/02
2.
Doxazosin XL treatment for benign prostate
hyperplasia
國內
輝瑞藥廠 程千里
93/0193/12
3.
The clinical study of Rofecoxib in reducing the risk of
prostate cancer in patients with benign prostate
hyperplasia
國際
MSD美商 楊啟瑞
默沙東
歐宴泉
92/0393/05
4.
Tolterodine L-Tartrate (Detrusitol FC) treatment for
overactive bladder
國內
東洋公司 蘇重光
93/02-
5.
An observational, multicenter study of Zometa® in bone
metastatic breast cancer, prostate cancer or multiple
myeloma patients under conditions of normal clinical
practice
國內
Novartis 歐宴泉
台灣諾華
94/11-
6.
A phase III, parallel group, randomized, open-label,
multi-center clinical trial of Zometa® in males receiving
Androgen Deprivation Therapy for advanced prostate
cancer
國際
Novartis
國際
歐宴泉
95/01
審核中
7.
The optimal dosage of cytoproterone (androcur) in
treating Taiwanese prostate cancer
國內
德國先靈 楊啟瑞
藥廠
歐宴泉
94/11-
五、成立本中心之必要性
1.
2.
3.
4.
5.
提昇病人照護醫療品質
本科空間及人員不足發展受限
整合本科之人力及資源
各醫學中心及醫學院的威脅
增加攝護腺癌之診斷病例以配合「達
文西機器人」設置
附件七
姓名
楊啟瑞主任
程千里主任
賀昊中醫師
泌尿外科各主治醫師執掌
負責項目
外科部主任
健保審查、尿失禁業務、人體試驗委員、新藥
臨床中心委員
健保審查、教育委員、評鑑委員、器官移植勸
募小組負責人
陳文銘醫師
備註
中山、國防授課
病歷審查9404-6月、
9504-6月 中山授課
出國進修
裘坤元醫師
醫療品管、腹腔鏡業務、藥事委員、健保聯合
窗口、榮民不給付審查、人事室人評會、UGY
導師、醫療品質審議委員會指標負責人、醫學
研究委員
病歷審查9401-3、
9501-03; 支援台安醫院
門診;教學門診
暨大、中華醫事技術學
院授課
歐宴泉醫師
PGY1導師、UGY導師、PGY主任、腫瘤業
務、教育委員、人體試驗委員、醫學倫理及法
律中心副主任、動物實驗委員、實證醫學種子
教官、人事成本小組、安寧療護委員
支援台安醫院門診
教學門診
病歷審查9410-12月
中山、暨大、中台授課
蘇重光醫師
移植業務、腹腔鏡業務、臨床路徑、醫療品質
審議委員會指標負責人、實證醫學種子教官
病歷審查9407-09月、
中山授課
達文西機器人:三總, 振興,中榮,義大,長庚
達文西機器人成敗的關鍵在於:
整合性攝護腺疾病防治中心之執行成效
台中榮總泌尿科達文西機器人參觀訓練行程
時 間
1.
醫
院
10/24-10/25 Indiana University-Prudue
University Indianapolis (IUPUI)
2. 10/25-10/26 Memorial Sloan-Kettering Cancer
Center, New York
3a. 10/27-10/28 Ohio State University Medical
Center (OSU)
3b. 11/22-11/23 Ohio State University Medical
Center (OSU)
4. 10/24
Henry Ford Hospital, Detroit
人
員
歐宴泉、李建儀
楊啟瑞、裘坤元
楊啟瑞、歐宴
泉、裘坤元
程千里、賀昊
中、蘇重光
程千里
六、業務分組
1. 衛教組: 病人衛教組; 癌症篩檢組
2. 治療組: 攝護腺肥大、慢性攝護炎組;
放射治 療及化學治療組
3. 試驗組: 臨床試驗組; 資料分析組
4. 研發組: 手術研發組; 基礎研發組
七、 SWOT分析
Strength優勢
1. 榮民、老年病患多
2. 攝護腺癌治療標準化成效卓越
3. 根除性攝護腺癌切除術是本院之招牌手術
4. 國際之臨床試驗之能力及經驗佳
保持優勢 建立不可取代的地位
Weakness缺點
1. 主治醫師臨床負荷大，且兼太多行政及
教學工作，人力明顯不足。
2. 資料頗多，臨床研究之結果發表尚嫌不
足，研究計劃未寫成論文。
3. 基礎研究投入時間太少，缺少醫學院，
不易有學校老師及研究生加入研究。
4. 空間極小，規劃不當，無法發揮整體功
能。
檢討缺點 還有許多改進的空間
Opportunity機會
1. 配合購置 ” 達文西機器人 ”施行腹腔鏡
2.
