Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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Bladder Preserving Treatment in Patients with Muscle Invasive Bladder Cancer

근침윤성 방광암 환자의 방광 보존적 치료 결과

  • Yu, Jeong-Il (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Oh, Dong-Ryol (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Huh, Seung-Jae (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Choi, Han-Yong (Departments of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lee, Hyon-Moo (Departments of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jeon, Seong-Soo (Departments of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Yim, Ho-Young (Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Won-Suk (Departments of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Lim, Do-Hoon (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ahn, Yong-Chan (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Won (Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 유정일 (성균관대학교 의과대학 삼성서울병원 방사선종양학과) ;
  • 오동렬 (성균관대학교 의과대학 삼성서울병원 방사선종양학과) ;
  • 허승재 (성균관대학교 의과대학 삼성서울병원 방사선종양학과) ;
  • 최한용 (성균관대학교 의과대학 삼성서울병원 비뇨기과) ;
  • 이현무 (성균관대학교 의과대학 삼성서울병원 비뇨기과) ;
  • 전성수 (성균관대학교 의과대학 삼성서울병원 비뇨기과) ;
  • 임호영 (성균관대학교 의과대학 삼성서울병원 혈액종양내과) ;
  • 김원석 (성균관대학교 의과대학 삼성서울병원 혈액종양내과) ;
  • 임도훈 (성균관대학교 의과대학 삼성서울병원 방사선종양학과) ;
  • 안용찬 (성균관대학교 의과대학 삼성서울병원 방사선종양학과) ;
  • 박원 (성균관대학교 의과대학 삼성서울병원 방사선종양학과)
  • Published : 2007.06.30
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Abstract

[ $\underline{Purpose}$ ]: This study analyzed the tumor response, overall survival, progression free survival and related prognostic factors in patients with muscle invasive bladder cancer subjected to bladder preserving treatment. $\underline{Materials\;and\;Methods}$: Between August 1995 and June 2004, 37 patients with muscle invasive (transitional cell carcinoma, clinically stage T2-4) bladder cancer were enrolled for the treatment protocol of bladder preservation. There were 33 males and 4 females, and the median age was 67 years (range $38{\sim}86\;years$). Transurethral resection of the bladder (TURB) was performed in 17 patients who underwent complete resection. The median radiation dose administered was 64.8 Gy (range $55.8{\sim}67\;Gy$). The survival rate was calculated by the Kaplan-Meier method. $\underline{Results}$: An evaluation of the response rate was determined by abdomen-pelvic CT and cystoscopy at three months after radiotherapy. A complete response was seen in 17 patients (46%). The survival rate at three years was 54.7%, with 54 months of median survival (range $3{\sim}91$ months). During the study, 17 patients died and 13 patients had died from bladder cancer. The progression free survival rate at three years was 37.2%. There were 24 patients (64.9%) who had disease recurrence: 16 patients (43.2%) had local recurrence, 6 patients (16.2%) had a distant recurrence, and 2 patients (5.4%) had both a local and distant recurrence. The survival rate (p=0.0009) and progression free survival rates (p=0.001) were statistically significant when compared to the response rate after radiotherapy. $\underline{Conclusion}$: The availability of complete TURB and appropriate chemoradiotherapy were important predictors for bladder preservation and survival.

