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1 저위험군및중간위험군국소전립선암의저선량근접치료 Low-Dose-Rate Brachytherapy for Low- and Intermediate-Risk Groups of Localized Prostate Cancer Dong Soo Park, Jong Jin Oh, Woong Ki Jang, Sang Hyun Jee, Hyun Soo Shin 1 From the Departments of Urology and 1 Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Korea Purpose: We applied low-dose-rate brachytherapy for low- and intermediate-risk groups of prostate cancer patients. Our initial experiences were analyzed to assess the result of low-dose-rate brachytherapy for lowand intermediate-risk groups of patients with localized prostate cancer. Materials and Methods: A total of 50 consecutive patients have been treated with brachytherapy for 1 year since April Among them, a total of 24 patients in the low- or intermediate-risk groups were enrolled: 10 of the 24 patients were in the low-risk group (clinical T1a-T2b, Gleason score [GS] of 2-6, PSA<10 ng/ml), and 14 patients were in the intermediate-risk group (clinical T2b-T2c, Gleason score of 7, or PSA ng/ml). Implantations were performed by practicing a real-time ultrasound-guided placement including prostatic capsular placement in the intermediate-risk group. All 24 patients were treated with 1 to 3 months of androgen-deprivation therapy. Results: In the low- and intermediate-risk groups, the median patients' ages were 64 and 70 years, respectively. The numbers of patients in the low-risk group according to clinical T stage were 4 cases of T1c and 6 cases of T2a. The intermediate-risk group included 4 patients of stage T2a, 3 patients of stage T2b, and 7 patients of T2c. Five patients with a GS 6 and 9 patients with a GS of 7 were classified as being in the intermediate-risk group. Serum PSA levels in the intermediate-risk group were less than 10 ng/ml in 11 patients and ng/ml in 3 patients. The median radiation doses delivered to 90% of the prostate in the low-risk and intermediate-risk groups were Gy (range, Gy) and Gy (range, Gy), respectively. Biochemical failure was not revealed in any case during follow-up. No patients experienced major complications. Conclusions: We can expect outstanding local control effect with low-dose-rate brachytherapy in low- and intermediate-risk prostate cancer. Our technique of modifying the insertion field in the intermediate-risk group is feasible and tolerable. However, long-term follow-up data are needed for this strategy. (Korean J Urol 2009;50: ) Key Words: Prostate, Cancer, Brachytherapy, Risk Korean Journal of Urology Vol. 50 No. 7: , July 2009 DOI: /kju CHA 의과학대학교분당차병원비뇨기과학교실, 1 방사선종양학교실 박동수ㆍ오종진ㆍ장웅기지상현ㆍ신현수 1 Received:February 16, 2009 Accepted:June 29, 2009 Correspondence to: Dong Soo Park Department of Urology, Bundang CHA Hospital, CHA University, 351, Yatap-dong, Seongnam , Korea TEL: FAX: dsparkmd@cha.ac.kr C The Korean Urological Association, 2009 이급속도로증가하였다. 1 국소전립선환자들에게효과적 서 론 인치료방법으로는근치적전립선적출술, 외부방사선치료 및근접치료가있다. 이중저선량근접치료즉방사성동위 전립선특이항원 (prostate-specific antigen; PSA) 측정검사 원소영구삽입술은일정기간방사선을방출하고자연소 가상용화되면서국소전립선암으로진단되는환자의비율 멸되는방사성동위원소를전립선내에심어암조직을파괴 656