3.
4.
根除性攝護腺切除術發揮潛力。
國內尚未有攝護腺疾病整合中心的設
置, 本院地處中科發展中心。
聯合健檢中心，泌尿科歷年之校友，
各榮院及中部醫院建立轉診合作。
建立治療模式，增加自費門診及自費
手術。
本科歷年來離職人員
姓名
吳立智
張 勳
陳明村
林榮生
盧松貴
蔡宗欣
黃一勝
唐麗光
陳建光
吳錫金
張兆祥
張吉隆
林合興
張元耀
郭振華
陳順郎
吳劭文
石宏文
林嘉祥
陳炫達
郭佳隴
盧嘉文
林修名
高育琳
王宗偉
王賢祥
何君彥
陳卷書
地 址
旅美
張勳泌尿科診所院長
書田醫院院長
中國醫藥學院附設醫院北港分院主任
苗栗盧松貴泌尿外科診所院長
成大泌尿科主任
新光醫院泌尿科主任
台東基督教醫院泌尿科主治醫師
桃園榮院泌尿科主任
中國醫藥大學醫學系主任
中國醫藥學院泌尿科主任
署立嘉義醫院外科部主任
省立中興醫院泌尿科主任
東勢協和醫院副院長
仁愛醫院主任
中山醫院泌尿科主治醫師
嘉義大林慈濟醫院泌尿科主任
澄清醫院泌尿科主治醫師
義守醫院泌尿科主任
竹東榮院泌尿科主任
埔里榮院泌尿科主任
仁慈醫院泌尿科主治醫師
署立豐原醫院泌尿科主治醫師
中山醫院泌尿科主任
埔里榮院泌尿科主治醫師
竹東榮院泌尿科主治醫師
永康榮院泌尿科主治醫師
嘉義榮院泌尿科主治醫師
Threat威脅
1. 中部醫院（中國、中山、仁愛）從本院出去的泌尿科
2.
3.
4.
5.
醫師積極經營（尤其攝護腺 手術）
中部部分醫院採BOT放射治療拉攏病人
腹腔鏡根除性攝護腺癌切除術，目前臺大醫院及中國
醫藥大學超越本院
中部之醫院及醫學院（中國、中山、彰基）臨床及基
礎已整合
秀傳彰濱醫院將由前台大校長陳維昭主持成立一般醫
學及全民健保示範醫院
危機就是轉機
直到失去機會
機會落在事先規劃的人
你才會體會到它的重要
八、本中心目標
• 近程（一年）：成立病友會，設立專屬網站，院內篩檢
•
•
與社區醫學網聯繫，讓中部地區民眾了解本院攝護腺治
療之實力與成果;增加自費手術項目。
中程（一年至二年）：與國內各大醫學中心、醫學院交
流;建立攝護腺疾病治療標準流程;建立訓練制度;加強
創新性手術之進展;成立達文西機器人訓練中心;增加自
費門診項目。
遠程（二年至三年）：成立攝護腺基礎醫學研究室，由
博士級研究員負責，將分子醫學、開發新療法，達到世
界一流醫學中心水準。
Ultimately, the secret of
quality is love. You have
to love your patient, you
have to love your
profession, you have to
love your God. If you have
love, you can then work
backward to monitor and
improve the system.
• Avedis Donabedian,
1919-2000
Prostate (Patient) Disease Center:
三類疾病, 三大責任, 三核心價值, 三方合作, 三大願景
P,BPH, PSA; D, inflammatory disease, DRE; C, cancer, center
Red:
服務, 視病猶親, 病人, 立足臺灣
Yellow: 教學, 品質優先, 醫護, 胸懷亞洲
Blue: 研究, 研究創新, 行政, 放眼全世界
喜樂關懷協會：病友合作分享,醫護關懷照顧,
攜手共創喜樂生命
喜樂的心乃是良藥(箴言17:22)
台灣第1c期攝護腺癌病患接受根除性
恥骨後攝護腺切除術之臨床研究
Clinical Study of Radical Retropubic
Prostatectomy in Taiwanese Patients
with T1c Prostate Cancer
Background of the Study (I)
1. Prostate cancer (PC): most commonly
2.
