KQ 6. 중간위험 전립선암환자에서 방사선치료와 6개월 동안 호르몬 요법을 병용하는 경우가 방사선 치료만 하는 경우 보다 생존율이 우수한가?

권고사항	권고수준	근거수준
중간위험 전립선암 환자는 방사선 치료 및 단기간의 신보조/동시/보조 호르몬 요법을 고려할 수 있다.	A	I

개요

고위험군 혹은 국소진행성전립선암 환자에서 방사선 치료와 단기간 호르몬 치료는 호르몬 치료의 부작용을 줄이면서 국소제어 및 무재발 생존율을 향상시키는 방법이었다^[1-3]. 이러한 관점에서 좀 더 예후가 좋은 중간위험전립선암환자에서도 방사선 단독 치료보다는 호르몬 치료를 추가할 경우 더 나은 예후를 기대할 수 있다는 연구결과가 제시되었다^[4]. 국내에서도 중간위험전립선암환자의 63%에서 방사선 치료와 호르몬 치료를 같이 시행하고 있다^[5]. RTOG 9408에서는 EBRT (66.6 Gy)를 시행받는 환자 1,979명을 4개월간 호르몬치료를 받는 군(n=987)과 그렇지 않는 군(n=992)으로 무작위 배정 후 중간 추적관찰 기간인 9.1년 동안 추적하였다. 이 연구에서 중간위험전립선암환자들은 방사선치료와 호르몬 치료를 같이 시행 받은 군에서 10년 전체 생존율이 62%로 방사선 단독 치료의 54% 보다 더 높았으며(HR for death with radiotherapy alone, 1.17; p=0.03) 10년 질병특이 사망률은 더 낮은 경향을 보였다(4% vs. 8%; HR for radiotherapy alone, 1.87; p=0.001)^[6]. D’Amico AV 등^[7]은 206명의 방사선 치료(70 Gy)를 받은 환자들을 6개월간 호르몬치료를 받는 군(n=102)과 그렇지 않는 군(n=104)으로 무작위 배정 후 중간 추적관찰 기간 7.6년 동안 추적하였다. 호르몬 치료를 같이 시행 받은 군에서 8년 전체 생존율이 74%로 방사선 단독 치료의 61% 보다 더 높았다(HR for death with radiotherapy alone, 4.1; p=0.01). RTOG 9910 trial^[8]에서는 중간위험전립선암환자들에서 방사선 치료 전 호르몬 치료 기간을 연장하는 경우(8주 vs. 28주)에 따른 10년 질병특이 생존율 95%와 96%로 차이가 없었으며(HR 0.81; p=0.45) 10년 전체 생존율도 66%와 67%로 차이가 없었다(HR 0.95;p=0.62). PSA를 기반으로 하는 10년 재발률도 27%와 27%로 차이가 없었다(HR 0.97; p=0.77).

위의 연구들을 기반으로 중간위험전립선암환자에서 방사선 치료와 단기 호르몬요법을 같이 시행하는 경우에 생존율의 향상을 기대할 수 있다. 그러나 호르몬요법의 기간을 6개월 이상으로 늘리는 것은 추가적인 치료효과를 기대하기는 어렵다.

기존 가이드라인 요약 및 수용성, 적용성 평가

2015년 대한비뇨기종양학회 전립선암 진료지침에서는 중간위험군 환자들의 경우 TROG 9601, DFCI (Dana-Farber Cancer Institute) 95096, RTOG 9408 연구들을 바탕으로 76-78 Gy의 조사량에 단기간 4-6개월 남성호르몬박탈요법을 추천하고 있다^[6,7,9]. 또한 저선량률 근접치료와 외부 방사선치료와 함께 4-6개월 신보조/동시/보조 남성호르몬박탈요법을 병합하여 치료해 볼 수 있다고 권장하고 있다. 2016년 유럽비뇨기과학회 가이드라인에서는 남성호르몬박탈요법이 가능한 환자에게 IMRT와 단기간 호르몬억제요법(4-6개월)을 권장하고 있으나 만약 동반된 질환들이 있을 경우나 성기능 장애에 대한 문제 등으로 호르몬 치료를 원치 않을 경우에는 76-80 Gy로 선량을 증가시킨 IMRT를 시행하거나 IMRT와 근접치료를 같이 시행할 것을 권장하고 있다^[4,6,10]. 2017년도 미국비뇨기과학회 전립선암 진료지침에서는 2가지 무작위 통제 임상시험 결과들^[6,7]을 토대로 외부 방사선치료와 남성호르몬박탈요법을 시행하는 것을 권장하고 있다. 하지만 최근 보고되고 있는 것과 같이 고선량 방사선 치료(74-80 Gy)의 효과가 입증된 상태에서 남성호르몬박탈요법이 도움이 되는지에 대하여 추가 연구가 필요하다고 보고하고 있다^[11-14]. EORTC 22991 연구^[15]에서는 78 Gy로 방사선치료를 받은 환자에서 남성호르몬박탈요법이 임상적무제발생존율을 향상시킬 수 있다고 보고하였다. 추가적으로 좋지 않은(unfavorable) 중간위험군 환자들에게 외부방사선치료와 남성호르몬박탈요법을 병합하는 것을 더 권장하고 있으며, 좋은(favorable) 중간위험군 환자들에게는 방사선치료 단독요법을 권유할 수도 있다고 하였다. 2016 NCCN 전립선암 가이드라인에서도 3가지 임상연구들^[6,7,9]을 바탕으로 중간위험군 환자들에게 외부 방사선치료와 남성호르몬박탈요법을 권장하고 있다. 또한 RTOG 9910 연구[8]를 바탕으로 남성호르몬박탈요법은 단기간(4-6개월)으로 시행할 것을 권장하고 있다. 2014년 NICE 전립선암 가이드라인은 중간위험군 환자들로 국한하지 않고 국소진행전립선암환자를 대상으로 범위를 넓혀 외부 방사선치료와 함께 6개월간의 신보조/동시/보조 남성호르몬박탈요법을 권유하고 있다. 마지막으로 2010년 CCAACN 진행전립선암 진료지침에서도 마찬가지로 국소진행성 전립선암 환자를 대상으로만 정의하여 중간위험군 환자들의 정확한 가이드라인은 제시하고 있지 않다.

KQ 6. 중간위험 전립선암환자에서 방사선치료와 6개월 동안 호르몬 요법을 병용하는 경우가 방사선 치료만 하는 경우보다 생존율이 우수한가?
지침(제목)	권고	권고등급	근거수준	page
1. 2015 KUOS	중간위험군 환자들에 있어, 4-6개월 간(고위험 환자군은 2-3년간)의 신보조/동시/보조 남성호르몬박탈요법과 함께 골반림프절 방사선치료를 고려해 볼 수 있다.	없음.	1b	22
2. EAU 2016	중간위험 전립선암환자에서 단기간 호르몬억제치료법(4-6개월)과 병용하여 76-78 Gy의 방사선치료를 시행한다.	A	1b	43,48
3. AUA 2017	2개의 무작위 통제 임상 시험의 결과를 토대로, unfavorable 중간위험군 환자들에게 호르몬 요법을 사용하면 기존의 외부선량 방사선 치료를 선택한 환자의 생존 기간이 연장 될 수 있 다	B	없음	29
5. NCCN 2016	중간위험 전립선암 환자는 골반 림프절 방사선 조사 및 4-6개월간 신 보조/동시/보조 호르몬요법을 고려할 수 있다.	없음	없음	10,28
6. NICE 2014	중간위험도 및 고위험 국소성 전립선암 환자에서는 외부선량 방사선 치료 전, 중, 후에 6개월 간 호르몬 억제치료를 병용할 수 있다.	없음	없음	277
9. CCAACN 2010	국소진행성 전립선암 환자에서는 방사선치료와 더불어 단기신보조 호르몬 요법을 고려할 수 있다. 방사선 요법과 관련하여 호르몬요법의 최적의 순서 및 지속기간은 아직 정의되지 않았다.	C	1,2	30,31

지침(제목)		1. 2015 KUOS	2. EAU 2016	3. AUA 2017	5. NCCN 2016	6. NICE 2014	9. CCAACN 2010
수용성	인구 집단(유병률, 발생률 등)이 유사하다.	예	아니오	아니오	아니오	아니오	아니오
	가치와 선호도가 유사하다.	예	예	예	예	예	예
	권고로 인한 이득은 유사하다.	예	예	예	예	예	예
	해당 권고는 수용할 만하다.	예	예	예	예	예	예
적용성	해당 중재/장비는 이용 가능하다.	예	예	예	예	예	예
	필수적인 전문기술이 이용 가능하다.	예	예	예	예	예	예
	법률적/제도적 장벽이 없다.	예	예	예	예	예	예
	해당 권고는 적용할 만하다.	예	예	예	예	예	예

업데이트 근거 요약

최근에는 고선량 방사선치료(74-80 Gy)가 표준치료화 되면서 남성호르몬박탈요법의 병용요법이 도움이 되는지에 대해서 많은 논란의 여지가 있다. 하지만 대부분의 연구들이 좋지 않은(unfavorable) 중간위험군 환자들의 경우 남성호르몬박탈요법의 병용이 도움이 된다고 보고를 하고 있으며 가장 최근 업데이트된 2017년 미국비뇨기과학회 전립선암 진료지침에서도 이와 같은 권장을 하고 있다^[16-19]. 또한 남성호르몬박탈요법을 병용하는 경우 동반질환을 동반하고 있는 경우 부작용이나 치료 예후가 좋지 않은 경우가 있어 2016년 유럽비뇨기과학회 가이드라인과 같이 권장사항에 포함시켜야 할 것으로 보인다^[18,20-22].

참고문헌

1. Pilepich MV, Krall JM, al-Sarraf M, et al. Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group. Urology 1995;45(4):616-23.

2. Roach M, 3rd, Bae K, Speight J, et al. Short-term neoadjuvant androgen deprivation therapy and externalbeam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol 2008;26(4):585-91.

3. Denham JW, Steigler A, Lamb DS, et al. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol 2005;6(11):841-50.

4. Krauss D, Kestin L, Ye H, et al. Lack of benefit for the addition of androgen deprivation therapy to doseescalated radiotherapy in the treatment of intermediate- and high-risk prostate cancer. Int J Radiat Oncol Biol Phys 2011;80(4):1064-71.

5. Chang AR, Park W. Radiotherapy in prostate cancer treatment: results of the patterns of care study in Korea.Radiat Oncol J 2017;35(1):25-31.

6. Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011;365(2):107-18.

7. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008;299(3):289-95.

