Topic 2.
Management of High-risk and Locally-advanced M0 Prostate Cancer
第三次
臺灣晚期攝護腺癌專家共識
3 rd Taiwan Advanced Prostate
Cancer Consensus
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 86%
13%
1%
46 39%
39%
22%
30 42%
25%
3%
96 85%
13%
2%
95 81%
15%
4%
30 90%
10%
0%
Q2-1
Do you recommend lymph node dissection in men with cN0 cM0 high-risk prostate cancer undergoing prostatectomy?
A. Lymph node dissection in cN0M0 high-risk prostate cancer (Q2-1,2,22)
Survey Panelists St.Gallen
196 78%
17%
6%
55
35 97%
0 3%
5 44
86%
9%
5%
6 Responders
1. Yes, in the majority of patients 2. In a minority of selected patients 3. No
Non-responder, abstain, unqualified to answer
What is the minimum number of lymph nodes removed you consider adequate in the majority of men with cN0 cM0 high-risk prostate cancer?
survey panelists St.Gallen
168 10%
49%
34%
7%
83
34 3%
35%
56%
6%
7 41
0 17%
54%
29%
8 Responders
1. <5 2. 5-10 3. 11-19 4. ≥20
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 10%
51%
31%
8%
46 6%
44%
50%
0%
30 22%
44%
44%
0%
96 10%
47%
31%
12%
95 8%
52%
29%
11%
30 0%
36%
43%
Option 4 21%
Q2-2
Q2-22
Which lymph node regions should be sampled (minimal requirement) in men with cN0 cM0 high-risk prostate cancer?
a. Obturator, b. External iliac, c. Internal iliac, d. Pre-sacral, e. Common iliac
在St. Gallen的共識中，都贊成lymph node 應該被sampled的區域包括:
Obturator node: 98%；External iliac LN: 85%；Internal iliacLN: 90%。
超過半數的台灣醫師在施行radical prostatectomy 時，都會例行性同時做Lymph node dissection，範圍以Obturator，External iliac，和Internal iliac LN為主。少數醫師會做 到Common iliac LN。參與實體會議的專家多半是senior，high volume experts，因此他 們傾向routine應摘取的淋巴結數目大約偏多(minimal LNs number: 11-19)。
•評論分析：
Survey Panelists 181
60%
14%
14%
11%
70
35 71%
3%
23%
3%
4 Responders
1. a+b+c 2. a+b+c+d 3. a+b+c+e 4. a+b+c+d+e
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 61%
11%
17%
11%
46 60%
32%
4%
4%
30 50%
17%
0%
33%
96 71%
8%
14%
8%
95 66%
13%
13%
9%
30 69%
10%
10%
Option 4 10%
Q2-3
For high-risk / very high-risk patients with life expectancy >10 yrs, no significant co-morbidities, MRI showed extracapsular extension (T3a), and negative bone scan, which of the followings do you most recommend?
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 4 Option 5 Option 6 Option 7
175 75%
6%
4%
14%
1%
1%
0%
46 11%
0%
7%
80%
2%
0%
0%
30 38%
5%
10%
48%
0%
0%
0%
96 68%
6%
4%
18%
3%
1%
0%
95 56%
10%
8%
24%
1%
1%
0%
30 80%
7%
3%
10%
0%
0%
0%
survey panelists 237
59%
5%
5%
30%
1%
0 0 14
38 79%
0 0 21%
0 0 0 1 Responders
1. Radical prostatectomy ± adjuvant therapy
2. Neoadjuvant ADT followed by radical prostatectomy 3. Radiotherapy with short-term (~6 months) ADT 4. Radiotherapy with long-term (18~36 months) ADT 5. Radiotherapy with life-long ADT
6. Primary life-long ADT only 7. Watchful waiting
Non-responder, abstain, unqualified to answer
B. Treatment modality for cT3 or cN1 M0 prostate cancer (Q2-3,4,5)
Q2-4
For high-risk / very high-risk patients with life expectancy >10 yrs, no significant co-morbidities, MRI: showed seminal vesicle invasion (T3b), and negative bone scan, which of the followings do you most recommend?