2 Dong Soo Park, et al:low-dose-rate Brachytherapy for Localized Prostate Cancer 657 하는근치요법이다. 1970년대초반에소개되어임상적적용을하였으며, 당시에는개복하여전립선에직접동위원소를삽입하였고, 이후 1980년대현재와같이회음부를통한전립선동위원소삽입술이확립되었다. 이후, 영상장비및시술도구와동위원소등의개발로시술이용이하며, 시간이단축되고, 정확하게시행할수있어최근임상적국소전립선암의확실한치료방법으로각광받고있다. 이는생화학적재발률이근치적전립선적출술과크게차이가나지않기때문이지만 2,3 최근에사용되고있는근접치료의기법은미국에서도아직까지 20년이상의장기간치료효과가불분명한것이사실이다. 게다가국내에서는 2001년에처음시행된증례보고 4 가있으나그이후에는전혀시행되지않았던실정이다. 하지만최근보고에의하면저위험군의조기전립선암의치료법으로근접치료를단독치료법으로적용하는비율이증가하고있고 5 저위험군혹은중간위험군환자들에게도저선량근접치료단독적용으로성공적으로치료될수있다고보고하고있다. 6 이에본연구에서는국소전립선암환자, 특히저위험군및중간위험군환자들을대상으로저선량근접치료를적용한초기경험에대해논하고자한다. 대상및방법 2007년 4월부터 1년간 50명의전립선암환자를대상으로근접치료를시행하였으며이중 48명에서저선량근접치료를시행하였다. 이들 48명환자의전립선암상태즉, 임상병기, PSA 측정치, 조직검사에서보고된 Gleason score를토대로위험도를크게네군, 즉, 저위험군, 중간위험군, 고위험군, 극위험군으로나누어분류하여이들중에서국소전립선암상태인저위험군 10명과중간위험군 14명환자를대상으로적용된치료방법을후향적으로분석하였다. 위험군분류는 National Comprehensive Cancer Network (NCCN) guidelines에따라분류하였는데, 저위험군은임상병기 T1a- T2a, Gleason score 2-6점, PSA<10 ng/ml 모두를만족해야하고중간위험군은임상병기 T2b-T2c, Gleason score 7, PSA ng/ml 중에한가지조건에해당되는경우이다. 반면에고위험군은임상병기 T3a, Gleason score 8-10, PSA>20 ng/ml 중에서한가지조건이라도부합되는경우이고극위험군은임상병기 T3b-T4이거나 T병기에관계없이국소림프절전이가있는경우로분류하였다. 근접치료는수술실내에서이루어지는사전치료계획과방사성동위원소시드삽입, 시술후방사선량측정의 3단계를거쳐진행되었다. 사전치료계획은전립선의용적을측정하는단계로서, TRUS를통한전립선의영상을 5 mm의 간격으로포착하여이를경직장초음파와연결된 I-plant TPS R (Implant Science, USA) 에전송, 환자의상태에맞는시드삽입계획을수립하였다. 방사성동위원소시드삽입은척추마취후쇄석위로환자를눕힌후진행하였다. 시드는 Best Medical (Springfield, USA) 회사의 iodine 125 ( 125 I) 를사용하였으며, Mick applicator (Mick Radio-Nuclear Instruments, Mount Vernon, USA) 를사용하여경직장초음파와 C-arm 유도하에삽입하였다. 시드삽입은사전치료계획에맞추어진행하면서동시에시술중실시간으로 I-plant TPS R 로방사선량을예측하여시드삽입위치와방사선량을수정, 보완하였다 (Fig. 1). 시술후방사선량측정은시드삽입의기술적인질과전립선내에삽입된시드로부터조사되는실제방사선량을검증하는단계로서, 시술후 1개월째골반 CT를시행하여얻은영상을이용하여전립선, 방광, 직장및요도에조사되는선량을계산하였다. 선량계산은 V200, V150, V100, V90, D100 및 D90을사용하여각각의비율 (%) 및선량 (Gy) 을측정하였다 (Fig. 2). 이중전립선에조사되는최소선량에해당되는전립선의 90% 에조사되는선량측정치인 D90을이용하여치료결과를분석하였다. 또한 1-3개월의전후보조호르몬요법은 24명전원에서시행하였다. 근접치료를통한방사선조사로인한독성에대해알아보기위하여환자의증후와증상을기준으로 Radiation Therapy Oncology Group (RTOG) 체계를이용한비뇨기계및위장관계독성의등급을평가하였다. 이를위해모든환자는시술후방사선량을평가하는시점인 1개월째외래로방문하여인터뷰를시행하였으며 PSA 검사는시술후 3개 Fig. 1. Transperineal brachytherapy. The patient is in the high lithotomy position with the transrectal ultrasound probe fixed to the stepper device. A needle containing radioactive seeds is implanted through the perineum by using a grid system.