8. Pisansky TM, Hunt D, Gomella LG, et al. Duration of androgen suppression before radiotherapy for localized prostate cancer: radiation therapy oncology group randomized clinical trial 9910. J Clin Oncol 2015;33(4):332-9.

9. Denham JW, Steigler A, Lamb DS, et al. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol 2011;12(5):451-9.

10. Kupelian PA, Ciezki J, Reddy CA, Klein EA, Mahadevan A. Effect of increasing radiation doses on local and distant failures in patients with localized prostate cancer. Int J Radiat Oncol Biol Phys 2008;71(1):16-22.

11. Al-Mamgani A, van Putten WL, Heemsbergen WD, et al. Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 2008;72(4):980-8.

12. Dearnaley DP, Jovic G, Syndikus I, et al. Escalated-dose versus control-dose conformal radiotherapy for prostate cancer: long-term results from the MRC RT01 randomised controlled trial. Lancet Oncol 2014;15(4):464-73.

13. Kuban DA, Tucker SL, Dong L, et al. Long-term results of the M. D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70(1):67-4.

14. Beckendorf V, Guerif S, Le Prise E, et al. 70 Gy versus 80 Gy in localized prostate cancer: 5-year results of GETUG 06 randomized trial. Int J Radiat Oncol Biol Phys 2011;80(4):1056-63.

15. Bolla M, Maingon P, Carrie C, et al. Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991. J Clin Oncol 2016;34(15):1748-56.

16. Castle KO, Hoffman KE, Levy LB, et al. Is androgen deprivation therapy necessary in all intermediate-risk prostate cancer patients treated in the dose escalation era? Int J Radiat Oncol Biol Phys 2013;85(3):693-9.

17. Edelman S, Liauw SL, Rossi PJ, Cooper S, Jani AB. High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity outcomes. Int J Radiat Oncol Biol Phys 2012;83(5):1473-9.

18. Bian SX, Kuban DA, Levy LB, et al. Addition of short-term androgen deprivation therapy to dose-escalated radiation therapy improves failure-free survival for select men with intermediate-risk prostate cancer. Ann Oncol 2012;23(9):2346-52.

19. Amini A, Rusthoven CG, Jones BL, Armstrong H, Raben D, Kavanagh BD. Survival outcomes of radiotherapy with or without androgen-deprivation therapy for patients with intermediate-risk prostate cancer using the National Cancer Data Base. Urol Oncol 2016;34(4):165 e161-9.

20. Pickles T, Tyldesley S, Hamm J, Virani SA, Morris WJ, Keyes M. Brachytherapy for Intermediate-Risk Prostate Cancer, Androgen Deprivation, and the Risk of Death. Int J Radiat Oncol Biol Phys 2018;100(1):45-52.

21. Lester-Coll NH, Johnson S, Magnuson WJ, et al. Weighing Risk of Cardiovascular Mortality Against Potential Benefit of Hormonal Therapy in Intermediate-Risk Prostate Cancer. J Natl Cancer Inst 2017;109(6).

22. Bian SX, Kuban DA, Levy LB, et al. The Influence of Age and Comorbidity on the Benefit of Adding Androgen Deprivation to Dose-escalated Radiation in Men With Intermediate-risk Prostate Cancer. Am J Clin Oncol 2016;39(4):368-73.

근거표

KQ6
Reference	1. Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011;365(2):107-18.
Study type	Randomized case-control study
Patients	Localized prostate cancer (RT alone 992 patients vs. RT+ADT 987 patients)
Purpose of Study	To evaluate whether adding short-term ADT to radiotherapy would improve survival among patients with nonbulky localized prostate adenocarcinomas and an initial PSA level of 20 ng per milliliter or less.
Study Results	The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and diseasespecific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients.
Level of Study	1
Reference	2. D’Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA 2008;299(3):289-95.
Study type	Randomized case-control study
Patients	Localized unfavorable risk prostate cancer (RT alone 104 patients vs. RT +ADT 102 patients)
Purpose of Study	To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality.
Study Results	As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P=.01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P<.001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P=.08).
Level of Study	1
Reference	3. Pisansky TM, Hunt D, Gomella LG, et al. Duration of androgen suppression before radiotherapy for localized prostate cancer: radiation therapy oncology group randomized clinical trial 9910. J Clin Oncol 2015;33(4):332-9.
Study type	Randomized case-control study
Patients	Intermediate-risk prostate cancer (n=1579)
Purpose of Study	To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer
Study Results	There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P=.45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P=.62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P=.07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P=.80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P=.77), respectively.
Level of Study	1

KQ 7. 중간위험 전립선암환자에서 근치적 전립선절제술 후 병리학적 불량 예후인자를 보일 경우 추가적인 방사선치료를 하는 경우가 보조요법을 하지 않는 경우보다 생존율이 우수한가?

권고사항	권고수준	근거수준
중간위험 전립선암환자에서 근치적 전립선절제술 후 병리학적 불량 예후인자 를 보일 경우 보조 또는 구제 방사선치료를 할 수 있다.	A	I

개요

보조요법으로서 방사선치료에 대하여는 전향적 무작위 연구가 몇몇 기관에서 발표된 바 있으며, SWOG 8794 연구에서 근치적 전립선절제술 후 pT3 환자 425명의 환자를 대상으로 보조요법(EBRT, external beam radiotherapy)을 시행한 군과 그렇지 않은 군을 나누어 12.6년 추적관찰 하였을 때 보조요법을 시행한 군이 그렇지 않은 군에 비하여 재발율을 낮추어주는 것을 확인할 수 있었다^[1].

EORTC 연구에서는 1,005명의 병리학적 불량예후인자를 보이는 환자를 대상으로 보조요법(EBRT)을 시행한 군과 그렇지 않은 군을 나누어 비교하였을 때 5년 생화학적 무재발 생존율이 각각 78%, 49%로 보조요법을 시행한 군에서 좋은 결과를 보여 주었다^[2]. 또 다른 그룹에서 시행한 연구에서도 268명의 병리학적 불량예후 인자를 보이며 PSA가 측정되지 않았던 환자에서 술 후 보조방사선치료를 시행한 군에서 5년 생화학적 무재발 생존율이 72%, 54%로 보조요법을 시행한 군에서 좋은 결과를 확인할 수 있었다^[3].

기존 가이드라인 요약 및 수용성, 적용성 평가

NICE 2016 guideline에서는 “수술 직후(immediate postoperative) 방사선 요법”은 positive surgical margin에서도 권장하고 있지 않다. 하지만 EAU guideline, NCCN guideline 등 주요 진료지침에서는 전립선절제술 시행 후 병리학적으로 불량한 예후를 보일 때 특히 pT3, positive surgical margin, Gleason 점수 8점 이상, 정낭침범이 있는 경우 보조 방사선 치료를 권고하고 있다. 이러한 진료지침은 비교적 최근의 중요한 3개의 무작위 임상시험에서 나타난 보조 방사선 치료의 무생화학적 재발 측면에서의 우수성에 그 기반을 두고 있다고 할 수 있다^[4-6].

KQ 7. 중간위험 전립선암환자에서 근치적 전립선절제술 후 병리학적 불량 예후인자를 보일 경우 추가적인 방사선치료를 하는 경우가 보조요법을 하지 않는 경우보다 생존율이 우수한가?
지침(제목)	권고	권고등급	근거수준	Page
1. 2015 KUOS	유해한 병리학적 요소들을 갖거나 측정 가능한 PSA를 보이고 전이의 증거는 없는 대부분의 환자들에 있어 보조/구제 방사선치료는 권장된다.	없음	없음	24
2. EAU 2016	In patients with pT3,N0M0 Prostate cancer and an undetectable PSA following RP, discuss adjuvant EBRT because it improves at least biochemical-free survival.	A	1a	48
5. NCCN 2016	Indications for adjuvant RT include pT3 disease, positive margin(s), Gleason score 8-10, or seminal vesicle involvement. Adjuvant RT is usually given within 1 year after RP and once any operative side effects have improved/stabilized. Paitents with positive surgical margins may benefit the most.	없음	없음	PROS-D 2 of 2
6. NICE 2014	Do not offer immediate postoperative radiotherapy after radical prostatectomy, even to men with marginpositive disease, other than in the context of a clinical trial. There are two randomised trials which have not shown any improvement in survival from immediate post operative radiotherapy.	없음	없음	280
9. CCAACN 2010	It is recommended that patients with extracapsular extension, seminal vesicle involvement or positive surgical margins receive post-operative EBRT within four months of surgery. The role of active surveillance and early salvage radiotherapy has not been defined.	B	II	37

지침(제목)		1. 2015 KUOS	2. EAU 2016	5. NCCN 2016	6. NICE 2014	9. CCAACN 2010
수용성	인구 집단(유병률, 발생률 등)이 유사하다.	예	아니오	아니오	아니오	아니오
	가치와 선호도가 유사하다.	예	예	예	아니오	예
	권고로 인한 이득은 유사하다	예	예	예	불확실	예
	해당 권고는 수용할 만하다.	예	예	예	아니오	예
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 적용할 만하다.	예	예	예	아니오	예

NICE 2014에서 수용성은 국내 진료 현실과 다른 가이드라인과 차이나는 부분이 있었다. 적용성 부분은 크게 무리가 없었으나 치료 시기의 문제에 대해서 추가 논의가 필요한 부분이 있었다.

업데이트 근거 요약

최근에는 보조 방사선 요법과 조기 구제 방사선 치료가 우수한 측면이 없다는 연구 결과도 발표되고 있으나^[7] 후향적 연구로 앞에서 언급된 3가지의 무작위 임상시험에 비하여 근거의 신뢰성이 떨어진다. 특히 가장 최근 연구에서도 pT3 또는 절제면 양성인 환자에서 보조 방사선치료를 시행한 군이 조기 구제 방사선치료(early-salvage radiotherapy)를 시행한 군 보다 무생화학적 재발률이 우수한 것으로 나타났다^[8,9]. 따라서 전립선 절제술 후 병리학적 불량 예후 인자를 보이는 경우 특히 pT3 또는 절제면 양성 보이는 경우에는 보조 방사선 치료를 고려할 수 있다.

참고문헌

1. Thompson IM, Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009;181:956-62.

2. 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.

3. 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.

4. Bolla M, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012;380:2018.

5. Wiegel T, et al. Adjuvant Radiotherapy Versus Wait-and-See After Radical Prostatectomy: 10-year Follow-up of the ARO 96-02/AUO AP 09/95 Trial. Eur Urol 2014;66:243.

6. Thompson IM, Jr., Tangen CM, Paradelo J, et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006;296:2329-35.

7. Fossati N, et al. Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0 Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multi-institutional Series. Eur Urol 2017;71(6):886-93.

