第三部分
Follow-up and Adjuvant / Salvage Treatments
評論分析:陳忠信
Cancer Consensus
局部侵犯性攝護腺癌
Locally Advanced Prostate Cancer
選項 1
所有專家 (N=46)
98%
泌尿科醫師 (N=33)
100%
放射腫瘤科醫師 (N=12)
92%
高治療量醫師 (N=33)
97%
資深醫師 (N=25)
96%
本題是指預期存活超過10年的病人,接受攝護腺根除術後,發現已有extracapsular exten- sion,但negative surgical margin。依據目前NCCN Guidelines Version 2.2016,攝護腺根除 術後,若有以下五種情況,可選擇adjuvant external beam radiotherapy (EBRT),包括: posi- tive surgical margin、extracapsular extension、seminal vesicle invasion、high Gleason score 與detectable postoperative PSA等,然而繼續觀察也是一項選擇。
SWOG 8794 (J Urol. 2009, 181: 956-62) 針對425名pT3的病人,隨機分派為adjuvant EBRT 與觀察兩組,結果發現adjuvant EBRT 較觀察組中位數存活時間,延長了1.9個月(OS: 15.2 vs. 13.3月)。另一個試驗EORTC 22911 (J Clin Oncol. 2007, 25: 4178-86)的分層分析中,
negative surgical margin的病人兩組間的結果並無差異。因此,針對此題中的病人,多數 專家均同意僅接受觀察即可,俟未來追蹤的變化再決定。
For patients with a life expectancy>10~15 years, DRE T2c, iPSA 21 ng/ml, after radical prostatectomy, pathology: significant extracapsular extension (pT3aN0), negative surgical margin (R0), and undetectable post-op nadir PSA, what do you do next? (單選)
【選項】
81% 1. Closely follow up PSA only
11% 2. Radiotherapy ± ADT after urinary continence recovery
0% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 2% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
3% 5. ADT without radiotherapy
2% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 0% 7. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪結果】
•評論分析:
子題3-1
3. Van der Kwast TH, Bolla M, Van Poppel H, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007; 25: 4178-86.
選項 1 2
所有專家 (N=46)
18%
77%
泌尿科醫師 (N=33)
23%
74%
放射腫瘤科醫師 (N=12)
8%
83%
高治療量醫師 (N=33)
15%
82%
資深醫師 (N=25)
20%
72%
For patients with a life expectancy>10~15 years, DRE T2c, iPSA 21 ng/ml, after radical prostatectomy, pathology: significant extracapsular extension (pT3aN0), negative surgical margin (R0), and post-op nadir PSA: 0.2~0.4 ng/ml, what do you do next? (單選)
【第一輪】
20% 1. Closely follow up PSA only
57% 2. Radiotherapy ± ADT after urinary continence recovery
8% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 6% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
6% 5. ADT without radiotherapy
2% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 0% 7. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
•參考文獻:
子題3-2
本題延續前一個病人的狀況,但多了detectable postoperative PSA。因此病人同時有兩個不 好的預後因子,significant extracapsular extension與detectable postoperative PSA。所以在第 二輪的投票中,多數專家已逐漸轉為支持RT。至於RT的時機,考量到漏尿的風險,多數專 家傾向待病人手術後,禁尿功能恢復,再施行RT。這樣的等候在EORTC 22911 (J Clin Oncol. 2007, 25: 4178-86)的試驗中,也有提及,需等病人無”major voiding problem”,才 會施行RT。