3 658 Korean Journal of Urology vol. 50, , July 2009 Table 1. Demographics of patients according to risk group Parameter Low (n=10) Risk group Intermediate (n=14) Age Median Range Prostate Mean volume (cc) Range Clinical T stage T1c 4 T2a 6 4 T2b 3 T2c 7 Gleason score < PSA (ng/ml) < D90 (Gy) Median Range PSA: prostate-specific antigen Fig. 2. Post-implantation computed tomography-based dosimetry analysis after 1 month. Dose-volume histogram of the prostate is shown. 월단위로시행하였다. 결 대상환자들의특성은저위험군과중간위험군에따라분류하여 Table 1에제시하였다. 대상환자들의나이는평균 68.5세 (47-83) 였고, 이중저위험군에해당하는환자들은평균 64세 (55-83), 중간위험군에해당하는환자들은평균 70세 (53-79) 였다. 술전 PSA 수치는평균 6.95 ng/ml ( , 중앙값 5.94 ng/ml) 였고, 저위험군의평균은 6.43 ng/ ml ( ), 중간위험군의평균은 7.28 ng/ml ( ) 였다. 사전계획시시행한경직장초음파를통해얻은전립선의용적은전체평균 g ( ), 저위험군의평균 ml ( ), 중간위험군의평균 ml ( ) 였다. 임상적인전체환자의 T병기는 T1c 4명으로모두저위험군에속했고, T2a는 10명으로저위험군 6명, 중간위험군 4 과 명이해당되었다. T2b, T2c에해당하는환자는모두중간위험군으로각각 3명, 7명이었다. Gleason score는 6점이하가 15명, 7점이 9명으로중간위험군중 5명이 6점의병리결과를나타냈다. PSA 수치는 10 미만인경우가 21명으로저위험군, 중간위험군각각 9명, 11명씩분포하였고, 나머지 3명은 ng/ml에분포하였다. PSA 추적측정결과는추적기간이짧아분석의의미는적으나모든환자에서급격한감소소견을보였다. 평균추적기간은 14.4개월 (6-24) 로저위험군에서 15.3개월 (6-24), 중간위험군에서 13.7개월 (6-24) 이었으며, PSA 수치는 3개월추적측정부터급격한감소를보였고, 의미있는상승을보인환자는없었다 (Table 2, Fig. 3). 삽입된 125 I seed의평균개수는 개 (54-138, 중앙값 109) 였고전립선에조사되는최소선량에해당되는전립선의 90% 에조사되는선량측정치인 D90의중앙값은전체 Gy ( ) 로저위험군은중앙값 Gy ( ), 중간위험군은중앙값 260 Gy ( ) 였다. 총 23명의환자중급성요폐를경험한환자는없었고, 비뇨기계및위장관계독성의등급평가시 RTOG GU toxicity grade 2 이하의경한배뇨증상을호소한환자는 1개월째추적관찰시총 16명 (66.6%) 으로저위험군 7명 (29.2%), 중간위험군 9명 (37.5%) 이었으나, grade 3 이상의배뇨증상을호소한환자는단한명있었다. 환자들이호소한증상은대부분급박뇨, 빈뇨, 배뇨통등의증상으로알파차단제혹은항콜린제등의보존적치료방법으로증상호전은뚜렷하지않았고 2-7개월의기간후호전되었고 RTOG GI

4 Dong Soo Park, et al:low-dose-rate Brachytherapy for Localized Prostate Cancer 659 toxicity grade 2 이하로경한항문및출혈, 배변습관변화등의증상변화를보이는위장관계독성을보인환자는저위험군에서 1명 (10%), 중간위험군에서 2명 (14.3%) 이었고, grade 3 이상의증상호소는없었다. Table 2. Postoperative outcome of PSA Low group (PSA: ng/ml), follow up per 3 month Patient No. Preoperative Intermediate group (PSA) Patient No. Preoperative PSA: prostate-specific antigen 고찰 125 I를이용한전립선암근접치료는경직장전립선초음파기술의발달과전립선내에삽입가능한방사성요오드시드의개발, 그리고컴퓨터화된치료계획시스템의발달로미국및유럽에서는 1990년대부터널리시행되고있다. 7 근접치료의큰장점중의하나는바로근접장기에는최소한의영향을끼치면서표적장기에최대한의방사선을조사할수있다는것이다. 