8. Buscariollo DL, et al. Long-term results of adjuvant versus early salvage postprostatectomy radiation: A large single-institutional experience. Pract Radiat Oncol 2017;7(2):e125-33.

9. Hwang WL, et al. Comparison Between Adjuvant and Early-Salvage Post prostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features. JAMA Oncol 2018:e175230. doi: 10.1001/jamaoncol.2017.5230. [Epub ahead of print]

근거표

KQ7
Reference	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.
Study type	Prospective Randomized trial
Patients	1,005
Purpose of Study	To evaluate the effect of radiotherapy after prostatectomy in patients with adverse risk factors
Study Results	Margin status assessed by review pathology was the strongest predictor of prolonged biochemical disease-free survival with immediate postoperative radiotherapy (heterogeneity, P<.01): by year 5, immediate postoperative irradiation could prevent 291 events/1,000 patients with positive margins versus 88 events/1,000 patients with negative margins. The hazard ratio for immediate irradiation was 0.38 (95% CI, 0.26 to 0.54) and 0.88 (95% CI, 0.53 to 1.46) in the groups with positive and negative margins, respectively. We could not identify a significant impact of the positive margin localization.
Level of Study	1
Reference	2. Bolla M, et al. Postoperative radiotherapy after radical prostatectomy for high-risk prostate cancer: long-term results of a randomised controlled trial (EORTC trial 22911). Lancet 2012;380:2018.
Study type	Prospective Randomized trial
Patients	1,005
Purpose of Study	To report the long-term results of a trial of immediate postoperative irradiation versus a wait-and-see policy in patients with prostate cancer extending beyond the prostate, to confirm whether previously reported progression-free survival was sustained
Study Results	1005 patients were randomly assigned to a wait-and-see policy (n=503) or postoperative irradiation (n=502) and were followed up for a median of 10.6 years (range 2 months to 16.6 years). Postoperative irradiation significantly improved biochemical progressionfree survival compared with the wait-and-see policy (198 [39.4%] of 502 patients in postoperative irradiation group vs 311 [61.8%] of 503 patients in wait-and-see group had biochemical or clinical progression or died; HR 0.49 [95% CI 0.41-0.59]; p<0.0001). Late adverse effects (any type of any grade) were more frequent in the postoperative irradiation group than in the wait-and-see group (10 year cumulative incidence 70.8% [66.6-75.0] vs 59.7% [55.3-64.1]; p=0.001).
Level of Study	1
Reference	3. Wiegel T, et al. Adjuvant Radiotherapy Versus Wait-and-See After Radical Prostatectomy: 10-year Follow-up of the ARO 96-02/AUO AP 09/95 Trial. Eur Urol 2014;66:243.
Study type	Prospective Randomized trial
Patients	388
Purpose of Study	To determine the efficiency of ART after a 10-yr follow-up in the ARO 96-02 study
Study Results	The median follow-up was 111 mo for ART and 113 mo for WS. At 10 yr, PFS was 56% for ART and 35% for WS (p<0.0001). In pT3b and R1 patients, the rates for WS even dropped to 28% and 27%, respectively. Of all 307 ITT2 patients, 15 died from PCa, and 28 died for other or unknown reasons. Neither metastasis-free survival nor overall survival was significantly improved by ART. However, the study was underpowered for these end points. The worst late sequelae in the ART cohort were one grade 3 and three grade 2 cases of bladder toxicity and two grade 2 cases of rectum toxicity. No grade 4 events occurred.
Level of Study	1
Reference	4. Hwang WL, et al. Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features. JAMA Oncol 2018;25:e175230.
Study type	Propensity score-matched cohort study
Patients	1,566
Purpose of Study	To compare the clinical outcomes of postoperative ART and ESRT administered to patients with prostatecancer with adverse pathological features.
Study Results	Of 1566 patients, 1195 with prostate-specific antigen levels lower than 0.1 ng/mL received ESRT and 371 patients with prostate-specific antigen levels of 0.1 to 0.5 ng/mL received ART. The median age (interquartile range) was 60 (55-65) years. After propensity score matching, the median (interquartile range) follow-up after surgery was similar between the ESRT and ART groups (73.3 [44.9-106.6] months vs 65.8 [40-107] months; P=.22). Adjuvant RT, compared with ESRT, was associated with higher freedom from biochemical failure (12-year actuarial rates: 69% [95% CI, 60%-76%] vs 43% [95% CI, 35%-51%]; effect size, 26%), freedom from distant metastases (95% [95% CI, 90%-97%] vs 85% [95% CI, 76%-90%]; effect size, 10%), and overall survival (91% [95% CI, 84%-95%] vs 79% [95% CI, 69%-86%]; effect size, 12%). Adjuvant RT, lower Gleason score and T stage, nodal irradiation, and postoperative androgen deprivation therapy were favorable prognostic features on multivariate analysis for biochemical failure. Sensitivity analysis demonstrated that the decreased risk of biochemical failure associated with ART remained significant unless more than 56% of patients in the ART group were cured by surgery alone. This threshold is greater than the estimated 12-year freedom from biochemical failure rate of 33% to 52% after radical prostatectomy alone, as determined by a contemporary dynamic nomogram.
Level of Study	2
Reference	5. Fossati N, et al. Long-term Impact of Adjuvant Versus Early Salvage Radiation Therapy in pT3N0Prostate Cancer Patients Treated with Radical Prostatectomy: Results from a Multiinstitutional Series. Eur Urol 2017;71(6):886-93.
Study type	Multicenter, retrospective study
Patients	510
Purpose of Study	To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT
Study Results	Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population.
Level of Study	3
Reference	6. Buscariollo DL, et al. Long-term results of adjuvant versus early salvage postprostatectomy radiation: A large single-institutional experience. Pract Radiat Oncol 2017;7(2):e125-e133.
Study type	Retrospective study
Patients	718
Purpose of Study	To evaluate freedom from biochemical failure (FFBF), freedom from androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS) after adjuvant radiationtherapy (ART) versus early salvage radiation therapy (ESRT) in men with prostate cancer and adverse pathologic features (pT3 and/or positive surgical margins).
Study Results	Median follow-up was 7.4 and 8.0 years for patients treated with ART and ESRT, respectively. Ten-year FFBF (69% vs 56%, P=.003) and 10-year FFADT (88% vs 81%, P=.046) rates were higher after ART; however, FFDM and OS did not significantly differ. After PS-matching, ART was associated with improved FFBF (P<.0001), FFADT (P=.0001), and FFDM (P=.02). Findings were confirmed in multivariable analyses in unmatched and PS-matched cohorts. Sensitivity analyses showed that FFBF benefit associated with ART lost statistical significance only after 38% of ART patients were assumed to have been cured by surgery and excluded from the model. This corresponds to the upper bound of patients with adverse pathologic features who did not recur after observation in prior randomized trials.
Level of Study	3

KQ 8. 중간위험 전립선암 환자 중 수술 후 림프절 전이가 있는 환자에서 보조남성호르몬 차단요법은 경과 관찰에 비해 생존율이 높은가?

권고사항	권고수준	근거수준
중간위험 전립선암 환자 중 수술 후 림프절 전이가 있는 환자에서는 보조남성 호르몬 차단요법이 경과 관찰보다 생존율이 높아 보조남성호르몬 차단요법을 권고한다.	A	I

개요

수술 후 림프절 전이가 있는 환자 중 중간위험 전립선암 환자만을 대상으로 보조남성호르몬 차단요법과 경과 관찰을 비교한 연구는 아직 없다.

보조남성호르몬 차단요법에 관한 연구는 주로 방사선치료에 병행하여 사용된 용법(combination therapy)으로 진행되고 있고 현재까지 근치적전립선절제술 후 시행된 연구는 소수가 발표된 실정이다. 하지만 환자들을 위험도에 따라 분류하지 않고 분석하였거나 고위험 환자와 함께 국소적으로 진행된 전립선암(locally advanced prostate cancer) 환자에 포함하여 분석하였다.

한 무작위 비교연구에서는 국소적으로 진행된 전립선암 환자(T3-4, any N; or any T, N+)에서 보조남성호르몬 차단요법은 무병생존의 연장은 있었으나 전체 생존의 연장은 관찰되지 않았다^[1]. 환자의 위험도에 따른 분류 없이 SEER data를 이용한 코호트 연구(cohort study)에서 수술 4개월 이내에 시행한 보조남성호르몬 차단요법은 전체 생존에서의 이점은 없었다^[5]. 국내에서 위험도에 따른 분류 없이 근치전립선절제술 후 림프절 전이가 진단된 40명의 환자를 대상으로 한 후향적 연구에서 보조 남성호르몬 박탈요법은 환자의 생존율과 병의 진행을 호전시키지 못하였다^[4].

기존 가이드라인 요약 및 수용성, 적용성 평가

수술 후 림프절 전이가 있는 중간위험 전립선암 환자만을 따로 언급한 기존의 진료지침은 없다.

수술 후 림프절 전이가 확인되면 수술 전 임상적 위험도와 상관없이 병리학적 국소진행성암(locally advanced disease)으로 분류하여 언급하고 있다.

EAU guideline과 NCCN guideline, CCAACN guideline에서는 공동으로 하나의 무작위 비교연구 결과를 언급하고 있으나 각각의 권고는 조금씩 다르다. 이들이 공통적으로 언급하고 있는 연구에서는 수술 후 림프절전이가 발견된 환자에 즉각적인 보조 남성호르몬 박탈요법을 시행한 경우 경과 관찰한 군에 비해 생존을 유의하게 연장함을 보였다^[2]. 하지만 이 연구에서는 대부분의 참여자들이 다량의 결절성 질환 및 다중 악성 종양의 특징(high-volume nodal disease and multiple adverse tumour characteristics) 등을 가지고 있었고 장기 추적 관찰에서 보조남성호르몬 차단요법의 기간에 따라 부작용도 함께 증가하였다^[3]. 따라서 EAU guideline에서는 수술 후 임파선 전이가 있는 환자에 관한 연구들은 매우 이질적인 환자들에 대한 결과로서 일괄적으로 적용하기는 어렵고 그러므로 개별화된 치료가 필요하다고 언급하고 있다. NCCN guideline에서는 수술 후 임파선 전이가 있을 때 보조남성호르몬 차단요법을 반드시 사용하기를 권고하고 있으며 CCAACN guideline에서는 완전하게 제거된 임파선 양성 질환(fully resected node-positive disease)일 경우 생존율에 이점이 있음을 언급하고 있다^[2].

NICE guideline에서는 국소진행성암 환자에서 수술 후 보조남성호르몬 차단요법은 독성이 증가하고^[6] 효과에 대한 증거 부족으로 권고하지 않는다.

