KQ 3. 저위험도 전립선암 환자에서 근치적 전립선절제술은 방사선 치료에 비해 생존율이 높은가?
| 권고사항 | 권고수준 | 근거수준 |
|---|---|---|
| 저위험도 전립선암 환자에서 근치적 전립선절제술과 방사선 치료는 생존율에 있어 유의한 차이가 없으므로, 근치적 전립선절제술 또는 방사선 치료를 모두 권고할 수 있다. | A | I |
개요
국소 또는 저위험도 전립선 암으로 진단받은 환자는 치료 후 다른 암종에 비해 비교적 장기간 생존한다[1,2]. 이러한 현실을 감안할 때, 저위험도 전립선암 환자와 그 임상의는 여러 치료의 장기적인 종양학적 결과를 이해하는 것이 중요하다. 임상적으로 저위험도 국소 전립선 암 환자의 주된 치료 방법은 근치적 전립선절제술, 방사선 치료, 능동적 감시 등이 있다. 그러나 이러한 치료법에 대한 직접적인 비교가 과거에는 거의 없었기 때문에 이러한 저위험도 국소 전립선암의 여러 치료 방법들의 상대적인 치료 효과에 대해서는 불일치와 불확실성이 계속되었다[3,4].
그러나 최근들어 이에 관한 연구들이 활발해져서 몇몇 연구들에서는 해부학적인 질환의 범위와 기타 예후 인자에 대해 방사선 치료의 결과는 전립선 절제술의 결과와 유사하다고 보고되고 있다[5,6]. 또한 다른 주요 연구결과들을 살펴보면 15만 명이 넘는 환자를 대상으로 하는 전립선 암에 대한 메타분석 연구에서 저 위험도 전립선암 환자에게 근치적 전립선 절제술과 방사선 치료의 결과를 비교한 무작위 연구는 없으며 T stage, Gleason score, PSA 값의 위험 그룹 비교는 방사선 치료와 수술 군간에 유사한 결과를 보고했다[7]. 그리고 또 다른 연구에서는 근접치료(brachytherapy)와 근치적 전립선 절제술의 저위험 및 중등 위험군의 치료 성공률을 후향적으로 비교한 결과 전립선암 특이 사망률은 0.5%로 비슷하였다[8].
무작위 3상 ProtecT 임상 시험에서 저위험도 환자에서 방사선 치료의 유효성을 수술 및 적극적인 모니터링과 비교한 결과 10년 전체 생존율과 전립선암 특이 생존율은 치료군 간의 차이가 없었다[9].
또한 임상적 진행 및 전이성 질환의 발생률은 수술과 방사선 치료군 간의 차이가 없었다.
최근에 발표 된 RCT (CHHiP, RTOG 04-15)의 5년 결과는 저위험도 또는 중간 위험도 전립선암 환자에서 중등도 저농축 방사선 치료(modestly hypofractionated RT)가 통상적으로 분획화된 방사선 치료(conventionally fractionated)보다 열등하지 않음을 보여주어 참고할 만하다[10,11].
기존 가이드라인 요약 및 수용성, 적용성 평가
기존 유럽 2017 전립선암 가이드라인[12]에 따르면 기대 수명이 10년 이상인 환자나 PSA 수치, Gleason score, clinical T stage (임상병기), biopsy (조직검사) 결과에 따라 low risk (저 위험도) 또는 intermediate risk (중등 위험도) 환자군에서 근치적 수술 또는 방사선치료를 권고등급 A, 근거수준 1로 시행할 것을 권고하고 있다. 2007 AUA 전립선암 가이드라인[13]에서는 저위험도 환자군에서 active surveillance (적극적 추적관찰), interstitial prostate brachytherapy (조직내 근접치료), external beam radiotherapy (외부방사선조사요법), and radical prostatectomy (근치적 전립선적출술) 중 한가지를 치료 방법으로 제시하고 있다. 2016 NCCN[14], 2014 NICE 가이드라인[15]에서도 방사선 치료와 근치적 전립선적출술을 모두 치료법으로 제시하고 있다. 요약하면 국외 가이드라인에 따르면 저위험도 전립선암의 치료에 있어 근치적 전립선절제술과 방사선 치료는 생존율에 있어 유의한 차이가 없으므로 근치적 전립선절제술 또는 방사선 치료를 모두 권고할 수 있다.