8 서론에서언급하였듯이저선량근접치료는생화학적치료효과에있어근치적전립선적출술혹은외부방사선치료방법과차이가나지않는반면, 2,3 이두가지치료법에비해서요자제기전및성기능에대한악영향은적은것으로알려져있다. 9,10 이러한치료효과이외에도근치적전립선적출술과비교하였을때짧은수술시간과짧은입원기간, 그리고시술후정상생활로의복귀가빠르다는점이큰장점이될수있고, 외부방사선치료와비교하였을때는근접장기로의방사선조사량을최소화할수있다는점을장점으로꼽을수있다. 보통방사선을방출하는물질을체내에주입한다는점이환자들에게있어심리적인부담이될수있으나, 전립선암의근접치료에사용되는 125 I는 60일정도의반감기를가지고 27 Kev 정도되는낮은에너지의방사선을방사하기때문에, 전립선에영구적으로삽입되더라도일반적으로접촉하는사람들에대한위험이거의없어안전하다. CaPSURE 자료에따르면, 저위험군국소전립선암환자에있어, 년에는오직 3.1% 에서만근접치료가시행되었으나, 앞서언급한장점들이부각되면서 년, 년, 년에는각각 4.0%, 8.9%, 21.7% 로증가하는추세를보이고있다. 특히 75세이상의환자들 Fig. 3. PSA decrease after 125 I seed implantation. (A) low-risk group; (B) intermediate-risk group. PSA: prostate-specific antigen.

5 660 Korean Journal of Urology vol. 50, , July 2009 의경우에는 년사이에 31.1% 에서근접치료를시행받은것으로알려져있다. 5 환자가전립선암으로진단되면, 의사는전립선암의임상병기, 혈청 PSA 수치, 그리고조직병리검사에서보고된 Gleason score에따라위험도를네군으로나누어치료방법을달리하게된다. 11 National Comprehensive Cancer Network (NCCN) guidelines에따르면, 저위험군은임상병기 T1a-T2a, Gleason score 2-6점, PSA<10 ng/ml 모두를만족하는경우, 중간위험군은임상병기 T2b-T2c, Gleason score 7, PSA ng/ml 중에한가지조건이라도있는경우로정의한다. 또한고위험군은임상병기 T3a, Gleason score 8-10, PSA >20 ng/ml 중에서한가지조건이라도부합하는경우이며, 극위험군은임상병기 T3b-T4이거나 T병기에관계없이국소림프절전이가있는경우로정의한다. 저위험군에서근접치료는단독치료만으로우수한결과를얻을수있다고알려져있으나, 중간위험군에서는아직논쟁의여지가있어단독치료만으로도효과가있다고보고하기도하고, 외부방사선치료혹은보조호르몬요법을병행해야한다고보고하기도한다. 일반적으로근접치료단독요법이가장적합한환자들은위험요소가적은즉, PSA 측정치가 10 ng/ml 미만이고 Gleason score가 6점이하인경우이다. 중간위험군이나고위험군의경우근접치료단독요법이적합하지않은치료법이라는배경에는근접치료법에사용되는방사선양이방사선에저항하는종양클론을극복하기에는불충분한방사선조사량또는선량이라는것이다. 또한전립선주위조직에전립선암이존재할가능성이있으며근접치료법으로는불충분한양의방사선이영향을주게되므로재발확률이높아질수있다. 저자들은국소진행성전립선암에서방사성동위원소영구삽입술의기법을변형시켜적용한결과를보고한바있다. 12 미국시애틀그룹의보고에의하면저위험군에서근접치료의장기간추적결과는 1986년부터 1987년까지초기 2년간의 10년생화학적재발성적과근접치료기법이성숙된후의 년 2년간의성적은큰차이를보였으며근접치료단독의최근성적은 87% 의생화학적무병재발률을보고하였다. 13 NCCN guidelines에서는중간위험군환자에대해서는 Gy의외부방사선치료를병행하는것을고려하고전립선용적이클경우에는추가적으로보조호르몬요법을시행할수도있다고권유한다. 방사선조사량은 125 I 근접치료를단독으로시행할경우에는 145 Gy를, 외부방사선치료를병행할경우에는 Gy의조사량으로치료할것을권유하고있다. 외부방사선치료는모든위험군에서적용되는일반적인치료방법으로그효과는전립선적출술과비슷하다고보고 되고있지만외부방사선치료는주변장기에미치는부작용으로인해전립선에조사되는방사선량을충분히줄수없다는한계가있다. 최근들어세기조절방사선치료등의치료기법이발달하면서방사선조사선량을증가시키는많은연구들이진행되어특히중간위험군인 PSA ng/ml 또는 Gleason score가 7인환자에서외부방사선조사량을증가시킴에따라 PSA 재발률이감소된다고보고하였다. 14 따라서중간위험군의경우저선량근접치료단독으로치료하는것에대한논쟁이있는시점에서방사선량을증가시키는방법으로써저선량근접치료와외부방사선치료의병합요법도고려해볼필요가있을것으로판단된다. 