기존 국내 전립선암진료지침에서는 수술 후 림프절전이가 발견된 경우 보조 남성호르몬 박탈요법을 고려할 수 있다고 하였으나 생존율이나 병의 진행에 도움이 되지는 않았다고 언급하고 있다^[4,5]

KQ 8. 중간위험 전립선암 환자 중 수술 후 림프절 전이가 있는 환자에서 보조남성호르몬 차단요법은 경과 관찰에 비해 생존율이 높은가?
지침(제목)	권고	권고등급	근거수준	Page
1. 2015 KUOS	국내연구결과 생존율을 호전 시키지 못했다(KJU 2011 52 741-5).	없음	없음	Chap8, 48
2. EAU 2016	Upon detection of nodal involvement during RP, Offer adjuvant ADT for node-positive (pN+)	A	1b	36
5. NCCN 2016	Significantly improved PFS with bicalutamide in the overall study population compared to placebo, but no overall survival benefit was seen. (J Urol 2004 172:1865-70.)	없음	없음	45
6. NICE 2014	Randomised trials report significant toxicity with adjuvant therapy in addition to radical prostatectomy (Kumar et al. 2006). With the exception of one small trial in node-positive men (Messing et al. 1999), these trials have not demonstrated significant benefit in overall survival. It is possible that modest survival benefits will emerge with longer follow-up.	없음	없음	263
9. CCAACN 2010	For node-positive disease androgen deprivation therapy (ADT) should be considered. For patients with fully resected node-positive disease (prostatectomy and lymphadenectomy), it is strongly recommended that patients be counselled on the overall survival benefit of ADT and weighed against the short- and longterm toxicities of androgen deprivation. It is further recommended that patients be counselled on the ‘benefit’ of improved survival in relation to the ‘risk’ of therapy - namely the impact of ADT on quality of life.	Grade C	없음	36

지침(제목)		1. 2015 KUOS	2. EAU 2016	5. NCCN 2016	6. NICE 2014	9. CCAACN 2010
수용성	인구집단(유병율, 발생율 등)이 유사하다.	예	아니오	아니오	아니오	아니오
	가치와 선호도가 유사하다.	예	예	예	예	예
	권고로 인한 이득은 유사하다.	예	예	예	아니오	예
	해당권고는 수용할 만하다.	예	예	예	아니오	예
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 적용할 만하다.	예	예	예	예	예

NICE 2014 가이드라인은 조금 더 조심스러운 권고를 하고 있으나 타 근거에서 이득이 있음을 보여주고 있어 수용성 평가가 달랐다.

업데이트 근거 요약

중간위험 전립선암 환자 중 수술 후 림프절 전이가 있는 환자에서 보조남성호르몬 차단요법의 이득에 관한 최근 연구는 없는 실정이다.

기존 진료지침에서 따로 다루고 있지는 않지만 최근 여러가지 치료 방법들이 개발되고 적용됨에따라 중간위험 전립선암 환자만을 따로 분류하여 치료할 필요성이 대두되고 있다. 이에 향후 중간위험 환자만을 대상으로 한 잘 계획되고 잘 진행된 전향적 무작위 비교연구가 반드시 필요하겠다.

참고문헌

1. McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU int 2006;97:247-54.

2. 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 nodepositive prostate cancer. N Engl J Med 1999;341:1781-8.

3. 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. Lancet Oncol 2006;7:472-9.

4. 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 J Urol 2011;52:741-5.

5. Wong YN, Freedland S, Egleston B, Hudes G, Schwartz JS, Armstrong K. Role of androgen deprivation therapy for node-positive prostate cancer. J Clin Oncol 2009;27:100-5.

6. Kumar S, Shelley M, Harrison C, Coles B, Wilt T, Mason M. Neo-adjuvant and adjuvant hormone therapy for localised prostate cancer [protocol for a Cochrane review]. Cochrage Database of Systematic Reviews 2006 Issue 2 Chichester (UK): John Wiley & Sons, Ltd.

근거표

KQ8
Reference	1. McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP. Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer. BJU int 2006;97:247- 54.
Study type	Three randomized, double-blind, placebo-controlled trial for combined analysis
Patients	4,052 patients for bicalutamide 150 mg and 4061 to standard care alone
Purpose of Study	To evaluate the efficacy and tolerability of bicalutamide 150 mg once daily in addition to standard care for localized or locally advanced, nonmetastatic prostate cancer.
Study Results	The large EPC trial programme is defining men who benefit or do not from early or adjuvant antiandrogen therapy. At a median follow-up of 7.4 years, in localized disease there is no benefit to PFS by adding bicalutamide to standard care, and there is a trend (hazard ratio, HR, 1.16; 95% confidence intervals, CI, 0.99-1.37; P=0.07) towards decreased survival in patients otherwise undergoing watchful waiting. However, in locally advanced disease, bicalutamide significantly improved PFS irrespective of standard care. Bicalutamide significantly improved overall survival in patients receiving radiotherapy (HR 0.65; 95% CI 0.44-0.95; P=0.03); this was driven by a lower risk of prostate cancerrelated deaths. Bicalutamide produced a trend towards improved overall survival in patients with locally advanced disease otherwise undergoing watchful waiting (HR 0.81; 95% CI 0.66- 1.01; P=0.06). No survival difference was evident in the prostatectomy subgroup.
Level of Study	1
Reference	2. 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. N Engl J Med 1999;341:1781-8.
Study type	multicenter, randomized controlled trial
Patients	47 patients in the immediate antiandrogen therapy group and 51 patients in the observation group
Purpose of Study	To 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 immediatetreatment 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	3. 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. Lancet Oncol 2006;7:472- 9.
Study type	multicenter, randomized controlled trial
Patients	47 patients in the immediate antiandrogen therapy group and 51 patients in the observation group
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	4. 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 J Urol 2011;52:741-5.
Study type	Retrospective case-control study
Patients	18 patients in ADT group and 22 patients in observation group
Purpose of Study	To assessed the role of ADT in disease progression after radical prostatectomy
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	5. Wong YN, Freedland S, Egleston B, Hudes G, Schwartz JS, Armstrong K. Role of androgen deprivation therapy for node-positive prostate cancer. J Clin Oncol 2009;27:100- 5.
Study type	Cohort study
Patients	209 patients received ADT within 120 days of RP and 522 patients never received ADT
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	A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and nonADT 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	2

KQ 9. 기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행시 골반림프절 절제술을 같이 시행하는 경우가 골반 림프절 절제술을 같이 시행하지 않는 경우에 비해 생존율을 높일 수 있는가?

권고사항	권고수준	근거수준
기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행 시 림프절 전이의 가능성이 있는 경우 골반림프절 절제술을 권고한다.	A	I

개요

전립선암 수술에 있어 골반림프절절제술(pelvic lymph node dissection, PLND)을 시행하는 환자의 선택은 림프절전이의 가능성을 고려하여 결정되고 있다. 골반림프절전이의 가능성은 술 전 전립선특이항원(PSA) 수치, 임상병기 및 조직검사 글리슨 점수를 사용하는 노모그람을 바탕으로 예측한다^[1].

그러나 중간위험 전립선암 환자에서 골반 림프절 절제술의 효용성에 있어서는 아직도 논란이 있다^[2,3].

골반 림프절 절제술은 정확한 병기의 설정 뿐만 아니라 미세 전이가 있는 일부 환자들에게 완치 기회를 제공할 수 있다는 점에서 효용이 있지만 이 자체가 수술에 따른 morbidity를 높이고 생존율에는 영향을 미치지 않는다는 연구 결과들도 보고되고 있다^[2,3].

중간위험 전립선암 환자에서 골반 림프절 절제술을 시행할 때 확대 골반 림프절 절제술을 시행함으로써 제한적 골반 림프절 절제술보다 2배 정도 전이성 병변을 더 많이 찾아 낼 수 있다^[4]. 확대 골반림프절절제술의 범위는 전측면으로는 외장골정맥, 외측면으로는 외측골반벽, 내측면으로는 방광벽, 후측면으로는 골반바닥(floor of pelvis), 근위면으로는 내장골동맥, 원위면으로는 Cooper 인대를 경계로 하고 있다. Choi 등^[5]은 제한적 림프절 절제술을 해도 중간위험군 및 고위험군에서 정확한 병기 설정에 도움을 줄 수 있다고 주장하였으며 개복수술과 로봇수술을 비교한 결과 고위험군에서는 개복 수술이 림프절절제술 시행에 더 효과적이었다고 보고하였다.

기존 가이드라인 요약 및 수용성, 적용성 평가

미국의 National Comprehensive Cancer Network (NCCN) 진료지침의 저자들은 골반림프절전이의 가능성이 2%보다 높은 경우 골반림프절절제술을 시행할 것을 권고하고 있으며 이러한 기준을 적용하면 47.7%의 불필요한 골반림프절절제술을 줄일 수 있는 반면 양성림프절을 놓치게 될 가능성은 12.1% 정도로 낮음을 근거로 하고 있다^[6]. NCCN 패널들은 Memorial Sloan Kettering Cancer Center (MSKCC)에서 제시하는 기준을 권장하고 있다^[6]. 이 경우 골반림프절절제술은 광범위 골반림프절절제술(extended PLND) 방식으로 시행하는 것이 추천된다^[7,8]. 이는 절제 림프절의 수가 증가할수록 림프절전이를 진단하게 될 가능성이 높아져 보다 정확한 병기를 설정할 수 있다는데 근거한다^[9-11]. NCCN에서는 골반림프절절제술을 시행하는 것이 생존율에 이득을 준다는 보고들을 제시하고 있으며 이는 미세전이 림프절을 제거할 수 있기 때문인 것으로 해석하고 있다^[10,12-14]. NCCN에서는 골반림프절절제술은 관혈적접근법, 복강경이나 로봇보조 접근법을 통한 근치전립선절제술 시행 시 모두에서 비교적 안전하게 시행할 수 있고 세 접근법 모두 골반림프절절제술로 인한 합병증의 발생률은 유사하다고 제시하였다.

EAU 가이드라인 역시 광범위 골반림프절절제술을 통해 예후에 대한 중요한 정보를 제공 받을 수 있음을 강조하며 중간위험도 전립선암 환자에 있어 골반림프절전이의 가능성이 5%보다 높은 경우 골반림프절절제술을 시행하는 것을 권고하고 있다. 이때 Briganti nomogram^[15,16] 혹은 MSKCC 노모그람을 이용하여 림프절 전이 가능성을 예측할 것을 권장한다^[17].

또한 AUA 가이드라인(2017)에서는 unfavorable 중간 위험도 전립선암(Gleason grade group 3) 환자에서 골반 림프절 절제술을 시행할 것을 권고하고 있다.

