KO 16. 근치적 전립선 절제술 후 림프절 전이가 확인된 경우 남성호르몬 박탈용법을 보조적으로 투여하는 것이 생화학적 재발이 확인된 이후 시작하는 것보다 생존율이 높은가? 문서 원본 보기

{| class="wikitable mw-collapsible"
!권고사항
!권고수준
!근거수준
|-
|고위험 전립선암 환자에서 근치적 전립선 절제술과 골반림프절절제술 후 림프절 전이가 확인되면 보조적 남성호르몬 박탈요법을 권고한다.
|B
|II
|}

==개요==

고위험 전립선암 환자에서는 근치적 전립선 절제술을 시행한 후에도 생화학적 재발이나 임상적 전이로 인하여 추가적인 치료가 필요한 경우가 많으며<sub>[1]</sub> 특히 근치적 전립선 절제술 및 골반림프절 절제술을 시행 받은 후 림프절 전이가 확인된 환자들은 예후가 좋지 않다<sup>[2,3]</sup>. 따라서 근치적 전립선 절제술 후 림프절 전이가 확인된 경우에는 추가적으로 체외방사선요법을 시행하거나<sup>[4]</sup> 남성호르몬 박탈요법을 시행할 수가 있는데 추가 치료의 적절한 시기와 방법에 대해서는 아직 논란이 존재한다.

Messing 등은 Eastern Cooperative Oncology Group (ECOG) randomized clinical trial에서 98명의 근치적 전립선 절제술 후 림프절 전이가 있는 환자들을 대상으로 남성호르몬 박탈요법을 즉시 시행한 군과 생화학적 재발 때까지 기다린 후 시행한 군을 비교한 후 즉각적인 남성호르몬 박탈 요법이 생존율을 향상시킨다는 연구 결과를 발표하였다. 47명의 남성호르몬 치료 군과 51명의 대조 군을 비교하여 분석하였으며 즉각적인 남성호르몬 박탈요법을 시행한 군에서 전체 생존율이 유의하게 높았음을 확인하였다(Hazard ratio=1.84 [95% CI 1.01 to 3.35], p=0.04)<sup>[5]</sup>. 하지만 등록된 환자 수가 적고 연구 디자인에 한계점이 발견되어 신뢰성은 떨어지는 것으로 알려져 있다. Boorjian 등은 2007년 507명의 근치적 전립선 절제술 후 림프절 전이가 있는 환자들을 대상으로 즉각적인 남성호르몬 박탈 요법 여부에 따라 생존율을 비교 분석하였다. 총 455명(89.7%)이 수술 후 즉각적인 남성호르몬 박탈요법을 시행 받았으며 이는 생화학적 재발의 위험과(P<0.001) 국소 재발의 위험을 유의하게 낮추었다(P=0.004). 하지만 암의 전신으로의 진행과 질병 특이 생존율에는 영향을 주지 못하였다(p=0.4)<sup>[6]</sup>.

또한 2007년 업데이트된 American Society of Clinical Oncology (ASCO) 가이드라인에선 기존의 임상 연구와 논문들을 메타 분석하여 전이성 또는 진행성 전립선암 환자에서 즉각적인 남성호르몬 박탈 요법은 질병 특이 사망률에 대한 상대적 위험도를 17% 감소시키나 질병 비 특이 사망률에 대한 상대적 위험도는 15% 증가시켜 전체 생존율에는 영향을 주지 않는 것으로 보고하였다<sup>[7-11]</sup>. 이후 Wong 등에 의한 연구에서도 731명의 림프절 전이가 있는 환자 중에 209명이 120일 이내의 호르몬 박탈 요법을 받았으나 전체 생존율은 증가시키지 못한 것으로 발표되었다(Hazard ratio=0.97 [95% CI 0.71 to 1.27]). 또한 질병 특이 생존율에도 유의한 차이가 없었다(Hazard ratio=0.97 [95% CI 0.56 to 1.68])<sup>[12]</sup>. 국내에서도 Park 등이 근치적 전립선 절제술 후 림프절 전이가 있는 40명을 대상으로 후향적 분석을 시행하였다. 즉각적인 남성호르몬 박탈요법을 시행 받은 군과(n=18) 대조 군(n=22)을 비교하였으며 5년 무 진행 생존율, 질병 특이 생존율, 전체 생존율은 남성호르몬 치료 군에서 각각 72.2%, 83.3%, 72.2%, 그리고 대조 군에서는 각각 77.2%, 86.4%, 72.8%로 차이가 없음을 발표하였다<sup>[13]</sup>.