| KQ 3. 저위험도 전립선암 환자에서 근치적 전립선절제술은 방사선 치료에 비해 생존율이 높은가? | ||||
|---|---|---|---|---|
| 지침(제목) | 권고 | 권고등급 | 근거수준 | page |
| 1. EAU 2016 | Offer both radical prostatectomy (RP) and radiotherapy (RT) in patients with low- and intermediaterisk PCa and a life expectancy >10 years. | A | 1b | 6,2,10 |
| 2. AUA 2007 | Among the treatment options for low-risk Pca, active surveillance, interstitial prostate brachytherapy, external beam radiotherapy, and radical prostatectomy are all options for treatment of the low-risk patient. Study outcomes data do not provide clear-cut evidence for the superiority of any one treatment. | 없음 | 없음 | 28 |
| 3. NCCN 2016 | EBRT is one of the principal treatment options for clinically localized prostate cancer. The NCCN Guidelines Panel consensus was that modern EBRT and surgical series show similar progression-free survival in patients with low-risk disease treated with radical prostatectomy or EBRT | 없음 | 없음 | MS-14 |
| 6. NICE 2014 | There is no strong evidence for the benefit of one treatment over another. | 없음 | 없음 | 175 |
| 지침(제목) | 1. EAU 2016 | 2. AUA 2007 | 3. NCCN 2016 | 6. NICE 2014 | |
|---|---|---|---|---|---|
| 수용성 | 인구 집단(유병률, 발생률 등)이 유사하다. | 아니오 | 아니오 | 아니오 | 아니오 |
| 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
2016년 NEJM에 발표된 Hamdy 등[9]의 연구결과는 Protec trial[16]의 10년간의 추적관찰 결과를 보여주었다. 이에 따르면 수술적 치료와 방사선 치료가 국소 전립선 환자들 사이에서는 전립선암 관련 사망률과 기타 원인 사망률 사이에 유의한 통계학적 차이가 없음을 보고하였다. Protect trial의 하위그룹들 분석에서도 저위험도 환자들에서 근치적전립선 적출술(13 men; 2.4 per 1000 personyears; 95% CI, 1.4 to 4.2)과 방사선치료(16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9)의 전이 발생에 있어서도 통계적 차이가 없었다. 또한 진행에 있어서도 근치적전립선 적출술(46 men;8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9)과 방사선치료(46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0)의 전이 발생에 있어서도 통계적 차이가 없었다. 또한 2010년 JAMA에 발표된 Julia H 등[17]의 연구에 따르면 총 309개의 논문들을 취합하여 저위험도 전립선암 환자들의 질 보정 생존년(Quality-adjusted life year/QALY)을 보고하였다. 방사선 치료군은 10.51 QALYs를 보였고 전립선 수술군은 10.23 QALYs를 보여 유사한 결과를 보여주었다. 2015년 Roach, M. 등[18]은 10년 전립선암 특이 생존율에서 방사선 치료와 수술군간의 차이가 1% 이하라 하였고, Schreiber D 등[19]도 유사한 결과를 발표했다.
2015년 Wolff RF 등의 메타분석연구[20]에 따르면 방사선 치료와 수술군간의 효과에 차이가 없었고, 2017년 Jayadevappa R 등[21]은 메타분석으로 대기요법에 비교한 생존 이득이 전립선 수술군(allcause HR=0.63 CI=0.45, 0.87; disease-specific HR=0.48 CI=0.40, 0.58)과 방사선 치료군(all-cause HR=0.65 CI=0.57, 0.74; disease-specific HR=0.51 CI=0.40, 0.65)에서 유사함을 보여주었다.
또한 기존 가이드라인에서 방사선 치료, 수술적 치료가 유의한 사망률에 있어 차이가 없고 기타 연구에서 방사선치료, 수술적 치료, 치료 안 한(능동적 감시) 군에서의 암 관련 사망률의 차이가 없음이 기존 권고안에 반영되어 있다. 그러므로 저위험도 전립선암에서 수술적 치료와 방사선 치료는 모두 권고할 수 있는 치료적 방안이다.
참고문헌
1. Albertsen PC, Fryback DG, Storer BE, Kolon TF, Fine J. Long-term survival among men with conservatively treated localized prostate cancer. Jama 1995;274(8):626-31.
2. Lu-Yao GL, Yao SL. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet (London, England) 1997;349(9056):906-10.
3. Fowler FJ, Jr., McNaughton Collins M, Albertsen PC, Zietman A, Elliott DB, Barry MJ. Comparison of recommendations by urologists and radiation oncologists for treatment of clinically localized prostate cancer. Jama 2000;283(24):3217-22.
4. Moul JW. Radical prostatectomy versus radiation therapy for clinically localized prostate carcinoma: the butcher and the baker selling their wares. Cancer 2002;95(2):211-4.
5. D’Amico AV, Whittington R, Malkowicz SB, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. Jama 1998;280(11):969-74.