기존의 국내 전립선암 진료지침과 EAU 및 NCCN guideline에서는 골반림프절전이의 가능성이 2% (혹은 5%) 보다 높은 경우 골반림프절절제술을 시행하는 것을 권고하고 있다. 상기 연구결과들을 토대로 “기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행 시 림프절 전이의 가능성이 있는 경우 골반림프절 절제술을 권고한다.”라고 추천한다.

KQ 9. 기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행시 골반 림프절 절제술을 같이 시행하는 경우가 골반 림프절 절제술을 같이 시행하지 않는 경우에 비해 생존율을 높일 수 있는가?
지침(제목)	권고	권고등급	근거수준	page
1. 2015 KUOS	근치적전립선절제술 시행 시에 림프절전이의 가능성이 2% 이상인 경우 골반림프절절제술을 포함하여 시행한다.	없음	없음	23
2. EAU 2016	An eLND should be performed in intermediate-risk Prostate cancer if the estimated risk for pN+ exceeds 5%	B	2b	34, 36
3. NCCN 2016	RP + PLND if predicted probability of lymph node metastasis ≥2%	없음	없음	MS-12, PROS-4

지침(제목)		1. 2015 KUOS	2. EAU 2016	3. NCCN 2016
수용성	인구 집단(유병률, 발생률 등)이 유사하다.	예	아니오	아니오
	가치와 선호도가 유사하다.	예	예	예
	권고로 인한 이득은 유사하다.	예	예	예
	해당 권고는 수용할 만하다.	예	예	예
적용성	해당 중재/장비는 이용 가능하다.	예	예	예
	필수적인 전문기술이 이용 가능하다.	예	예	예
	법률적/제도적 장벽이 없다.	예	예	예
	해당 권고는 적용할 만하다.	예	예	예

가이드라인 모두 수용 가능한 것으로 판단되고 적용성에 있어서 기존 치료 방법의 적용집단에 관한 문제로 특별한 문제는 없는 것으로 보인다.

업데이트 근거 요약

중간위험 그룹 중에서 소위 “low intermediate-risk” (글리슨 점수≤6, 임상병기≤2b, 전립선특이항원 10-20 ng/mL) 환자들의 경우 실제 림프절 전이가 3% 정도로 매우 낮게 보고된다. 이러한 환자군은 노모그람을 그대로 적용하여 골반임파선절제술을 시행하는 것에 신중을 기하는 것이 좋다[18,19].

참고문헌

1. Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003;169:145-7.

2. Briganti A, Giannarini G, Karnes RJ, Gandaglia G, Ficarra V, Montorsi F. What evidence do we need to support the use of extended pelvic lymph node dissection in prostate cancer? Eur Urol 2015;67:597-8.

3. Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol 2012;61:1132-8.

4. Kim KH, Lim SK, Kim HY, Shin TY, Lee JY, Choi YD, et al. Extended vs standard lymph node dissection in robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer: a propensity-scorematching analysis. BJU Int 2013;112:216-23.

5. Choi D, Kim D, Kyung YS, Lim JH, Song SH, You D, et al. Clinical experience with limited lymph node dissection for prostate cancer in Korea: single center comparison of 247 open and 354 robot-assisted laparoscopic radical prostatectomy series. Korean J Urol 2012;53:755-60.

6. Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798-803.

7. Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, et al. Pelvic lymph node dissection in prostate cancer. Eur Urol 2009;55:1251-65.

8. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52:29-37.

9. Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175:1320-4; discussion 1324-5.

10. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172:1840-4.

11. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68:121-5.

12. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169:849-54.

13. Wagner M, Sokoloff M, Daneshmand S. The role of pelvic lymphadenectomy for prostate cancer--therapeutic? J Urol 2008;179:408-13.

14. 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. J Urol 2004;172:2252-5.

15. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection:the essential importance of percentage of positive cores. Eur Urol 2012;61: 480-7.

16. Dell’Oglio P, Abdollah F, Suardi N, Gallina A, Cucchiara V, Vizziello D, et al. External validation of the European association of urology ecommendations for pelvic lymph node dissection in patients treated with robot-assisted radical prostatectomy. J Endourol 2014;28: 416-23.

17. Hinev AI, Anakievski D, Kolev NH, Hadjiev VI. Validation of nomograms predicting lymph node involvement n patients with prostate cancer undergoing extended pelvic lymph node dissection. Urol int 2014;92:300-5.

18. Mandel P, Kriegmair MC, Veleva V, Salomon G, Graefen M, Huland H, et al. The role of pelvic lymph node dissection during radical prostatectomy in patients with Gleason 6 intermediate-risk prostate cancer. Urology 2016;93:141-6.

19. Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol 2017;72:84-109.