최근미국내에서근접치료법을시행하는의사들을대상으로한중간위험군에대한시술행태에대한조사에따르면, 조직검사에서신경주위침범이없는경우에 Gleason score 7 (3+4), PSA ng/ml, 임상병기 T1c, 30% 미만의양성코아인경우에는모든환자에서근접치료를단독시행한다고하였다. 또한임상병기 T1c, Gleason score 7 (4+ 3), 30% 미만의양성코아인환자의 80% 는근접치료를단독시행한다고하였고, 임상병기 T2a, PSA ng/ml 또는 Gleason score 7 (3+4), 30% 미만의양성코아인경우에는 80-90% 의의사들이근접치료를단독시행한다고하였다. 조직검사에서신경주위침범이없는경우에임상병기 T2b, Gleason score 7 (3+4), PSA ng/ml, 67% 양성코아일때에는 50-60% 의사들이근접치료단독을선택하였다. 15 이러한조사결과를치료기법과연관시켜볼때중간위험군에적용하는근접치료단독요법의기술에대한변화를주면더욱많은중간위험군환자에서근접치료단독으로적용이가능할것으로생각한다. 한편호르몬요법과의병용치료법은단기요법보다는장기요법이더효과적이라고보고하고있지만이런결과들의문제점은포함된대상환자들이다양하고외부방사선치료의치료선량이 Gy로적게조사되었기때문에정확한효과를도출하기는어렵다. 이러한문제점의해결을위해외부방사선치료선량을평균 78 Gy ( ) 로선량증가를시도한 RTOG 9406 보고에서는뚜렷한결과를얻지못하였다. 하지만아직도이에대한여러임상연구들이진행되고있으며특히고위험군에서의호르몬병용요법의효과에대한연구들이활발하게이루어지고있다. 16 저자들이시행한초기경험에서도근접치료와단기간의호르몬치료를병용하였고따라서장기간의추적관찰을통하여결과를확인해야하는숙제가남아있다. 본연구에서는추적기간이짧아 PSA 조절률에대한논의를진행하기에무리가있으나, 이에대한연구결과는많은논문을통해알려져있다. Guedea 등 17 은총 965명의유럽

6 Dong Soo Park, et al:low-dose-rate Brachytherapy for Localized Prostate Cancer 661 5개국국소전립선암환자를대상으로 4년동안추적관찰한결과 3년 PSA 조절률이저위험군 93%, 중간위험군 88% 인것으로보고하고있다. Kwok 등 18 도 105명의국소전립선암환자를대상으로진행한 5년추적관찰결과 PSA 조절률을저위험군, 중간위험군각각 85%, 63% 로보고하고있다. Blasko 등 19 은 230명의 T1-T2병기의전립선암환자에서 103 Pd를사용한결과를보고하였는데, 저위험군및중간위험군에서각각 94%, 82% 의 PSA 조절률을보인다고보고하였다. Stone과 Stock 20 은근접치료후배뇨, 성기능및직장에대한영향에대해연구하였는데, 배뇨증상및불편지수가보통술후 6개월째가장심하고, 2-3년정도유지되다점차좋아진다고보고하였다. 게다가대상환자들을 7년까지추적관찰하였을때에도, 거의모든환자들에서배뇨증상의악화는관찰되지않았다. 이러한배뇨증상의악화는방사선유발전립선염에기인하는것으로생각할수있는데, 본연구에서는총 23명중 16명 (69.6%) 의환자에서 RTOG GU toxicity grade 2 이하의배뇨증상을호소하였는데, 추적관찰기간이최대 16개월미만으로배뇨증상의소실에대한분석은어려운실정이나, grade 3 이상의배뇨증상은단한명의환자에서만관찰되었다. Mabjeesh 등 21 은이러한배뇨증상, 특히요폐의예측인자에대해연구하여경직장초음파시전립선용적과시술전 International Prostate Symptom Score (IPSS) 가시술후요폐에대한독립적인예측인자로작용한다고주장하였다. 최근의 NCCN guidelines에따르면전립선의용적이 60 cc 이상이거나 IPSS 15 이상일경우근접치료의적당한대상이될수없다고언급하고있다. Stock 등 22 은근접치료후생화학적재발의가장확실한예측인자로서전립선에조사되는선량이라고언급하였는데, 전립선의 90% 에조사된총조사량이 140 Gy 이상일경우 PSA 조절률이 92% 에이르는반면, 그양이 140 Gy 미만일경우 PSA 조절률이 62% 밖에이르지못한다고보고하였다. NCCN guidelines에서도역시권고선량으로 145 Gy를언급하고있지만, Kao 등 23 은 D90이 180 Gy 이상일경우생화학적재발이매우감소한다는결과를보고하였다. 본연구에서는추적기간이짧아이에대한분석은어려운상태이지만 D90에대한기본자료를토대로향후어떠한의미가있는지조사할예정이다. 결론저위험군전립선암환자의경우근접방사선치료가전립선적출술이나외부방사선치료에비해요자제기전혹은성기능에대한부작용이적으면서, 충분한정도의 PSA 조 절률을얻을수있는것이명백하지만간과되고있는실정이다. 