1. Van der Kwast TH, Bolla M, Van Poppel H, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007; 25: 4178-86.
本題的病人同時有兩個不好的預後因子,significant extracapsular extension與positive surgical margin,不過並無detectable postoperative PSA。據此,第一輪投票的結果相當分 歧,而第二輪的結果依然無較統一的答案。比較明顯的是,泌尿科醫師似乎傾向於僅需觀 察,但放射腫瘤科醫師則傾向於adjuvant RT,甚至有17%建議,應立即接受adjuvant RT。
此題考驗著兩科醫師對於PSA生理意義的解讀。
prostatectomy, pathology: significant extracapsular extension (pT3aN0), positive surgical margin (R1), and undetectable post-op PSA, what do you do next? (單選)
【第一輪】
50% 1. Closely follow up PSA only
35% 2. Radiotherapy ±ADT after urinary continence recovery
10% 3. Radiotherapy ±ADT immediately even though urinary continence has not recovered 2% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
2% 5. ADT without radiotherapy
1% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 0% 7. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
選項
1 2 3
所有專家 (N=46)
59%
32%
7%
泌尿科醫師 (N=33)
71%
23%
3%
放射腫瘤科醫師 (N=12)
25%
58%
17%
高治療量醫師 (N=33)
55%
36%
9%
資深醫師 (N=25)
60%
24%
12%
選項 2 3
所有專家 (N=46)
91%
7%
泌尿科醫師 (N=33)
90%
6%
放射腫瘤科醫師 (N=12)
92%
8%
高治療量醫師 (N=33)
91%
9%
資深醫師 (N=25)
84%
12%
For patients with a life expectancy>10~15 years, DRE T2c, iPSA 21 ng/ml, after radical prostatectomy, pathology: significant extracapsular extension (pT3aN0), negative surgical margin (R0), and post-op nadir PSA: 0.2~0.4 ng/ml, what do you do next? (單選)
【第一輪】
9% 1. Closely follow up PSA only
64% 2. Radiotherapy ± ADT after urinary continence recovery
22% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 2% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
1% 5. ADT without radiotherapy
0% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 1% 7. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
子題3-4
本題的病人同時有三個不好的預後因子,significant extracapsular extension,positive surgical margin,與detectable postoperative PSA。所以,無論是第一輪或是第二輪的結 果,或是泌尿科醫師與放射腫瘤科醫師,均顯示約9成的專家同意RT。此外,第二輪的專 家在選擇RT的時間點上,漸趨轉為待病人的禁尿功能恢復後,再施行RT。
選項 1 2
所有專家 (N=46)
84%
14%
泌尿科醫師 (N=33)
90%
10%
放射腫瘤科醫師 (N=12)
67%
25%
高治療量醫師 (N=33)
82%
15%
資深醫師 (N=25)
72%
24%
prostatectomy, pathology: seminal vesicle invasion (pT3bN0), negative surgical margin (R0), and undetectable post-op nadir PSA, what do you do next? (單選)
【第一輪】
69% 1. Closely follow up PSA only
18% 2. Radiotherapy ± ADT after urinary continence recovery
5% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 1% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
4% 5. ADT without radiotherapy
1% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 2% 7. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
•參考文獻:
本題的病人有另一種不好的預後因子seminal vesicle invasion,但surgical margin是乾淨 的,且無detectable postoperative PSA。針對這樣的病人,EORTC 22911 (J Clin Oncol.
2007, 25: 4178-86)的次群分析發現,給予adjuvant RT可能可以改善PSA failure rate,
但因樣本數太少,其效果並無統計意義。此題中病人雖然有seminal vesicle invasion,
但病理上並無法證明可能有殘留腫瘤(positive surgical margin),腫瘤指標也無法證實仍 有其他攝護腺或攝護腺癌組織(detectable PSA)。故在兩輪的投票中,繼續觀察是主要 的建議。第二輪投票更已達共識水準(84%)。泌尿科醫師與放射腫瘤科醫師的意見仍有 些許差異,泌尿科醫師較少選擇adjuvant RT。