3.
diagnosed cancer in most countries, major
public health concern
PC: 6th commonly diagnosed cancer, 8th cause
of cancer death in Taiwan
Prevalence of clinical prostate cancers between
Asians and Whites: quite difference. Incidence
of latent PC in Taiwan was 33%, similar to
Japan and USA (Yang CR, 1999;Yatani R, 1988; Kabalin
JN, 1988).
Frequency of unsuspected prostate cancer detected
by autopsy and cystoprostatectomy
Authors
Incidence(%)
Method of study
No. case studied
Franks, 1954
Scott, 1969
McNeal, 1969
Baron and Angrist, 1941
Yatani R, 1988
38
46
36
41
34.6
Autopsy
Autopsy
Autopsy
Autopsy
Autopsy
180 (>50 yrs)
158 (>70 yrs)
122 (>40 yrs)
50 (>50 yrs)
660 (>50 yrs)
Winfield, 1987
Pritchett, 1987
Montie, 1988
Kabalin, 1989
Yang, 1998
28
27
46
38
32.7
Cystoprostatectomy
Cystoprostatectomy
Cystoprostatectomy
Cystoprostatectomy
Cystoprostatectomy
80 (>43 yrs)
165 (>34 yrs)
84 (>34 yrs)
66 (>31 yrs)
49 (>45 yrs)
Background of the Study (II)
4. Digital rectal examination (DRE) and serum
prostate specific antigen (PSA): detect early
prostate cancer ?
5. PSA screening test and systematic prostate
biopsies
under transrectal ultrasound
(TRUS)-guidance, T1c PC has increased
from 2.7% in 1989 to 47.2% in 1994 (Pound
CR,1997) and 78% (screening study, Humphrey PA,
1996).
PSA < 4ng/ml
PSA Circulating Forms in Serum
Bound form
PSA
PSA bound to α-2
macroglobulin
=occult form
Free form
ACT
PSA
PSA
PSA bound to α-1antichymotrypsin (ACT)
=complex form
Principle of Assays:
use of monoclonal antibodies
ACT
< PSA >
<
PSA
>
PSA-RIACT
Complex
form
Free form
ACT
< PSA
<
PSA
>
FPSA-RIACT
The impact of PSA and TRUS-guidance sextant
biopsy on stage migration of prostate cancer in
Taichung Veterans General Hospital
Stage (﹪)
Period
T1a –T1b
T1c
T2
T3
D*
Pre-PSA era（19831989）
24
0
16
10
50
PSA era（19901994）
10
4
37
24
25
TRUS Bx. era
（1995-1998）
10
14
41
16
19
PSA screening era
（1999-2002）
7
24
35
17
17
* D: node or bone
metastasis
Aim of the Study
• We endeavor to detect early prostate
cancer and reported the clinical outcome
of stage T1a, T1b and T1c in the literature.
• To understand the clinicopathological
features and outcome of Taiwanese
patients with stage T1c prostate cancer
MATERIALS AND METHODS (I)
1.Fifty-five patients with stage T1c PC received
radical retropubic prostatectomy (RRP) Jan.
1996 to Dec. 2000. (14.3%, 55/ 385 PC)
2. Clinical data: patient age, PSA, free-to-total (F/T)
PSA ratio.
3. Sextant biopsies of the prostate. A 18-gauze
biopsy gun (Bard, USA) under transrectal
urologic ultrasound (TRUS)-guidance (Bruel and
Kjer 3535, Denmark). The PSA density (PSAD)=
PSA/ prostate volume
MATERIALS AND METHODS (II)
4. Needle biopsy were assessed : Gleason score,
number of cancer positive cores, maximum %
cancer of one core, more % cancer of one lobe.
% cancer of biopsies= area of cancer at site 1 +
area of cancer at site 2 +..../ total area in all
sextant biopsies x 100%).
5. Whole-mount prostatectomy specimens were
processed. The tumors were evaluated for Gleason
score, tumor location and tumor volume = areas x
thickness (3 mm) x tissue shrinkage factor (1.5).
RRP was classified as extracapsular tumor
extension (ECE) or organ-confined disease (OCD).