목 적: 근침윤성 방광암으로 진단받고 방광 보존적 치료를 시행받은 환자를 대상으로 종양 반응 정도 및 생존율을 분석하고 이에 영향을 주는 예후 인자를 알아보고자 하였다. 대상 및 방법: 1995년 9월부터 2004년 6월까지 삼성서울병원에서 방광암으로 진단 받고 방광 보존적 치료를 받은 환자 39명 중 편평상피암 환자 1명과 선암 환자 1명을 제외한 37명의 환자를 후향적으로 분석하였다. 성별로는 남녀가 각각 33명, 4명이었으며 연령은 $38{\sim}86$세(중앙값 67세)였다. 조직학적으로 모두 이행상피암이었다. 임상적으로 원발 병소 병기는 T2, T3, T4가 각각 19명, 13명, 5명이었다. 경요도방광절제술(TURB) 시 완전 절제와 부분절제가 각각 17명과 19명에서 시행되었고, 조직 검사만 시행된 경우가 1명 있었다. 항암화학방사선병용요법을 받은 환자가 24명, 유도 항암화학요법 후 방사선 치료를 받은 환자가 8명, 방사선 치료만 받은 환자가 6명이었고 보조항암화학요법을 시행받은 환자가 18명이었다. 방사선 치료는 $10{\sim}15\;MV$ 광자선을 사용하였으며 하루에 $1.8{\sim}2.0\;Gy$로 전골반을 대상으로 $45{\sim}46\;Gy$를 4문 조사한 후 방광에만 국한하여 3차원 입체조형치료로 $10.8{\sim}22.0\;Gy$ (중앙값 19.8 Gy) 추가하여 총 $55.8{\sim}67\;Gy$ (중앙값 64.8 Gy)를 조사하였다. 항암화학치료는 Cisplatin을 기본으로 하여 $2{\sim}6$회(중앙값 3회) 시행하였다. 각 변수 간의 상관 관계 분석은 Chi-Square test를 이용하였다. 생존율은 Kaplan-Meier 법으로 산출하였고 두 군 간의 비교는 Log-rank test 이용하였다. 생존율에 영향을 미치는 요인들의 다변량 분석은 Cox 비례위험 모델을 이용하였다. 유의수준 0.05 미만을 의미있는 것으로 판단하였다. 결 과: 치료 반응 평가는 치료 종료 후 3개월 전후에 시행한 요세포 검사, 방광 내시경 소견 및 복부골반 전산화단층촬영을 종합하여 판단하였는데, 완전 관해, 비완전 관해가 각각 16명(43%), 20명(54%)이었다. 대상 환자의 3년 전체 생존율은 54.7%였고 중앙 생존 기간은 54개월($3{\sim}91$개월)이었다. 3년 무진행 생존율은 37.2%였다. 추적 관찰 중 24명(64.9%)이 재발하였는데 국소 재발이 17명(46%), 원격 전이가 6명(16%), 국소 재발과 원격 전이가 동시에 나타난 경우가 1명(3%) 있었다. 국소 재발의 구제 요법으로 근치적 방광절제술이 시행된 경우는 없었고 TURB만 시행하거나 항암화학치료가 병행되기도 하였다. 치료 후의 반응 정도가 전체 생존율(p=0.006)과 무진행 생존율(p=0.001)에 통계적으로 의미있는 인자였고, TURB의 정도가 전체 생존율(p=0.091)과 무진행 생존율(p=0.081), 방사선 조사선량이 무진행 생존율(p=0.07)에서 통계적 의의에 접근하였다. 결 론: 방광 보존적 치료 시 치료 후 반응 정도가 전체 생존율과 무진행 생존율에 있어 중요한 예후 인자임을 알 수 있었다. 또한, TURB를 가능한 충분히 시행하고 병소 부위에 방사선 조사선량을 높이는 것이 방광보존 치료에서 중요하리라 생각된다. 그리고, 방광보존 치료 후 치료 반응 판정에서 완전 관해가 오지 않은 경우는 수술 등의 적극적인 구제 치료가 필요하겠다. 향후 방광 보존을 위한 항암화학 방사선 병용치료 프로토콜에 따른 임상 경험을 더 쌓아야 할 것으로 생각된다.