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 4 Option 5 Option 6 Option 7 Option 8
175 52%
6%
2%
33%
3%
2%
0%
2%
46 2%
0%
4%
93%
0%
0%
0%
0%
30 24%
5%
5%
57%
0%
0%
0%
10%
96 47%
6%
3%
39%
0%
3%
0%
2%
95 38%
9%
7%
39%
2%
2%
0%
3%
30 57%
7%
0%
33%
0%
0%
0%
3%
Survey Panelists 238
40%
5%
3%
47%
2%
1%
0 3%
13
40 47.5%
0 0 52.5%
0 0 0 0 0 Responders
1. Radical prostatectomy ± adjuvant therapy
2. Neoadjuvant ADT followed by radical prostatectomy 3. Radiotherapy with short-term (~6 months) ADT 4. Radiotherapy with long-term (18~36 months) ADT 5. Radiotherapy with life-long ADT
6. Primary life-long ADT only 7. Watchful waiting
8. Order 2nd generation image study such as 18F-choline PET or 68Ga-PSMA PET/CT
Non-responder, abstain, unqualified to answer
Q2-5
For high-risk / very high-risk patients with life expectancy >10 yrs, no significant co-morbidities, MRI showed regional LN enlargement (≤ 2 LNs, ≤ 1.5 cm each), and negative bone scan, which of the followings do you most recommend?
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 4 Option 5 Option 6 Option 7 Option 8
175 7%
4%
5%
44%
15%
18%
7%
0%
46 18%
5%
7%
7%
25%
39%
0%
0%
30 5%
5%
14%
19%
33%
24%
0%
0%
96 10%
3%
3%
43%
17%
19%
4%
0%
95 8%
3%
6%
33%
17%
27%
7%
0%
30 17%
3%
0%
53%
7%
20%
0%
0%
Survey Panelists 233
9%
4%
6%
35%
19%
23%
5%
0 18
40 7.5%
0 5%
52.5%
10%
25%
0 0 1 Responders
1. Order 2nd generation image study such as 18F-choline PET or 68Ga-PSMA PET/CT
2. CT-guided LN biopsy/aspiration if accessible
3. Intend to do radical prostatectomy but abandon if frozen section of pelvic LN dissection confirm LN metastasis
4. Radical prostatectomy + pelvic LN dissection without waiting for frozen section report adjuvant therapy
5. Neoadjuvant ADT for 3-6 months, followed by CT/MRI to see if the nodes regresses in size
6. Radiotherapy with life-long ADT 7. Primary life-long ADT only 8. Watchful waiting
Non-responder, abstain, unqualified to answer
台灣醫師相當信賴MRI結果選擇治療方案。在第一輪通訊投票中，國內RO和URO對於治 療T3a與T3b的病人意見差異較大。放射腫瘤科醫師較常使用 Radiotherapy with long-term ADT treatment。泌尿科醫師則是傾向於選擇radical prostatectomy ± adjuvant therapy。
根據2017 EAU guideline建議，high risk病人不會送frozen section，即使LN positive，還 是把radical prostatectomy完成。有文獻指出，high risk病人，clinical node negative，
接受radical prostatectomy，縱使pathology node positive，追蹤十年的存活期比沒開刀 的好2倍，但證據等級不高。對於年輕、performance status很好的病人，開刀配合adju- vant therapy似乎是一個可行的選項。
•評論分析：
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 23%
42%
35%
46 45%
36%
18%
30 24%
62%
14%
96 14%
41%
44%
95 28%
36%
37%
30 7%
43%
50%
Q2-6
In men post-prostatectomy with pT3bN0, with undetectable postoperative PSA, do you recommend adjuvant radiation therapy when he has recovered urinary continence?
C. Role of adjuvant radiation therapy in high risk pN0 prostate cancer (Q2-6,7,8)
Survey Panelists St.Gallen
232 28%
43%
30%
19
39 18%
54%
28%
1 48
40%
33%
27%
3 Responders
1. Yes, in the majority of patients 2. Only if margin positive
3. No
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 42%
28%
29%
46 70%
20%
9%
30 76%
14%
10%
96 30%
28%
42%
95 47%
20%
33%
30 13%
37%
50%
Q2-7
In men post-prostatectomy with pN0, positive surgical margin, undetectable postoperative PSA, do you recommend adjuvant radiation when he has recovered urinary continence?