6. PSA failure as two serial serum PSA > 0.2 ng/ml.
RESULTS
Mr. 謝, 65 y/o, T1c, PSA: 7.6, PV: 30ml, Bx G:2+3=5, 7%
TV: 0.23 ml (TZ), G:2+3=5, organ-confined disease
post-op PSA<0.01, freedom-from PSA failure at 5y 9m
Mr. 白, 69 y/o,T1c, PSA:80, PV: 52 ml, Bx G:3+3=6 , 15%
TV:11.22ml (TZ), G:3+4=7, ECE(+)
post-op PSA<0.01, PSA failure at 2 yrs. 10 mos.
TABLE I. Preoperative clinical characteristics of 55
patients with stage T1c prostate cancer
Clinical characteristic
Organ-confined disease
Extracapsular extension
(number: 37)
(number: 18)
Age (year)
PSA level (ng/ml)
68.8±4.3
8.3±3.7
69.2±5.2
18.4±21.3**
PSA density
Cancer-positive biopsy core
Percentage of cancer in biopsy
% cancer of biopsies
% cancer of one lobe
% cancer of one core
Biopsy Gleason score
0.226±0.133
1.4±0.65
0.556±0.498#
1.8±0.81
12.0±7.7
22.3±13.4
45.5±17.3
4.5±1.3
20.0±14.6**
32.2±18.9*
58.6±21.4*
5.6±1.9**
key: * p<0.05 **p<0.01 #p<0.0001
TABLE II. Pathologic findings of surgical specimens from
patients with stage T1c prostate cancer
Clinical characteristic
Organ-confined disease
Extracapsular extension
(number: 37)
(number: 18)
Gleason score
5.9±1.3
6.8±0.9*
Tumor location
Peripheral lobe
Transitional lobe
Peripheral + transitional lobe
13 (35.1%)
11 (29.8%)
13 (35.1%)
1 (5.6%)
2 (11.1%)
15 (83.3%)**
Tumor volume (ml)
<0.5
0.5-3.9
≧4
1.86±1.77
11 (29.7%)
20 (54.1%)
6 (16.2%)
8.27±6.73#
0 (0%)
8 (44.4%)
10 (55.6%)**
key: * p<0.05 **p<0.01 #p<0.0001
TABLE III. Preoperative predictors of extracapsular
tumor extension in patients with stage T1c prostate
cancer
Variable*
Cases of extracapsular
extension/case number
Relative risk
p value
9/15 (60%)
9/40 (22.5%)
2.7
0.0213
PSA ng/ml
≧10
< 10
PSA density
≧0.35
< 0.35
11/14 (78.6%)
7/41 (17.1%)
4.6
0.00006
% cancer of biopsies ≧20%
< 20%
% cancer of one lobe ≧30%
< 30%
% cancer of one core ≧50%
< 50%
9/15 (60%)
9/40 (22.5%)
10/21 (47.6%)
8/34 (23.5%)
13/29 (44.8%)
5/26 (19.2%)
2.7
0.0213
2.0
0.0815
2.3
0.05
Biopsy Gleason score ≧6
<6
12/20 (60%)
6/35 (17.1%)
3.5
0.0023
TABLE IV. Best model to predict tumor extracapsular
extension (ECE) in stage T1c prostate cancer receiving
retropubic radical prostatectomy
Condition
PSAD
1
2
3
4
5
6
7
8
9
10
≧0.35
≧0.35
≧0.35
≧0.35
≧0.35
≧0.35
Biopsy Gleason
score
Percent cancer
in biopsies
PSA (ng/ml)
≧6
≧20%
≧10
≧6
≧6
≧6
≧6
≧6
≧6
≧20%
≧20%
≧20%
≧20%
≧20%
≧10
≧10
≧10
≧10
≧10
Incidence of
ECE
90% (9/10)
83.3% (5/6)
81.8% (9/11)
100% (5/5)
88.9% (8/9)
100% (5/5)
80% (8/10)
88.9% (8/9)
100% (5/5)
83.3% (5/6)
Table Ｖ. Preoperative clinical characteristics of 55
patients with stage T1c prostate cancer classified by
PSA failure
P valve
PSA(-)
n=40
PSA(+)
n=15
mean±std
mean±std
Age (year)
69.0 ± 4.3
68.8 ± 5.4
0.932
PSA level (ng/ml)
8.3± 3.7
20.5 ± 22.8
0.038*
Free/total PSA ratio
19.3 ± 6.8
15.9 ± 9.4
PSA density
0.246 ± 0.144
0.570 ± 0.548
0.071
% cancer of biopsies
12.7 ± 9.1
19.8 ± 14.0
0.031*
Biopsy Gleason score
4.5 ± 1.3
5.9 ± 1.7
0.002**
Clinical characteristic
* P<0.05 **P<0.01
0.092
TABLE VI.
