Surgical treatment for prostate cancer

Transcription

1 Focused Issue of This Month pissn / eissn 전립선암의수술적치료 최돈경 서성일 성균관대학교의과대학삼성서울병원비뇨기과 Surgical treatment for prostate cancer Don Kyoung Choi, MD Seong Il Seo, MD Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea With the recent increase in the elderly population, and the Westernization of the diet and increased consumption of meat products, a significant rise in the incidence of prostate cancer has been noted in the Republic of Korea. In cases with localized prostate cancer and sufficiently long life expectancy, the standard treatment is surgical resection of the prostate. Such surgical treatment is so far the only modality demonstrated through randomized prospective studies to be beneficial in terms of disease-specific survival; this procedure involves not only surgical removal of the prostate but also pelvic lymphadenectomy for accurate staging and neurovascular bundle preservation to aid in postoperative functional recovery. Prostatectomy can be carried out either with an open technique, laparoscopically, or under robot assistance. Reviews of the literature and meta-analyses have shown that laparoscopic and robot-assisted procedures offer significant reductions in blood loss and transfusion rates and advantages in terms of recovery from postoperative complications such as incontinence and impotence over open prostatectomy. However, no long-term oncologic outcomes are available for laparoscopic or robot-assisted procedures, and the long-term prevalence of incontinence and impotence for these two methods doesnot differ significantly from those for open prostatectomy, despite the laparoscopic and robot-assisted procedures being far more costly. Therefore, surgical treatment of prostate cancer should be carefully decided on following ample deliberation of various factors including the stage, age, comorbidities, and economic status of the patient and provision of sufficient information to the patient. Key words: Prostatic neoplasms; Prostatectomy; Urologic surgical procedures 서론 전립선암은전세계적으로남성에서발병하는암중에서 두번째로많은암이며, 미국의경우에는 80 년대후반에서 Received: October 4, 2014 Accepted: October 18, 2014 Corresponding author: Seong Il Seo siseo@skku.edu Korean Medical Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 90년대초반사이에새롭게진단된전립선암환자들의수가급격하게증가하여남성에서가장흔한폐암을앞질렀다. 우리나라에서도전립선암은지난 15년사이에 2배이상증가하여 2003년이후부터현재까지남성에서발생하는 10대암중발생률 5위를차지하고있으며남성에서가장급격하게증가하고있는암이다 [1]. 이러한변화는전립선특이항원 (prostate specific antigen, PSA) 검사의도입으로조기진단이가능한것이그원인으로꼽히며이러한변화를반영하여 2000년부터 2011년사이에우리나라전립선암의변화추이를보면전립선특이항원, 병리학적병기, 병리학적글 전립선암의수술적치료 15

