untitled

Size: px

Start display at page:

Download "untitled"

태경 증
5 years ago
Views:

1 전립선특이항원선별검사도입에따른전립선암의임상병리학적특성의변화 Changes in Prostate Cancer Pattern according to Prostate-Specific Antigen Screening Test Jong Kyou Kwon, In Ho Chang, Tae Hyoung Kim, Soon Chul Myung From the Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea Purpose: The aim of this study was to investigate the changes in the clinical and prognostic parameters of prostate cancer in Korean men in the eras before and after prostate-specific antigen (PSA) testing. Materials and Methods: The medical records of 303 patients treated for prostate cancer between 1982 and 2005 were reviewed with respect to age, chief complaints, clinical stage, tumor grade, treatment options, and prognosis. We classified the patients as follows: those treated in the pre- PSA era ( , n=81), and those treated in the PSA era ( , PSA era phase 1, n=92; and , PSA era phase 2, n=130). Results: There was no significant difference in age or clinical stage between patients treated before and those treated during the PSA era, although there was a downward migration of grade. The cancer-specific survival rates were also not different in all cases and in metastatic prostate cancer cases between the pre-psa era and the PSA era, although the overall survival rates were significantly greater in all cases in phase 2 of the PSA era than in the pre-psa era or in phase 1 of the PSA era (p<0.05). However, the cancer-specific survival rates for localized or locally advanced prostate cancer were significantly greater in phase 2 of the PSA era than in the pre-psa era or in phase 1 of the PSA era (p<0.05). Conclusions: We observed a downward migration of tumor grade, but there were no migrations in the age of patients or clinical stage, and these findings have not contributed to changes in the cancer survival of Korean men with prostate cancer after the advent of PSA testing. (Korean J Urol 2009;50: ) Key Words: Prostatic neoplasms, Prostate-specific antigen, Mass screening, Survival rate Korean Journal of Urology Vol. 50 No. 5: , May 2009 DOI: /kju 중앙대학교의과대학비뇨기과학교실 권종규ㆍ장인호ㆍ김태형ㆍ명순철 Received:January 22, 2009 Accepted:March 30, 2009 Correspondence to: In Ho Chang Department of Urology, Chung- Ang University Hospital, 224-1, Heuksuk-dong, Dongjak-gu, Seoul , Korea TEL: FAX: caucih@dreamwiz.com This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A085138). C The Korean Urological Association, 2009 서론전립선암은서구에서는매우흔한암이나, 한국에서는위암, 폐암, 간암, 대장암, 식도암, 방광암, 췌장암에이어 8번째로흔한암으로알려져있다. 1,2 하지만, 최근한국남성의전립선암발생률은다른아시아나라들과마찬가지로급속히증가하는추세이다. 3 전립선암의발생률은 년과 년사이에 28.2% 까지증가했으며, 4 5년상대생존율은 1993년과 2002년사이에 59.1% 에서 70.6% 로 증가했다. 5 이발생률과생존율의증가는한국남성의모든암중에서가장두드러지며, 이러한배경하에국내에서도혈청전립선특이항원 (prostate-specific antigen; PSA) 을이용한광범위한암선별검사의필요성이대두되고있다. 5 미국과일본에서는이미 PSA 도입에따른전립선암의임상특징변화에대한역학연구들이수행되었으며, PSA 선별검사로국소전립선암이증가하여전립선암환자의생존율이증가하였다. 6,7 그러나, 국내에서 PSA 검사법이도입되기전후의전립선암의임상적인특징및예후의변화에대한연구는아직보고된적이없다. 439