Keywords

References

  1. Cheon J, Kim CS, Lee ES, et al. Survey of incidence of urological cancer in South Korea: a 15-year summary. lnt J Urol 2002;9:445-454 https://doi.org/10.1046/j.1442-2042.2002.00500.x
  2. Pollack A, Zagars GK, Cole CJ, Dinney CP, Swanson DA, Grossman HB. The relationship of local control to distant metastasis in muscle invasive bladder cancer. J Urol 1995; 154:2059-2063 https://doi.org/10.1016/S0022-5347(01)66693-X
  3. Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001;19:666-675 https://doi.org/10.1200/JCO.2001.19.3.666
  4. Birkenhake S, Martus p, Kuhn R, Schroll KM, Sauer R. Radiotherapy alone or radiochemotherapy with platin derivatives following transurethral resection of the bladder. Organ preservation and survival after treatment of bladder cancer. Strahlenther Onkol 1998;174:121-127 https://doi.org/10.1007/BF03038494
  5. Freiha F, Reese J, Torti FM. A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer. J Urol 1996;155:495-499 https://doi.org/10.1016/S0022-5347(01)66430-9
  6. Ghoneim MA, el-Mekresh MM, el-Baz MA, el-Allar lA, Ashamallah A. Radical cystectomy for carcinoma of the bladder: critical evaluation of the results in 1,026 cases. J Urol 1997; 158:393- 399 https://doi.org/10.1016/S0022-5347(01)64487-2
  7. Lehmann J, Retz M, Stockle M. The role of adjuvant chemotherapy for muscle invasive bladder cancer. World J Urol 2001;19:133-140. https://doi.org/10.1007/s003450000194
  8. Shipley WU, Winter KA, Kaufman DS, et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03. J Clin Oncol 1998; 16:3576-3583
  9. Stockle M, Meyenburg W, Wellek S, et al. Adjuvant polychemotherapy of nonorgan-confined bladder cancer after radical cystectomy revisited: long-term results of a controlled prospective study and further clinical experience. J Urol 1995; 153:47-52 https://doi.org/10.1097/00005392-199501000-00019
  10. Shipley WU, Rose MA. Bladder cancer. The selection of patients for treatment by full-dose irradiation. Cancer 198555: 2278-2284 https://doi.org/10.1002/1097-0142(19850501)55:9+<2278::AID-CNCR2820551435>3.0.CO;2-#
  11. Sauer R, Birkenhake S, Kuhn R, Willekind C, Schroll KM, Martus P. Efficacy of radiochemotherapy with platin derivatives compared to radiotherapy alone in organ-sparing treatment of bladder cancer. lnt J Radiat Oncol Biol Phys 1998;40:121-127 https://doi.org/10.1016/S0360-3016(97)00579-8
  12. Birkenhake S, Leykamm S, Martus P, Sauer R. Concomitant radiochemotherapy with 5-FU and cisplatin for invasive bladder cancer. Acute toxicity and first results. Strahlenther Onkol 1999;175:97-101 https://doi.org/10.1007/BF02742341
  13. Gospodarowicz MK, Hawkins NV, Rawlings GA, et al. Radical radiotherapy for muscle invasive transitional cell carcinoma of the bladder: failure analysis. J Urol 1989;142:1448-1453 https://doi.org/10.1016/S0022-5347(17)39122-X
  14. Rodel C, Grabenbauer GG, Kuhn R, et al. Combinedmodality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol 2002;20:3061-3071 https://doi.org/10.1200/JCO.2002.11.027
  15. Mills RD, Turner WH, Fleischmann A, Markwalder R, Thalmann GN, Studer UE. Pelvic lymph node metastases from bladder cancer: outcome in 83 patients after radical cystectomy and pelvic lymphadenectomy. J Urol 2001;166:19-23 https://doi.org/10.1016/S0022-5347(05)66067-3
  16. Vieweg J, Gschwend JE, Herr HW, Fair WR. Pelvic lymph node dissection can be curative in patients with node positive bladder cancer. J Urol 1999;161:449-454 https://doi.org/10.1016/S0022-5347(01)61921-9
  17. Dalbagni G, Genega E, Hashibe M, et al. Cystectomy for bladder cancer: a contemporary series. J Urol 2001;165: 1111-1116 https://doi.org/10.1016/S0022-5347(05)66440-3