2 리슨점수 (Gleason score) 등이시간이지남에따라점차낮아져초기에발견되는경향이많아지고있는것을알수있다 [2]. 최근에는이러한초기국소전립선암환자 (localized prostate cancer) 에서수술적치료보다는적극적감시요법을사용하는것도강구되고있는현실이나현재까지는기대여명이 10년이상인국소전립선암환자에있어서수술적전립선적출술 (radical prostatectomy) 은표준치료로여겨지고있어이에본종설에서는현재국소전립선암의치료방법으로서의수술적치료방법의전반적인내용과개복수술이외에도최근 10년사이에꾸준히증가하며새로운표준치료가되어가고있는복강경및로봇보조하복강경전립선적출술에대하여알아보고자한다. 근치적전립선적출술 국소전립선암에서수술적전립선적출술은기대여명이충분한환자에서표준치료로여겨지고있다 [3]. 근치적전립선절제술은전립선, 양측정낭, 정관그리고절제연양성을피하기위하여충분한주변조직을함께제거하는술기로목표는전립선내에국한된종양을완전히제거하고요자제능을보존하며필요하다면발기능까지유지시키는것으로하고있다. 수술적치료방법에는개복수술의방법으로회음부접근법과후치골접근법, 복강경수술법과로봇보조하복강경수술법이있다. 개복수술중회음부접근법의경우숙련된술자에의해시행될경우고려할만한수술법으로비교적출혈이적고수술시간이짧은것으로알려져있으나골반림프절절제술을동시에시행할수없으며직장손상및변실금등의가능성이있다라는단점이있다 [4]. 그에반해후치골접근법은해부학적구조가접근이쉬우며비교적좋은시야와골반림프절절제술을동시에시행할수있다라는장점이있으며신경보존술이가능하고절제연양성율이낮다라는장점이있어회음부접근법에비해좀더선호되고있는개복수술의방법이다. 복강경수술법의경우개복수술에비해출혈이적고시야가좋으며술후통증이적고회복이빠르다는장점이있다. 하지만수술방법이어렵고의사가 술기를능숙하게시행하기에학습곡선이길며종양학적결과에대해서는아직이견이있다라는단점이있다. 로봇보조하복강경수술법은기술적으로복강경에비하여쉽고 3차원시야가가능하다는것이기존복강경수술법보다나은것으로알려져있으며방광요도문합이용이하여초기결과로는긍정적이나아직장기적으로입증된종양학적결과가없다라는단점을가지고있다. 근치적전립선적출술에대한이론적근거를전체적인결과로봤을때, 대규모무작위연구에서국소전립선암환자 695명을대상으로수술적치료와보존적치료를비교분석한결과 (median age, 65; median follow-up, 6.2 years), 8년정도후에보존적치료를시행한 14% 환자에서전이가발견되었고수술적치료를시행한환자의 7% 에서원격전이가발견되어수술적치료방법이조금더우수한것으로나타났으며보존적치료와비교하여수술적치료의상대위험도를보았을때 (adjusted for age, Gleason score, cancer stage), 0.45로보존적치료에비하여더낮은것으로확인되었다 (95% confidence interval [CI], 0.25 to 0.84) [5]. 그외에도 Mayo Clinic에서 2,518명의전립선적출술을시행받은환자를대상으로 (mean age, 63; mean followup, 5.6 years) 진행된연구에서국소전립선암환자의 5년무병생존율 (disease free survival) 은 T1 환자에서 83%, T2 환자에서 73% 그리고 T3 환자에서 63% 로확인되었으며 [6], 국소전립선암 2,091 명의환자만을대상으로시행한또다른연구에서는 (mean age, 58.1 years) 생화학적재발 (biochemical failure, PSA level higher than 0.2 ng per ml, biochemical recurrence) 만을대상으로하였을때생화학적재발이없는기간은 5년에 84%, 10년에 72% 그리고 15년에 63% 로확인되었다 [7]. 근치적전립선적출술은고령의환자에서도효과적인치료방법으로생각되는데 70세이상의환자에서 10년암특이생존율은저위험전립선암환자에서 99.5%, 중간위험전립선암환자에서는 97.5%, 고위험전립선암환자에서 94% 를보였다 [8]. 이러한사실에비추어잠재적인수술관련합병증을고려하였을때수술적치료의대상은기대여명이 10년이상인환자들이될것이며나이자체가근치적전립선적출술의금기가되지는않으나동반질 16 대한의사협회지

3 Choi DK Seo SI Surgical treatment for prostate cancer 환이많을수록전립선이외의질환으로사망할가능성이높아지므로추정되는기대여명을판단하여환자와수술시행을결정하는것이중요하다고할수있겠다 [9-11]. 근치적전립선적출술은국소전립선암에서전향적무작위연구를통하여암특이생존율측면의이득을보여준유일한전립선암에대한치료법으로써 [12], 전통적인개복술식은후치골및회음부접근을통한전립선적출술은지난 30여년간널리시행되어왔으며, 장기적인치료효과가입증되어왔다. 또한경험이많은숙련된술자가시행할경우수술합병증발생이감소하며수술결과가향상되는것으로알려져있다 [13,14]. 하지만 2000 년도이후복강경하전립선적출술및로봇보조하복강경전립선적출술과같은최소침습적수술방법이널리이용되고있으며개복수술에비하여출혈량및수혈률이적다라는장점이있으며개복수술에비하여종양학적수술결과에도큰차이가없는것으로밝혀졌다 [15,16]. 