근거표

KQ9
Reference	1. Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003;169:145-7.
Study type	Randomized prospective study
Patients	123 patients undergoing radical prostatectomy
Purpose of Study	To assess the value of an extended node dissection in detecting nodal metastasis
Study Results	Mean patient age was 61 years. Clinical stage was T1c in 88 patients (72%), T2a in 26 (21%), T2b in 7 (6%) and T3 in 2 (1%). Mean preoperative prostate specific antigen was 7.4 ng./ml. Pelvic lymph node metastasis was histologically confirmed in 8 patients (6.5%). Positive nodes were found on the side of the extended dissection in 4 patients, on the side of the limited dissection in 3 and on both sides in 1. Complications possibly attributable to the node dissection included lymphocele in 4 patients, lower extremity edema in 5, deep venous thrombosis in 2, ureteral injury in 1 and pelvic abscess in 1. These complications occurred 3 times more often on the side of the extended dissection (p=0.08).
Level of Study	1
Reference	2. Briganti A, Giannarini G, Karnes RJ, Gandaglia G, Ficarra V, Montorsi F. What evidence do we need to support the use of extended pelvic lymph node dissection in prostate cancer? Eur Urol 2015;67:597-8.
Study type	Expert opinion
Patients
Purpose of Study	To discuss the role of pelvic lymph node dissection (PLND) at the time of radical prostatectomy (RP)
Study Results	Even a prospective randomised trial might not provide a definitive answer as to the key clinical questions concerning the role of PLND at the time of RP, and might potentially lead to misleading conclusions. So what should we do? Knowledge of the biology of the disease should inform us on the type of treatment we should offer to our patients, and not vice versa. In this regard, novel biomarkers and genetic signatures may certainly help in closing this gap.
Level of Study	6
Reference	3. Briganti A, Abdollah F, Nini A, Suardi N, Gallina A, Capitanio U, et al. Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection. Eur Urol 2012;61:1132-8.
Study type	Retrospective study
Patients	1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center.
Purpose of Study	To assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).
Study Results	Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥ 50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p=0.8). Lack of a central scan review represents the main limitation of our study.
Level of Study	3
Reference	4. Kim KH, Lim SK, Kim HY, Shin TY, Lee JY, Choi YD, et al. Extended vs standard lymph node dissection in robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer: a propensity-score-matching analysis. BJU Int 2013;112:216-23.
Study type	Retrospective study
Patients	905 patients underwent robot-assisted radical prostatectomy and lymph node dissection (LND) by a single surgeon between June 2006 and January 2011
Purpose of Study	To To compare the pathological and biochemical outcomes between extended lymph node dissection (eLND) and standard lymph node dissection (sLND) in patients undergoing robot-assisted radical prostatectomy for intermediate- or high-risk prostate cancer.
Study Results	The median (range) follow-up period was 36 (12-77) months and the median number of lymph nodes removed was 21 and 12 in the eLND and sLND groups, respectively. Propensity-score matching resulted in 141 patients in each group. Although patients who underwent eLND had a higher clinical stage, biopsy Gleason score and number of positive cores than those treated with sLND in the entire cohort, there were no preoperative between-group differences in the matched cohort. In the matched cohort, lymph node metastases were detected at a significantly higher rate in the eLND than in the sLND group (12.1 vs. 5.0%, P=0.033). In the matched cohort, the 3-year biochemical recurrence-free survival rates were 77.8 and 73.5% in the eLND and sLND groups, respectively, which was not significant (hazard ratio 0.85, P=0.497).
Level of Study	3
Reference	5. Choi D, Kim D, Kyung YS, Lim JH, Song SH, You D, et al. Clinical experience with limited lymph node dissection for prostate cancer in Korea: single center comparison of 247 open and 354 robot-assisted laparoscopic radical prostatectomy series. Korean J Urol 2012;53:755-60.
Study type	Retrospective study
Patients	601 consecutive patients undergoing radical prostatectomy and bilateral limited PLND by either RRP (n=247) or RALP (n=354) in Asan Medical Center.
Purpose of Study	To demonstrate our clinical experience with limited PLND and the difference in its yield between open retropubic radical prostatectomy (RRP) and robot-assisted laparoscopic radical prostatectomy (RALP) for prostate cancer patients in Korea.
Study Results	The mean patient age was 64.9 years and the mean preoperative prostate-specific antigen was 9.8 ng/ml. The median number of removed lymph nodes per patient was 5 (range, 0 to 20). The numbers of patients of each risk group were 167, 199, and 238, and the numbers of patients with tumor-positive lymph nodes were 1 (0.6%), 4 (2.0%), and 17 (7.1%) in the low-, intermediate-, and high-risk groups, respectively. In the high-risk group, the lymph node-positive ratio was higher in RRP (14.9%) than in RALP subjects (2.4%).
Level of Study	3
Reference	6. Cagiannos I, Karakiewicz P, Eastham JA, Ohori M, Rabbani F, Gerigk C, et al. A preoperative nomogram identifying decreased risk of positive pelvic lymph nodes in patients with prostate cancer. J Urol 2003;170:1798-803.
Study type	Retrospective study
Patients	7,014 patients treated with radical prostatectomy at 6 institutions between 1985 and 2000.
Purpose of Study	To develope a preoperative nomogram for prediction of lymph node metastases in patients with clinically localized prostate cancer.
Study Results	Overall 5,510 patients with complete clinical and pathological information were included in the study. Lymph nodes metastases were present in 206 patients (3.7%). Pretreatment PSA, biopsy Gleason sum, clinical stage and institution represented predictors of lymph node status (p<0.001). Bootstrap corrected predictive accuracy of the 3-variable nomogram (clinical stage, Gleason sum and PSA) was 0.76. Inclusion of a fourth variable, which accounts for institutional differences in lymph node metastases, yielded an area under the receiver operating characteristics curve of 0.78. The negative predictive value of our nomograms was 0.99 when they predicted 3% or less chance of positive lymph nodes.
Level of Study	3
Reference	7. Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, et al. Pelvic lymph node dissection in prostate cancer. Eur Urol 2009;55:1251-65.
Study type	Systematic review
Patients
Purpose of Study	To systematically review the available literature concerning the role of PLND and its extent in PCa staging and outcome.
Study Results	Despite recent advances in imaging techniques, PLND remains the most accurate staging procedure for the detection of lymph node invasion (LNI) in PCa. The rate of LNI increases with the extent of PLND. Extended PLND (ePLND; ie, removal of obturator, external iliac, hypogastric with or without presacral and common iliac nodes) significantly improves the detection of lymph node metastases compared with limited PLND (lPLND; ie, removal of obturator with or without external iliac nodes), which is associated with poor staging accuracy. Because not all patients with PCa are at the same risk of harbouring nodal metastases, several nomograms and tables have been developed and validated to identify candidates for PLND. These tools, however, are based mostly on findings derived from lPLND dissections performed in older patient series. According to these prediction models, a staging PLND might be omitted in low-risk PCa patients because of the low rate of lymph node metastases found, even after extended dissections (<8%). The outcome for patients with positive nodes is not necessarily poor. Indeed, patients with low-volume nodal metastases experience excellent survival rates, regardless of adjuvant treatment. But despite few retrospective studies reporting an association between PLND and PCa progression and survival, the exact impact of PLND on patient outcomes has not yet been clearly proven because of the lack of prospective randomised trials.
Level of Study	1
Reference	8. Heidenreich A, Ohlmann CH, Polyakov S. Anatomical extent of pelvic lymphadenectomy in patients undergoing radical prostatectomy. Eur Urol 2007;52:29-37.
Study type	Systematic review
Patients
Purpose of Study	To critically evaluate the current status on PLND in prostate cancer
Study Results	The anatomical lymphatic drainage of the prostate includes the obturator fossa, and the external and internal iliac arteries; therefore, at least these areas should be included in PLND. According to the current clinical studies, extended PLND (ePLND) significantly increases the yield of both total lymph nodes and lymph node metastases independent of the risk classification of pCA. Lymph node metastases will be detected in about 5-6%, 20- 25%, and 30-40% of low-, intermediate-, and high-risk pCA, respectively. Exclusively 25% of all positive lymph nodes are located in the area around the internal iliac artery. With regard to progression-free and cancer-specific survival, retrospective analysis of the SEER data and additional case-control studies indicate a direct positive relationship between the number of removed lymph nodes and long-term oncological outcome in patients with limited lymph node involvement or negative lymph nodes. In these patients, cancer-specific survival is improved by about 15-20%. On the basis of results of large case-control studies, complication rates of ePLND are not significantly increased.
Level of Study	1
Reference	9. Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, et al. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175:1320-4; discussion 1324-5.
Study type	Retrospective study
Patients	5,038 patients who underwent radical retropubic prostatectomy between 1983 and 2003.
Purpose of Study	To examine the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer.
Study Results	The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p=0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p<0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p=0.01).
Level of Study	3
Reference	10. Allaf ME, Palapattu GS, Trock BJ, Carter HB, Walsh PC. Anatomical extent of lymph node dissection: impact on men with clinically localized prostate cancer. J Urol 2004;172:1840-4.
Study type	Retrospective study
Patients	2,135 patients (RP + ePLND) and 1,865 patients (RP + limited PLND)
Purpose of Study	To evaluate the influence of the anatomical extent of pelvic lymph node dissection performed at radical prostatectomy on lymph node yield, staging accuracy and time to prostate specific antigen progression.
Study Results	Extended lymph node dissection removed more lymph nodes (mean 11.6 vs 8.9, p<0.0001) and detected more lymph node positive disease (3.2% vs 1.1%, p<0.0001) than the more anatomically limited technique. This finding held true for patients across all pathology groups. Among men with lymph node positive disease involving less than 15% of extracted nodes, the 5-year prostate specific antigen progression-free rate for extended lymph node dissection was 43% versus 10% for the more limited lymph node dissection (p=0.01).
Level of Study	3
Reference	11. Joslyn SA, Konety BR. Impact of extent of lymphadenectomy on survival after radical prostatectomy for prostate cancer. Urology 2006;68:121-5.
Study type	Retrospective study
Patients	13,020 patients who underwent radical prostatectomy (with or without lymphadenectomy) for prostate cancer obtained from the Surveillance, Epidemiology, and End Results Program (1988 to 1991).
Purpose of Study	To determine whether more extended lymphadenectomy, along with radical prostatectomy, resulted in a decreased risk of prostate cancer-specific death at 10 years.
Study Results	Patients undergoing excision of at least 4 lymph nodes (node-positive and node-negative patients) or more than 10 nodes (only node-negative patients) had a lower risk of prostate cancer-specific death at 10 years than did those who did not undergo lymphadenectomy. The removal of a greater number of nodes was associated with a greater likelihood of the presence of positive nodes. The presence of more than one positive node was associated with a greater risk of prostate cancer-related death.
Level of Study	3
Reference	12. Bader P, Burkhard FC, Markwalder R, Studer UE. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003;169:849-54.
Study type	Retrospective study
Patients	367 patients with clinically organ confined prostate cancer underwent meticulous pelvic lymph node dissection and radical prostatectomy.
Purpose of Study	To determine progression rate and survival of patients with positive nodes following radical prostatectomy according to the number of metastases.
Study Results	Of the patients 92 (25%) had histologically proven lymph node metastases. Followup of more than 1 year was available in 88 patients (96%), and median followup was 45 months (range 13 to 141). Of 19 patients (22%) who died of prostate cancer 16 had more than 1 positive node. Of the 39 patients with only 1 positive node 15 (39%) remained without signs of clinical or chemical progression. Whereas of the 20 and 29 patients with 2 or more positive lymph nodes only 2 (10%) and 4 (14%), respectively, remained disease-free. Time to prostate specific antigen relapse, symptomatic progression and tumor related death were significantly affected by the number of positive nodes.
Level of Study	3
Reference	13. Wagner M, Sokoloff M, Daneshmand S. The role of pelvic lymphadenectomy for prostate cancer--therapeutic? J Urol 2008;179:408-13.
Study type	Systematic review
Patients
Purpose of Study	To analyze the current literature on the role of pelvic lymphadenectomy in prostate cancer.
Study Results	Staging pelvic lymphadenectomy provides valuable prognostic data and it may be therapeutic. Extended lymph node dissection increases the detection of positive nodes. The number of positive or negative nodes resected may increase survival. The observed survival benefits may be due to the elimination of micrometastatic disease.
Level of Study	1
Reference	14. 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: longterm results. J Urol 2004;172:2252-5.
Study type	Retrospective study
Patients	1,936 patients who underwent radical retropubic prostatectomy and pelvic lymph node dissection for clinically organ confined prostate cancer.
Purpose of Study	To determine the prognostic factors that affect recurrence and survival in patients with lymph node positive prostate cancer.
Study Results	Followup was 1 to 24 years (median 11.4). Overall median survival was 15 years. Overall clinical recurrence-free survival at 5, 10 and 15 years was 80%, 65% and 58%, respectively. Patients who had 1 or 2 positive lymph nodes had a clinical recurrence-free survival of 70% and 73% at 10 years, respectively, vs 49% in those who had 5 or more involved lymph nodes (p=0.0031). When stratified by lymph node density, patients with a lymph node density of 20% or greater were at higher risk for clinical recurrence compared to those with a density of less than 20% (relative risk=2.32, p<0.0001). On stratified log rank test only prostate cancer T stage, and the number and percent of positive lymph nodes correlated with recurrence-free and overall survival.
Level of Study	3
Reference	15. Briganti A, Larcher A, Abdollah F, Capitanio U, Gallina A, Suardi N, et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 2012;61:480-7.
Study type	Retrospective study
Patients	588 patients with clinically localised PCa
Purpose of Study	To update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP).
Study Results	The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p<0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p≤0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively.
Level of Study	3
Reference	16. Dell’Oglio P, Abdollah F, Suardi N, Gallina A, Cucchiara V, Vizziello D, et al. External validation of the European association of urology recommendations for pelvic lymph node dissection in patients treated with robot-assisted radical prostatectomy. J Endourol 2014;28:416-23.
Study type	Retrospective study
Patients	615 patients treated with RARP and PLND
Purpose of Study	To specifically assess the accuracy of the EAU recommendation for PLND among men treated with robot-assisted radical prostatectomy (RARP).
Study Results	Median of lymph nodes (LNs) removed was 9 (interquartile range: 6-13). The rate of LNI was 5%. External validation of the Briganti nomogram showed good accuracy (81.8%). A nomogram-derived cutoff of 5% would allow the avoidance of 75% of PLND at the cost of missing of 19.4% of patients with LNI. When the same analyses were repeated in men with at least 10 and 15 LNs removed, the 5% cutoff was associated with a reduction in PLND and with an LNI missing rates of 67.6% and 59.3% and 17.4% and 6.2%, respectively. Similarly, the prediction accuracy increased to 81.2% and 85.3%, respectively. The decision curve analysis showed an increase in the net-benefit in the prediction range between 2.5% and 54%.
Level of Study	3
Reference	17. Hinev AI, Anakievski D, Kolev NH, Hadjiev VI. Validation of nomograms predicting lymph node involvement in patients with prostate cancer undergoing extended pelvic lymph node dissection. Urol int 2014;92:300-5.
Study type	Retrospective study
Patients	256 PCa patients who underwent extended pelvic lymph node dissection (ePLND) and radical prostatectomy (RP) were obtained from two Bulgarian institutions
Purpose of Study	To validate Briganti’s nomograms predicting the probability of lymph node involvement (LNI) in prostate cancer (PCa).
Study Results	All of Briganti’s nomograms showed a higher predictive accuracy as compared with the updated MSKCC nomogram. The respective AUC values were calculated as 0.847, 0.837, 0.858 and 0.875 for the four Briganti nomograms, and 0.770 for the updated MSKCC nomogram, respectively. Despite the potential for heterogeneity in patient selection and management, all predictions demonstrated high concordance with actual observations. Compared with other similar prognostic tools the updated Briganti nomogram (version 2012) showed the highest predictive accuracy and should therefore be preferred.
Level of Study	3
Reference	18. Mandel P, Kriegmair MC, Veleva V, Salomon G, Graefen M, Huland H, et al. The role of pelvic lymph node dissection during radical prostatectomy in patients with Gleason 6 intermediate-risk prostate cancer. Urology 2016;93:141-6.
Study type	Retrospective study
Patients	1,383 patients with low intermediate-risk cancer (biopsy Gleason grade ≤6, cT ≤2b, and prostate-specific antigen (PSA) 10-20 ng/mL) undergoing radical prostatectomy with or without PLND
Purpose of Study	To analyze the benefit of pelvic lymph node dissection (PLND) in patients with biopsy Gleason grade ≤6, cT ≤2b, and prostate-specific antigen (PSA) 10-20 ng/mL.
Study Results	In the main study cohort (PSA 10-20 ng/mL), PLND was performed in 867 (62.7%) patients with a median number of removed LNs of 11 (interquartile range 16-6). Positive LNs were detected in 3.3% of these patients. Compared to the main study cohort, patients with preoperatively higher PSA ≥20 ng/mL (or lower PSA <10 ng/ml) underwent PLND in 83.8% (32.7%) of the cases, with 8.0% (1.8%) showing positive LNs. Median followup in the main study cohort was 84.5 months. Biochemical recurrence (BCR) occurred in 20.6% of these men. The 5-year and 10-year BCR-free survival rates were 82.2% and 75.6% for those with PLND, and 83.4% and 75.8% for patients without PLND. PLND was not a significant factor influencing BCR-free, metastasis-free, or cancer-specific survival in the main study cohort.
Level of Study	3
Reference	19. Fossati N, Willemse PM, Van den Broeck T, van den Bergh RCN, Yuan CY, Briers E, et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol 2017;72:84-109.
Study type	systematic review
Patients	66 studies recruiting a total of 275,269 patients were included (44 full-text articles and 22 conference abstracts)
Purpose of Study	To systematically review the relevant literature assessing the relative benefits and harms of PLND for oncological and non-oncological outcomes in patients undergoing radical prostatectomy for PCa.
Study Results	There were high risks of bias and confounding in most studies. Conflicting results emerged when comparing biochemical and clinical recurrence, while no significant differences were observed among groups for survival. Conversely, the majority of studies showed that the more extensive the PLND, the greater the adverse outcomes in terms of operating time, blood loss, length of stay, and postoperative complications. No significant differences were observed in terms of urinary continence and erectile function recovery.
Level of Study	1