2 440 Korean Journal of Urology vol. 50, , May 2009 본연구의목적은 PSA의도입전후기간에있어서전립선암환자의임상특징및예후변화에대해서알아보고자하였다. 대상및방법본연구는 1982년부터 2005년사이에본원에서전립선암으로진단받은환자 303명 ( 평균나이 71세 [48-93]) 을대상으로후향적조사를시행하였다. 전립선암은전립선침생검또는경요도전립선절제술을통한조직검사로확진하였다. 본원에서 PSA 검사는 1996년 1월부터가능하였기때문에, 그이전에내원한환자들에대해서는경직장초음파 (transrectal ultrasound; TRUS) 또는직장수지검사 (digital rectal examination; DRE) 에서이상소견을보이는경우에전립선조직검사를시행하였으며, PSA 검사가가능해진이후로는 DRE 또는 TRUS에서이상소견이보이거나, PSA가 4.0 ng/ ml보다높게측정된경우에전립선조직검사를시행하였다. 총대상환자 303명을, PSA가도입되기전인 1996년 1월이전에진단받은환자 81명 (26.7%) (pre-psa era군 ) 과, PSA 가도입된이후인 1996년 1월이후에진단받은환자 222명 (73.3%) (PSA-era군) 으로분류하였다. 또한 PSA-era군을각각동일한기간으로분류하여 1996년 1월과 2000년 12월사이에진단된환자 92명 (30.4%) (PSA era phase 1군 ) 과, 2001 년 1월과 2005년 12월사이에진단된환자 130명 (42.9%) (PSA era phase 2군 ) 으로세분하였다. 각환자들의진료기록을통해나이, 임상적병기, Gleason score, 암진단당시 PSA치, 치료방법, 예후를조사하여임상적으로 T1/T2인환자들을국소전립선암으로분류하였다. 국소진행성전립선암환자는 DRE에서임상적으로 T3/ T4에해당되거나, MRI에서립선피막외로진행된소견을보이는경우로분류하였다. CT에서골반림프절의직경이 1 cm 이상인림프절병증이동반된환자, 또는골반외전이를동반한환자, 특히골주사검사에서골전이소견이있는환자는전이성전립선암으로분류하였다. 조직검사에의한암의등급은 WHO 분류시스템에따라분류했다. 통계분석은 SPSS software package version 14.0 (Statistical Package for Social Sciences TM, Chicago, USA) 을이용하였다. Pre-PSA era군과 PSA era군간의주소, 나이, 임상병기, Gleason score, 암진단당시 PSA치, 치료방법, 예후등에따른환자들의특징들을 chi-square 검정과분산분석 Table 1. Demographics of patients with prostate cancer in the pre and post PSA eras Pre PSA era PSA era phase 1 PSA era phase 2 p-value No. of cases Age (years) Mean±SD 69.9± ± ±8.2 Median 70 (55-89) 74 (48-93) 69 (48-86) Initial presentation (%) Bone pain/neurologic sign 5 (6.2) 9 (9.8) 12 (9.2) Hematuria 5 (6.2) 5 (5.4) 9 (6.9) High PSA 7 (7.6) 31 (23.8) <0.05 Other symptom 4 (4.9) 4 (4.3) 5 (3.8) Voiding problem 67 (82.7) 67 (72.8) 73 (56.2) <0.05 Clinical stage (%) 0.15 Localized 24 (29.6) 30 (32.6) 53 (40.8) Locally advanced 7 (8.6) 10 (10.9) 19 (14.6) Metastatic 50 (61.7) 52 (56.5) 58 (44.6) Serum PSA level Mean±SD (ng/ml) 219.2± ±1, Median (ng/ml) 66.9 (1.9-1,906) ( ,039) < (%) 12 (13.5) 36 (28.1) < (%) 44 (49.4) 60 (46.9) >100 (%) 33 (37.1) 32 (25.0) Gleason score (%) < (23.5) 23 (25.0) 39 (30.0) 7 10 (12.3) 27 (29.3) 43 (33.1) (64.2) 42 (45.7) 48 (36.9) PSA: prostate-specific antigen, SD: standard deviation