따라서 현재까지의 발표된 논문 및 가이드라인에서는 즉각적인 남성호르몬 박탈 요법이 전체 생존율 향상에 기여한다는 확실한 근거는 없으므로 의사의 판단이 가장 중요하며 즉각적인 남성호르몬 박탈 요법을 강하게 권고하지 않고 있다.

==기존 가이드라인 요약 및 수용성, 적용성 평가==

2015년 대한비뇨기종양학회가 발간한 전립선진료지침에 따르면 골반림프절절제술 후 림프절 전이가 확인된 경우 남성호르몬 박탈요법을 시작하는 것을 권고하고 있으나<sup>[5]</sup> 경우에 따라 술 후 PSA 감시를 통하여 재발이 확인된 이후 치료를 시작할 수도 있다고 기술되어 있다<sup>[11,12]</sup>. 2016년 EAU (European Association of Urology) 가이드라인에서는 골반림프절절제술 후 림프절 전이가 확인된 경우 남성호르몬 박탈요법을 시작하는 것을 권고하고는 있으나 광범위림프절 절제술 후 림프절 전이가 2개 이하이면서 PSA <0.1 ng/mL, 전이 림프절의 피막 외 침범이 없을 경우에는 경과 관찰을 할 수 있다고 기술하고 있다<sup>[5,14]</sup>. 2016년 NCCN (National Comprehensive Cancer Network) 가이드라인에서는 즉각적인 남성호르몬 박탈요법을 시작하거나(category 1) 경과 관찰 후 증상의 발현이나 PSA 상승이 있을 경우 시작할 수 있다고 기술하고 있다<sup>[5,11,12]</sup>. 그러나 2014년 NICE (National Institute for Health and Care Excellence) 및 2010년 CCAACN (Cancer Council Australia/Australian Cancer Network) 가이드라인에서는 2006년 발표된 Cochrane database of systematic review에서 5년 전체 생존율에 차이가 없는 것을 인용하여(P=0.2) 골반림프절절제술 후 림프절 전이가 확인되더라도 즉각적인 남성호르몬 박탈요법을 시작하는 것은 권고하지 않고 있다<sup>[5,15]</sup>.

{| class="wikitable mw-collapsible"
! colspan="5" |KQ 16. 고위험 전립선암 환자에서 근치적 전립선 절제술 후 림프절 전이가 확인된 경우 남성호르몬 박탈용법을 보조적
으로 투여하는 것이 생화학적 재발이 확인된 이후 시작하는 것보다 생존율이 높은가?
|-
!지침(제목)
!권고
!권고등급
!근거수준
!page
|-
|1. 2015 KUOS
|골반림프절절제술 후 림프절 전이가 확인된 경우 남성호르몬 박탈요법을 시작한다. 하지만, 경우에 따라 술 후 PSA 감시를 통하여 재발이 확인된 이후 치료를 시작할 수도 있다.
|A
|1b 
|28
|-
|2. EAU 2016 
|Upon detection of nodal involvement during RP:

•Offer adjuvant ADT for node-positive (pN+); 1b A

•Discuss adjuvant ADT with additional radiotherapy;2b A 

•Offer observation (expectant management) to a patient after eLND and <2 nodes show microscopic involvement with a PSA <0.1 ng/mL and absence of
extranodal extension. 2b B
|A
|1b (LN pathology 결과에 따라 설명하고 있음)
|36
|-
|5. NCCN 2016
|Lymph node metastasis: ADT (category 1) ± EBRT(category 2B) or Observation
|A
|표시는 없지만 RCT 바탕으로 guideline 작성됨
|PROS-5
|-
|6. NICE 2014
|Do not offer adjuvant hormonal therapy in addition to radical prostatectomy, even to men with margin-positive disease, other than in the context of a clinical trial.
|A
|Ib
|263
|-
|9. CCAACN 2010
|For locally advanced prostate cancer (pT3 or higher), anti-androgens as an adjuvant monotherapy to radical prostatectomy are not recommended.
|B
|II
|34
|}
{| class="wikitable mw-collapsible"
! colspan="2" |지침(제목)
!1. 2015 KUOS
!2. EAU 2016 
!5. NCCN 2016
!6. NICE 2014
!9. CCAACN 2010
|-
| rowspan="4" |수용성
|인구 집단(유병률, 발생률 등)이 유사하다.
|예
|아니오
|아니오
|아니오
|아니오
|-
|가치와 선호도가 유사하다.
|예
|예
|예
|예
|예
|-
|권고로 인한 이득은 유사하다
|예
|예
|예
|예
|예
|-
|해당 권고는 수용 할 만하다. 
|예
|예
|예
|아니오
|아니오
|-
| rowspan="4" |적용성
|해당 중재/장비는 이용 가능하다. 
|예
|예
|예
|예
|예
|-
|필수적인 전문기술이 이용 가능하다.
|예
|예
|예
|예
|예
|-
|법률적/제도적 장벽이 없다. 
|예
|예
|예
|예
|예
|-
|해당 권고는 적용 할 만하다. 
|예
|예
|예
|아니오
|아니오
|}

가이드라인이 서로 다른 권고를 보여주고 있고 내용상 즉각적인 치료를 권고하지 않는 부분이 있다. 하지만 재발이나 림프절 전이여부에 따라 치료를 권고하고 있다. 이러한 관점에서 적용성과 수용성 여부를 판단하였다.

==업데이트 근거 요약==

근치적 전립선 절제술 후 림프절 전이가 있는 환자에서 즉각적인 남성호르몬 박탈요법을 시행하는 것이 생존율 향상에 이점이 있는지에 대해서는 대규모 무작위 대조군 시험이 부족한 관계로 아직 논란이 존재한다. 하지만 2017년도 발표된 대규모 다 기관 연구에서 Touijer 등은 1338명의 근치적 전립선 절제술 후 림프절 전이가 있는 환자들을 경과 관찰 군(28%), 남성호르몬 박탈요법 시행 군 (49%), 남성호르몬 박탈요법과 체외방사선요법을 같이 시행한 군(23%)으로 나누어 생존율을 비교한 결과 즉각적인 남성호르몬 박탈요법을 시행한 군이 생화학적 재발 때까지 경과 관찰한 군에 비해 질병 특이 생존율은 유의하게 향상시켰으나(Hazard ratio=0.64, 95% CI: 0.43 to 0.95, p=0.027) 전체 생존율에는 영향을 미치지 못했다고 보고하였다(Hazard ratio=0.9, 95% CI: 0.65 to 1.25, p=0.5)<sup>[16]</sup>.

이러한 결과는 남성호르몬 박탈요법으로 인한 종양학적 생존율 증가가 질병 비특이적 사망률 증가로 인해 상쇄되고 있음을 의미한다. 앞선 연구들에서도 수술 후 남성호르몬 박탈요법은 전체 생존율은 증가시키지 못했으나 질병 특이 사망률에 대한 위험은 감소시키며 생화학적 재발과 국소 재발의 위험을 낮춘다는 결과는 보고되어 왔다<sup>[6,11]</sup>. 하지만 수술 후 남성호르몬 박탈요법의 명확한 시작 시기에 대해서는 2018년 업데이트된 NCCN (National Comprehensive Cancer Network) 가이드라인에서도 여전히 경과 관찰 후 증상의 발현이나 PSA 상승이 있을 경우 시작 할 수 있다고 기술하고 있어 반드시 즉각적으로 치료를 시작하도록 권고하기는 어렵다.

==참고문헌==

1. Yossepowitch O, Eggener SE, Bianco FJ, Jr., Carver BS, Serio A, Scardino PT, et al. Radical prostatectomy for clinically localized, high risk prostate cancer: critical analysis of risk assessment methods. The Journal of Urology 2007;178(2):493-9; discussion 9.

2. Daneshmand S, Quek ML, Stein JP, Lieskovsky G, Cai J, Pinski J, et al. Prognosis of patients with lymph node positive prostate cancer following radical prostatectomy: long-term results. The Journal of Urology 2004;172(6 Pt 1):2252-5.