VI Pathologic findings of surgical specimens from patients with
stage T1c prostate cancer classified by PSA failure
PSA(+)
n=15
P valve
Pathology characteristic
PSA(-)
n=40
Gleason score
6.0 ± 1.3
6.7 ± 0.7
0.037*
33/7
4/11
0.0002**
ECE(-) / ECE(+)
Tumor location
0.0123*
Peripheral lobe
14 (35%)
0 ( 0%)
Transitional lobe
10 (25%)
3 (20%)
Peripheral + transitional lobe
16 (40%)
12 (80%)
Tumor volume (ml)
2.71 ± 3.20
7.27 ± 7.35
0.0005**
0.015*
<0.5
11 (27.5%)
0 ( 0 %)
0.5 - 3.9
20 (50 %)
8 (53.3%)
≧4
9 (22.5%)
7 (46.7%)
TABLE VII.
Clinical parameter predictors of PSA
failure with stage T1c prostate cancer
Varibalbe
Cases of PSA
failure /case
number
Relative risk
( 95% CI )
P valve
* P < 0.05 **P< 0.01
PSA ng/ml
≧10
7/15 (46.7%)
2.3
＜10
8/40 ( 20 % )
( 1.03 - 5.31 )
≧0.35
7/14 ( 50 % )
2.6
＜0.35
8/41 (19.5%)
( 1.14 - 5.78 )
≧20%
7/15 (46.7%)
2.3
＜20%
8/40 ( 20 % )
( 1.03 - 5.31 )
≧6
11/20 ( 55 % )
4.8
＜6
4/35 (11.4%)
( 1.76 - 13.1 )
0.086
PSA density
0.039*
% cancer of biopsies
0.086
Biopsy Gleason score
0.001**
TABLE VIII. Pathologic parameter predictors of PSA
failure in patients with stage T1c prostate cancer
Varibalbe
Cases of PSA
Failure /case number
Relative
risk
( 95% CI )
P valve
* P < 0.05 **P< 0.001
Pathology Gleason score
≧6
14/36 (38.9%)
7.4
＜6
1/19 ( 5.3% )
( 1.05 - 51.9 )
0.019*
Pathology Gleason score
≧7
11/28 (39%)
2.6
＜7
4/27 (15%)
(0.96 – 7.32 )
0.0829
Extracapsular tumor extension
(ECE)
Presence
11/18 (61.1%)
5.7
Absence
4/37 (10.8%)
( 2.09 - 15.3 )
≧2.5 ml
14/26 (53.9%)
15.6
＜2.5 ml
1/29 ( 3.5% )
( 2.2 - 110.6 )
0.0002**
Tumor volume
0.0001**
TABLE IX.
IX Multivariate survival analysis for Cox
proportional hazardous model in clinical parameter predictors
Model
Risk
Coefficients
Relative risk
Factors
(SE)
(95% CI)
P valueb
1
0.001*
I
Biopsy Gleason score
＜6 (n=35)
≧6 (n=20)
a
1.786
5.964
( 0.591 )
(1.874-18.978 )
Four variables parameters including PSA, PSA density, % cancer of biopsies and biopsy Gleason score
( classified by ≧6 or ＜6) were put into Cox proportional hazardous model (forward regression method) for
multivariate survival analysis.
b P value by Wald statistic. * P<0.01
Table X. Multivariate survival analysis for Cox proportional
hazardous model in pathologic parameter predictors
Model
Risk
Coefficients
Relative risk
Factors
(SE)
(95% CI)
P valueb
II
0.129
Extracapsular tumor extension
(ECE)
absence (n=37)
presence (n=18)
Tumor
1
0.999
2.715
( 0.659 )
( 0.747-9.872)
0.029*
volume
＜2.5 (n=29)
≧2.5 (n=26)
1
2.525
12.486
( 1.154 )
( 1.301-119.844)
Four variables parameters including pathology biopsy Gleason score ( classified by ≧6 or ＜6), extracapsular
tumor extension, tumor location and tumor volume were put into Cox proportional hazardous model (forward
regression method) for multivariate survival analysis.
b P value by Wald statistic. * P<0.05
a
Table XI.