3 Jong Kyou Kwon, et al:changes in Prostate Cancer Pattern according to PSA Screening Test 441 (ANOVA) 을이용하여비교하였다. 전체생존율과암특이생존율및병기분류는 Kaplan-Meier 방법과 log-rank test를이용해통계적으로분석하였으며, p값이 0.05 미만인경우통계적으로유의한것으로판정하였다. 결과 Pre-PSA era군및 PSA era군의전립선암환자들에대한인구학적특성을조사하였다 (Table 1). 전립선암의진단당시호소한주증상은 pre-psa era군과 PSA era군모두배뇨문제였으며, PSA era군에서배뇨문제의비율이더감소했다. PSA era군내에서증상없이건강검진에서 PSA 상승으로전립선암을발견하는비율은 PSA era phase 1군은 92명중 7명 (7.6%) 에서, PSA era phase 2군에서는 130명중 31명 (23.8%) 으로증가하였다. 국소전립선암이 PSA era phase 1 군 (32.6%) 에비해 PSA era phase 2군 (40.8%) 에서증가하는양상을보였지만, 나이와임상병기에서세군간의통계적으로유의한차이는없었다. 나이를구간별로나누어시행한비교에서도차이는나타나지않았다. 그러나 pre-psa era 군에비해 PSA era군에서유의하게낮은조직학적등급을보였다. 높은조직학적등급을보인경우 (Gleason score 8-10) 역시 pre-psa era군 (64.2%), PSA era phase 1군 (45.7%), PSA era phase 2군 (36.9%) 사이에유의한차이가있었다 (p<0.01). PSA era phase 1군에비해 PSA era phase 2군에서낮은 PSA를보였으며 (p<0.05), 특히 PSA가 10 이하인환자는 PSA era phase 1군 (13.5%) 보다 PSA era phase 2군 (28.1%) 에서증가하였다. 치료방법에따라각군을비교하였을때 (Table 2), 근치적전립선절제술을시행한비율은 pre-psa era군 (0%) 에비해 PSA era군 (PSA era phase 1군 6.5%, PSA era phase 2군 20%) 에서증가하였다 (p<0.01). 고환절제술을받은비율은 pre-psa era군 (39.5%) 에비해 PSA era군 (PSA era phase 1군 38%, PSA era phase 2군 13.8%) 에서감소하였다. 이를국소전립선암또는국소진행성전립선암, 전이성전립선암으로나누어초기치료방법을비교하였을때 (Table 2), 국소전립선암, 또는국소진행성전립선암에서근치적전립선절제술을시행받은비율은 pre-psa era군 (0%) 에비해 PSA era군 (PSA era phase 1군 12.5%, PSA era phase 2군 33.3%) 에서증가하였으며 (p<0.01), 전이성전립선암에서고환절제술을시행한비율은 pre-psa era군 (48.3%) 에비해 PSA era군 (PSA era phase 1군 42.3%, PSA era phase 2군 17.2%) 에서감소하였다 (p<0.01). 전체대상환자들중 164명 (54.1%) 이사망했으며, 97명 (59.1%) 은전립선암으로사망하였다 (Table 3). Pre PSA era군과 PSA era군 (phase 1, 2) 의비교에서생존율의유의한차이는나타나지않았다. PSA era군을 phase 1, 2로나누어비교하였을때, 전체생존율은 PSA era phase Table 3. Cause of death (n=164) Cause of death n (%) Prostate cancer Unspecified Non genitourinary cancer Other genitourinary cancer Ischemic heart disease Cerebrovascular disease Diabetes Trauma Chronic renal failure Disease of respiratory system Hypertension Septicemia 97 (59.1) 27 (16.5) 13 (7.9) 5 (3.0) 4 (2.4) 2 (1.3) 2 (1.3) 2 (1.3) Total 164 (100) Table 2. Comparison of treatment options in the pre and post PSA eras Pre-PSA era PSA era phase 1 PSA era phase 2 T L M T L M T L M No. of cases Surveillance 7 (8.6) 7 (22.6) 0 (0.0) 5 (5.4) 5 (12.5) 0 (0.0) 6 (4.6) 5 (6.9) 1 (1.7) Radical prostatectomy a 0 (0.0) 0 (0.0) 0 (0.0) 6 (6.5) 5 (12.5) 1 (1.9) 26 (20.0) 24 (33.3) 2 (3.4) Surgical castration b 32 (39.5) 8 (25.8) 24 (48.3) 35 (38.0) 13 (32.5) 22 (42.3) 18 (13.8) 8 (11.1) 10 (17.2) LHRH and/or antiandrogen b 37 (45.7) 14 (45.2) 23 (46.5) 45 (48.9) 16 (40.0) 29 (55.8) 69 (53.1) 31 (43.1) 38 (65.5) Radiation therapy 5 (6.2) 2 (6.5) 3 (6.2) 1 (1.1) 1 (2.5) 0 (0.0) 11 (8.5) 4 (5.6) 7 (12.1) PSA: prostate-specific antigen, LHRH: luteinizing hormone-releasing hormone, T: total patient (n=202), L: localized or locally advanced prostate cancer patients (n=143), M: metastatic prostatic cancer patients (n=160), Statistical significance: a : p<0.01, b : p<0.05