1. Van der Kwast TH, Bolla M, Van Poppel H, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007; 25: 4178-86.
For patients with a life expectancy>10~15 years, DRE T2c, iPSA 21 ng/ml, after radical prostatectomy, pathology: seminal vesicle invasion (pT3bN0), negative surgical margin (R0), and post-op nadir PSA: 0.2~0.4 ng/ml, what do you do next? (單選)
【第一輪】
20% 1. Closely follow up PSA only
58% 2. Radiotherapy ± ADT after urinary continence recovery
10% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 2% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
9% 5. ADT without radiotherapy
0% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 1% 7. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
子題3-6
承接上題,病人除了有seminal vesicle invasion,更有detectable postoperative PSA,不過 surgical margin是乾淨的。多數專家(無論是泌尿科醫師或是放射腫瘤科醫師),在兩輪的 投票中,均認為須接受RT。此題與Q3-2 (extracapsular extension + detectable postopera- tive PSA)類似,專家們均建議RT。
但另一個需要注意的重點是,部分專家考慮,也許detectable PSA來自於microscopic metastasis。特別是在沒有positive surgical margin的情況下,卻有detectable PSA,micro- scopic metastasis是很有可能存在的,故有16%泌尿科醫師選擇給予荷爾蒙治療,但並無 放射腫瘤科醫師持此觀點。
選項 1 2 5
所有專家 (N=46)
9%
75%
11%
泌尿科醫師 (N=33)
13%
68%
16%
放射腫瘤科醫師 (N=12)
0%
92%
0%
高治療量醫師 (N=33)
9%
76%
9%
資深醫師 (N=25)
8%
68%
16%
選項 1 2
所有專家 (N=46)
52%
45%
泌尿科醫師 (N=33)
58%
42%
放射腫瘤科醫師 (N=12)
42%
50%
高治療量醫師 (N=33)
55%
42%
資深醫師 (N=25)
52%
44%
prostatectomy, pathology: seminal vesicle invasion (pT3bN0), positive surgical margin (R1), and undetectable post-op nadir PSA, what do you do next? (單選)
【第一輪】
38% 1. Closely follow up PSA only
50% 2. Radiotherapy ± ADT after urinary continence recovery
8% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 2% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
0% 5. ADT without radiotherapy
1% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 1% 7. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
承接Q3-5題,病人除了有seminal vesicle invasion,更有positive surgical margin,但並無 detectable postoperative PSA。兩輪的投票中,均無法達成共識,但第二輪的投票中,繼 續觀察的比率上升。此結果與Q3-3 (extracapsular extension + posivie surgical margin) 相 似,綜此,專家對於positive surgical margin是否真的有殘留腫瘤,或殘留的腫瘤是否需要 立即處置,有相當大的分歧。
EORTC 22911與ARO 96-02/AUO AP 09/95 (J Clin Oncol. 2009; 27: 2924-30)兩試驗,均發 現對於這些有positive surgical margin的病人給予adjuvant RT,對於病人的biochemical-free 與progression-free survial 有幫助。相反地,另一個觀察性研究發現 (Eur Urol. 2008; 54:
88-94),其實positive surgical margin的病人,若採用先觀察,等候PSA大於0.2 ng/ml再接 受salvage RT,其cancer-specific survival 仍可接受 (seminal vesicle invasion: 80%, extracap- sular extension + positive surgical margin: >97%),而7年內真的需要接受salvage RT的比例 僅有20%。
1. Van der Kwast TH, Bolla M, Van Poppel H, et al. Identification of patients with prostate cancer who benefit from immediate postoperative radiotherapy: EORTC 22911. J Clin Oncol 2007; 25: 4178-86.
2. Wiegel T, Bottke D, Steiner U, et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009; 27: 2924-30.
3. Loeb S, Roehl KA, Viprakasit DP, Catalona WJ. Long-term rates of undetectable PSA with initial observation and delayed salvage radiotherapy after radical prostatectomy. Eur Urol 2008; 54: 88-94.