Survey Panelists St.Gallen
230 51%
26%
23%
21
39 54%
20%
26%
1 50
48%
27%
51%
2 Responders
1. Yes, in the majority of patients
2. Only if multifocal or extensive margins 3. No
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
手術後PSA undetectable，但病理報告有high risk recurrence factor時，究竟要不要進行 adjuvant radiotherapy (RT)，國內外的專家意見並無共識。約半數的國內專家會傾向給 予positive margins的患者adjuvant RT。而對於治療pT3b和Gleason 8-10的患者，國內外 專家都傾向不給予或是選擇性的給予adjuvant RT。
Swindle et al在2018年報導中，證明有positive surgical margin的患者，其cancer recurrence rate較高。三個大型的randomized trials (EORTC 22911, SWOG 8794, ARO 96-02)也都顯 示，adjuvant RT after surgery給予positive margins , GS 8-10, LN+, SV+的患者，可以增 加其存活率與降低轉移的風險。
•評論分析：
175 17%
25%
58%
46 23%
27%
50%
30 20%
45%
35%
96 10%
22%
67%
95 21%
27%
52%
30 0%
33%
67%
Q2-8
In men post-prostatectomy with pN0, Gleason 8-10 or Gleason Grade Group 4 or 5 tumor, undetectable postoperative PSA, do you recommend adjuvant radiation when he has recovered urinary continence?
Survey Panelists St.Gallen
230 19%
27%
54%
21
40 7.5%
7.5%
85%
1 50
20%
24%
56%
1 Responders
1. Yes, in the majority of patients
2. Only if multifocal or extensive margins 3. No
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 30%
42%
28%
46 59%
30%
11%
30 46%
31%
23%
96 26%
46%
28%
95 31%
49%
21%
30 31%
48%
21%
Q2-9
If you recommend adjuvant radiation therapy in men with high-risk pN0 disease post-pros- tatectomy, what field of radiation therapy do you recommend in the majority of men?
D. Treatment modality of adjuvant radiation therapy in high risk pN0 prostate cancer (Q2-9,10,11,12)
Survey Panelists St.Gallen
200 38%
39%
24%
51
42 62%
5%
33%
0 43
41%
51%
8%
8 Responders
1. Prostatic bed only
2. Prostatic bed plus whole pelvis
3. I do not recommend adjuvant radiation therapy on-responder, abstain, unqualified to answer
國內放射腫瘤專家認為，LN negative，surgical margin positive到底要照whole pelvis還 是prostatic bed就好，目前沒有很好的RCT研究。一般來說，照whole pelvis會讓副作用 增加，但對overall survival可能沒有明顯的幫忙。因此多數放射腫瘤專家，傾向於只照 prostatic bed，對於LN+，年紀較輕，Gleason score較高，術前PSA較高的病人，會考慮 prostatic bed plus whole pelvis。
•評論分析：
If you recommend adjuvant radiation therapy in men with high-risk pN0 disease post-pros- tatectomy, do you recommend adding ADT?
Survey St.Gallen
41 36%
32%
32%
9 1
Panelists 201
46%
28%
25%
29 21
33 55%
21%
24%
8 1 Responders
1. Yes, in the majority of patients 2. In a minority of selected patients 3. No
4. Abstain (I do not recommend adjuvant radiation therapy)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 45%
27%
29%
46 56%
23%
21%
30 37%
53%
11%
96 47%
25%
28%
95 49%
27%
23%
30 46%
19%
35%
Q2-10
If you recommend adding ADT to adjuvant radiation therapy in men with pN0 post-prostatectomy, what duration of ADT do you recommend in the majority of men?
Survey Panelists St.Gallen
184 23%
34%
40%
3%
40 27
37 8%
35%
57%
3 0 33
39%
43%
18%
17 1 Responders
1. 3-6 months 2. 6-12 months 3. 18-36 months 4. Lifelong
5. Abstain (I do not recommend adjuvant radiation the rapy ±ADT)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 24%
34%
40%
3%
46 33%
27%
39%
0%
30 0%
47%
47%
6%
96 29%
26%
42%
3%
95 25%
31%
39%
5%
30 30%
39%
30%
Option 4 0%
Q2-12
In which subgroup of men with high-risk pN0 prostate cancer do you recommend ADT with adjuvant radiation therapy?