4 442 Korean Journal of Urology vol. 50, , May 2009 Fig. 1. Kaplan-Meier survival curves of prostate cancer in the pre and post prostate-specific antigen (PSA) eras. (A) Overall survival curves of all cases. (B) Cancer-specific survival curves of all cases. (C) Cancer-specific survival curves of localized or locally advanced prostate cancer. (D) Cancer-specific survival curves of metastatic prostate cancer. 2군에서 pre-psa era군및 PSA era phase 1군에비해유의하게높았으나 (p<0.05), 전체암특이생존율의차이는없었다 (Fig. 1). 또한전이성전립선암인경우 pre-psa era군과 PSA era군간의암특이생존율에는차이가없었으나, 국소전립선암또는국소진행성전립선암에서암특이생존율은 pre-psa era군과 PSA era phase 1군보다 PSA era phase 2군에서증가하였다 (p<0.05) (Fig. 1). Pre-PSA era군, PSA era phase 1군, PSA era phase 2군의전체 5년암특이생존율은각각 69.7%, 65.8%, 82.2% 였으며, 국소전립선암및국소진행성전립선암은각각 71.0%, 77.5%, 94.4%, 전이성전립선암은각각 44.0%, 30.8%, 51.1% 였다 (Table 4). Table 4. Cancer-specific survival rate according to clinical stage (%) Pre PSA era PSA era phase 1 PSA era phase 2 All patients Local or locally advanced Metastatic PSA: prostate-specific antigen 고 찰 전립선암은 1984년이래미국에서발생하는가장흔한 악성종양으로, 전체암의 1/3을차지하고있다. 8 미국에서 전립선암의발생률은 PSA가선별검사로도입된지 5년째