•參考文獻:
選項 2 3
所有專家 (N=46)
91%
7%
泌尿科醫師 (N=33)
90%
6%
放射腫瘤科醫師 (N=12)
92%
8%
高治療量醫師 (N=33)
91%
9%
資深醫師 (N=25)
84%
12%
prostatectomy, pathology: seminal vesicle invasion (pT3bN0) and positive surgical margin (R1), and post-op nadir PSA 0.2~0.4 ng/ml, what do you do next? (單選)
【第一輪】
7% 1. Closely follow up PSA only
67% 2. Radiotherapy ± ADT after urinary continence recovery
20% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 1% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
2% 5. ADT without radiotherapy
1% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 1% 7. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
本題的病人同時有三個不好的預後因子,seminal vesicle invasion,positive surgical margin,與detectable postoperative PSA。無論是第一輪或是第二輪的結果,專家們均 無懸念,約9成同意儘早RT。相似的,第二輪的專家在選擇RT的時間點上,漸趨轉為 待病人的禁尿功能恢復後,再施行。
For patients with a life expectancy>10~15 years, DRE T2c, iPSA 21 ng/ml, after radical prostatectomy, pathology: organ-confined, negative surgical margin (R0), but microscopic nodal involvement (pT2N1), and undetectable post-op nadir PSA, what do you do next? (單選)
【第一輪】
39% 1. Closely follow up PSA only
34% 2. Radiotherapy ± ADT after urinary continence recovery
6% 3. Radiotherapy ± ADT immediately even though urinary continence has not recovered 1% 4. Radiotherapy only for Gleason ≧8 or with Gleason grade 5
19% 5. ADT without radiotherapy
0% 6. ADT without radiotherapy, only for Gleason ≧8 or with Gleason grade 5 1% 7. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
子題3-9
病人僅有microscopic nodal involvement,但negative surgical margin,也無detectable postoperative PSA。第一輪與第二輪投票均無共識,但泌尿科醫師較偏向觀察。相對 地,放射腫瘤科醫師則傾向adjuvant RT。僅有不到兩成的專家 (第一輪19%,第二輪 9%),建議要給予荷爾蒙治療。
然而,ECOG EST 3886 (Lancet Oncol. 2006; 7: 472-9)的隨機試驗中,給予有micro- scopic nodal involvement的病人立即的ADT,可有效延長病人的cancer-specific surviv- al (Evidence level 1),值得注意的是,該研究中,全部病人的78%,術後PSA都unde- tectable。但是此研究並未比較adjuvant RT與adjuvnat ADT。
選項 1 2 5
所有專家 (N=46)
57%
30%
9%
泌尿科醫師 (N=33)
65%
19%
13%
放射腫瘤科醫師 (N=12)
33%
58%
0%
高治療量醫師 (N=33)
58%
30%
6%
資深醫師 (N=25)
64%
16%
16%
with node-positive prostate cancer. J Clin Oncol 2014; 32: 3939-47.
3. NCCN guideline version 2.2016
選項 1 2
所有專家 (N=46)
80%
16%
泌尿科醫師 (N=33)
77%
16%
放射腫瘤科醫師 (N=12)
83%
17%
高治療量醫師 (N=33)
85%
12%
資深醫師 (N=25)
72%
20%
For patients with a life expectancy 10~15 years, after radical prostatectomy, pathology:
pT3aN0R0 (negative surgical margin), ECOG PS 0, PSA recurrence (>0.2 ng/ml) within 2 years of prostatectomy, and no evidence of distant metastasis, what do you do next? (單選)
【第一輪】
55% 1. Salvage radiotherapy (± ADT) as soon as possible 21% 2. Salvage radiotherapy (± ADT) when PSA > 0.5 ng/mL 11% 3. Salvage radiotherapy (± ADT) when PSA > 1 ng/mL
3% 4. Salvage radiotherapy (± ADT) only if images show suspected local recurrence 2% 5. Salvage radiotherapy (± ADT) only if biopsy confirms local recurrence
1% 6. Salvage ADT 6% 7. Observation only 1% 8. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
病人體能狀況良好,手術病理報告顯示為pT3a且negative surgical margin,然在術後兩 年內發生PSA recurrence (> 0.2 ng/ml),並無遠端轉移之明顯證據。第一輪投票結果顯 現,有87%的專家建議應予salvage RT,55%更建議應立即執行salvage RT,其他則建 議須待PSA逐步上升到0.5或1 ng/ml後才需執行。
其實針對是否需進行salvage RT與何時應執行salvage RT,截至本文撰寫時,仍無random- ized trials發表,僅有兩篇retrospective cohorts可供參考。Johns Hopkins (JAMA. 2008;
299: 2760-9) 曾經報導一組cohort 635位病人,發生PSA recurrence,接受salvage RT比 未接受者死亡率較低 (多變數分析下的死亡風險比Hazard ratio = 0.32)。其中,針對PSA doubling time小於6個月的病人,salvage RT更能顯現其保護效果,減少死亡風險達84%
子題3-10
因此,第二輪投票的結果,無論是泌尿科醫師或放射腫瘤科醫師,均達成共識,認為 應盡速讓病人接受salvage RT。
1. Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy.