KQ 10. 중간위험 전립선암 환자에서 신경보존 술식을 시행한 것은 기능적 성적(발기부전, 요실금)이 우수한가?

권고사항	권고수준	근거수준
중간위험 전립선암 환자에서 근치적 전립선 절제술을 할 때 신경 보존 술식을 시행 하는 것이 기능적 성적이 우수하므로 신경보존 술식을 권고한다	A	I

개요

중간 위험 전립선암 환자에서 근치적 전립선절제술은 표준적 치료로 받아들여지고 있다. 근치적 전립 선절제술의 종양학적 성적은 좋으나 수술 후 생길 수 있는 발기부전과 요실금이 환자의 삶의 질을 떨어뜨리는 주요한 원인이 된다^[1].

근치적 전립선절제술을 시행하면서 신경보존 술식을 시행하는 것은 기능성 성적(발기부전, 요실금)이 우수한 것으로 이미 알려져 있다. 신경보존 술식을 시행한 경우에 그렇지 않은 경우보다 국제전립선증상점수(IPSS)가 8.4점 높은 것으로 조사되었고^[1] 요실금 회복에서 좋은 경과를 보였다^[2]. 또한 광범위 전립선절제술을 시행한 환자보다 신경보존 술식을 시행한 환자에서 초기 요실금 회복에 유리함이 있었다^[3]. 1,249명을 대상으로 한 대규모 연구에서 신경보존 술식을 시행한 경우 그렇지 않은 경우보다 수술 후 2년 뒤 1.8배 요자제능이 높은것으로 나타났다^[4].

근치적 전립선절제술 이후 발기능 회복과의 연관성에 대해서 메타분석을 시행한 결과 연령, 술전 발기능, 기타 기저질환과 더불어 신경보존 술식이 중요한 인자로 분석되었다^[5]. 술전 발기능이 정상이었던 환자군에서 신경보존 술식을 시행하였을 때 31-68%에서 발기능이 보존되었다고 보고하였다^[6].

기존 가이드라인 요약 및 수용성, 적용성 평가

NCCN, AUA, NICE 가이드라인에서는 신경보존 술식이 발기부전이나 배뇨 기능을 개선시킨다고 보고하고 있으며^[1,7,8] 특히 Dubbleman 등^[9]은 수술 전에 발기부전이 없던 환자들에서 양측 신경 보존술식을 시행했을 경우 성기능은 18-76%까지, 단측 신경 보존술식을 시행했을 경우 13-56%의 수술 후 성기능이 보존될 수 있음을 보고하였다. EAU guideline에 따르면 수술전 성기능이 유지되어 있고 전립선암의 피막침범 가능성이 낮은 경우(T1c, GS <7 and PSA <10 ng/ml) 신경보존 술식이 시행되어야 한다고 권고하고 있다. 또한 NCCN guideline에서도 술후 기능성 성적에 있어서 여러 가지 요인이 관여하지만 신경보존 술식이 중요한 인자라고 판단하고 있다.

따라서 기존의 EAU, AUA, NCCN, NICE 가이드라인을 근거로 하여 중간위험전립선암 환자에서 신경보존 술식을 시행하는 것은 기능성 성적(발기부전, 요실금)이 우수하므로 신경보존 술식이 가능한 병기라면 시행하는 것이 바람직하다.

KQ 10. 중간위험 전립선암 환자에서 신경보존 술식을 시행한 것은 기능적 성적(발기부전, 요실금)이 우수한가?
지침(제목)	권고	권고등급	근거수준	page
1. EAU 2016	Offer a nerve-sparing surgery in pre-operatively potent patients with low risk of extracapsular disease (T1c, GS < 7 and PSA < 10 ng/mL, or refer to Partin tables/nomograms).	B	없음	71
2. AUA 2007	Depending on tumor characteristics and the patient’s sexual function, either nerve-sparing (to preserve erectile function) or non-nerve-sparing radical prostatectomy is commonly performed.	없음	없음	14
3. NCCN 2016	1. Recovery of erectile function is related directly to the degree of preservation of the cavernous nerve, age at surgery, and preoperative erectile function. Improvement in urinary function was reported with nerve sparing techniques. 2. Nerve-sparing procedures appear to result in preserved function for many men, though selection factors may bias the results of some of the early studies of this technique as erectile dysfunction rates were reported for only preoperatively potent men	없음	없음	1. 48/ 2. 40
6. NICE 2014	In a systematic review of 14 observational studies (Dubbelman et al. 2006) between 64% and 100% of men were potent before radical prostatectomy (RP). The reported rates of post-operative potency were 18% to 76% for bilateral nerve-sparing RP, 13% to 56% for unilateral nerve-sparing RP and 0% to 34% for non-nerve sparing RP	A	I

지침(제목)		1. EAU 2016	2. AUA 2007	3. NCCN 2016	6. NICE 2014
수용성	인구 집단(유병률, 발생률 등)이 유사하다.	예	예	예	예
	가치와 선호도가 유사하다.	예	예	예	예
	권고로 인한 이득은 유사하다.	예	예	예	예
	해당 권고는 수용할 만하다.	예	예	예	예
적용성	해당 중재/장비는 이용 가능하다.	예	예	예	예
	필수적인 전문기술이 이용 가능하다.	예	예	예	예
	법률적/제도적 장벽이 없다.	예	예	예	예
	해당 권고는 적용할 만하다.	예	예	예	예

가이드라인 모두 수용 가능한 것으로 판단되고 적용성에 있어서 기존 치료 방법의 적용집단에 관한 문제로 특별한 문제는 없는 것으로 보인다.

업데이트 근거 요약

CEASAR (Comparative Effectiveness Analysis of Surgery and Radiation) 연구에 따르면^[10] 양측 신경 보존 술식을 시행한 75명의 환자에서 단측 신경보존 술식을 시행하거나 신경보존 술식을 시행하지 않은 환자 군보다 3년 후 성기능이 더 우수하였다. Tsikis ST 등^[11]은 술 후 발기 부전이 생긴 환자들에서 요실금이 발생 빈도가 더 높아 술 후 발기부전이 요실금의 위험 인자가 될 수 있다는 가설을 제기하였으며 신경 보존 술식을 시행할 때 정낭을 보존하는 것은 수술 후 요실금이나 발기부전 회복에 도움이 되지 않는다는 보고가 있다^[12]. 또한 신경보존 술식을 시행할 때 전립선 첨부를 주의하여 세밀하게 박리하는 것이 요실금 회복에 도움이 된다는 보고도 있다^[13].

근치적 전립선절제술을 시행함에 있어서 신경보존 술식은 이미 널리 행해지고 있는 술기이며 이에 따른 기능성 성적이 우수함은 여러 메타 분석 논문^[14,15]과 최신 가이드라인을 통해 권고되는 사항이다.

참고문헌

1. Abel EJ, Masterson TA, Dechet C, et al. Nerve-sparing prostatectomy and urinary function: a prospective analysis using validated quality-of-life measures. Urology 2009;76:1336-40.

2. R Deborah, M Eric, P Pavlovich, et al. Urinary outcomes are significantly affected by nerve sparing quality during radical prostatectomy. Urol 2013;82:1348-54.

3. David B.S., M. Francesca Monn, Liang Cheng, et al. Oncologic and quality-of-life outcomes with wide resection in robot-assisted laparoscopic radical prostatectomy. Urol Oncol 2015;33:9-14.

4. Suardi N, Moschini M, Briganti A, et al. Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery. BJU Int 2013;111(5):717-22.

5. Ficarra V, Novara G, Montorsi F, et al. Systematic review and meta-analysis of studies reporting potency rates after robot-assisted radical prostatectomy. Eur Urol 2012;62:418-30.

6. Y Vette, Dubbelman, R Gert, et al. Sexual Function Before and After Radical Retropubic Prostatectomy: A Systematic Review of Prognostic Indicators for a Successful Outcome. Eur Urol 2006;50:711-20.

7. Walsh PC. Patient-reported impotence and incontinence after nerve-sparing radical prostatectomy. J Urol 1988;159:308.

8. Montorsi F, Padma-Nathan H, McCullough A, Brock GB, Broderick G, Ahuja S, Whitaker S, Hoover A, Novack D, Murphy A, Varanese L. Tadalafil in the treatment of erectile dysfunction following bilateral nerve sparing radical retropubic prostatectomy: A randomized, double-blind, placebo controlled trial. J Urol 2004;172:1036-41.

9. Dubbelman YD, Dohle GR, Schröder FH. Sexual function before and after radical retropubic prostatectomy:A systematic review of prognostic indicators for a successful outcome. Eur Urol 2006;50(4):711-8.

10. Avulova S, Zhao Z, Lee D, et al. The Effect of Nerve Sparing Status on Sexual and Urinary Function: 3-Year Results from the CEASAR Study. J Urol 2017 16. pii: S0022-5347(17)78114-1.