또한중간위험군환자역시술자의술기에따라차이를보이나많은연구에서근접방사선치료단독요법으로성공적인치료가가능한것으로보고하고있다. 따라서효과가명백한저위험군환자뿐만아니라중간위험군환자에서도근접방사선치료를하나의독립적인치료방법으로활용하는것을제안하는바이다. REFERENCES 1. Jang TL, Han M, Roehl KA, Hawkins SA, Catalona WJ. More favorable tumor features and progression-free survival rates in a longitudinal prostate cancer screening study: PSA era and threshold-specific effects. Urology 2006;67: Blasko JC, Mate T, Sylvester JE, Grimm PD, Cavanagh W. Brachytherapy for carcinoma of the prostate: techniques, patient selection, and clinical outcomes. Semin Radiat Oncol 2002;12: Potters L, Morgenstern C, Calugaru E, Fearn P, Hassal A, Presser J, et al. 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol 2005;173: Oh MM, Bahk YW, Tropper SE. Preliminary report of clinical experience of iodine-125 seed implant for early prostatic cancer: the first case in Korea. Korean J Urol 2001;42: Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR. The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol 2004;22: Potters L, Fearn P, Kattan MW. External radiotherapy and permanent prostate brachytherapy in patients with localized prostate cancer. Brachytherapy 2002;1: Merrick GS, Butler WM, Galbreath RW, Lief JH. Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer. Int J Radiat Oncol Biol Phys 2001;51: Blasko JC, Ragde H, Grimm PD, Cavanagh W. Prostate brachytherapy: importance of technique. J Clin Oncol 1996;14: Ragde H, Blasko JC, Grimm PD, Kenny GM, Sylvester JE, Hoak DC, et al. Interstitial iodine-125 radiation without adjuvant therapy in the treatment of clinically localized prostate carcinoma. Cancer 1997;80: Merrick GS, Butler WM, Wallner KE, Galbreath RW, Anderson RL, Kurko BS, et al. Erectile function after prostate brachytherapy. Int J Radiat Oncol Biol Phys 2005;62: Shipley WU, Scardino PT, Kaufman DS, Katan MW. Treatment of early stage prostate cancer. In: Vogelzang NJ, Scardino PT, Shipley WU, Debruyne FM, Linehan WM, editors.