JAMA 2008; 299: 2760-9.
2. Cotter SE, Chen MH, Moul JW, et al. Salvage radiation in men after prostate-specific antigen failure and the risk of death. Cancer 2011; 117: 3925-32.
3. Carrie C, Hasbini A, de Laroche G, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol 2016;
17: 747-56.
•參考文獻:
選項 1 2 3 7
所有專家 (N=46)
52%
32%
7%
7%
泌尿科醫師 (N=33)
42%
35%
10%
10%
高治療量醫師 (N=33)
55%
33%
0%
9%
放射腫瘤科醫師 (N=12)
75%
25%
0%
0%
資深醫師 (N=25)
40%
32%
12%
12%
For patients with a life expectancy 5~10 years, after radical prostatectomy, pathology:
pT3aN0R0 (negative surgical margin), ECOG PS 0, PSA recurrence (>0.2 ng/ml) within 2 years of prostatectomy, and no evidence of distant mets, what do you do next? (單選)
【第一輪】
35% 1. Salvage radiotherapy (± ADT) as soon as possible 24% 2. Salvage radiotherapy (± ADT) when PSA > 0.5 ng/mL 15% 3. Salvage radiotherapy (± ADT) when PSA > 1 ng/mL
5% 4. Salvage radiotherapy (± ADT) only if image showed suspected local recurrence 4% 5. Salvage radiotherapy (± ADT) only if biopsy confirmed local recurrence
7% 6. Salvage ADT 11% 7. Observation only 0% 8. None of the above
0% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
承接上題,但病人的預期餘命較短,僅有5~10年。第一輪投票結果顯現, 74%的專家建 議應予salvage RT,但35%更建議,應立即執行salvage RT,其他則建議,須待PSA逐步 上升到0.5或1 ng/ml後才需執行。相較於前一題 (Q3-10) 於第二輪投票有明顯共識,此題 的第二輪投票結果,則仍有明顯分歧,特別是泌尿科醫師與放射腫瘤科醫師間差異極 大。對於此餘命較短僅有5~10年的病人,泌尿科醫師偏向略為保守的治療,如延後病 人接受salvage RT的時機。反之,放射腫瘤科醫師則不受影響,多數仍建議應盡速接受 salvage RT。第二輪討論中可以發現,泌尿科醫師擔心salvage RT的副作用,會影響病
子題3-11
biochemical recurrence (PSA >2 ng/ml) but no distant metastasis at 5 years after radiotherapy (definitive EBRT + 2 years of adjuvant ADT), what do you do next? (單選)
【選項】
3% 1. Salvage prostatectomy without pathological proof of local recurrence 38% 2. Salvage prostatectomy only if biopsy proves local recurrence
3% 3. Salvage energy ablation (cryoablation or HIFU) without pathological proof of local recurrence
28% 4. Salvage energy ablation (cryoablation or HIFU), only if biopsy proves local recurrence 0% 5. Brachytherapy without pathological proof of local recurrence
3% 6. Brachytherapy, only if biopsy proves local recurrence 21% 7. Restart ADT alone
2% 8. Chemohormonal therapy 0% 9. Clinical trials
1% 10. Observation
1% 11. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪結果】
•評論分析:
此題中的病人體能狀況良好,接受RT與2年的ADT,於治療起始5年時發現PSA recurrence。
第一輪投票中,69%的專家認為須確認是局部復發後,才進行salvage prostatectomy (38%)、
cryoablation (28%)、或brachytherapy (3%)。另有21%的專家認為應直接給予ADT。
在RT失敗後,有許多挽救性的局部治療方式曾被提出,例如salvage radical prostatectomy (J Urol. 1995; 153: 104-10)、salvage cryoablation (BJU Int. 2007; 100: 760-4)、與 salvage brachytherapy (Cancer. 2007; 110: 1405-16)。然而,孰優孰劣並無直接對照的 選項
2 4 7
所有專家 (N=46)
64%
22%
11%
泌尿科醫師 (N=33)
53%
31%
16%
放射腫瘤科醫師 (N=12)
92%
0%
0%
高治療量醫師 (N=33)
70%
15%
12%
資深醫師 (N=25)