5 Jong Kyou Kwon, et al:changes in Prostate Cancer Pattern according to PSA Screening Test 443 인 1992년에최고치를보인이후, 1995년까지가파르게감소하다이후 PSA 도입전과비슷한속도로서서히증가했으며, 국소전립선암및국소진행성전립선암의발생률이증가한반면전이성전립선암의발생률은감소했다. 6,9,10 또한 DRE에서종괴가촉지되지않아전적으로 PSA에의존하여진단된경우가 1987년부터 2001년사이에새롭게전립선암으로진단된경우의 75% 를차지했다. 11 이에따라임상적으로국소전립선암으로진단되어근치적전립선절제술을시행받은환자들의비율이점점증가하고있다. 10 국소전립선암의증가는 5년, 10년생존율의증가와연관이있어, 각각 100%, 92% 로보고되고있다. 12 결과적으로미국에서 PSA 검사로전립선암의조기발견이증가하여방사선치료및근치적전립선절제술의빈도를증가시켜암특이생존율이향상되었다. 10,12 본연구에서는 PSA 도입으로인한전립선암의병기나전립선암으로진단된환자의평균연령의차이는없었다. PSA 검사가도입된이후, 국소및국소진행성전립선암이 38.2% (pre-psa era) 에서 55.4% (PSA era phase 2) 로증가하는경향을보였지만, 전이성전립선암환자의비율이상대적으로줄었으나높았다. 연구대상의대부분이배뇨증상으로인해전립선암으로진단되었으며, 건강검진에서 PSA 가상승하여전립선암을진단받은경우는적었다. 이것은연구기간이아직 PSA 선별검사가정착되지않아대상환자들이전립선검진을목적이아닌배뇨증상으로내원한경우가많았기때문으로생각한다. 실제로국내에서 PSA 선별검사를받은 50세이상남성은약 15% 로, 미국의 75% 에비해무척낮다. 4,13 Okihara 등 14 이일본에서시행한연구결과에따르면 1,125 명의전립선암환자들을 PSA 도입이전 (1975년에서 1988 년사이 ) 에치료받은군 (n=182), PSA 도입초기 (1988년에서 1997년사이 ) 에치료받은군 (n=301; PSA era) 과 PSA 도입후기 (1998년에서 2002년사이 ) 에치료받은군 (n=642; PSA era) 으로나누었을때, 미국에비해전립선암의발생률이낮았음에도불구하고국소전립선암의비율이 PSA 도입전 (21%) 에비해 PSA 도입후 (PSA 도입초기 35%, PSA 도입후기 48%) 유의하게증가했다. 일본에서 PSA 선별검사를받은남자들의수가 44.8% 임을고려할때, 한국의전립선암발견율은최근급격히증가한것으로생각할수있으며, PSA 검사가서구나일본수준으로좀더활성화된다면앞으로임상병기의하향과진단시점의연령을낮출수있을것이다. 본연구에서전체생존율은 PSA era phase 2군에서유의하게높았음에도불구하고, 암특이생존율은전체전립선암과전이성전립선암에서는 PSA 도입전후기간사이에유의 한차이가없었다. 그러나국소전립선암또는국소진행성전립선암에서암특이생존율은 PSA era phase 2군에서다른군에비해유의하게높았다. Jung 등 5 의연구에따르면한국에서생존율향상이가장높았던암은전립선암이며, 5년전체생존율은 1993년과 2002년사이에 59.1% 에서 70.6% 로증가했다. 저자들의연구에서도전립선암의전체생존율은 PSA era phase 2군에서유의하게높았으나, 암특이생존율은차이가없었다. 이러한결과는영양상태의향상과더불어의료기술의발달로전립선암환자들이전립선암과관련된원인으로인한사망보다전립선암외적인원인에의해사망할위험성이높아나타난것으로생각하나, PSA 선별검사로진단된전립선암이적어이에대한추가적인연구가필요할것이다. 15 본연구에서는 PSA 검사도입에따른임상병기와전립선암으로진단받은환자의나이의변화는없었으며, 전체환자와전이성전립선암에서암특이생존율의의미있는차이는없었다. 또한전이성전립선암군의치료방법에있어서 PSA era phase 2군에서고환절제술이감소하고호르몬치료의비중이증가한것외에는의미있는변화는없었으며, 이는전이성전립선암의비율에큰변화가없었기때문으로생각한다. 본연구결과국소및국소진행성전립선암특이생존율은 PSA era phase 2군에서다른군에비해유의하게높게나타났으며, PSA era phase 2군에서근치적전립선절제술을받은비율이의미있게상승하였다. 이는서구와마찬가지로근치적전립선절제술과같은치료방법들이조기암에있어서효과적이라고생각한다. 16 본연구는다기관, 전향적연구가아니며, 시기적으로서로다른기간에시행하여, 결과에대한직접비교가어려울수있다는한계점이있다. 또한, 암특이생존율이국소전립선암또는국소적진행성전립선암에서유의하게높게나타나 PSA 도입으로인한생존율증가가관찰되지만, 이러한결과는 length bias와 lead-time bias에의한것일가능성도있다. 또한, 본연구에서는 PSA 선별검사를통해전립선암으로진단받은환자는단지 23.8% (130명중 31명 ) 로나타나, PSA 검사도입으로인한생존율향상에대한평가를위해서는대규모집단에서 PSA 선별검사를시행한결과와비교해볼필요가있다. 마지막으로, 본연구에서는 PSA 절단치 4.0 ng/ml를기준으로하였으나최근보고들에의하면더낮은 PSA 절단치를기준으로한연구도필요하다 한국인에서전립선암의발생률과사망률은급속히증가하고있다. 미국에서는 PSA를이용한조기진단으로전립선암생존율을증가시키려는노력을하고있다. 10,12 따라서국내에서도 PSA를이용한전립선암선별검사를확대할필요가있다.