3. Zwergel U, Lehmann J, Wullich B, Schreier U, Remberger K, Zwergel T, et al. Lymph node positive prostate cancer: long-term survival data after radical prostatectomy. The Journal of Urology 2004;171(3):1128-31.

4. Abdollah F, Karnes RJ, Suardi N, Cozzarini C, Gandaglia G, Fossati N, et al. Impact of adjuvant radiotherapy on survival of patients with node-positive prostate cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014;32(35):3939-47.

5. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. The Lancet Oncology 2006;7(6):472-9.

6. Boorjian SA, Thompson RH, Siddiqui S, Bagniewski S, Bergstralh EJ, Karnes RJ, et al. Long-term outcome after radical prostatectomy for patients with lymph node positive prostate cancer in the prostate specific antigen era. The Journal of Urology 2007;178(3 Pt 1):864-70; discussion 70-1.

7. Schroder FH, Kurth KH, Fossa SD, Hoekstra W, Karthaus PP, Debois M, et al. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study. The Journal of Urology 2004;172(3):923-7.

8. Kirk D. Timing and choice of androgen ablation. Prostate Cancer and Prostatic Diseases 2004;7(3):217-22.

9. Nair B, Wilt T, MacDonald R, Rutks I. Early versus deferred androgen suppression in the treatment of advanced prostatic cancer. The Cochrane Database of Systematic Reviews 2002(1):Cd003506.

10. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. The New England Journal of Medicine 1999;341(24):1781-8.

11. Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. Journal of Clinical Oncology 2007;25(12):1596-605.

12. Wong YN, Freedland S, Egleston B, Hudes G, Schwartz JS, Armstrong K. Role of androgen deprivation therapy for node-positive prostate cancer. Journal of Clinical Oncology 2009;27(1):100-5. 

13. Park S, Kim SC, Kim W, Song C, Ahn H. Impact of adjuvant androgen-deprivation therapy on disease prog ression in patients with node-positive prostate cancer. Korean Journal of Urology 2011;52(11):741-5.

14. Ghavamian R, Bergstralh EJ, Blute ML, Slezak J, Zincke H. Radical retropubic prostatectomy plus orchiectomy versus orchiectomy alone for pTxN+ prostate cancer: a matched comparison. The Journal of Urology 1999;161(4):1223-7; discussion 7-8.

15. Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. The Cochrane Database of Systematic Reviews 2006(4):Cd006019.

16. Touijer KA, Karnes RJ, Passoni N, Sjoberg DD, Assel M, Fossati N, et al. Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies. European Urology 2017.