60%
24%
12%
試驗可供參照。不過,無論何種挽救性局部治療的文獻報告,均會於證實病人確有攝 護腺局部復發,且無遠處轉移,才會執行局部挽救性治療。此外NCCN guidelines version 2.2016也針對這些病人且擁有三項特徵,預期餘命>10年、cT1-2、與目前PSA<10 ng/ml,才評估是否需要進行局部挽救性治療。如非上述病人,則建議僅須重啟ADT或 觀察即可。因此,部分專家建議給予病人荷爾蒙治療即可。在第二輪的投票中,專家 們的決定與前輪間並未變化太大,泌尿科醫師與放射腫瘤科醫師間的差異也不大。多 數專家仍贊同只要確認有局部復發的證據,即應接受局部挽救性治療。
1. Rogers E, Ohori M, Kassabian VS, Wheeler TM, Scardino PT. Salvage radical prostatec tomy: outcome measured by serum prostate specific antigen levels. J Urol 1995; 153:
104-10.
2. Ismail M, Ahmed S, Kastner C, Davies J. Salvage cryotherapy for recurrent prostate cancer after radiation failure: a prospective case series of the first 100 patients. BJU int 2007; 100: 760-4.
3. Allen GW, Howard AR, Jarrard DF, Ritter MA. Management of prostate cancer recurrences after radiation therapy-brachytherapy as a salvage option. Cancer 2007; 110: 1405-16.
4. NCCN guideline version 2.2016
•參考文獻:
選項 2 4 8 9
所有專家 (N=46)
40%
12%
19%
23%
泌尿科醫師 (N=33)
37%
13%
20%
20%
高治療量醫師 (N=33)
34%
16%
16%
28%
放射腫瘤科醫師 (N=12)
42%
8%
17%
33%
資深醫師 (N=25)
36%
16%
8%
32%
have biochemical recurrence while on adjuvant ADT (M0 CRPC), but no distant metastasis after definitive radiotherapy, what do you do next? (單選)
【第一輪】
35% 1. Salvage radiotherapy (± ADT) as soon as possible 24% 2. Salvage radiotherapy (± ADT) when PSA > 0.5 ng/mL 15% 3. Salvage radiotherapy (± ADT) when PSA > 1 ng/mL
5% 4. Salvage radiotherapy (± ADT) only if image showed suspected local recurrence 7% 1. Salvage prostatectomy without pathological proof of local recurrence
27% 2. Salvage prostatectomy only if biopsy proves local recurrence
3% 3. Salvage energy ablation (cryoablation or HIFU) without pathological proof of local recurrence
15% 4. Salvage energy ablation (cryoablation or HIFU), only if biopsy proves local recurrence 0% 5. Brachytherapy without pathological proof of local recurrence
2% 6. Brachytherapy, only if biopsy proves local recurrence 4% 7. Restart ADT alone
25% 8. Chemohormonal therapy 8% 9. Clinical trials
5% 10. Observation 1% 11. None of the above
2% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
此題中的病人體能狀況良好,接受RT及adjuvant ADT過程中,就出現PSA recurrence,定 義上屬於未轉移的CRPC (m0 CRPC)。第一輪投票中,有54%的專家認為可接受局部挽救
截至目前為止,針對m0 CRPC的病人,並無科學證據,顯示何種治療可有效延長病人的 存活時間。NCCN guideline version 2.2016也提到這類的病人,並無特別建議,但鼓勵 參與臨床試驗,或是僅繼續目前的治療,並增減anti-androgen、corticosteroid等。但是 化學治療並非NCCN選項之一,直至病人發生轉移後,再依據mCRPC的治療決策進行。
Stampede study比較研究中的次群體非轉移攝護腺癌病人,接受ADT或ADT合併化學治 療的療效,結果顯示ADT合併化學治療,可以延長failure-free survival,但並不能延長 病人overall survival。
第一輪投票時,有許多專家並不知道,台灣已經參與多個全球性m0 CRPC的新藥臨床試 驗,且仍在收案中,故選擇臨床試驗的比率不高。經會議討論後,在第二輪的投票結 果中,已有高達23%專家轉向臨床試驗。話雖如此,專家對於這類病人應該是做全身性 的治療(化學治療或二線荷爾蒙的臨床試驗),或是局部性挽救治療,意見仍然分歧。
1. NCCN guideline version 2.2016
2. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016; 387(10024): 1163-77.