7 662 Korean Journal of Urology vol. 50, , July 2009 Comprehensive textbook of genitourinary oncology. 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 2006; Park DS, Jang WK, Oh JJ, Jee SH, Shin HS. Application of low dose rate brachytherapy in locally advanced prostate cancer. Korean J Urol Oncol 2008;6: Grimm PD, Blasko JC, Sylvester JE, Meier RM, Cavanagh W. 10-year biochemical (prostate-specific antigen) control of prostate cancer with (125)I brachytherapy. Int J Radiat Oncol Biol Phys 2001;51: Pollack A, Zagars GK, Starkschall G, Antolak JA, Lee JJ, Huang E, et al. Prostate cancer radiation dose response: results of the M. D. Anderson phase III randomized trial. Int J Radiat Oncol Biol Phys 2002;53: Frank SJ, Grimm PD, Sylvester JE, Merrick GS, Davis BJ, Zietman A, et al. Interstitial implant alone or in combination with external beam radiation therapy for intermediate-risk prostate cancer: a survey of practice patterns in the United States. Brachytherapy 2007;6: Lee I, Sandler H. Hormone therapy and radiotherapy for intermediate risk prostate cancer. Semin Radiat Oncol 2008;18: Guedea F, Aguilo F, Polo A, Langley S, Laing R, Henderson A, et al. Early biochemical outcomes following permanent interstitial brachytherapy as monotherapy in 1050 patients with clinical T1-T2 prostate cancer. Radiother Oncol 2006;80: Kwok Y, DiBiase SJ, Amin PP, Naslund M, Sklar G, Jacobs SC. Risk group stratification in patients undergoing permanent (125)I prostate brachytherapy as monotherapy. Int J Radiat Oncol Biol Phys 2002;53: Blasko JC, Grimm PD, Sylvester JE, Badiozamani KR, Hoak D, Cavanagh W. Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 2000;46: Stone NN, Stock RG. Long-term urinary, sexual, and rectal morbidity in patients treated with iodine-125 prostate brachytherapy followed up for a minimum of 5 years. Urology 2007; 69: Mabjeesh NJ, Chen J, Stenger A, Matzkin H. Preimplant predictive factors of urinary retention after iodine 125 prostate brachytherapy. Urology 2007;70: Stock RG, Stone NN, Tabert A, Iannuzzi C, DeWyngaert JK. A dose-response study for I-125 prostate implants. Int J Radiat Oncol Biol Phys 1998;41: Kao J, Stone NN, Lavaf A, Dumane V, Cesaretti JA, Stock RG. (125)I monotherapy using D90 implant doses of 180Gy or greater. Int J Radiat Oncol Biol Phys 2008;70:96-101

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