XI Multivariate survival analysis for Cox proportional
hazardous model in clinical and pathologic parameter predictors
Coefficient
Relative risk
Risk
Model
Factors
(SE)
(95% CI)
P valueb
III
PSA ng/ml
0.0406*
＜10 (n=40)
≧10 (n=15)
1
1.129
3.093
( 0.551 )
( 1.050-9.111 )
Tumor volume
0.0019*
＜2.5 (n=29)
≧2.5 (n=26)
1
3.314
27.494
( 1.070 )
( 3.37-223.75 )
Eight variables parameters including PSA, PSA density, % cancer of biopsies, biopsy Gleason score ( classified by ≧6
or ＜6), pathology biopsy Gleason score ( classified by ≧6 or ＜6), extracapsular tumor extension, tumor location and
tumor volume were put into Cox proportional hazardous model (forward regression method) for multivariate survival
analysis.
b
P value by Wald statistic. * P<0.05
a
1
1.0
0.9524
.9
.8
Tumor volume< 2.5ml
(Total: 29 cases,
Number Events= 1 cases,
Number Censored= 28 cases)
0.7308
11
.7
.6
0.5329
.5
Tumor volume ≧2.5ml
(Total: 26 cases,
Number Events= 14 cases,
Number Censored= 12 cases)
.4
.3
0.3947
1
p<0.0001
.2
.1
0.0
0
1
2
3
4
5
Year
Figure. I Freedom from PSA failure survival in 55 patients received radical
retropubic prostatectomy for T1c prostate cancer calssified by
tumor volume ≧2.5ml or <2.5 ml.
6
DISCUSSION
Discussion (I) RRP vs. ECE
• RRP
with
neurovascular
(NV)
bundle
preservation for localized PC (Walsh PC, 1983).
Preoperative prediction of ECE at RRP is
important for NV preserving.
• Since PC with ECE might not be cured by a RRP
with NV preserving. ECE in 38-50% of patients
who had undergone bilateral NV-sparing RRP
presumed OCD (Catalona WJ, 1990; Bigg SW 1990).
Discussion (II) T1c : Variety
• Stage T1c PC is a unique group which may
include insignificant cancer, localized PC,
locally-advanced PC or metastatic PC.
• Disease-free survival in T1c group was
similar to T1a to T2a group but better
than in the T2b/c group (Lerner SE, 1996) .
T1c PC are pathologically similar to stage
T2 PC (Cookson MS, 1997)
Comparison the insignificant and minimal disease of T1c prostate cancer
among Epstein’s , Carter’s and this series
Series
Number
Insignificant
Minimal
This series (1996-2000)
n=55
3.6%
12.7%
40%
43.6%
Epstein (1988-1992)
n=157
16%
10%
37%
37%
Carter(1994-1996)
n=240
17%
12%
52%
19%
1. Insignificant ( OCD,tumor< 0.2 ml , Gleason score< 7).
2. Minimal ( OCD, tumor 0.2-0.5 ml, Gleason < 7).
3. Moderate ( tumor ≧0.5 ml, or ECE, Gleason <7)
4. Advanced (ECE with Gleason score ≧ 7 or more, or SM(+), SV(+),LN(+)
OCD: organ-confined disease; ECE: extracapsular tumor extension
SM: surgical margin; SV: seminal vesicle; LN: lymph node
Moderate
Advanced
Pathologic findings and tumor volume of patients with stage
T1c prostate cancer from different series.
Number
This series
(n=55)
Ogawa
1998
(n=54)
Oesterling 1993
(n=208)
Carter 1997
(n=240)
Tumor volume
Mean (ml)
3.96
3.94
6.4
Nil
<0.5 ml
20%
11%
Nil
33%
0.5-3.9ml
50.9%
49%
Nil
62%
≧4.0 ml
29.1%
29%
Nil
5%
5.1
6.2
Nil
Nil
67.2%
59%
53%
72%
9%
13%
12%
4%
Gleason score
Pathologic stage
OCD
SV(+) or L N(+)
OCD: organ-confined disease; SV: seminal vesicle; LN: lymph node
Pathologic staging in patients with nonpalpable stage T1c
disease receiving radical prostatectomy
Series
Year
No. of
Pts
Organ
Confined
Surgical Margin
(SM)
Positive
Lymph node(LN)
Positive
Oesterling et al.