현재로봇보조전립선적출술이전통적인개복수술을대체하는추세로변화되어가고있으나기능적, 종양학적및비용-효과측면에서장기적인우월성은명확하지않은상태로전향적인비교연구들이현재진행되고있는상태이다. Comprehensive Cancer Network) guideline에따르면노모그램상에서림프절전이확률이 2% 이하에서는생략가능하다고주장하고있으며이기준을적용할경우에 12.1% 환자에서임파선전이가된환자를놓칠수있으나 47.7% 에서불필요한골반림프절절제술을피할수있다고제시하고있다. 한편 European Association of Urology에서는노모그램상림프절전이확률이 7% 이상인경우광범위골반림프절절제술을시행할것을권유하고있다 [18]. 골반림프절절제술의범위는전측으로는외장골정맥, 외측으로는골반외벽, 내측으로는방광벽, 후측으로는골반저, 원위부는쿠퍼인대, 근위부로는내장골동맥이며광범위하게이루어져야한다. 폐쇄와 (obturator fossa) 주변에국한되어시행되는제한적림프절절제술은 50% 가량의림프절전이를누락시킬수있다고보고되고있다 [17]. 골반림프절절제술은림프절의절제숫자가많을수록림프절전이를발견한가능성이높아지고정확한병기결정을가능하게하며또한몇몇연구에서는이러한골반림프절절제술의시행이미세전이를제거함으로써생존율을향상시킬수있다라는보고를하기도하였다 [19,20]. 골반림프절절제술 신경보존술식 술전영상검사의경우 5 mm 이하크기의림프절전이는발견할수없다는영상학적단점으로인해전립선적출술과같이시행되는골반림프절절제술은림프절병기결정에가장신뢰할수있는방법으로사용되고있다. 림프절전이는환자의질병의진행과생존율에영향을미치는예후인자로써골반림프절절제술은정확한병기의설정과향후추가적인호르몬치료및방사선치료를결정하게요인으로작용하게된다. 골반림프절시행여부는림프절전이확률을바탕으로결정하게되며일반적으로저위험도국소전립선암 (PSA <10 ng/ml, Gleason score <7, 임상병기 T2a) 에서는생략할수도있다. 림프절전이의확률은치료전 PSA 수치, Gleason score 또는임상병기를조합한노모그램을사용하여추정이가능하며 [17], NCCN (National 근치적전립선적출술을시행함에있어서술후기능적인측면을유지하는것은환자의삶의질의향상을위해중요한역할을한다 [21,22]. 해면체신경다발 (cavernosal neurovascular bundle) 은전립선의아래외측방향으로주행하며직접적으로전립선막 (prostate capsule) 으로향하고있다. 이러한신경다발은환자의발기능을유지하는기능을하며환자의술후삶의질의향상에영향을미치는것으로알려져있다. 신경보존술식은전립선의표면으로부터신경다발을주의깊게분리하여신경다발을자르거나전기소작하지않고그대로유지하는것을목표로한다. 이러한신경보존술식은국소전립선암에서전립선막외침범의가능성이낮은환자에게서사용하는것을원칙으로하고있으며, 고위험전립선암에서는종양학적결과에나쁜영향을미칠수있 전립선암의수술적치료 17

4 기때문에신경보존술식을시행하는것을선택적으로사용할것을권하고있다 [23,24]. 전립선암에서신경보존술식의시행은환자의병기에따라다양한접근법을통하여이루어지며전립선암의위치에따라양측을보존하기도하고편측만보존하기도하며국소전립선암에서전립선막외침범확률이낮은환자에서는막내강 (intrafascial) 으로접근하는방법을사용하며전립선막외침범확률이상대적으로높은환자에서는막외강 (extrafascial) 으로접근하는방법을사용하기도한다 [25]. 수술술기에따른비교 개복수술에의존하던전립선적출술에도 2000년도에들어오면서복강경하전립선적출술이널리시도되었다. 이러한시도는최근로봇이개발되면서로봇보조하복강경전립선적출술이개복수술을대체하는방향으로진행되고있다. 이러한변화에따라수많은논문들이수술술기에따른장단점을비교하여결과를발표하였으나이러한비교연구들은대부분단일술자, 단일기관, 후향적연구들이많아질적으로우수한무작위전향적인다기관연구는많지않은것이현실이다 [26]. 수술방법에따라술중합병증에대한메타분석을보면개복수술과로봇보조하복강경전립선적출술을비교하였을때, 실혈량 (weighted mean differences [WMD], ; 95% CI, to ; P< ) 및수혈률에서 (odd ratio [OR], 7.55; 95% CI, 3.56 to 15.64; P< ) 개복수술에비해로봇보조하복강경전립선적출술이월등히좋은것으로알려졌다. 반면수술시간 (WMD, -15.8; 95% CI, to 37; P=0.56) 및합병증발생비율 (OR, 1.25; 95% CI, 0.53 to 2.93; P=0.61) 에는두수술술기에유의한차이를보이지않는것으로보였다. 복강경하전립선적출술과로봇보조하복강경전립선적출술과의비교에서는수술시간 (WMD, 34.78; 95% CI, to 70.93; P=0.06), 실혈량 (WMD, 54.21; 95% CI, to ; P=0.41), 합병증발생비율 (OR, 1.4; 95% CI, 0.73 to 2.69; P=0.31) 로비슷한결과를보였다. 다만수혈율은 (OR, 2.56; 95% CI, 1.32 to 4.96; P=0.005) 로봇보조하복강경전립선적출술에서더낮은결과를보였다. 