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 |