1993
208
53%
34%
3%
Epstein et al.
1994
157
51%
17%
4%
Scaletsky et al.
1994
142
68%
28%
1.4%
Humphrey et al.
1996
78
59%
35%
0
Carter et al.
1997
240
72%
N/A
4% (+SV)
Ogawa et al.
1998
54
59%
N/A
13% (+SV)
Present series
2001
55
67%
26%
4%
* +SV : seminal vesicle involvement
Discussion (III) ECE vs. PSAD,Gleason
• From our data, PSAD and biopsy Gleason
score were the two best predictors for ECE,
with the best cut-off values being PSAD
≧0.35 and biopsy Gleason score ≧6.
• Ogawa O, 1998: PSAD ≧0.3 as a good
predictor for ECE in T1c PC.
• Carter HB, 1997: the best pretreatment
predictors of significant tumor were PSAD
>0.15 with the needle biopsy findings.
• Wills M. 1998: biopsies with a Gleason
score≧ 7 and > 1/6 (+) only 10% were
OCD.
Discussion (IV) ECE vs. PSA, F/T PSA
• As PSA increases, the incidence of ECE
increased (Ogawa O, 1998; Sanwick JM, 1998; Cookson
MS, 1996; Partin AW, 1993). Cut off of 10 ng/ ml
(Cookson). PSA cut-off of 17 ng/mL : 90% of
OCD (Ogawa).
• F/T PSA ratio provides useful prediction of
pathological features of patients with T1c PC.
(Morote J , 1999; Southwick PC, 1999; Elgamal AA, 1996).
>15% free PSA favorable outcome (Southwick
PC, 1999). It seemed not to be a good
predictor in this study, because different
assays and limited cases.
Discussion (V) ECE vs. Biopsy
• Preoperative sextant needle biopsy (number of
cores, site positive, % of positive cores, % cancer
in all cores) to predict pathologic features
(Sanwick JM1998,; Wills ML, 1998; Epstein JI 1999; Sebo
TJ, 2000).
• Our results revealed the relative risks of ECE were
2.7, 2.0 and 2.3 with ≧20% cancer in biopsies,
≧30% cancer in one lobe and ≧50% cancer in
one core, respectively.
Discussion (VI) PSA failure vs. TV
• PSA failure was 49% for tumor > 4 ml and 26%
for tumor < 4ml in patients with clinical T2 PC who
received RRP (Epstein JI, 1993), or a relative risk of
progression of 1.9 fold. In our series, we classify
tumor volume (TV) ≧4ml or < 4ml, the relative
risk of PSA failure was only 2.1 fold.
• TV ≧2.5 ml as cutoffs, the relative risk of PSA
failure as 12.5 to 27.5 folds in univariate and
multivariate survival analysis. Four year freedomfrom PSA disease survival for TV <2.5 ml was 95%,
and for TV ≧2.5ml was 39%.
Discussion (VI) PSA failure vs. PSA, Gleason
• Five-year freedom from PSA failure survival was
81% for low risk (PSA<10 ng/ml, Gleason score
<7) and 40% for high risk (PSA>10 ng/ml,
Gleason score ≧7) (Kupelian PA, 1997) .
• In our series, preoperative biopsy Gleason score is
a good predictor, with the relative risk of PSA
failure 4.8 fold higher for biopsy Gleason score ≧6
vs. <6. Preoperative PSA (RR: 3.09 fold, ≧10 vs.
<10) to be a good predictor of PSA failure in
multivariate analysis.
CONCLUSION
•
This is the first report related to prediction of
extracapsular tumor extension (ECE) and PSA failure
among Taiwanese patients with stage T1c prostate cancer
in an area with low age-specific prevalence of clinical
prostate cancers.
•
The 4 strongest predictors for ECE were PSAD
≧0.35, biopsy Gleason score ≧6, ≧20 percent
cancer in biopsies and PSA ≧10 ng/ml.
•
The single most significant predictor for PSA
failure was tumor volume≧2.5 ml. Other
significant predictors included PSA ≧10 ng/ml,
biopsy Gleason score ≧6, PSAD ≧0.35,
pathology Gleason score≧6 and the presence of
ECE.