==근거표==

{| class="wikitable mw-collapsible"
!KQ16
|
|-
!Reference
|1. Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. The Lancet Oncology 2006;7(6):472-9.
|-
!Study type
|Randomized controlled trial
|-
!Patients
|Immediate ADT (n=47) and observed (n=51)
|-
!Purpose of Study
|To determine whether immediate ADT extends survival in men with node-positive prostate cancer who have undergone radical prostatectomy and pelvic lymphadenectomy compared with those who received ADT only once disease progressed
|-
!Study Results
|At median follow-up of 11.9 years (range 9.7-14.5 for surviving patients), men assigned immediate ADT had a significant improvement in overall survival (hazard ratio 1.84 [95% CI 1.01-3.35], p=0.04), prostate-cancer-specific survival (4.09 [1.76-9.49], p=0.0004), and progression-free survival (3.42 [1.96-5.98], p<0.0001). Of 49 histopathology slides received (19 immediate ADT, 30 observation), 16 were downgraded from the original Gleason score (between groups ≤6, 7, and ≥8) and five were upgraded. We recorded similar proportions of score changes in each group (p=0.68), and no difference in score distribution by treatment (p=0.38). After adjustment for score, associations were still significant between treatment and survival (overall, p=0.02; disease-specific, p=0.002; progression-free survival, p<0.0001).
|-
!Level of Study
|1
|-
!Reference
|2. Boorjian SA, Thompson RH, Siddiqui S, Bagniewski S, Bergstralh EJ, Karnes RJ, et al. Long-term outcome after radical prostatectomy for patients with lymph node positive prostate cancer in the prostate specific antigen era. The Journal of Urology 2007;178(3 Pt 1):864-70;discussion 70-1.
|-
!Study type
|Case-control study
|-
!Patients
|Of the 507 patients 455 (89.7%) were treated with adjuvant hormonal therapy
|-
!Purpose of Study
|To examine the impact of lymph node metastases on the outcome of patients following radical prostatectomy and investigated prognostic factors that affect survival
|-
!Study Results
|Ten-year cancer specific survival for patients with positive lymph nodes was 85.8% with 56% of the men free from biochemical recurrence at last followup. On multivariate analysis pathological Gleason score 8-10 (p=0.004), positive surgical margins (p=0.016), nondiploid tumor ploidy (p=0.023) and 2 or greater positive nodes (p=0.001) were adverse predictors of cancer specific survival. Tumor stage, year of surgery and total number of nodes removed did not significantly affect outcome. Adjuvant hormonal therapy decreased the risk of biochemical recurrence (p<0.001) and local recurrence (p=0.004) but it was not associated with systemic progression (p=0.4) or cancer specific survival (p=0.4)
|-
!Level of Study
|3
|-
!Reference
|3. Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, et al. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. Journal of Clinical Oncology 2007;25(12):1596-605.
|-
!Study type
|Systematic review, Meta-analysis
|-
!Patients
|Seven randomized controlled trials (four new), one systematic review, one meta-analysis (new), one Markov model, and one delta-method 95% CI procedure for active controlled trials (new) informed the guideline update.
|-
!Purpose of Study
|To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa).
|-
!Study Results
|In metastatic or progressive PCa, immediate versus symptom-onset institution of ADT results in a moderate decrease (17%) in relative risk (RR) for PCa-specific mortality, a moderate increase (15%) in RR for non-PCa-specific mortality, and no overall survival advantage. Therefore, the Panel cannot make a strong recommendation for early ADT initiation.
|-
!Level of Study
|1
|-
!Reference
|4. Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. The New England Journal of Medicine 1999;341(24):1781-8.
|-
!Study type
|Randomized controlled trial
|-
!Patients
|Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy
|-
!Purpose of Study
|Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy.
|-
!Study Results
|After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome.
|-
!Level of Study
|1
|-
!Reference
|5. Wong YN, Freedland S, Egleston B, Hudes G, Schwartz JS, Armstrong K. Role of androgen deprivation therapy for node-positive prostate cancer. Journal of Clinical Oncology 2009;27(1):100-5.
|-
!Study type
|Case-control study
|-
!Patients
|A total of 731 men were identified, 209 of whom received ADT within 120 days of RP
|-
!Purpose of Study
|To determine the impact of adjuvant androgen deprivation therapy (ADT) for patients who have node-positive prostate cancer in the prostate-specific antigen (PSA) era.
|-
!Study Results
|There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition.
|-
!Level of Study
|3
|-
!Reference
|6. Park S, Kim SC, Kim W, Song C, Ahn H. Impact of adjuvant androgen-deprivation therapy on disease progression in patients with node-positive prostate cancer. Korean Journal of Urology 2011;52(11):741-5.
|-
!Study type
|Case-control study
|-
!Patients
|Of 937 patients who underwent RP, we identified 40 (4.2%) who had lymph node metastasis. A total of 18 received adjuvant ADT (ADT group) and 22 were observed (observation group).