•參考文獻:
選項 2 4 7 8 9
所有專家 (N=46)
9%
9%
74%
0%
0%
泌尿科醫師 (N=33)
7%
10%
77%
0%
0%
高治療量醫師 (N=33)
13%
6%
75%
0%
0%
放射腫瘤科醫師 (N=12)
17%
8%
67%
0%
0%
資深醫師 (N=25)
8%
4%
80%
0%
0%
years who have biochemical recurrence (PSA >2 ng/ml) but no distant metastasis at 5 years after radiotherapy (definitive EBRT + 2 years of adjuvant ADT), what do you do next? (單選)
【第一輪】
0% 1. Salvage prostatectomy without pathological proof of local recurrence 8% 2. Salvage prostatectomy only if biopsy proves local recurrence
6% 3. Salvage energy ablation (cryoablation or HIFU) without pathological proof of local recurrence
19% 4. Salvage energy ablation (cryoablation or HIFU), only if biopsy proves local recurrence 1% 5. Brachytherapy without pathological proof of local recurrence
3% 6. Brachytherapy, only if biopsy proves local recurrence 43% 7. Restart ADT alone
7% 8. Chemohormonal therapy 2% 9. Clinical trials
8% 10. Observation 0% 11. None of the above
2% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
承接Q3-12,但此題中的病人預期存活期較短,其接受RT與2年的ADT後,於治療起始後 5年時,發現PSA recurrence。與Q3-12題的結果不同,此題第一輪投票中,反而有43%的 專家認為需給予ADT,而僅有37%的專家認為,須進行局部挽救性治療。第二輪投票時,
專家甚至已就ADT達成共識。NCCN guidelines version 2.2016針對這些預期餘命小於10 年RT failure的病人,的確是建議觀察或僅ADT。
1. NCCN guideline version 2.2016
•參考文獻:
選項 4 7 8 9
所有專家 (N=46)
16%
14%
28%
28%
泌尿科醫師 (N=33)
20%
20%
23%
27%
高治療量醫師 (N=33)
9%
16%
28%
28%
放射腫瘤科醫師 (N=12)
8%
0%
33%
33%
資深醫師 (N=25)
12%
12%
24%
36%
who have biochemical recurrence while on adjuvant ADT (M0 CRPC), but no distant metastasis after definitive radiotherapy, what do you do next? (單選)
【第一輪】
0% 1. Salvage prostatectomy without pathological proof of local recurrence 6% 2. Salvage prostatectomy only if biopsy proves local recurrence
6% 3. Salvage energy ablation (cryoablation or HIFU) without pathological proof of local recurrence
15% 4. Salvage energy ablation (cryoablation or HIFU), only if biopsy proves local recurrence 0% 5. Brachytherapy without pathological proof of local recurrence
2% 6. Brachytherapy, only if biopsy proves local recurrence 15% 7. Restart ADT alone
31% 8. Chemohormonal therapy 13% 9. Clinical trials
8% 10. Observation 1% 11. None of the above
2% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
承接Q3-13題,此題中的病人預期餘命小於10年,接受RT及adjuvant ADT過程中,就出 現PSA recurrence,定義上屬於未轉移的m0 CRPC。相較於Q3-13題的結果,此題第一輪 投票中,有29%的專家認為可接受局部挽救性治療,31%則給予化學治療,也有13%的 專家提出可參與臨床試驗治療。
截至目前為止,針對m0 CRPC的病人並無嚴謹的科學證據,顯示何種治療可有效延長病 人的存活時間。NCCN guideline version 2.2016對這類病人的建議,並未依據預期餘命 的長短進行分類;雖無特別建議,但傾向可安排他們參與臨床試驗;或是僅繼續目前 的治療,並增減anti-androgen、corticosteroid等,但是化學治療並非NCCN選項之一。
由於第一輪投票時,許多數專家並不知道,台灣已經參與多個m0 CRPC的試驗,經會議 討論與提示後,在第二輪的投票中,高達28%專家轉向臨床試驗。相較於Q3-13題的病 人,本題專家對於這類病人較偏向做全身性的治療 (化學治療或二線荷爾蒙的輪床試驗),
而較少局部性挽救治療。
1. NCCN guideline version 2.2016
•參考文獻:
when do you think is about time to initiate metastasis survey? (單選)
【第一輪】
27% 1. High PSA level or unfavorable PSA kinetics
8% 2. Until symptomatic, such as LUTS, BW loss, bone pain, obstructive uropathy, etc.