6 444 Korean Journal of Urology vol. 50, , May 2009 결 본연구에서 PSA 도입으로인해전립선암의조직학적분화도의감소는관찰되었지만, 진단당시연령및임상병기의변화는관찰되지않았으며, 그결과전체적인암특이생존율의차이도없었다. 그러나아직까지한국에서는 PSA 선별검사가널리도입되지않았고, 비록단일기관의연구이기는하지만저자들의연구결과 PSA 선별검사가조기암의암특이생존율을증가시킨것으로나타나, 향후 PSA 선별검사의활성화와전립선암생존율의변화에대한보다대규모의추가적인연구가필요할것으로생각한다. 론 REFERENCES 1. Shin HR, Won YJ, Jung KW, Kong HJ, Yim SH, Lee JK, et al. Nationwide cancer incidence in Korea, : first result using the national cancer incidence database. Cancer Res Treat 2005;37: Korean National Statistical Office. The cause of death statistics, Seoul: Korean National Statistical Office; Sim HG, Cheng CW. Changing demography of prostate cancer in Asia. Eur J Cancer 2005;41: Park SK, Sakoda LC, Kang D, Chokkalingam AP, Lee E, Shin HR, et al. Rising prostate cancer rates in South Korea. Prostate 2006;66: Jung KW, Yim SH, Kong HJ, Hwang SY, Won YJ, Lee JK, et al. Cancer survival in Korea : a population-based study. J Korean Med Sci 2007;22(Suppl):S Newcomer LM, Stanford JL, Blumenstein BA, Brawer MK. Temporal trends in rates of prostate cancer: declining incidence of advanced stage disease, 1974 to J Urol 1997; 158: Okihara K, Kitamura K, Okada K, Mikami K, Ukimura O, Miki T. Ten year trend in prostate cancer screening with high prostate-specific antigen exposure rate in Japan. Int J Urol 2008;15: Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, et al. Cancer statistics, CA Cancer J Clin 2004;54: Stephenson RA, Smart CR, Mineau GP, James BC, Janerich DT, Dibble RL. The fall in incidence of prostate carcinoma. On the down side of a prostate specific antigen induced peak in incidence--data from the Utah Cancer Registry. Cancer 1996;77: Hankey BF, Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, et al. Cancer surveillance series: interpreting trends in prostate cancer--part I: evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates. J Natl Cancer Inst 1999;91: Derweesh IH, Kupelian PA, Zippe C, Levin HS, Brainard J, Magi-Galluzzi C, et al. Continuing trends in pathological stage migration in radical prostatectomy specimens. Urol Oncol 2004;22: American Cancer Society. Cancer facts and figures Atlanta: American Cancer Society; Sirovich BE, Schwartz LM, Woloshin S. Screening men for prostate and colorectal cancer in the United States: Does practice reflect the evidence? JAMA 2003;289: Okihara K, Nakanishi H, Nakamura T, Mizutani Y, Kawauchi A, Miki T. Clinical characteristics of prostate cancer in Japanese men in the eras before and after serum prostate-specific antigen testing. Int J Urol 2005;12: Simone NL, Singh AK, Cowan JE, Soule BP, Carroll PR, Litwin MS. Pretreatment predictors of death from other causes in men with prostate cancer. J Urol 2008;180: Desireddi NV, Roehl KA, Loeb S, Yu X, Griffin CR, Kundu SK, et al. Improved stage and grade-specific progression-free survival rates after radical prostatectomy in the PSA era. Urology 2007;70: Park HK, Hong SK, Byun SS, Lee SE. Comparison of the rate of detecting prostate cancer and the pathologic characteristics of the patients with a serum PSA level in the range of 3.0 to 4.0 ng/ml and the patients with a serum PSA level in the range 4.1 to 10.0 ng/ml. Korean J Urol 2006;47: Sohn DW, Byun SS, Lee SE. Predictive factors and characteristics of the prostate cancer in patients with serum PSA levels equal or less than 4.0 ng/ml. Korean J Urol 2005;46: Lee SW, Byun SS, Lee SE. The diagnostic significance of abnormal findings on transrectal ultrasonography in patients with serum prostate-specific antigen levels equal or less than 4.0 ng/ml. Korean J Urol 2006;47:752-6

( )Jkstro011.hwp

( )Jkstro011.hwp 비인강암의방사선치료결과및생존율에관한예후인자분석 2005 2 1 2005 3 28. :, Tel: 053)250-7665, Fax: 053)250-7984 E-mail: jhkim@dsmc.or.kr 정영연외 2 인 : 비인강암의예후인자분석 정영연외 2 인 : 비인강암의예후인자분석 Carcinoma of the nasopharynx treated by radiotherapy