|-
!Purpose of Study
|The survival benefits of adjuvant androgen-deprivation therapy (ADT) in prostate cancer and lymph node metastasis remain unclear. We assessed the role of ADT in disease progression after radical prostatectomy (RP).
|-
!Study Results
|The 5-year PFS, CSS, and OS of the entire cohort were 75.0%, 85.0%, and 72.5%, respectively. In the ADT group, 6 patients (33.3%) showed clinical progression at a median 42.7 months. The 5-year PFS, CSS, and OS rates of this group were 72.2%, 83.3%, and 72.2%, respectively. In the observation group, 14 patients (63.6%) received salvage therapy owing to BCR. Nine patients (40.9%) with BCR in the observation group showed
clinical progression at a median 43.4 months after RP. The 5-year PFS, CSS, and OS rates of this group were 77.2%, 86.4%, and 72.8%, respectively. In the observation group, the BCR rate was lower in patients with pT3a or less disease than in those with pT3b disease.
|-
!Level of Study
|3
|-
!Reference
|7. Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and locally advanced prostate cancer. The Cochrane Database of Systematic Reviews 2006(4):Cd006019.
|-
!Study type
|Systematic review
|-
!Patients
|MEDLINE (1966-2006), EMBASE, The Cochrane Library, Science Citation Index, LILACS, and SIGLE
|-
!Purpose of Study
|The objective of this review was to undertake a systematic review and, if possible, a meta-analysis of neo-adjuvant and adjuvant hormone therapy in localised or locally advanced prostate cancer.
|-
!Study Results
|Men with prostate cancer have different clinical outcomes based on their risk (T1-T2, T3-T4, PSA levels and Gleason score). However, the majority of studies included in this review did not report results by risk groups; therefore, it was not possible to perform sub-group analysis. Neo-adjuvant hormonal therapy prior to prostatectomy did not improve overall survival (OR 1.11, 95% CI 0.67 to 1.85, P=0.69). However, there was a significant reduction in the positive surgical margin rate (OR 0.34, 95% CI 0.27 to 0.42, P<0.00001) and a significant improvement in other pathological variables such as lymph node involvement, pathological staging and organ confined rates. There was a borderline significant reduction of disease recurrence rates (OR 0.74, 95% CI 0.55 to 1.0, P=0.05), in favour of treatment. The use of longer duration of neo-adjuvant hormones, that is either 6 or 8 months prior to prostatectomy, was associated with a significant reduction in positive surgical margins (OR 0.56, 95% CI 0.39 to 0.80, P=0.002). In one study, neo-adjuvant hormones prior to radiotherapy significantly improved overall survival for Gleason 2 to 6patients; although, in two studies, there was no improvement in disease-specific survival (OR 0.99, 95% CI 0.75 to 1.32, P=0.97). However, there was a significant improvement in both clinical disease-free survival (OR 1.86, 95% CI 1.93 to 2.40, P<0.00001) and biochemical disease-free survival (OR 1.93, 95% CI 1.45 to 2.56, P<0.00001). Adjuvant androgen deprivation following prostatectomy did not significantly improve overall survival at 5years (OR 1.50, 95% CI 0.79 to 2.85, P=0.2); although one study reported a significant disease-specific survival advantage with adjuvant therapy (P=0.001). In addition, there was a significant improvement in disease-free survival at both 5 years (OR 3.73, 95%CI 2.30
to 6.03, P<0.00001) and 10 years (OR 2.06, 95% CI 1.34 to 3.15, P=0.0009). Adjuvant therapy following radiotherapy resulted in a significant overall survival gain apparent at 5 (OR 1.46, 95% CI 1.17 to 1.83, P=0.0009) and 10 years (OR 1.44, 95% CI 1.13 to 1.84, P=0.003); although there was significant heterogeneity (P=0.09 and P=0.07, respectively). There was also a significant improvement in disease-specific survival (OR 2.10, 95% CI 1.53 to 2.88, P=0.00001) and disease-free survival (OR 2.53, 95% CI 2.05 to 3.12, P<0.00001) at 5 years.
|-
!Level of Study
|1
|-
!Reference
|8. Touijer KA, Karnes RJ, Passoni N, Sjoberg DD, Assel M, Fossati N, et al. Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies. European Urology 2017.
|-
!Study type
|Case-control study
|-
!Patients
|1,338 patients with LNM after RP from three tertiary care centers.
|-
!Purpose of Study
|To evaluate the association between three different management strategies and survival in prostate cancer with LNM after RP.
|-
!Study Results
|ADT+EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32-0.66, p<0.0001) or observation (HR: 0.41, 95% CI: 0.27-0.64, p<0.0001). Higher-risk patients benefited more from ADT+EBRT than lower-risk patients. Ten-year mortality risk difference between ADT+EBRT, observation, or ADT alone ranged from 5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT+EBRT was also associated with better CSS than observation or ADT alone (p<0.0001), ADT had better CSS compared to observation (HR: 0.64, 95% CI: 0.43-0.95, p=0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95% CI:1.45-6.40, p=0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95% CI: 0.65-1.25, p=0.5).
|-
!Level of Study
|3
|-
|}