Survey Panelists St.Gallen
176 19%
8%
73%
38 37
35 9%
0 91%
3 3 29
28%
3%
69%
14 8 Responders
1. pT stage ≥3b
2. Gleason 8-10 or Gleason Grade Group 4 or 5 3. In both subgroups (pT stage ≥3b and/or Gleason score ≥8)
4. I do not recommend concurrent ADT
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 19%
6%
57%
18%
46 8%
5%
64%
23%
30 5%
16%
74%
5%
96 15%
6%
55%
24%
95 17%
7%
59%
17%
30 18%
11%
46%
Option 4 25%
對於在high risk pN0, post-prostatectomy的患者，給予adjuvant RT。國內外的專家傾向 同時加上ADT治療，但是在ADT治療的時間長度，國外專家偏向6-12 months ADT, 國內 專家偏向給予較長的ADT (18-36 months)的治療。尤其針對pT stage ≥3b and/or Gleason score ≥8的患者。
•評論分析：
Q2-11
Survey URO RO MO High Vol Senior UO N
Option 1 Option 2 Option 3
175 46%
23%
31%
46 62%
7%
31%
30 61%
22%
17%
96 47%
18%
35%
95 55%
19%
25%
30 46%
21%
32%
Q2-13
Do you recommend adjuvant radiation therapy in men with pN1 disease (adequate LN sampling) and no local adverse factors (no pT3b, no R1) and undetectable postoperative PSA and who have recovered urinary continence?
E. Treatment modality of adjuvant radiation therapy in pN1 prostate cancer (Q2-13,14,15,16,17)
Survey Panelists St.Gallen
217 50%
20%
30%
34
39 72%
13%
15%
2 50
26%
30%
44%
2 Responders
1. Yes, in the majority of patients 2. In a minority of selected patients 3. No
Non-responder, abstain, unqualified to answer
If you recommend adjuvant radiation therapy in men with pN1 disease (adequate LN sampling) post-prostatectomy, what field of radiation therapy do you recommend in the majority of men?
Q2-14
Survey Panelists St.Gallen
38 3%
97%
0 3 0 33
0 97%
3%
17 2 Responders
1. Prostatic bed only
2. Prostatic bed plus whole pelvis 3. Other field definition
4. Abstain (including I do not recommend adjuvant radiation therapy)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
175 3%
97%
0%
46 0%
100%
0%
30 0%
93%
7%
96 2%
98%
0%
95 1%
99%
0%
30 0%
100%
0%
166 2%
97%
1%
49 36
In which subgroup of men with pN1 (adequate sampling) post-prostatectomy do you recommend adjuvant radiation therapy?
Q2-15
Survey Panelists St.Gallen
35 69%
23%
3%
6%
0
5 0 34
17%
50%
15%
3%
15%
18 0 Responders
1. In all patients
2. In men with 1 or 2 positive lymph nodes in the presence of intermediate- or high-grade, non-organ confined disease and in those with 3 to 4 lymph nodes 3. In patients with ≤2 positive lymph nodes independent of grade and T-stage
4. In patients with ≤3 positive lymph nodes independent of grade and T-stage
5. In patients with ≤4 positive lymph nodes independent of grade and T-stage
6. Abstain (including I do not recommend adjuvant radiation therapy)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 5
175 55%
29%
9%
2%
5%
46 69%
31%
0%
0%
0%
30 38%
56%
6%
0%
0%
96 51%
35%
9%
2%
4%
95 58%
28%
9%
2%
3%
30 58%
26%
11%
0%
5%
161 57%
32%
7%
1%
3%
60 30
Option 4
If you recommend adjuvant radiation therapy in men with pN1 disease do you recommend adding ADT?
Q2-16
Survey Panelists St.Gallen
200 87%
10%
3%
33 18
41 98%
2%
0 1 0 37
100%
0 0 15 0 Responders
1. Yes, in the majority of patients 2. In a minority of selected patients 3. No
4. Abstain (I do not recommend adjuvant radiation therapy)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
96 85%
9%
5%
95 84%
10%
6%
175 86%
10%
3%
46 92%
3%
5%
30 83%
17%
0%
30 85%
12%
4%
If you recommend adjuvant radiation therapy and ADT in the majority of men with pN1 disease what duration of ADT do you recommend?
Q2-17
Survey Panelists St.Gallen
196 7%
17%
62%
14%
32 23
41 0 5%
90%
5%
1 0 37
11%
30%
57%
2%
13 0 Responders
1. 3-6 months 2. 6-12 months 3. 18-36 months 4. Lifelong
5. Abstain (I do not recommend adjuvant radiation therapy)
Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
96 13%
15%
56%
16%
175 9%
19%
57%
16%
46 5%
11%
74%
11%
30 0%
17%
72%
11%
95 11%
20%
53%
16%
30 4%
12%
65%
Option 4 19%
大家同意pN1的患者，是屬於systemic disease。因此國內外專家大多數主張要給予 adjuvant RT在prostatic bed plus whole pelvis，並且加上18-36 months ADT。
•評論分析：
Q2-18
At what confirmed PSA level do you recommend starting salvage radiation therapy in the majority of men with isolated rising PSA alone after prostatectomy?