54% 3. Either PSA or symptoms
9% 4. Periodically (eg. every 6 to 24 months) 0% 5. None of the above
1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
Watchful waiting (即observation),定義為確保病人生活品質,但不主動提供治癒性的治 療方法,僅在癌症有可能會危及或已危及病人生活品質時,才給予緩和性的治療,如 palliative TURP或ADT等。因此,watchful waiting為有多種共病(co-morbidities)或預期壽 命不長的局部攝護腺癌病人的選項之一。其追蹤方式至今沒有固定模式,對於何時需要 進行metastasis survey也無定論。此題僅用於調查專家們的意見,第一輪中有54%的專家 會依據病人的PSA升高或出現症狀,來決定是否進行metastasis survey。第二輪中,此比 例提高到90% (達成共識),且泌尿科醫師與放射腫瘤科醫師間並無太大差別。
選項 3
所有專家 (N=46)
90%
泌尿科醫師 (N=33)
87%
放射腫瘤科醫師 (N=12)
100%
高治療量醫師 (N=33)
94%
資深醫師 (N=25)
92%
For patients with LAPC, what do you think the definition of a successful treatment is?
【第一輪】
20% 1. Closely follow up PSA only
58% 2. Radiotherapy ± ADT after urinary continence recovery
67% 1. Disease cured, without significant treatment-related complications 7% 2. Disease cured, even with significant treatment-related complications
13% 3. Patients die of other causes, even though there is biochemical or local recurrence but no metastasis
11% 4. Patients die of other causes, even though there is asymptomatic metastasis 1% 5.Patients die of other causes, even though there is symptomatic metastasis 1% X. Abstain (棄權,不表示意見)
Y. Unqualified to answer (平常臨床業務,不處理此類病人)
【第二輪】
•評論分析:
相較於多數癌症,大部分攝護腺癌屬於進展較慢的一個,故有相當比例的病人雖罹患攝 護腺癌,即使未治療,也不會死於此疾病。既然如此,如何定義成功的攝護腺癌治療,
就有相當的討論空間。第一輪的投票結果,74%的專家認為須治癒攝護腺癌,且67%的 專家甚至認為除了治癒,更應無顯著的治療副作用。第二輪的結果與第一輪類似。
然而另一層考量是,如同active surveillance或watchful waiting,可以避免掉治療造成的 副作用,只要病人死亡時,不是死於攝護腺癌,也沒有攝護腺癌造成的痛苦,是否就算 治療成功? 若是真的要做到根治疾病,且沒有併發症,則真正的成功率可能就不高了。
選項 1 2 3
所有專家 (N=46)
79%
7%
9%
泌尿科醫師 (N=33)
73%
10%
10%
放射腫瘤科醫師 (N=12)
92%
0%
8%
高治療量醫師 (N=33)
78%
6%
13%
資深醫師 (N=25)
80%
4%
12%