6. Gretzer MB, Trock BJ, Han M, Walsh PC. A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic Radiation and Oncology criteria. The Journal of Urology 2002;168(4 Pt 1):1419-22.
7. Nilsson S, Norlen BJ, Widmark A. A systematic overview of radiation therapy effects in prostate cancer. Acta Oncol 2004;43(4):316-81.
8. Arvold ND, Chen MH, Moul JW, et al. Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low or intermediate risk disease. The Journal of Urology 2011;186(1):91-6.
9. Hamdy FC, Donovan JL, Lane JA, et al. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. The New England Journal of Medicine 2016;375(15):1415-24.
10. Dearnaley D, Syndikus I, Mossop H, et al. Conventional versus hypofractionated high-dose intensitymodulated radiotherapy for prostate cancer: 5-year outcomes of the randomised, non-inferiority, phase 3 CHHiP trial. The Lancet Oncology 2016;17(8):1047-60.
11. Lee WR, Dignam JJ, Amin MB, et al. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer. J Clin Oncol 2016;34(20):2325-32.
12. Mottet N, Bellmunt J, Bolla M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. European Urology 2017;71(4):618-29.
13. Thompson I, Thrasher JB, Aus G, et al. Guideline for the management of clinically localized prostate cancer: 2007 update. The Journal of Urology 2007;177(6):2106-31.
14. Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. Journal of the National Comprehensive Cancer Network: JNCCN 2016;14(1):19-30.
15. Graham J, Kirkbride P, Cann K, Hasler E, Prettyjohns M. Prostate cancer: summary of updated NICE guidance. BMJ (Clinical research ed) 2014;348:f7524.
16. Lane JA, Donovan JL, Davis M, et al. Active monitoring, radical prostatectomy, or radiotherapy for localised prostate cancer: study design and diagnostic and baseline results of the Protect randomised phase 3 trial. The Lancet Oncology 2014;15(10):1109-18.
17. Hayes JH, Ollendorf DA, Pearson SD, et al. Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis. Jama 2010;304(21):2373-80.
18. Roach M, 3rd, Ceron Lizarraga TL, Lazar AA. Radical Prostatectomy Versus Radiation and Androgen Deprivation Therapy for Clinically Localized Prostate Cancer: How Good Is the Evidence? International Journal of Radiation Oncology, Biology, Physics 2015;93(5):1064-70.
19. Schreiber D, Rineer J, Weiss JP, et al. Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer. Radiation Oncology Journal 2015;33(1):21-8.
20. Wolff RF, Ryder S, Bossi A, et al. A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer. European journal of cancer (Oxford, England : 1990) 2015;51(16):2345-67.
21. Jayadevappa R, Chhatre S, Wong YN, et al. Comparative effectiveness of prostate cancer treatments for patient-centered outcomes: A systematic review and meta-analysis (PRISMA Compliant). Medicine 2017;96(18):e6790.
근거표
| KQ3 | |
|---|---|
| Reference | 1. MB Gretzer, BJ Trock, Han M, et al. A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic Radiation and Oncology criteria. J Urol 2002;168:1419-22. |
| Study type | Retrospective study |
| Patients | 2,691 men who underwent anatomical radical prostatectomy for localized disease |
| Purpose of Study | To evaluate how the American Society for Therapeutic Radiation and Oncology (ASTRO) criteria affect the interpretation of failure when applied to radical prostatectomy. |
| Study Results | Using actuarial analysis of the data defining failure as the first PSA 0.2 ng/ml or greater, biochemical freedom from failure at 5, 10 and 15 years was 85%, 77% and 68%, respectively. In contrast, when backdating was used in this series, almost all failures occurred early with rare late failures (freedom from failure 82%, 80% and 80% at 5, 10 and 15 years, respectively). The difference in failure became even more pronounced when ASTRO criteria were applied requiring 3 consecutive increases, and backdating failure to the midpoint between nadir and first PSA (freedom from failure 90%, 90% and 90% at 5, 10 and 15 years, respectively). |
| Level of Study | 3 |
| Reference | 2. S Nilsson, BJ Norlen, A Widmark: A systematic overview of radiation therapy effects in prostate cancer. Acta Oncol 2004;43:316-81. |
| Study type | Meta-analysis |
| Patients | 152,614 |
| Purpose of Study | To randomize studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer |
| Study Results | There are no randomized studies that compare the outcome of surgery (radical prostatectomy) with either external beam radiotherapy or brachytherapy for patients with clinically localized low-risk prostate cancer. However, with the advent of widely accepted prognostic markers for prostate cancer (pre-treatment PSA, Gleason score, and T-stage), such comparisons have been made possible. There is substantial documentation from large single-institutional and multi-institutional series on patients with this disease category (PSA <10, GS < or=6, < or=T2b) showing that the outcome of external beam radiotherapy and brachytherapy is similar to those of surgery. *There is fairly strong evidence that patients with localized, intermediate risk, and high risk (pre-treatment PSA > or=10 and/or GS > or=7 and/or > T2) disease, i.e. patients normally not suited for surgery, benefit from higher than conventional total dose. No overall survival benefit has yet been shown. |
| Level of Study | 1 |
| Reference | 3. ND Arvold, Chen MH, JW Moul, et al. Risk of death from prostate cancer after radical prostatectomy or brachytherapy in men with low or intermediate risk disease. J Urol 2011;186:91-6. |
| Study type | Prospective study |
| Patients | 5,760 men with low risk prostate cancer (prostate specific antigen 10 ng/ml or less, clinical category T1c or 2a and Gleason score 6 or less), and 3,079 with intermediate risk prostate cancer (prostate specific antigen 10 to 20 ng/ml, clinical category T2b or T2c, or Gleason score 7). |
| Purpose of Study | To estimated the risk of prostate cancer specific mortality following radical prostatectomy or brachytherapy in men with low or intermediate risk prostate cancer using prospectively collected data. |
| Study Results | After a median follow up of 4.2 years (IQR 2.0-7.4) for low risk and 4.8 years (IQR 2.2- 8.1) for intermediate risk men, there was no significant difference in the risk of prostate cancer specific mortality among low risk (adjusted hazard ratio 1.62, 95% CI 0.59-4.45, p=0.35) or intermediate risk men (AHR 2.30, 95% CI 0.95-5.58, p=0.07) treated with brachytherapy compared with radical prostatectomy. The only factor associated with an increased risk of prostate cancer specific mortality (AHR 1.05, 95% CI 1.01-1.10, p=0.03) was increasing age at treatment in intermediate risk men. |
| Level of Study | 2 |
| Reference | 4. Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016;375:1415-24. |
| Study type | Retrospective study |
| Patients | 82,429 |
| Purpose of Study | The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths. |
| Study Results | There were 17 prostate-cancer-specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years; 95% CI, 1.9 to 4.9) (P=0.004 for the overall comparison). Higher rates of disease progression were seen in the activemonitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years; 95% CI, 6.7 to 12.0) (P<0.001 for the overall comparison). |
| Level of Study | 2 |
| Reference | 5. Hayes JH, Ollendorf DA, Pearson SD, et al. Active surveillance compared with initial treatment for men with low-risk prostate cancer: a decision analysis. JAMA 2010;304(21):2373-80. |
| Study type | Similar meta analysis |
| Patients | 309 article |
| Purpose of Study | To examine the quality-of-life benefits and risks of active surveillance compared with initial treatment for men with low-risk, clinically localized prostate cancer. |
| Study Results | Active surveillance was associated with the greatest QALE (11.07 quality-adjusted life-years [QALYs]), followed by brachytherapy (10.57 QALYs), IMRT (10.51 QALYs), and radical prostatectomy (10.23 QALYs). Active surveillance remained associated with the highest QALE even if the relative risk of prostate cancer-specific death for initial treatment vs active surveillance was as low as 0.6. However, the QALE gains and the optimal strategy were highly dependent on individual preferences for living under active surveillance and for having been treated. |
| Level of Study | 1 |
| Reference | 6. Jayadevappa R, Chhatre S, Wong YN, et al. Comparative effectiveness of prostate cancer treatments for patient-centered outcomes: A systematic review and meta-analysis (PRISMA Compliant. Medicine (Baltimore) 2017;96(18):e6790. |
| Study type | Meta analysis |
| Patients | 58 article |
| Purpose of Study | To analyzed the comparative effectiveness of PCa treatments through systematic review and meta-analysis with a focus on outcomes that matter most to newly diagnosed localized PCa patients. |
| Study Results | Our search strategy yielded 58 articles, of which 29 were RCTs, 6 were prospective studies, and 23 were retrospective studies. The studies provided moderate data for the patientcentered outcome of mortality. Radical prostatectomy demonstrated mortality benefit compared to watchful waiting (all-cause HR=0.63 CI=0.45, 0.87; disease-specific HR=0.48 CI=0.40, 0.58), and radiation therapy (all-cause HR=0.65 CI=0.57, 0.74; disease-specific HR=0.51 CI=0.40, 0.65). However, we had minimal comparative information about tradeoffs between and within treatment for other patient-centered outcomes in the short and long-term. |
| Level of Study | 1 |