F. Timing and treatment modality of salvage radiation therapy (Q2-18, 19, 20, 21)
Survey Panelists
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 4 Option 5 Option 6
217 1%
4%
48%
20%
5%
23%
34 48
4%
40%
46%
10%
0 0 3
42 0 0 67%
33%
0 0 0
96 2%
0%
47%
24%
6%
2%
95 2%
0%
44%
20%
6%
28%
175 1%
3%
46%
21%
5%
25%
46 2%
9%
58%
16%
0%
14%
30 0%
0%
38%
19%
19%
25%
30 0%
0%
52%
31%
0%
17%
Responders 1. <0.1 ng/mL 2. 0.1 ng/mL 3. 0.2 ng/mL 4. 0.5 ng/mL 5. 1.0 ng/mL 6. >1 ng/mL
Non-responder, abstain, unqualified to answer
St.Gallen
Q2-19
What value is most close to the highest level of PSA at which you will still consider salvage radiation therapy (even if not ideal) in men with isolated rising PSA alone after prostatectomy?
Survey Panelists
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3 Option 4 Option 5 Option 6
213 18%
19%
33%
10%
6%
14%
38 46
13%
22%
28%
13%
2%
22%
6
42 12%
7%
45%
12%
10%
14%
0
96 21%
23%
37%
8%
3%
8%
95 21%
23%
28%
10%
6%
11%
175 20%
20%
37%
8%
6%
9%
46 19%
19%
14%
9%
9%
30%
30 6%
6%
53%
24%
0%
12%
30 31%
28%
31%
3%
7%
0%
Responders 1. 0.5 ng/mL 2. 1 ng/mL 3. 2 ng/mL 4. 5 ng/mL 5. 10 ng/mL 6. No upper limit
Non-responder, abstain, unqualified to answer
St.Gallen
Do you recommend adding ADT in combination with salvage radiation therapy?
Q2-20
Survey Panelists St.Gallen
229 70%
22%
8%
22
42 83%
17%
0 0 49
61%
29%
10%
1 Responders
1. Yes, in the majority of patients
2. In a minority of selected patients e.g. based on PSA level and PSA-DT
3. No
Non-responder, abstain, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
96 70%
19%
11%
95 74%
17%
19%
175 70%
22%
8%
46 71%
19%
10%
30 70%
25%
5%
30 57%
30%
13%
If you recommend adding ADT in combination with salvage radiation therapy which duration of ADT do you recommend in the majority of men?
Q2-21
Survey Panelists St.Gallen
214 13%
22%
54%
11%
20 17
42 2%
7%
89%
2%
1 0 44
34%
41%
25%
0 6 1 Responders
1. ADT for 3-6 months 2. ADT for 6-12 months 3. ADT for 18-36 months 4. Lifelong
5. Abstain (Including I do not recommend adding ADT) Non-responder, unqualified to answer
Survey URO RO MO High Vol Senior UO
N Option 1 Option 2 Option 3
96 14%
24%
52%
11%
95 12%
26%
49%
13%
175 13%
20%
55%
12%
46 10%
31%
59%
0%
30 11%
26%
37%
26%
30 14%
24%
59%
Option 4 3%
2017 EAU Guideline建議，在post-RP PSA level未超過0.5 ng/mL時，就可以開始Salvage RT (sRT)。國內外多數的專家大多主張PSA level超過0.2 ng/mL時，就應給予salvage RT，
而且合併ADT治療。St. Gallen專家傾向ADT治療應少於一年，但是國內專家則一致認為 ADT應合併治療18-36 months.
兩個大型的臨床試驗，GETUG-AFU 16 (Lancet Oncol 2016) 和RTOG 9601 (NEJM 2017)
，皆顯示sRT合併ADT治療，對於PSA progression-free survival和OS有顯著的改善。目 前仍有許多正在進行的臨床試驗，希望找出最佳的RT時間點，來治療high risk/locally advanced PC的患者 (aRT vs sRT)。
•評論分析：