  18. Chahal R, Sundaram SK, Iddenden R, Forman DF, Weston PM, Harrison SC. A study of the morbidity, mortality and long-term survival following radical cystectomy and radical radiotherapy in the treatment of invasive bladder cancer in Yorkshire. Eur Urol 2003;43:246-257 https://doi.org/10.1016/S0302-2838(02)00581-X
  19. McDougal WS. Metabolic complications of urinary intestinal diversion. J Urol 1992;147:1199-1208 https://doi.org/10.1016/S0022-5347(17)37517-1
  20. Kim HL, Steinberg GD. The current status of bladder preservation in the treatment of muscle invasive bladder cancer. J Urol 2000; 164:627-632 https://doi.org/10.1016/S0022-5347(05)67267-9
  21. Quilty PM, Duncan W. Primary radical radiotherapy for T3 transitional cell cancer of the bladder: an analysis of survival and control. lnt J Radiat Oncol Biol Phys 1986;12:853-860 https://doi.org/10.1016/0360-3016(86)90376-7
  22. Shipley WU, Kaufman DS, Tester WJ, Pilepich MV, Sandler HM. Overview of bladder cancer trials in the Radiation Therapy Oncology Group. Cancer 2003;97:2115-2119 https://doi.org/10.1002/cncr.11282
  23. Zietman AL, Sacco D, Skowronski U, et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J Urol 2003;170: 1772-1776 https://doi.org/10.1097/01.ju.0000093721.23249.c3
  24. Tester W, Caplan R, Heaney J, et al. Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer: results of Radiation Therapy Oncology Group phase II trial 8802. J Clin Oncol 1996;14:119-126 https://doi.org/10.1200/JCO.1996.14.1.119
  25. Moonen L, vd Voet H, de Nijs R, Hart AA, Horenblas S, Bartelink H. Muscle-invasive bladder cancer treated with external beam radiotherapy: pretreatment prognostic factors and the predictive value of cystoscopic re-evaluation during treatment. Radiother Oncol 1998;49: 149-155 https://doi.org/10.1016/S0167-8140(98)00089-9
  26. Morrison R. The results of treatment of cancer of the bladder - a clinical contribution to radiobiology. Clin Radiol 1975;26: 67-75 https://doi.org/10.1016/S0009-9260(75)80017-1
  27. Chung WK, Oh BR, Ahn SJ. The prognostic factors affecting survival in muscle invasive bladder cancer treated with radiotherapy. J Korean Soc Ther Radiol Oncol 2002;20:130-138
  28. Duncan W, Quilty PM. The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. Radiother Oncol 1986;7:299-310 https://doi.org/10.1016/S0167-8140(86)80059-7
  29. Hayter CR, Paszat LF, Groome PA, Schulze K, Math M, Mackillop WJ. A population-based study of the use and outcome of radical radiotherapy for invasive bladder cancer. lnt J Radiat Oncol Biol Phys 1999;45:1239-1245 https://doi.org/10.1016/S0360-3016(99)00306-5
  30. Cho JH, Lim JH, Seong JS. Bladder preservation by combined modality therapy for invasive bladder cancer: a five-year follow-up. J Korean Soc Ther Radiol Oncol 2001;19:359-368
  31. Mameghan H, Fisher R, Mameghan J, Brook S. Analysis of failure following definitive radiotherapy for invasive transitional cell carcinoma of the bladder. lnt J Radiat Oncol Biol Phys 1995;31 :247-254 https://doi.org/10.1016/0360-3016(94)E0135-7
  32. Yoon SM, Yang KM, Lee HS. Combined modality therapy with selective bladder preservation for muscle invading bladder cancer. J Korean Soc Ther Radiol Oncol 2001;19:237-244
  33. Shipley WU, Prout GR Jr, Einstein AB, et al. Treatment of invasive bladder cancer by cisplatin and radiation in patients unsuited for surgery. Jama 1987;258:931-935 https://doi.org/10.1001/jama.258.7.931
  34. Jacobsen AB, Lunde S, Ous S, et al. T2/T3 bladder carcinomas treated with definitive radiotherapy with emphasis on flow cytometric DNA ploidy values. lnt J Radiat Oncol Biol Phys 1989; 17:923-929 https://doi.org/10.1016/0360-3016(89)90137-5