종양학적결과로보았을때로봇보조하복강경전립선적출술과개복수술을비교한최근논문에서양성변연율은저위험전립선암에서로봇보조하복강경에서 8.0% 이었으며개복수술의 9.2% 결과와비교하여유의한차이를보이지는않았으나 (OR, 0.89; 95% CI, 0.71 to 1.12; P=0.321), 중간위험도전립선암환자에서는로봇보조하복강경에서 15.0% 로개복수술의 21.0% 보다우수한결과를보였으며 (OR, 0.66; 95% CI, 0.59 to 0.75; P<0.001), 또한고위험환자에서도로봇보조복강경하전립선적출술에서양성변연율은 15.1% 로개복수술의 20.6% 에비하여우수한결과를보이는것으로나타났다 (OR, 0.70; 95% CI, 0.63 to 0.77; P<0.001). 수술후보조요법의측면으로보았을때, 로봇보조하복강경전립선적출술에서개복수술에비해 6개월이내에추가방사선치료나호르몬치료를사용하는비율이더낮은것으로보고되었다 (OR, 0.75; 95% CI, 0.69 to 0.81; P<0.001) [27]. 종양학적측면이외에수술후환자의기능적인측면에서봤을때, 요자제력의회복은로봇보조하복강경전립선적출술에서개복수술과비교하였을때빠른회복을보이나 (mean time 44 vs. 160 days, P<0.05), 술후 1년이지났을때요자제력을갖는환자의비율은양군에서유의한차이를보이지않는것으로나타났다 (91.8% vs. 93.7%, P=0.344) [28]. 지금까지발표된누적조사에서도개복술, 복강경, 로봇보조하복강경에서 1년경과후에요자제력은로봇보조하복강경전립선적출술에서우수하지만유의한차이를보이지않는것으로보고되었다 (weighted mean continence, 80.0% vs. 84.8% vs. 92%) [27]. 발기력측면에서살펴보면로봇보조하복강경수술에서개복수술에비하여발기의회복이빠르고더높은비율로회복하는것으로보였으며누적조사를살펴보면양측신경보존술을시행하였을때누적발기능은로봇보조하복강경수술에서 93%, 개복수술에서 60.6%, 복강경하수술에서 54% 정도로나타나로봇보조복강경수술이우수한결과를보여주고있다 [29]. 하지만이러한분석에서경계하여야할점은발기능을평가하는데있어방법론적으로정립 18 대한의사협회지

5 Choi DK Seo SI Surgical treatment for prostate cancer 된것이없다는것이며무작위전향적인장기간연구가아직없다는단점도있어수술방법에대한우수성의판단은조금더유보되어야할것으로보인다. 결론 최근전립선암의수술적치료방법은비약적인발전을이루었다. 단순개복술식뿐만아니라복강경과로봇보조복강경수술법과같은새로운수술방법이도입되고있으며장기적인효과는아직밝혀지지않았지만수술후에빠른회복과요실금및발기능과같은기능적인측면에서의장점은일부밝혀지고있다. 하지만이러한수술적인치료및수술방법을선택하는데있어가장중요하게고려하여야할것은환자의수술전병기, 나이및동반질환등에따른기대여명, 수술전환자의기능적인측면, 금전적측면까지종합적으로판단하는것이다. 따라서환자개개인에상태에따른올바른수술술기와수술방법의선택은앞으로도중요하게생각될것으로보이며수술적치료방법을선택함에있어환자에게정확한정보를제공하는것또한매우중요한부분이다. 찾아보기말 : 전립선암 ; 전립선적출술 ; 비뇨기과수술적치료 ORCID Don Kyoung Choi, Seong Il Seo, REFERENCES 1. Song K, Song C, Ahn H. Continuing trends of the clinical parameter migration in patients with prostate cancer in Korea. Korean J Urol 2007;48: Kim D, Choi D, Lim JH, Yoon JH, Jeong IG, You D, Hong JH, Ahn H, Kim CS. Changes in prostate cancer aggressiveness over a 12-year period in Korea. Korean J Urol 2012;53: Singh J, Trabulsi EJ, Gomella LG. Is there an optimal management for localized prostate cancer? Clin Interv Aging 2010;5: Bishoff JT, Motley G, Optenberg SA, Stein CR, Moon KA, Browning SM, Sabanegh E, Foley JP, Thompson IM. Incidence of fecal and urinary incontinence following radical perineal and retropubic prostatectomy in a national population. J Urol 1998; 160: Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Haggman M, Andersson SO, Spangberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlen BJ; Scandinavian Prostatic Cancer Group Study Number 4. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med 2002;347: Blute ML, Bergstralh EJ, Iocca A, Scherer B, Zincke H. Use of Gleason score, prostate specific antigen, seminal vesicle and margin status to predict biochemical failure after radical prostatectomy. J Urol 2001;165: Han M, Partin AW, Zahurak M, Piantadosi S, Epstein JI, Walsh PC. Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer. J Urol 2003;169: Siddiqui SA, Sengupta S, Slezak JM, Bergstralh EJ, Leibovich BC, Myers RP, Zincke H, Blute ML. Impact of patient age at treatment on outcome following radical retropubic prostatectomy for prostate cancer. J Urol 2006;175: Bianco FJ Jr, Scardino PT, Eastham JA. Radical prostatectomy: long-term cancer control and recovery of sexual and urinary function ( trifecta ). Urology 2005;66: Albertsen PC, Hanley JA, Gleason DF, Barry MJ. Competing risk analysis of men aged 55 to 74 years at diagnosis managed conservatively for clinically localized prostate cancer. JAMA 1998; 280: Tewari A, Johnson CC, Divine G, Crawford ED, Gamito EJ, Demers R, Menon M. Long-term survival probability in men with clinically localized prostate cancer: a case-control, propensity modeling study stratified by race, age, treatment and comorbidities. J Urol 2004;171: Bill-Axelson A, Holmberg L, Filen F, Ruutu M, Garmo H, Busch C, Nordling S, Haggman M, Andersson SO, Bratell S, Spangberg A, Palmgren J, Adami HO, Johansson JE; Scandinavian Prostate Cancer Group Study Number 4. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst 2008;100: Augustin H, Hammerer P, Graefen M, Palisaar J, Noldus J, Fernandez S, Huland H. Intraoperative and perioperative morbidity of contemporary radical retropubic prostatectomy in a consecutive series of 1243 patients: results of a single center between 1999 and Eur Urol 2003;43: Lepor H, Nieder AM, Ferrandino MN. Intraoperative and postoperative complications of radical retropubic prostatectomy in a consecutive series of 1,000 cases. J Urol 2001;166: Ryu J, Kwon T, Kyung YS, Hong S, You D, Jeong IG, Kim CS. Retropubic versus robot-assisted laparoscopic prostatectomy for prostate cancer: a comparative study of postoperative complications. Korean J Urol 2013;54: 전립선암의수술적치료 19

6 16. So BK, Choi JD, Lee SY, Kim HS, Park SY, Seo SI. Experience of 100 laparoscopic radical prostatectomies performed by a single surgeon: an analysis of surgical and functional outcomes. Korean J Urol 2011;52: Joung JY, Cho IC, Lee KH. Role of pelvic lymph node dissection in prostate cancer treatment. Korean J Urol 2011;52: Briganti A, Blute ML, Eastham JH, Graefen M, Heidenreich A, Karnes JR, Montorsi F, Studer UE. Pelvic lymph node dissection in prostate cancer. Eur Urol 2009;55: Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, Eastham JA, Scardino PT. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer. J Urol 2006;175: Wagner M, Sokoloff M, Daneshmand S. The role of pelvic lymphadenectomy for prostate cancer: therapeutic? J Urol 2008;179: Shikanov S, Woo J, Al-Ahmadie H, Katz MH, Zagaja GP, Shalhav AL, Zorn KC. Extrafascial versus interfascial nerve-sparing technique for robotic-assisted laparoscopic prostatectomy: comparison of functional outcomes and positive surgical margins characteristics. Urology 2009;74: Ponnusamy K, Sorger JM, Mohr C. Nerve mapping for prostatectomies: novel technologies under development. J Endourol 2012;26: Kamat AM, Jacobsohn KM, Troncoso P, Shen Y, Wen S, Babaian RJ. Validation of criteria used to predict extraprostatic cancer extension: a tool for use in selecting patients for nerve sparing radical prostatectomy. J Urol 2005;174: Ohori M, Kattan MW, Koh H, Maru N, Slawin KM, Shariat S, Muramoto M, Reuter VE, Wheeler TM, Scardino PT. Predicting the presence and side of extracapsular extension: a nomogram for staging prostate cancer. J Urol 2004;171: Wright JL, Izard JP, Lin DW. Surgical management of prostate cancer. Hematol Oncol Clin North Am 2013;27: Ficarra V, Novara G, Artibani W, Cestari A, Galfano A, Graefen M, Guazzoni G, Guillonneau B, Menon M, Montorsi F, Patel V, Rassweiler J, Van Poppel H. Retropubic, laparoscopic, and robotassisted radical prostatectomy: a systematic review and cumulative analysis of comparative studies. Eur Urol 2009;55: Coelho RF, Rocco B, Patel MB, Orvieto MA, Chauhan S, Ficarra V, Melegari S, Palmer KJ, Patel VR. Retropubic, laparoscopic, and robot-assisted radical prostatectomy: a critical review of outcomes reported by high-volume centers. J Endourol 2010;24: Krambeck AE, DiMarco DS, Rangel LJ, Bergstralh EJ, Myers RP, Blute ML, Gettman MT. Radical prostatectomy for prostatic adenocarcinoma: a matched comparison of open retropubic and robot-assisted techniques. BJU Int 2009;103: Tewari A, Srivasatava A, Menon M; Members of the VIP Team. A prospective comparison of radical retropubic and robot-assisted prostatectomy: experience in one institution. BJU Int 2003;92: Peer Reviewers Commentary 본논문은국소전립선암의치료방법으로써수술적치료방법의전반적인내용과최근 10년사이에꾸준히증가하면새로운표준치료가되어가고있는복강경및로봇보조복강경전립선적출술에대한논문이다. 전립선암의수술적치료에대한전반적인내용을잘설명하고있다는점에서큰도움이되는논문이라생각된다. [ 정리 : 편집위원회 ] 20 대한의사협회지