11. Tsikis ST, Nottingham CU, Faris SF, et al. The Relationship Between Incontinence and Erectile Dysfunction After Robotic Prostatectomy: Are They Mutually Exclusive? J Sex Med 2017;14(10):1241-7.

12. Gilbert SM, Dunn RL, Miller DC, et al. Functional Outcomes Following Nerve Sparing Prostatectomy Augmented with Seminal Vesicle Sparing Compared to Standard Nerve Sparing Prostatectomy: Results from a Randomized Controlled Trial. J Urol 2017;198(3):600-7.

13. Uwe Michl, Pierre Tennstedt, Lena Feldmeier, et al. Nerve-sparing Surgery Technique, Not the Preservation of the Neurovascular Bundles, Leads to Improved Long-term Continence Rates After Radical Prostatectomy European Urology 2016;69(4):590-1.

14. Fairleigh Reeves, Patrick Preece, Jada Kapoor, et al. Preservation of the Neurovascular Bundles Is Associated with Improved Time to Continence After Radical Prostatectomy But Not Long-term Continence Rates:Results of a Systematic Review and Meta-analysis. European Urology 2015;68(4):692-704.

15. Nguyen LN, Head L, Witiuk, et al. The Risks and Benefits of Cavernous Neurovascular Bundle Sparing during Radical Prostatectomy: A Systematic Review and Meta-Analysis. J Urol 2017;198(4):760-9.

근거표

KQ10
Reference	1. David B.S., M. Francesca Monn, Liang Cheng, et al. Oncologic and quality-of-life outcomes with wide resection in robot-assisted laparoscopic radical prostatectomy. Urol Oncology 2015;33:9-14.
Study type	Original article
Patients	483 Patients undergoing RALP (2004-2013) for intermediate- or high-risk prostate adenocarcinoma
Purpose of Study	To assess urinary quality-of-life (QoL) and oncologic outcomes between wide resection (WR) robot-assisted laparoscopic radical prostatectomy (RALP) and non-WR (NWR) RALP in men with intermediate- or high-risk (Cancer of the Prostate Risk Assessment [CAPRA]-9 >2) prostate adenocarcinoma.
Study Results	A total of 483 RALP cases met inclusion criteria—129 (26.7%) underwent WR and 354 (73.3%) underwent NWR-RALP. There were no demographic differences between groups. Burden of disease was greater in patients undergoing WR (P<0.001). There was no difference in+SM rates between WR and NWR (P=0.505). Adjusting for demographics and CAPRA-9 score, WR patients had a clinically relevant 27% decrease in posterolateral+SM (odds ratio=0.73; 95% CI: 0.38-1.41; P=0.351). WR was not associated with worse BCRFS (hazard ratio=1.24; 95% CI: 0.83-1.86, P=0.30). Adjusting for pathology, University of California, Los Angeles and Extended Prostate Cancer Index Composite urinary domain scores were similar between WR and NWR groups
Level of Study	3
Reference	2. R Deborah, M Eric, P Pavlovich, et al. Urinary outcomes are significantly affected by nerve sparing quality during radical prostatectomy. J Urology 2013;82:1348-54.
Study type	Original article
Patients	A total of 102 preoperatively potent men underwent laparoscopic or robotic radical prostatectomy
Purpose of Study	To assess the effect of nerve sparing (NS) quality on self-reported patient urinary outcomes after radical prostatectomy.
Study Results	Patients with at least 1 neurovascular bundle spared completely, along with its supportive tissues (NS grade 4/4), noted significantly improved Expanded Prostate Cancer Index Composite urinary functional and continence outcomes as early as 1 month postoperatively and up to 12 months. Significantly less urinary bother was also noted in these men by 9-12 months postoperatively. Multivariate analysis revealed that bilateral or unilateral excellent NS (at least 1 bundle graded 4/4), increasing time from surgery, young patient age, and ower body mass index positively and significantly affected urinary functional outcomes, including pad use. Men who received excellent unilateral NS recovered urinary function about as well as men who had both neurovascular bundles spared in similar fashion.
Level of Study	3
Reference	3. Y Vette, Dubbelman, R Gert, et al. Sexual Function Before and After Radical Retropubic Prostatectomy: A Systematic Review of Prognostic Indicators for a Successful Outcome. Eur Urol 2006;50:711-20.
Study type	Systemic review
Patients	literature concerning sexual function after RRP and focused on prognostic indicators for a successful sexual outcome.
Purpose of Study	Erectile dysfunction is common after surgery for prostate cancer. Potency rates after radical retropubic prostatectomy (RRP) vary widely among different studies. Since the introduction of the nerve-sparing technique potency rates have increased. Erectile function recovery rates for selected groups of patients are high. However, studies from community practices have shown less favourable outcomes after RP
Study Results	Most important prognostic factors for the return of potency after RRP are preservation of the neurovascular bundles, age of the patient and sexual function before the operation. Neurogenic and vasculogenic factors seem to play an important role in the aetiology of the erectile dysfunction after surgery. The role of preserving the accessory pudendal artery is not certain, although some investigators found significant hemodynamic changes after sacrificing the accessory pudendal artery. Colour Doppler ultrasound studies in combination with intracavernous injection of vasoactive drugs or after PDE-5 inhibitors administration has shown to be a reliable test for vascular factors
Level of Study	1
Reference	4. Yang DY, Monn MF, Kaimakliotis HZ, et al. Oncologic and quality-of-life outcomes with wide resection in robot-assisted laparoscopic radical prostatectomy. Urol Oncol 2015;33:70. e9-14.
Study type	Retrospective study
Patients	483 patients
Purpose of Study	To assess urinary quality-of-life (QoL) and oncologic outcomes between wide resection (WR) robot-assisted laparoscopic radical prostatectomy (RALP) and non-WR (NWR) RALP in men with intermediate- or high-risk (Cancer of the Prostate Risk Assessment [CAPRA]-9 >2) prostate adenocarcinoma.
Study Results	A total of 483 RALP cases met inclusion criteria-129 (26.7%) underwent WR and 354 (73.3%) underwent NWR-RALP. There were no demographic differences between groups. Burden of disease was greater in patients undergoing WR (P<0.001). There was no difference in+SM rates between WR and NWR (P=0.505). Adjusting for demographics and CAPRA-9 score, WR patients had a clinically relevant 27% decrease in posterolateral+SM (odds ratio=0.73; 95% CI: 0.38-1.41; P=0.351). WR was not associated with worse BCRFS (hazard ratio=1.24; 95% CI: 0.83-1.86, P=0.30). Adjusting for pathology, University of California, Los Angeles and Extended Prostate Cancer Index Composite urinary domain scores were similar between WR and NWR groups.
Level of Study	3
Reference	5. Karl A, Buchner A, Tympner C, et al. The natural course of pT2 prostate cancer with positive surgical margin: predicting biochemical recurrence. World J Urol 2015;33:973-9.
Study type	Retrospective study
Patients	956 patients with pT2R1N0/Nx tumors
Purpose of Study	To predict biochemical recurrence respecting the natural course of pT2 prostate cancer with positive surgical margin (R1) and no adjuvant/neoadjuvant therapy.
Study Results	Preoperatively intended omission of pelvic lymph node dissection had a protective effect on BCR in T2 tumors (p=0.002), suggesting that lower malignant potential as evidenced by R1 Nx cancers had lower preoperative PSA, a higher proportion of T1c cancers and smaller tumor volume. In multivariate analysis, GS of the regular prostatectomy specimen was the only statistically significant parameter for pT2R1 prostate cancer (Table 3, p=0.003). This observation remained stable even if data were analyzed respecting each center separately or if larger centers were compared versus smaller centers.
Level of Study	3
Reference	6. Suardi N, Moschini M, Briganti A, et al. Nerve-sparing approach during radical prostatectomy is strongly associated with the rate of postoperative urinary continence recovery. BJU Int 2013;111(5):717-22.
Study type	Retrospective study
Patients	The study included 1,249 patients treated with radical prostatectomy between 2003 and 2010
Purpose of Study	To demonstrate that nerve-sparing radical prostatectomy (NSRP) is associated with higher rates of urinary continence (UC) recovery compared with non-nerve-sparing procedures in patients with surgically treated organ-confined prostate cancer.
Study Results	At a mean follow-up of 42.2 months (range 1-78), 993 patients (79.5%) recovered UC. Overall, UC recovery rate at 1 and 2 years was 76% and 79%, respectively. On univariable Cox regression analysis, age at surgery, preoperative risk group, medical comorbidities and nerve-sparing status were significantly associated with UC recovery (all P≤0.001). On multivariable analysis, age, risk group and nerve-sparing status were also independently associated with UC recovery (all P<0.003). Patients treated with bilateral NSRP had a 1.8-fold higher chance of full UC recovery
Level of Study	3

중간위험도 전립선암 환자의 치료

목차

KQ 6. 중간위험 전립선암환자에서 방사선치료와 6개월 동안 호르몬 요법을 병용하는 경우가 방사선 치료만 하는 경우 보다 생존율이 우수한가?

개요

기존 가이드라인 요약 및 수용성, 적용성 평가

업데이트 근거 요약

참고문헌

근거표

KQ 7. 중간위험 전립선암환자에서 근치적 전립선절제술 후 병리학적 불량 예후인자를 보일 경우 추가적인 방사선치료를 하는 경우가 보조요법을 하지 않는 경우보다 생존율이 우수한가?

개요

기존 가이드라인 요약 및 수용성, 적용성 평가

업데이트 근거 요약

참고문헌

근거표

KQ 8. 중간위험 전립선암 환자 중 수술 후 림프절 전이가 있는 환자에서 보조남성호르몬 차단요법은 경과 관찰에 비해 생존율이 높은가?

개요

기존 가이드라인 요약 및 수용성, 적용성 평가

업데이트 근거 요약

참고문헌

근거표

KQ 9. 기대여명이 10년 이상인 중간위험 전립선암 환자에서 근치적 전립선절제술 시행시 골반림프절 절제술을 같이 시행하는 경우가 골반 림프절 절제술을 같이 시행하지 않는 경우에 비해 생존율을 높일 수 있는가?

개요

기존 가이드라인 요약 및 수용성, 적용성 평가

업데이트 근거 요약

참고문헌

근거표

KQ 10. 중간위험 전립선암 환자에서 신경보존 술식을 시행한 것은 기능적 성적(발기부전, 요실금)이 우수한가?

개요

기존 가이드라인 요약 및 수용성, 적용성 평가

업데이트 근거 요약

참고문헌

근거표

둘러보기 메뉴

검색